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PubMed1996

Epitope Mapping by Label-Free Biomolecular Interaction Analysis

The diversity of B-cell response to a large immunogen gives rise to a series of antibodies that can be used for epitope mapping of an antigen. This is based on the relative reaction pattern for all antibodies in relation to each other and other ligands to the studied protein. With the introduction of an instrument system, BIAcore, label-free real-time biomolecular interaction analysis (BIA) was made possible. It is based on biosensor technology, with a carboxymethyl-dextran-coated gold surface and an integrated fluidics for transport of liquid. The basic idea is to measure label-free binding of an analyte from a continuous flow to an immobilized ligand in real time. With an automatic approach, quantitative analysis and sequential injection characteristic biospecific binding parameters such as affinity and kinetic constants can be measured. The instrument system was adopted at an early stage for epitope mapping. With label-free detection, antibodies from tissue culture media can be analyzed without purification. Binding of both antigen and a series of antibodies can be individually determined in molar ratio by sequential injections. The quantitative aspects of BIA offer the possibility of further refined epitope mapping. The relative binding pattern for 30 monoclonal antibodies against HIV-1 p24 core protein has been analyzed. Multideterminant analysis and peptide identification of binding sites were performed. Verification of the binding pattern has also been performed in relation to mapping with ELISA as well as the binding to peptides derived from the antigen sequence. Functional domains of proteins in relation to an epitope map have been identified for Taq polymerase.

Journal Article↗
PubMed1991

Lumbar percutaneous discectomy. Initial experience in 28 cases.

Since November 1988, 28 patients with lumbar L5 radiculopathy refractory to conservative care and with a radiologically verified central or mediolateral disc herniation at the level of L4/L5 had had a percutaneous discectomy. Radiological verification consisted of spinal CT +/- myelography, +/- myelo-CT, +/- MRI. A short-term follow-up analysis of at least 2 months taking the clinical and functional status as well as the professional reintegration into account revealed a 64.3% (18/28 patients) satisfactory outcome and a 32.1% (10/28 patients) failure rate. Of the latter 28.6% (8/28 patients) required further open surgery. One patient whose pain had only partially in regressed was shown at open operation to have a sequestered cranial prolapse as revealed by spinal CT after the percutaneous procedure. There were no major complications. One patient developed a sequestered extraforaminal herniation through the nucleotomy canal three weeks after the procedure. One patient bled for 2 minutes. There were no major vessel injuries. One patient reported local muscular pain, and enhanced nerve root pain after introduction of the trocar sleeve.

Adult↗
PubMed1994

Acetylcholine sweat test: an effective way to select patients for lumbar sympathectomy.

Although lumbar sympathectomy can benefit patients with critical limb ischaemia, many derive no benefit from the procedure. The poor prediction of outcome may be related to pre-existing damage to the sympathetic fibres. We assessed sympathetic nerve function with the acetylcholine sweatspot test before and after lumbar sympathectomy in 31 patients with critical limb ischaemia. Of 9 patients with normal sympathetic function or minor denervation preoperatively (sweatspot score > or = 8), 8 showed improvement in pain and/or healing of ischaemic lesions after sympathectomy. The procedure did not achieve denervation in the patient without improvement, as shown by persisting sympathetic activity postoperatively. By contrast, among the 22 patients with lower sweatspot scores, indicating severe or complete sympathetic denervation, only 1 showed improvement (partial) after lumbar sympathectomy. 9 patients underwent oximetry before and after the operation; in this subgroup there was a positive correlation between preoperative sweatspot score and the change in tissue partial pressure of oxygen (r2 = 0.35). Preoperative assessment of sympathetic nerve function by means of a sensitive, quantitative test of autonomic integrity can predict the outcome of the procedure with high sensitivity and specificity. A postoperative test allows verification of sympathetic denervation. We recommend use of this simple test in selecting patients for lumbar sympathectomy.

Acetylcholine↗
PubMed2000

An integrated service digital network (ISDN)-based international telecommunication between Samsung Medical Center and Hokkaido University using telecommunication helped radiotherapy planning and information system (THERAPIS).

