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Quantitative assessment of the morphology of renal arteries from X-ray images: quantitative vascular analysis.

RATIONALE AND OBJECTIVES: With the advent of interventional vascular procedures, objective and reproducible tools are needed to assist clinical decision-making and to assess intervention efficacy. The success of quantitative coronary arteriography (QVA) in objectively assessing cardiovascular morphology has initiated the software development for quantitative analysis of peripheral vasculature. The objective of this study was to evaluate the applicability and quality of a new QVA package applied to renal arteries. METHODS: A calibration method was developed using markers mounted on a catheter's shaft, ensuring accurate calibration even with small catheter sizes. Given the high prevalence of ostial stenoses in peripheral vessels, a dedicated vessel analysis method was developed to assess these stenoses. Its reproducibility was determined in renal angiography. Variance component analysis was performed to evaluate sources of variability, using angiograms from 74 patients suspected of renovascular hypertension. RESULTS: For intraobserver variability, the 95% confidence intervals of differences in percent diameter stenosis and minimal lumen diameter were -1.99%-1.04% (P = 0.53, n = 48) and -0.081 mm-0.023 mm (P = 0.27, n = 48), respectively. For the interobserver variability, intervals were -1.86%-2.80% (P = 0.69, n = 66) and -0.46 mm-0.053 mm (P = 0.12, n = 46), respectively. CONCLUSIONS: The contribution of intraobserver variation was negligible. The contribution of interobserver variation for different parameters was negligible or comparable with the variation caused by image acquisition. These conclusions demonstrate that QVA can reproducibly measure renal artery geometry.

Calibration↗

Computer-assisted surgical treatment of orbitozygomatic fractures.

Orbitozygomatic fractures pertain to the most common injuries in craniofacial trauma patients. Accurate fracture reduction is of high importance for a successful outcome. This pilot study was performed to assess the potential benefit of surgical navigation to aid in orbitozygomatic fracture reduction. A non-comparative series of five consecutive patients with severely displaced orbitozygomatic fractures was treated using the guidance of computed tomography (CT)-based surgical navigation. Using a previously developed software platform, the fracture was reduced virtually by a three-dimensional shifting of the orbitozygomatic complex within the patient's preoperative multimodal CT data set. This treatment plan was transferred to a navigation system. Fracture reduction was performed according to the treatment plan using surgical navigation. Intraoperative control of fracture reduction by comparing the real with the virtual bone position using surgical navigation showed up as a helpful tool. Accurate treatment planning and immediate evaluation of craniofacial surgery outcome are the benefits of the new approach demonstrated. A major drawback of the presented approach is a high consumption of human and financial resources. A larger clinical series with long-term follow-up will be needed to determine reproducibility and cost-effectiveness. In addition to bone repositioning, a future application may include simulation of craniofacial osteotomies.

Feasibility Studies↗

Three-dimensional virtual cholangioscopy: a reliable tool for the diagnosis of common bile duct stones.

OBJECTIVE: Our goal was to evaluate the clinical reliability of a new software system employing 3-dimensional (3D) virtual anatomic reconstruction and intraluminal virtual exploration for detection of choledocholithiasis and preoperative visualization of the biliary anatomy. SUMMARY BACKGROUND DATA: Virtual reality systems have been proposed for gastroscopy, bronchoscopy, and colonoscopy, as well as for the 3D reconstruction of liver anatomy and hepatic lesions. The impact of these systems in preoperative diagnostics has not been established due to the lack of large clinical series evaluating their reliability. METHODS: From November 2000 to July 2002, all patients presenting to our Institute with suspected choledocholithiasis were prospectively included in the study. All patients underwent conventional magnetic resonance cholangiopancreatography (MRCP) and either intraoperative cholangiogram (IOC) or endoscopic retrograde cholangiopancreatography (ERCP). The digital data from MRCP were incorporated into an original virtual reality software system to generate a 3D reconstruction. All 3D reconstructions were evaluated by a surgeon and a computer software engineer who were blind to the results of the IOC or ERCP. Sensitivity and specificity were then calculated based on the results of either the IOC or ERCP. RESULTS: Sixty-five patients were enrolled in the study. The average time required to reconstruct the images into navigable virtual reality was 7.5 minutes (range, 4-13.5). The 3D virtual cholangioscopy had sensitivity and specificity rates of 71% and 91%, respectively, compared with 61% and 86% of the standard MRCP. CONCLUSION: : The 3D virtual cholangioscopy provides detailed preoperative reconstruction of biliary anatomy and reliable identification of choledocholithiasis with acceptable sensitivity and specificity in a clinical setting. Newer software developments may further enhance its accuracy, so that virtual cholangioscopy might challenge or replace more invasive diagnostic measures in the near future.

