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Restriction map construction using a 'complete sentences compatibility' algorithm.

We have developed a new algorithm 'Complete sentences compatibility' (CSC) which uses single and double digestion fragments to rapidly determine restriction maps of circular DNA. From possible combinations of fragments of each simple digestion, which we call 'sentences of decomposition', we construct a restriction map which combines the sentences while taking into account compatibility rules. The algorithm can also deal with experimental errors of fragment weight and can suggest solutions that account for non-readable bands (fragments of zero length or multiple bands) on the gel. Because experiments using pairs of restrictive enzymes often result in multiple solutions, a complementary algorithm tries to reduce the number of proposed solutions by establishing consensus maps. The restriction map construction algorithm was tested on real cases, some containing more than fifteen fragments. Execution times range from 1-10 s on an IBM PC compatible microcomputer.

Algorithms

Validation of closed-loop subcutaneous insulin infusion algorithm--application of subcutaneous insulin absorption kinetics.

For long-term glycemic normalization with a closed-loop control system, a subcutaneous insulin infusion algorithm has been developed based on the pharmacokinetics of subcutaneously administered insulin. A 3-compartmental model was applied to mathematically express the relation between the insulin injected subcutaneously as an input and the plasma insulin response as an output. A computer simulation study using this model showed that the following insulin infusion algorithm is feasible for closed-loop glycemic control by selecting appropriate parameters (Kp/Kd/Kc = 0.0056/0.92/-0.11), IIR(t) = Kp G(t)+Kd d G(t)/dt+Kc, where IIR(t) is the subcutaneous insulin infusion rate at time t (min), G(t) is the blood glucose concentration and Kp, Kd, Kc are the constants. In 5 pancreatectomized dogs, subcutaneous insulin infusion with this algorithm made it possible to keep postprandial glycemic levels after oral glucose load (2 g/kg) at 168 +/- 14 mg/dl (mean +/- SEM) in 60 min and maintained normoglycemia from 180 to 300 min with the total amount of infused insulin being 0.14 +/- 0.019 U/kg. In 5 insulin-dependent diabetic patients, the peaks of postprandial glycemic levels after meal load (450 kcal) were controlled to 176 +/- 36 mg/dl at 90 min and were reduced to 98 +/- 13 mg/dl at 300 min with the total amount of infused insulin being 0.172 +/- 0.063 U/kg. The mean peak plasma insulin level was 49 +/- 11 microU/ml at 90 min. These results indicate the clinical controllability of postprandial glycemia with the closed-loop subcutaneous insulin infusion algorithm in diabetic patients.

Algorithms

A response algorithm for the low-pressure alarm condition.

A response algorithm consists of a logical sequence of maneuvers to be performed in response to a specific condition. With the advent of alarm-equipped monitors that alert anesthesiologists to the presence of potentially hazardous clinical conditions, a need has arisen to develop the corresponding alarm-oriented responses expected from anesthesiologists; this problem, however, has not been satisfactorily addressed in the literature. An algorithm is proposed that guides the anesthesiologist through the three limbs of the ventilation system--gas supply system, breathing circuit, and mechanical ventilator--in response to a low-pressure alarm condition during automatic mechanical ventilation. The three-limbed algorithm rapidly and efficiently localizes the likely cause of the low-pressure condition without compromising patient safety; in the event that the search for a cause is fruitless, a default mode of ventilation is employed. A discussion is provided of common causes (e.g., disconnections), alarm-defeating circumstances (false negatives), and potential algorithm-defeating situations (multiple faults).

Algorithms

Self-stabilization of neuronal networks. I. The compensation algorithm for synaptogenesis.

Between the extreme views concerning ontogenesis (genetic vs. environmental determination), we use a moderate approach: a somehow pre-established neuronal model network reacts to activity deviations (reflecting input to be compensated), and stabilizes itself during a complex feed-back process. Morphogenesis is based on an algorithm formalizing the compensation theory of synaptogenesis (Wolff and Wagner 1983). This algorithm is applied to randomly connected McCulloch-Pitts networks that are able to maintain oscillations of their activity patterns over time. The algorithm can lead to networks which are morphogenetically stable but preserve self-maintained oscillations in activity. This is in contrast to most of the current models of synaptogenesis and synaptic modification based on Hebbian rules of plasticity. Hebbian networks are morphogenetically unstable without additional assumptions. The effects of compensation on structural and functional properties of the networks are described. It is concluded that the compensation theory of synaptogenesis can account for the development of morphogenetically stable neuronal networks out of randomly connected networks via selective stabilization and elimination of synapses. The logic of the compensation algorithm is based on experimental results. The present paper shows that the compensation theory can not only predict the behavior of synaptic populations (Wagner and Wolff, in preparation), but it can also describe the behavior of neurons interconnected in a network, with the resulting additional system properties. The neuronal interactions--leading to equilibrium in certain cases--are a self-organizing process in the sense that all decisions are performed on the individual cell level without knowing the overall network situation or goal.