This study introduces the integrated service digital network (ISDN)-based international teleradiotherapy system (THERAPIS) in radiation oncology between hospitals in Seoul, South Korea and in Sapporo, Japan. THERAPIS has the following functions: (1) exchange of patient's image data, (2) real-time teleconference, and (3) communication of the treatment planning, dose calculation and distribution, and of portal verification images between the remote hospitals. Our preliminary results of applications on eight patients demonstrated that the international telecommunication using THERAPIS was clinically useful and satisfactory with sufficient bandwidth for the transfer of patient data for clinical use in radiation oncology.

Japan↗
PubMed2006

A structure-based approach to retinoid X receptor-alpha inhibition.

In this paper we describe a structure-based approach designed to identify novel ligands for retinoid X receptor-alpha (RXRalpha). By using a virtual approach based on a modified scoring function, we have selected 200 potential candidates on the basis of their predicted ability of docking into the ligand-binding site of the target. Subsequent experimental verification of the compounds in in vitro and cell-based assays led to the identification of a number of novel high affinity ligands for RXRalpha. The compounds are capable of displacing 9-cis-retinoic acid with IC(50) values in the 10 nm and 5 mum range and exhibit marked antagonistic activity in cellular assays. The inhibitory scaffolds discovered with this method form the basis for the development of novel RXRalpha ligands with potential therapeutic properties.

Animals↗
PubMed1990

Viscoplasticity of respiratory tissues.

Low-frequency mechanical behavior of various respiratory tissues shows certain similarities. In this study we test the hypothesis that rate-independent plastic processes along with rate-dependent viscoelastic processes are responsible. We considered oscillatory responses of several respiratory tissues measured over prescribed ranges of frequency (up to 6 Hz) and amplitude of forcing. These included the excised cat lung, the human chest wall in vivo, and two components of the chest wall: the excised dog rib cage and the excised rabbit abdominal viscera; some data were previously reported and some are new. We analyzed these data using the viscoplastic model of Hildebrandt (J. Appl. Physiol. 28: 365-372, 1970). It consists of three compartments: a plastoelastic compartment mechanically in parallel with a viscoelastic compartment, both in series with a lumped inertia. We fitted oscillatory data of the above respiratory tissues to the model by a least-squares technique. The fit was qualitatively consistent with the observations and exhibited moderately good to very good quantitative correspondence. As an independent verification of this approach, we obtained the stress relaxation after a step-volume change. Based on the oscillatory response of cat lungs, the calculated stress relaxation function was found to be generally consistent with corresponding observations. This study indicates that both plasticity and viscoelasticity appear to be important determinants of mechanical behavior of respiratory tissues at low frequencies and that inertial effects are negligible.

Animals↗
PubMedDate not supplied

Testosterone and dyslexia.

Geschwind, Behan and Galaburda have presented empirical research which indicates an association between left-handedness, immune disorders, and learning difficulties. Moreover, they have presented an hypothesis that purports to explain these associations, i.e. the 'testosterone hypothesis'. This article seeks to show that their hypothesis cannot explain: (a) which types and degrees of the conditions will appear, (b) why these conditions appear more often in males than in females, and (c) why these conditions seem to run in families. Moreover, this article attempts to show (d) that the hypothesis does not make clear the distinction between genetic and environmental factors, and that environmental factors are of greater importance. In addition, the hypothesis leads to great importance being given to purely random factors, because random factors alone determine whether or not a person with hemispherical symmetry will develop abnormal dominance Furthermore, this article argues that an hypothesis of this type should be based on a clear dividing line between latent and manifest symptoms, particularly when these are used to define research samples. Finally, (e) this article seeks to raise doubt as to the possible verification or falsification of the hypothesis by means of empirical studies.

Brain↗
PubMed1999

Computer imaging and workflow systems in the business office.

