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Planning replacement of natural gas distribution systems under constraints on acceptable risk from explosions.

Natural gas distribution systems in the United States were developed primarily in the first half of this century, utilizing materials such as cast iron and then steel. Over time, cast iron and steel pipe sections became weak from corrosion and are subject to failure which in turn can lead to explosions and possible injury and loss of life. Gas utilities maintain system integrity through repair-replacement programs where pipe sections are prioritized for replacement in any given year through cost-benefit analysis; however, the total annual amount to be budgeted for replacement is left to engineering judgment. This approach has left some utilities vulnerable to criticism that their current replacement rate on cast iron pipe is not great enough and that public safety is being compromised. This paper addresses the problem situation by formulating a linear programming replacement decision model which augments cost-benefit analysis with explicit constraints on acceptable risk to human life from fire/explosion. The model is illustrated for a hypothetical utility.

Cost-Benefit Analysis

Information content of the multibreath nitrogen washout: effects of experimental error.

Methods that recover a continuous distribution of specific ventilation (ventilation-to-volume ratio, VA/V) from the multibreath N2 washout curve theoretically can resolve up to four modes of ventilation and reveal the major characteristics of the underlying distribution if experimental error is absent. This paper quantitatively assesses the effects of experimental error on resolution. The washout curves from five typical distributions were studied using linear programming and Monte Carlo methods. A measurement error of 0.1% was assumed in the mixed-expired N2 signal. Only 7 of the first 17 breaths contribute independent information about the underlying distribution, and only rough resolution of the underlying distribution is possible in the presence of error. Only two modes of ventilation plus an estimate of dead space can be confidently resolved. It is not possible to separate VA/V greater than 10 from dead space. A 10-fold reduction in experimental error will not greatly improve resolution. Experimental error, by reducing the linear independence of the defining kernels, significantly limits the information content and resolution of the multibreath N2 washout.

Humans

Rehabilitation of the patient with chronic back pain. A search for outcome predictors.

This prospective study was initiated 3 years ago to evaluate the outcome and to identify predictors of success or failure in patients admitted to a rehabilitation program for chronic low-back pain. Multiple parameters were evaluated, including psychologic data (MMPI, personal interview, pain drawing, etc.), physical measurements (flexibility, strength and endurance), and demographic data concerning the patient's home and working environment. Information was available on each patient admitted to the program prior to his admission, at completion of the program, 6 weeks following completion of the program and 3 months following completion of the program. A telephone interview was carried out 2 1/2 years following the patient's discharge from the program. Linear regression analysis was used to identify the important independent variables with regard to the dependent variables of relief of back pain, return to work and increased activities at home. Demographic data were of no value as a predictor with the exception of age and returning to work. The patients over the age of 50 returned to work with much less frequency than those less than 50. Psychologic information from the MMPI and similar tests were of no value. The personal preadmission interview of a trained psychologist, however, was a good predictor of an individual's eventual return to work and overall improvement. Worker's Compensation and other litigation was a negative factor in a patient's prognosis. The treatment team's prognosis at the time of discharge from the program was the best overall predictor of a patient's chance of success or failure in the longterm.

Activities of Daily Living

High-performance liquid chromatographic analysis of methadone hydrochloride oral solution.

A direct and rapid high-performance liquid chromatographic assay for methadone hydrochloride in a flavored oral solution dosage form is described. A syrup sample, one part diluted with three parts of water, is introduced onto a column packed with octadecylsilane bonded on 10 micrometer porous silica gel (reversed phase). A formic acid-ammonium formate-buffered mobile phase is linear programmed with acetonitrile. The absorbance is monitored continuously at 280 or 254 nm, using a flow-through, UV, double-beam photometer. An aqueous methadone hydrochloride solution is used for external standardization. The relative standard deviation was not more than 1.0%. Drug recovery from a syrup base was better than 99.8%.

Administration, Oral

Fast structure alignment for protein databank searching.

A fast method is described for searching and analyzing the protein structure databank. It uses secondary structure followed by residue matching to compare protein structures and is developed from a previous structural alignment method based on dynamic programming. Linear representations of secondary structures are derived and their features compared to identify equivalent elements in two proteins. The secondary structure alignment then constrains the residue alignment, which compares only residues within aligned secondary structures and with similar buried areas and torsional angles. The initial secondary structure alignment improves accuracy and provides a means of filtering out unrelated proteins before the slower residue alignment stage. It is possible to search or sort the protein structure databank very quickly using just secondary structure comparisons. A search through 720 structures with a probe protein of 10 secondary structures required 1.7 CPU hours on a Sun 4/280. Alternatively, combined secondary structure and residue alignments, with a cutoff on the secondary structure score to remove pairs of unrelated proteins from further analysis, took 10.1 CPU hours. The method was applied in searches on different classes of proteins and to cluster a subset of the databank into structurally related groups. Relationships were consistent with known families of protein structure.

Amino Acid Sequence

Predicted and observed shapes of human mandibular condyles.