Animals

Toward an automated analysis system for nuclear magnetic resonance imaging. II. Initial segmentation algorithm.

Image segmentation algorithms based on hierarchical clustering have been developed for analysis of T1 and T2 nuclear magnetic resonance images. Application of these algorithms to simultaneous T1-T2 images of healthy volunteers extracted fundamental tissue types in the brain. These algorithms also were used both to identify the extent of the region of involvement of a subject with a history of a grade 3 astrocytoma of the right frontal lobe of the brain, and to characterize the tissue within the region of involvement. These results suggest that a simple segmentation algorithm can produce reasonable clustering of tissue types within the brain.

Biometry

Rheumatology algorithms for primary care physicians.

Primary care physicians were trained on three rheumatology topics to assess the effectiveness of an educational strategy for continuing medical education. Algorithm training was shown to be at least as effective as that based on standard prose monographs. Both training groups improved their knowledge of patient management skills but there were no statistically significant differences between groups in the amount learned. When algorithms were used to design text materials, the designed texts required less study time than did the annotated clinical algorithms alone. That difference was significant for the shoulder pain materials (P less than 0.05) but not for the osteoporosis materials. The ratio of knowledge gained to study time was significantly higher for the algorithm group on the low back pain topic (P less than 0.05) but not for the other topics. Taped interview problems tests were studied as a method for assessing patient management skills related to problem-specific indicator conditions and were found to produce interrater reliability greater than 0.80 on five of the six tests.

Clinical Protocols

Adverse drug reactions causing hospital admission in an elderly population: experience with a decision algorithm.

An adverse drug reaction (ADR) decision algorithm was used in the review of 100 consecutive hospital admissions of elderly patients cared for by family physicians. The algorithm is a valid methodologic alternative to using pharmacological experts for verification of an ADR. In this study, the algorithm was easily applied by family physicians, and the results were similar to those reported by expert clinical pharmacologists. Nine percent of our elderly patients' hospital admissions were caused by ADRs that were due to usual doses of medications commonly prescribed for elderly patients. Average age of patients and number of medications were similar for persons with and without ADRs. The algorithm can be useful to physicians investigating ADRs for clinical research, physician education, quality assurance, and improved patient care.

Aged

Quantitative structure-activity relationships. V. A simple simple algorithm for Fujita-Ban and Free-Wilson analyses.

For quantitative structure-activity analyses a simple algorithm for the calculation of de novo group contributions by Fujita-Ban analysis is given. This algorithm corresponds in all details to a computer program for linear multiple regression analysis. However, the transformation of the original matrix to the normal equations matrix is easily achieved without a computer. The normal equations matrix can be solved with a modern desk calculator being equipped with a matrix ROM. Two examples are given to explain the algorithm; the calculation of all important statistical parameters is illustrated. As for quantitative structure-activity analyses this algorithm can be applied as well for the calculation of other additive parameters, such as pi from log P-values or omega from equilibrium constants.

Electronic Data Processing

SPECT liver imaging using an iterative attenuation correction algorithm and an external flood source.

The results obtained from the inclusion of a new intrinsic attenuation correction algorithm into a protocol for SPECT liver imaging are presented in this study. A total of six patients were evaluated with this protocol. The new algorithm uses a transmission tomographic acquisition that is obtained before a standard emission tomograph, and requires the use of an external flood source. The transmission tomograph results in an attenuation image, or map, of the patient. The attenuation map then serves as input into the final intrinsic correction algorithm, that also uses data from a standard emission acquisition. The results of the six patients studied show that the algorithm can correct for attenuation effects without degrading image quality. In all the cases studied, the attenuation corrected images made the cases easier to interpret than did the images obtained without attenuation correction.

Aged

Streamlining Diagnosis of Bardet-Biedl Syndrome: New Diagnostic Algorithm With Updated Criteria.