Computer imaging and workflow technology automates many business processes that currently are performed using paper processes. Documents are scanned into the imaging system and placed in electronic patient account folders. Authorized users throughout the organization, including preadmission, verification, admission, billing, cash posting, customer service, and financial counseling staff, have online access to the information they need when they need it. Such streamlining of business functions can increase collections and customer satisfaction while reducing labor, supply, and storage costs. Because the costs of a comprehensive computer imaging and workflow system can be considerable, healthcare organizations should consider implementing parts of such systems that can be cost-justified or include implementation as part of a larger strategic technology initiative.

Admitting Department, Hospital↗
PubMed2000

A human factors approach for Japanese experiment module development.

NASDA has been developing the Japanese Experiment Module (JEM) in the International Space Station (ISS) program since 1985. From the experience of developing the JEM systems, the author will specify a conceptual framework of a human factors approach in space. First, human factors engineers should identify all the factors affecting the astronauts, hardware, and software in the manned space system being developed. In the JEM development, four major factors were identified: Habitability, Operation, Physiology, and Psychology. Second, the several phases of the JEM development cycle should be considered. Each phase is aimed at transforming the system requirements into actual functioning systems, analyzing and reviewing the design specification to ensure JEM meets or exceeds the requirements, and verifying the JEM crew-interface systems design. In the verification process, human factors engineers should consider the environment to which test subjects and models are exposed in the verification: 1 G, 0 G, isolated, confined and extreme environments.

Adaptation, Psychological↗
PubMed2001

Modeling and simulation for space medicine operations: preliminary requirements considered.

The NASA Space Medicine program is now developing plans for more extensive use of high-fidelity medical simulation systems. The use of simulation is seen as means to more effectively use the limited time available for astronaut medical training. Training systems should be adaptable for use in a variety of training environments, including classrooms or laboratories, space vehicle mockups, analog environments, and in microgravity. Modeling and simulation can also provide the space medicine development program a mechanism for evaluation of other medical technologies under operationally realistic conditions. Systems and procedures need preflight verification with ground-based testing. Traditionally, component testing has been accomplished, but practical means for "human in the loop" verification of patient care systems have been lacking. Medical modeling and simulation technology offer potential means to accomplish such validation work. Initial considerations in the development of functional requirements and design standards for simulation systems for space medicine are discussed.

Aerospace Medicine↗
PubMed1994

Sodium balance in very-low-birth-weight infants.

Maintaining sodium balance in the VLBW infant is not straightforward. Several predisposing factors appear in more than one imbalance constellation. In addition, the same patient circumstance can produce two types of imbalance. Understanding the physical properties of electrolytes and water enables critical care nurses to anticipate outcomes of specific situations in the neonatal ICU. Careful assessment of renal function, urine output, and water balance are crucial in determining proper treatment of sodium balance disorders. The high potential risk of errors in the neonatal ICU requires verification of all fluid and electrolyte orders, as well as serial safety checks of IV fluids and additives to avoid complications. An expert nurse's ability to predict the needs of VLBW infants places the nurse in a pivotal position to recognize subtle changes before actual physiologic change occurs. Although the multiple variations can be confusing to the bedside clinician, sorting through them helps in selecting interventions that are timely and improve the outcomes and morbidity of our smallest patients at risk.

Humans↗
PubMed1997

The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.

The complete nucleotide sequence of Saccharomyces cerevisiae chromosome VII has 572 predicted open reading frames (ORFs), of which 341 are new. No correlation was found between G+C content and gene density along the chromosome, and their variations are random. Of the ORFs, 17% show high similarity to human proteins. Almost half of the ORFs could be classified in functional categories, and there is a slight increase in the number of transcription (7.0%) and translation (5.2%) factors when compared with the complete S. cerevisiae genome. Accurate verification procedures demonstrate that there are less than two errors per 10,000 base pairs in the published sequence.

Base Sequence↗
PubMed2001

Verification of IMRT dose distributions using a water beam imaging system.