Cholangiography↗

Independent component analysis in the study of focal seizures.

Independent component analysis (ICA) is a novel technique that can separate statistically independent elements from complex signals. It has demonstrated its utility in separating artifacts and analyzing interictal discharges in EEG. ICA has been used recently in ictal recordings, showing the possibility of isolating the ictal activity. The goal of our study was to analyze focal seizures with ICA, decomposing the elements of the seizures to understand their genesis and propagation, and to differentiate between various types of focal seizures. We studied 26 focal seizures of temporal, frontal, or parietal origin. Only seizures with suspected focal onset were included in the study. The EEG recordings were acquired by using standard video-EEG equipment, with scalp electrodes. All the off-line analysis was carried out on a PC by means of specific software developed in the Matlab environment. ICA components were calculated with the use of the JADE (Joint Approximate Diagonalization of Eigen-matrices) algorithm. The decomposition of the seizures varied according to the EEG seizure pattern. In the seizures with focal rhythmic theta slow or sharp waves, the rhythmic activity was separated into one to five components, having an initial component with a clear concordance with the focus, whereas the others had an onset a few milliseconds later and corresponded to neighboring areas. In the 6 frontal seizures with regional rhythmic low voltage fast activity, 4 to 10 components were found, practically with a simultaneous timing, having a frontal distribution. In the three frontal seizures with a diffuse attenuation of the EEG signal, it was not possible to differentiate components of cerebral origin from the components of muscle artifact. ICA is an interesting tool to study the nature of focal seizures. The results depend on the EEG pattern. In the seizures with a clear EEG focal pattern, ICA may be useful to separate components of the ictal onset from the propagated activity.

Brain Mapping↗

Retroviruses and yeast retrotransposons use overlapping sets of host genes.

A collection of 4457 Saccharomyces cerevisiae mutants deleted for nonessential genes was screened for mutants with increased or decreased mobilization of the gypsylike retroelement Ty3. Of these, 64 exhibited increased and 66 decreased Ty3 transposition compared with the parental strain. Genes identified in this screen were grouped according to function by using GOnet software developed as part of this study. Gene clusters were related to chromatin and transcript elongation, translation and cytoplasmic RNA processing, vesicular trafficking, nuclear transport, and DNA maintenance. Sixty-six of the mutants were tested for Ty3 proteins and cDNA. Ty3 cDNA and transposition were increased in mutants affected in nuclear pore biogenesis and in a subset of mutants lacking proteins that interact physically or genetically with a replication clamp loader. Our results suggest that nuclear entry is linked mechanistically to Ty3 cDNA synthesis but that host replication factors antagonize Ty3 replication. Some of the factors we identified have been previously shown to affect Ty1 transposition and others to affect retroviral budding. Host factors, such as these, shared by distantly related Ty retroelements and retroviruses are novel candidates for antiviral targets.

Blotting, Southern↗

Theory of the intermediate tilted smectic phases and their helical rotation.

A molecular-statistical theory for the entire sequence of the chiral tilted smectic phases is derived. Uniaxial and biaxial subphases were found to be stable in different temperature ranges depending on the molecular parameters. The model of a chiral molecule possessing a strong transverse terminal dipole moment and a quadrupole moment located in the molecular core was used. Direct dispersion and electrostatic interactions (modulated by shape) between molecules located in the same or in the neighboring smectic layers are taken into account. An effective long-range interaction arises after the minimization of the free energy with respect to polarization vectors. If the molecular quadrupole moment is small, only uniaxial phases with different periodicities arise. Their periodicity may be tens and hundreds of layers (Sm-C*), or approximately two layers (Sm-C*)(Sm-C*A), or several layers (Sm-C*alpha). In the presence of the nonpolar biaxial ordering (in addition to polarization) there is a cap-shaped border in the phase diagram that separates Sm-C*A, Sm-C*, and Sm-C*alpha. If the molecules are nonchiral, Sm-CA, Sm-C, and the de Vries's phases arise instead of the three phases mentioned above. If the molecular quadrupole moment is large, the left "arm" of the border breaks into two lines, and a sequence of biaxial subphases arises in the area between these two lines. Among these biaxial subphases, the one with periodicity of three smectic layers appears to be the broadest in the temperature range. In addition, the subphases with different periodicities were found to be stable in narrow temperature ranges. The long helical rotation in every biaxial subphase is calculated. It is found to change sign between the three-layer subphase and Sm-C*, and may diverge in the four-layer subphase if it arises. All calculations are done with help of (A)FLC Phase Diagram Plotter software developed by the first author and available at his web-page.