Considerable advances have been made in our understanding of Bardet-Biedl syndrome (BBS), particularly in its core clinical features and molecular genetics, warranting an update to the existing diagnostic criteria framework. Using a rigorous, evidence-based, and consensus-driven process, a multidisciplinary group of international experts and patient-led organizations developed an updated diagnostic algorithm. This algorithm provides practical, updated guidance for clinicians, including a pathway for accurately incorporating genetic findings into the diagnostic process. We recommend that a clinical diagnosis requires either 4 major criteria or 3 major and 2 minor criteria. Revised major criteria are retinal dystrophy, obesity (or overweight in individuals <&#x2009;2&#x2009;years old), congenital anomalies of the kidney and urinary tract or chronic kidney disease, hypogonadism/genital anomalies, neurodevelopmental/neurocognitive manifestations, and postaxial polydactyly. The diagnosis can also be established with a positive genetic testing result in patients exhibiting &#x2265;&#x2009;1 major criterion, provided that genetic findings should be interpreted in the context of the patient's clinical presentation, age, family history, and overlap with related ciliopathies. These consensus criteria offer a simple algorithm incorporating updated definitions for major and minor criteria and genetic testing to support a timely and accurate diagnosis of patients with BBS, inform genetic counseling, and potentially facilitate earlier access to treatment. Trial Registration: CRIBBS Registry; ClinicalTrials.gov: NCT02329210.

Humans

Generating three-dimensional genome structures with a variational quantum algorithm.

Chromosome conformation capture experiments have revealed the underlying spatial interactions that govern three-dimensional (3D) genome organization and topology. Detecting 3D contacts between genomic loci considerably enhances our understanding of fundamental regulatory processes. Modeling 3D structures from experimental contact matrices can further contextualize the relationship between 3D genome organization and regulation. While classical algorithms have been successful in reconstructing genomic conformations, we investigate the prospect of quantum computation to aid in modeling the conformational space. In this context, we propose a novel variational quantum algorithm (VQA) to model the distribution of 3D genomic structures from experimental contact data. Through rigorous evaluations, we demonstrate the capability of our algorithm to sample ensembles of viable 3D conformations that agree well with experimental and simulated contact data. Furthermore, we extend our methodology to model the conformational space of a single cell or a population of cells. In the advent of sufficient quantum utility, the insights gained from this study can serve as a foundation for investigating high-resolution, large-scale ensembles of genomic conformations through generative VQAs.

Algorithms

Effects of limited input distance constraints upon the distance geometry algorithm.

In this paper we examine the distance geometry (DG) algorithm in the form used to determine the structure of proteins. We focus on three aspects of the algorithm: bound smoothing with the triangle inequality, the random selection of distances within the bounds, and the number of distances needed to specify a structure. Computational experiments are performed using simulated and real data for basic pancreatic trypsin inhibitor (BPTI) from nmr and crystallographic measurements. We find that the upper bounds determined by bound smoothing to be a linear function of the true crystal distance. A simple model that describes the results obtained with randomly selected trial distances is proposed. Using this representation of the trial distances, we show that BPTI DG structures are more compact than the true crystal structure. We also show that the DG-generated structures no longer resemble test structures when the number of these interresidue distance constraints is less than the number of degrees of freedom of the protein backbone. While the actual model will be sensitive the way distances are chosen, our conclusions are likely to apply to other versions of the DG algorithm.

Algorithms

An efficient algorithm for sequencing peptides using fast atom bombardment mass spectral data.

An efficient algorithm is described for sequencing peptides from sequence ions appearing in fast atom bombardment (FAB) and FAB tandem mass spectra. The following features are incorporated in the algorithm. The members of the set of sequence ions are represented by all possible combinations of N- and C-terminal fragment ions. From the known N- and C-terminating groups and molecular weight (MW) of the peptide, the sequence ions are mathematically re-expressed as N-terminal residue ions and arranged in ascending order. The peptide sequence is computed, in a stepwise iterative procedure, from the mass differences between the mathematically re-expressed N-terminal residue ions and the predicted peptide subsequences for the neighboring ions of lower mass. These mass differences correspond to combinations of known amino acid residues which have previously been computed and tabulated, based upon the FAB fragmentation rules for peptides. The algorithm was successfully applied to sequence the following peptides from their respective FAB or FAB tandem mass spectrum: decapeptyl (MW 1310), angiotensin II (MW 1045), and two 'unknown' peptides (MW 1227 and 1485, respectively). Two criteria used to predict the correct peptide sequence from among many possibilities are the minimum number of amino acid residues and the maximum fragmentation probability per amino acid residue.