A water beam imaging system (WBIS) has been developed and used to verify dose distributions for intensity modulated radiotherapy using dynamic multileaf collimator. This system consisted of a water container, a scintillator screen, a charge-coupled device camera, and a portable personal computer. The scintillation image was captured by the camera. The pixel value in this image indicated the dose value in the scintillation screen. Images of radiation fields of known spatial distributions were used to calibrate the device. The verification was performed by comparing the image acquired from the measurement with a dose distribution from the IMRT plan. Because of light scattering in the scintillator screen, the image was blurred. A correction for this was developed by recognizing that the blur function could be fitted to a multiple Gaussian. The blur function was computed using the measured image of a 10 cm x 10 cm x-ray beam and the result of the dose distribution calculated using the Monte Carlo method. Based on the blur function derived using this method, an iterative reconstruction algorithm was applied to recover the dose distribution for an IMRT plan from the measured WBIS image. The reconstructed dose distribution was compared with Monte Carlo simulation result. Reasonable agreement was obtained from the comparison. The proposed approach makes it possible to carry out a real-time comparison of the dose distribution in a transverse plane between the measurement and the reference when we do an IMRT dose verification.

Calibration↗
PubMed1999

Image registration of BANG gel dose maps for quantitative dosimetry verification.

BACKGROUND: The BANG (product symbol SGEL, MGS Research Inc., Guilford, CT) polymer gel has been shown to be a valuable dosimeter for determining three-dimensional (3D) dose distributions. Because the proton relaxation rate (R2) of the gel changes as a function of absorbed dose, MR scans of the irradiated gel can be used to generate 3D dose maps. Previous work with the gel, however, has not relied on precise localization of the measured dose distribution. This has limited its quantitative use, as no precise correlation exists with the planned distribution. This paper reports on a technique for providing this correlation, thus providing a quality assurance tool that includes all of the steps of imaging, treatment planning, dose calculation, and treatment localization. METHODS AND MATERIALS: The BANG gel formulation was prepared and poured into spherical flasks (15.3-cm inner diameter). A stereotactic head ring was attached to each flask. Three magnetic resonance imaging (MRI) and computed tomography (CT) compatible fiducial markers were placed on the flask, thus defining the central axial plane. A high-resolution CT scan was obtained of each flask. These images were transferred to a radiosurgery treatment-planning program, where treatment plans were developed. The gels were irradiated using our systems for stereotactic radiosurgery or fractionated stereotactic radiotherapy. The gels were MR imaged, and a relative 3D dose map was created from an R2 map of these images. The dose maps were transferred to an image-correlation program, and then fused to the treatment-planning CT scan through a rigid body match of the MRI/CT-compatible fiducial markers. The fused dose maps were imported into the treatment-planning system for quantitative comparison with the calculated treatment plans. RESULTS: Calculated and measured isodose surfaces agreed to within 2 mm at the worst points within the in-plane dose distributions. This agreement is excellent, considering that the pixel resolution of the MRI dose maps is 1.56 x 1.56 mm, and the treatment-planning dose distributions were calculated on a 1-mm dose grid. All points within the dose distribution were well within the tolerances set forth for commissioning and quality assurance of stereotactic treatment-planning systems. Moreover, the quantitative evaluation presented here tests the accuracy of the entire treatment-planning and delivery process, including stereotactic frame rigidity, CT localization, CT/MR correlation, dose calculation, and radiation delivery. CONCLUSION: BANG polymer gel dosimetry coupled with image correlation provides quantitative verification of the accuracy of 3D dose distributions. Such quantitative evaluation is imperative to ensure the high quality of the 3D dose distributions generated and delivered by stereotactic and other conformal irradiation systems.

Gels↗
PubMed1976

[Diagnosis of pulmonary hypertension with the aid of electrokymography].