Journal Article↗

Chronobiology of Aging in Albizzia julibrissin: I. An Automated, Computerized System for Monitoring Leaflet Movement; The Rhythm in Constant Darkness.

We are using leaflet movements in Albizzia julibrissin as a model system for investigating the chronobiology of aging. To monitor leaflet movements during long dark periods with adequate temporal and spatial resolution, we designed an automated, computerized photoelectric monitoring system. Each of 12 leaflet pairs was positioned in an individual light-proof container, with one leaflet immobilized. The angle of the mobile leaflet was monitored by a photosensor array using a low intensity infrared beam. Leaflet position was determined by custom-developed software, using information on the shading patterns of the sensors. Data on leaflet angle as a function of time were collected and stored on a floppy disc and then printed in numerical and graphical form.Oscillations of young, middle-aged, and old leaflets persist during 7 d of darkness with a periodicity close to 24 h. Period length appears to be age-independent, but rhythmic wave form is age-dependent. The older the leaflet, the earlier and more completely it opens and the less completely it closes.

Journal Article↗

Automated and accurate deposition of structures solved by X-ray diffraction to the Protein Data Bank.

The RCSB Protein Data Bank (PDB) has a number of options for deposition of structural data and has developed software tools to facilitate the process. In addition to ADIT and the PDB Validation Suite, a new software application, pdb_extract, has been designed to promote automatic data deposition of structures solved by X-ray diffraction. The pdb_extract software can extract information about data reduction, phasing, molecular replacement, density modification and refinement from the output files produced by many X-ray crystallographic applications. The options, procedures and tools for accurate and automated PDB data deposition are described here.

Automation↗

Scheduling nursing personnel on a microcomputer.

Suggests that with the shortage of nursing personnel, hospital administrators have to pay more attention to the needs of nurses to retain and recruit them. Also asserts that improving nurses' schedules is one of the most economic ways for the hospital administration to create a better working environment for nurses. Develops an algorithm for scheduling nursing personnel. Contrary to the current hospital approach, which schedules nurses on a person-by-person basis, the proposed algorithm constructs schedules on a day-by-day basis. The algorithm has inherent flexibility in handling a variety of possible constraints and goals, similar to other non-cyclical approaches. But, unlike most other non-cyclical approaches, it can also generate a quality schedule in a short time on a microcomputer. The algorithm was coded in C language and run on a microcomputer. The developed software is currently implemented at a leading hospital in Taiwan. The response to the initial implementation is quite promising.

Algorithms↗

Gene mapping and marker clustering using Shannon's mutual information.

Finding the causal genetic regions underlying complex traits is one of the main aims in human genetics. In the context of complex diseases, which are believed to be controlled by multiple contributing loci of largely unknown effect and position, it is especially important to develop general yet sensitive methods for gene mapping. We discuss the use of Shannon's information theory for population-based gene mapping of discrete and quantitative traits and for marker clustering. Various measures of mutual information were employed in order to develop a comprehensive framework for gene mapping analyses. An algorithm aimed at finding so-called relevance chains of causal markers is proposed. Moreover, entropy measures are used in conjunction with multidimensional scaling to visualize clusters of genetic markers. The relevance chain algorithm successfully detected the two causal regions in a simulated scenario. The approach has also been applied to a published clinical study on autoimmune (Graves') disease. Results were consistent with those of standard statistical methods, but identified an additional locus of interest in the promotor region of the associated gene CTLA4. The developed software is freely available at http://www.Int.ei.tum.de/download/InfoGeneMap/.