Algorithms

Statistical evaluation of cell kinetic data from DNA flow cytometry (FCM) by the EM algorithm.

Flow cytometric DNA measurements yield the amount of DNA for each of a large number of cells. A DNA histogram normally consists of a mixture of one or more constellations of G0/G1-, S-, G2/M-phase cells, together with internal standards, debris, background noise, and one or more populations of clumped cells. We have modelled typical DNA histograms as a mixed distribution with Gaussian densities for the G0/G1 and G2/M phases, an S-phase density, assumed to be uniform between the G0/G1 and G2/M peaks, observed with a Gaussian error, and with Gaussian densities for standards of chicken and trout red blood cells. The debris is modelled as a truncated exponential distribution, and we also have included a uniform background noise distribution over the whole observation interval. We have explored a new approach for maximum-likelihood analyses of complex DNA histograms by the application of the EM algorithm. This algorithm was used for four observed DNA histograms of varying complexity. Our results show that the algorithm works very well, and it converges to reasonable values for all parameters. In simulations from the estimated models, we have investigated bias, variance, and correlations of the estimates.

Algorithms

Clinical performance of a polymerase chain reaction testing algorithm for diagnosis of HIV-1 infection in peripheral blood mononuclear cells.

The clinical performance of a modified polymerase chain reaction (PCR) testing algorithm was evaluated for confirming the presence of HIV-1 proviral DNA in peripheral blood mononuclear cells. A whole cell lysate, rather than phenol-purified DNA, was used for PCR amplification, under systematically optimized conditions designed and verified within each PCR run to detect as few as 10 copies of proviral DNA. A sequential testing algorithm was designed requiring reactivity in duplicate (with corresponding non-reactivity in negative controls) with at least two sets of primers, before reporting a specimen as HIV-1-positive. In 196 specimens from patients staged according to the Walter Reed staging system, the PCR test sensitivity and the coculture isolation rate (in parentheses) were found to be: 97% (71%), 100% (85%), and 100% (76%) in stage 1, stage 2, and stage 3 specimens, respectively; and 100% (100%) in stage 4, 5, and 6 specimens. Results were uniformly negative for PCR and coculture isolation from 21 blind negative specimens and 105 (negative) donor leukopacks. These data indicate that this PCR testing algorithm is more accurate than tissue culture isolation methods, especially with early stage patients, and results in detection of HIV-1 in virtually 100% of seropositive individuals, with no false positives.

Acquired Immunodeficiency Syndrome

Volume rendering and connectivity algorithms for MR angiography.

Several display algorithms for three-dimensional angiographic data are evaluated. The mathematical analysis assumes additive Gaussian noise to predict the background distribution function for maximum intensity projection, sum projection, and connectivity display methods. In the maximum intensity projection method the mean noise level increases with the number of voxels in the ray, while in the sum projection the noise distribution width increases with the projection thickness, but the mean level remains constant. Comparisons of maximum intensity projection, sum projection, and connectivity algorithms applied to an MR angiogram of the circle of Willis are made. Measurements of the noise distribution are in agreement with the analysis. Algorithms combining connectivity with maximum intensity and sum projection are also evaluated. In these methods, a projection image is created using only the voxels marked by connectivity, typically with a 6% threshold of the data. Fine vessels are resolved and background noise is reduced in agreement with the analysis.

Algorithms

Describing protein structure: a general algorithm yielding complete helicoidal parameters and a unique overall axis.

We present a general and mathematically rigorous algorithm which allows the helicoidal structure of a protein to be calculated starting from the atomic coordinates of its peptide backbone. This algorithm yields a unique curved axis which quantifies the folding of the backbone and a full set of helicoidal parameters describing the location of each peptide unit. The parameters obtained form a complete and independent set and can therefore be used for analyzing, comparing, or reconstructing protein backbone geometry. This algorithm has been implemented in a computer program named P-Curve. Several examples of its possible applications are discussed.

Algorithms

CLIX: a search algorithm for finding novel ligands capable of binding proteins of known three-dimensional structure.

A computer algorithm, CLIX, capable of searching a crystallographic data-base of small molecules for candidates which have both steric and chemical likelihood of binding a protein of known three-dimensional structure is presented. The algorithm is a significant advance over previous strategies which consider solely steric or chemical requirements for binding. The algorithm is shown to be capable of predicting the correct binding geometry of sialic acid to a mutant influenza-virus hemagglutinin and of proposing a number of potential new ligands to this protein.

Algorithms