Electrokymography was carried out in 198 patients with cor pulmonale and mitral defect with clinical signs of elevated blood pressure in the pulmonary circulation. The electrokymographic signs of pulmonary hypertension were developed, as well as those for the evaluation of the functional state of the myocardium of both ventricles. In making the diagnosis of elevated--pressure in the pulmonary artery system of special importance is the analysis of the electrokymogrammes of the pulmonary artery, right atrium and right ventricle, and the determination of the pulse wave speed along the pulmonary vessels. The study of the electrokymogrammes and their comparison with the clinical pattern permitted to classify all the electrokymographic criteria of pulmonary hypertension into true and relative ones, requiring verification. A differentiated analysis of the systolic and diastolic phases of the left and right ventricles was conducted. All the phases of the cardiac cycle were calculated with due regard of the contractions rate. The phase analysis permitted to assess separately the functional state of the myocardium of both halves of the heart. Electrokymography helped to reveal pulmonary hypertension that could be often diagnosed with its aid at an early stage. It permitted to diagnos an initial reduction of the contractile finction of the right ventricle.

Electrokymography↗
PubMed1964

VARIETIES OF INFORMATION REQUESTS IN A MEDICAL LIBRARY.

In an analysis of the information requests received and recorded in the Cleveland Medical Library over a two-year period, the requests were classified in four groups according to whether they were direct inquiries (factual), indirect (subject), biographical and directory, or requests for verification of literature citations. An attempt was made to discover some of the major characteristics and the volume of activity in each class. The results reflect the information services supplied by a single library with its own unique clientele and functions, rather than provide a means of generalizing about information services in all libraries, although they may give us some useful insights. Detailed analyses are made of direct and of biographical and directory questions. The largest number of inquiries received were those in which literature references on a specified subject were requested (indirect inquiries); these represented over 50 percent of the total. Most of the requests in this category called for limited coverage (five articles or less) in the recent literature (not over five years). Requests for verification of citations ranked next with 25 percent of the total, followed by direct (factual) inquiries (12 percent) and biographical and directory inquiries (9 percent), although it is recognized that these last two classes are probably underrepresented in the sample.

Bibliographies as Topic↗
PubMed2000

Advances in random matrix theory, zeta functions, and sphere packing.

Over four hundred years ago, Sir Walter Raleigh asked his mathematical assistant to find formulas for the number of cannonballs in regularly stacked piles. These investigations aroused the curiosity of the astronomer Johannes Kepler and led to a problem that has gone centuries without a solution: why is the familiar cannonball stack the most efficient arrangement possible? Here we discuss the solution that Hales found in 1998. Almost every part of the 282-page proof relies on long computer verifications. Random matrix theory was developed by physicists to describe the spectra of complex nuclei. In particular, the statistical fluctuations of the eigenvalues ("the energy levels") follow certain universal laws based on symmetry types. We describe these and then discuss the remarkable appearance of these laws for zeros of the Riemann zeta function (which is the generating function for prime numbers and is the last special function from the last century that is not understood today.) Explaining this phenomenon is a central problem. These topics are distinct, so we present them separately with their own introductory remarks.

Journal Article↗
PubMed2002

Improving the development of event-driven control systems in the batch processing industry. A case study.

This paper presents the results of an academia-industry collaborative project whose main objective was to test novel techniques for the development of event-driven control systems in the batch processing (e.g., pharmaceutical, fine chemicals, food) industries. Proposed techniques build upon industrial standards and focus on (i) formal synthesis of phase control logic and its automatic translation into procedural code, and (ii) verification of the complete discrete-event control system via dynamic simulation. In order to test the techniques in an engineering environment, a complete discrete-event control system was produced for a benchmark batch process plant based on a standard development method employed by one of the industrial partners. The control system includes functional process specification, control architecture, distributed control system (DCS) proprietary programming code for procedural control at equipment, unit, and process cell levels, and human-machine interfaces: A technical assessment of the development method and the obtained control system was then carried out. Improvements were suggested using the proposed techniques in the specification, code generation and, verification steps. The project assessed the impact of these techniques from both an engineering and economic point of view. Results suggest that the introduction of computer aided engineering (CAE) practices based on the benchmarked techniques and a structured approach could effect a 75% reduction of errors produced in the development process. This translates into estimated overall savings of 7% for green-field projects. Figures were compared with other partners' experience. It is expected that the work load on a given project will shift, increasing the load on process engineers during the specification stage and decreasing the load on the software engineers during the code writing.

Algorithms↗