Algorithms↗

Low-cost optoelectronic system for three-dimensional artwork texture measurement.

A new optoelectronic system based on a projection unit in which light, coming from a laser diode coupled to an optic fiber impinges on a diffractive optical element (DOE) to produce sinusoidal fringes is proposed for three-dimensional (3-D) texture measurement. If the projected fringe pattern is viewed at an angle different from the projection angle, the fringe profile is phase-modulated by the 3-D object shape. The 3-D map information is obtained with the aid of a fringe analyzer based on phase-shifting synthetic moiré pattern, Fast Fourier Transform (FFT), signal demodulation techniques and a robust and fast phase unwrapping performed by a specially developed software. The proposed system is based on a simple and low cost equipment; furthermore, it is suitable for in situ measurements also by nonskilled operators. Some experimental examples illustrate its performance.

Algorithms↗

Open-and-shut cases in coiled-coil assembly: alpha-sheets and alpha-cylinders.

The coiled coil is a ubiquitous protein-folding motif. It generally is accepted that coiled coils are characterized by sequence patterns known as heptad repeats. Such patterns direct the formation and assembly of amphipathic alpha-helices, the hydrophobic faces of which interface in a specific manner first proposed by Crick and termed "knobs-into-holes packing". We developed software, SOCKET, to recognize this packing in protein structures. As expected, in a trawl of the protein data bank, we found examples of canonical coiled coils with a single contiguous heptad repeat. In addition, we identified structures with multiple, overlapping heptad repeats. This observation extends Crick's original postulate: Multiple, offset heptad repeats help explain assemblies with more than two helices. Indeed, we have found that the sequence offset of the multiple heptad repeats is related to the coiled-coil oligomer state. Here we focus on one particular sequence motif in which two heptad repeats are offset by two residues. This offset sets up two hydrophobic faces separated by approximately 150 degrees -160 degrees around the alpha-helix. In turn, two different combinations of these faces are possible. Either similar or opposite faces can interface, which leads to open or closed multihelix assemblies. Accordingly, we refer to these two forms as alpha-sheets and alpha-cylinders. We illustrate these structures with our own predictions and by reference to natural variants on these designs that have recently come to light.

Amino Acid Motifs↗

Modelling the impact of an influenza pandemic on critical care services in England.

The UK Influenza Pandemic Contingency Plan does not consider the impact of a pandemic on critical care services. We modelled the demand for critical care beds in England with software developed by the Centers for Disease Control (Flusurge 1.0), using a range of attack rates and pandemic durations. Using inputs that have been employed in UK Department of Health scenarios (25% attack rate and 8-week pandemic duration) resulted in a demand for ventilatory support that exceeded 200% of present capacity. Demand remained unsustainably high even when more favourable scenarios were considered. Current critical care bed capacity in England would be unable to cope with the increased demand provided by an influenza pandemic. Appropriate contingency planning is essential.

Bed Occupancy↗

Confocal microscopy as a tool for the study of the intranuclear topography of chromosomes.

A scanning confocal microscope was used to investigate the spatial positions of specific regions within blood cell nuclei. These centromeric regions were fluorescently labelled by in-situ hybridization to suspended nuclei with a centromere-1-specific DNA probe. The 3-D image data sets, obtained by optical sectioning of the cells, were used to determine the spatial position of the centromeric regions in the nuclei by means of specially developed software. The centromeres were found to be localized near the nuclear boundary. This spatial pattern was tested against a random distribution model by means of the Kolmogorov-Smirnov test. The difference between the two patterns was at a P less than 0.01 significance level.

Blood Cells↗

Digital three-dimensional visualization of cellular organelles studied by medium- and high-voltage electron microscopy.

Tilted thick sections (one-half to several micrometers) of biological specimens observed with medium- to high-voltage electron microscopes are extremely useful for the study of the three-dimensional (3-D) structure of organelles. If high resolution in 3-D visualization and 3-D reconstruction is needed, many images corresponding to various angles of rotation and tilt must be recorded. This necessitates very time-consuming work--including eventual photographic processing--before good positioning of the object is defined. We have developed software which permits very rapid and precise determination of the tilt-axis, the registration of tilted views, 3-D measurements and 3-D visualization. Images are digitized either from negative films or directly with a camera fitted to the microscope. The application of the software is performed in minutes and allows for a rapid check of the quality of the tilt-series and of the features of interest of the object. Application of the software to the study of the 3-D structure of active components of the nucleolus stained with silver is shown.

Cell Nucleolus↗

Automated alignment and pattern recognition of single-molecule force spectroscopy data.

Recently, direct measurements of forces stabilizing single proteins or individual receptor-ligand bonds became possible with ultra-sensitive force probe methods like the atomic force microscope (AFM). In force spectroscopy experiments using AFM, a single molecule or receptor-ligand pair is tethered between the tip of a micromachined cantilever and a supporting surface. While the molecule is stretched, forces are measured by the deflection of the cantilever and plotted against extension, yielding a force spectrum characteristic for each biomolecular system. In order to obtain statistically relevant results, several hundred to thousand single-molecule experiments have to be performed, each resulting in a unique force spectrum. We developed software and algorithms to analyse large numbers of force spectra. Our algorithms include the fitting polymer extension models to force peaks as well as the automatic alignment of spectra. The aligned spectra allowed recognition of patterns of peaks across different spectra. We demonstrate the capabilities of our software by analysing force spectra that were recorded by unfolding single transmembrane proteins such as bacteriorhodopsin and NhaA. Different unfolding pathways were detected by classifying peak patterns. Deviant spectra, e.g. those with no attachment or erratic peaks, can be easily identified. The software is based on the programming language C++, the GNU Scientific Library (GSL), the software WaveMetrics IGOR Pro and available open-source at http://bioinformatics.org/fskit/.

Algorithms↗

The spectrum of allergenic pollens in Italy. A computerized method of aerobiological monitoring.

The monitoring of airborne pollens that provoke allergy is of interest to clinicians to enable them to correlate chronologically the relationship between pollen concentrations in the atmosphere and the symptoms of patients with pollen-related allergies. In Italy there are now 60 centres for monitoring airborne allergenic pollens, the data from which are compiled and filed using software developed by the Italian Association of Aerobiology (AIA) and run on personal computers. These data are then fed into a central data bank to which all centres have access. This information system makes it possible to achieve the following objectives: 1) to standardise monitoring methods, 2) to recognise varieties of pollen that cause allergies, 3) to improve the exchange and comparison of information among operators by compiling the results in graphs, and 4) to notify clinicians about atmospheric concentrations of allergenic pollens so that improved therapy can be provided.

Air Pollution↗

Sensitive titration microcalorimetric study of the binding of Salmonella O-antigenic oligosaccharides by a monoclonal antibody.

The binding of several oligosaccharide haptens by a monoclonal antibody, Se155-4, specific for Salmonella serogroup B O-antigen was studied by titration microcalorimetry. In the software developed by Wiseman et al. [Wiseman, T., Williston, S. & Brandts, J.F. (1989) Anal. Biochem. 17, 131-137] the number of binding sites/macromolecule is one of the optional regression parameters in the non-linear least-squares analysis of the calorimetric data. Instead, an approach was adopted in which the concentration of binding sites was treated as a regression parameter, obviating the requirement for precise values of antibody absorption coefficients and minimizing effects due to partially inactive antibody preparations. Furthermore, performing the least-squares analysis in two steps, first using a differential heat mode and then an integral heat mode, was shown to yield the most accurate results. The technique gave accurate results using not more than 1-2 mumol ligand and less than 7 mg antibody. Haptens 2-5 were oligomers of the O-antigenic repeating unit varying in chain length by 2-5 repeating units and a trisaccharide glycoside 1, which filled the binding site. The latter hapten exhibited a favourable entropy contribution to binding (delta Go = -31 kJ.mol-1; delta Ho = -21 kJ.mol-1 and -T delta So -10 kJ.mol-1), while all four oligomers 2-5 showed a constant binding energy delta Go = -33 kJ.mol-1, composed of increasingly stronger enthalpy forces compensated by an increasingly unfavourable entropy contribution. These observations are compared with results from enzyme immunoassays and a high-resolution crystal structure for the dodecasaccharide 3 bound to the Fab derived from Se155-4.

Antibodies, Monoclonal↗