A mathematical model based on linear programming was used to study the directions of the joint forces used to maintain the human jaw in three-dimensional static equilibrium when producing bite forces of 100 N to a maximum of 1000 N down the long axis of a central incisor, first premolar, first molar and third molar. Seven different versions of the model were studied. The two simplest versions minimized the total muscle tension and the total joint load, respectively. Assuming that the joint force direction must be normal to some part of the articular surface of the condyle, neither version produced directions consistent with the observed shapes of human condyles. The other five versions minimized different combinations of muscle tensions and joint loads. Two of these versions produced joint force directions compatible with the shapes of condyles. Both minimized total muscle tension plus the (vertical) joint load on the back of the condyle. The results suggest that joint mechanoreceptors (probably non-directional) as well as muscle receptors contribute to the neuromuscular control of bite forces. Our results are consistent with some recent observations [Marshall and Tatton, Exp. Brain Res. 83, 137-150 (1990)] of the cat knee joint.

Biomechanical Phenomena

Determination of doughing and manipulation times of acrylic resin denture base material and a proposal for a specification for a packing plasticity test.

The doughing and manipulation times of a range of acrylic resin denture base polymers are presented in this study. The methods evaluated were: (i) probing following American Society for testing materials specification, F451-76; (ii) hole penetration following British Standard, 2487: 1989 and International Standard Organisation, 1567: 1988; (iii) probing using a penetrometer employing a 20 g load and 1 mm diameter needle; (iv) oscillating rheometer apparatus used at a fixed frequency of 1 Hz by sweeping through a programmed linear increase in strain. The results indicate that each of the methods is capable of evaluating the doughing and manipulation times of the unprocessed polymers. It is concluded that the Bohlin VOR Oscillating Rheometer is excellent for investigating the flow properties of denture base polymers but it cannot be recommended for a standards specification test because of the high cost. The penetrometer method has been shown to be superior to the current standards specification test and would be ideal for a packing plasticity standards test.

Denture Bases

Physiological prediction of muscle forces--II. Application to isokinetic exercise.

The successful application of a physiological model of the musculoskeletal system capable of accounting for nonequilibrium dynamic loading and predicting individual muscle forces in the knee is presented. The model incorporates rigid-body mechanics and musculoskeletal physiology. Unknown muscle and joint contact forces outnumber the equilibrium equations resulting in an indeterminant problem. Mathematical optimization is utilized to resolve the indeterminacy. The model is used to estimate individual muscle forces during isokinetic exercise. Five subjects were tested at speeds of 60 degrees/s and 180 degrees/s. A newly proposed optimal criterion, minimizing muscular activation, results in muscle force predictions which have significantly higher correlations with myoelectric activity than other linear and nonlinear optimal criteria. The results demonstrate that properly constrained linear programming methods do not limit the number of active muscles and allow for uniform recruitment of the active muscles.

Adult

An algorithm for design of beam compensators.

Beam compensators are optimally designed to give a uniform dose to any plane or midsurface that intersects a single beam, or to give a uniform dose to the volume defined by the intersection of two or more beams. The primary and scatter components are taken into account separately, as well as the patient's shape and internal heterogeneities. The design of the beam compensators is formulated as a linear programming problem and solved with a variation of the Simplex Method. Beam weighting factors are also obtained as part of the solution.

Algorithms

Large scale optimization of beam weights under dose-volume restrictions.

The problem of choosing weights for beams in a multifield plan which maximizes tumor dose under conditions that recognize the volume dependence of organ tolerance to radiation is considered, and its solution described. Structures are modelled as collections of discrete points, and the weighting problem described as a combinatorial linear program (LP). The combinatorial LP is solved as a mixed 0/1 integer program with appropriate restrictions on normal tissue dose. The method is illustrated through the assignment of weights to a set of 10 beams incident on a pelvic target. Dose-volume restrictions are placed on surrounding bowel, bladder, and rectum, and a limit placed on tumor dose inhomogeneity. Different tolerance restrictions are examined, so that the sensitivity of the target dose to changes in the normal tissue constraints may be explored. It is shown that the distributions obtained satisfy the posed constraints. The technique permits formal solution of the optimization problem, in a time short enough to meet the needs of treatment planners.

Humans

Computer-aided optimization of choice and positioning of bone plates and screws used for internal fixation of mandibular fractures.

The present study describes a biomechanical integrated model of the mandibular system in which the maxilla and mandible, the masticatory muscles, and the temporomandibular joints are regarded as one system. In this model, strains in plate-osteosynthesis devices for internal fixation of mandibular fractures can be minimized by optimizing their positions. The model evaluates maximal bite force strategies on all possible dental elements; it uses a linear programming technique and a muscle architecture model, resulting in muscle recruitment patterns. The shape of a "standard" lower jaw is digitized by means of a three-dimensional (3-D) coordinate retrieval device and drawn on a computer screen after its dimensions have been changed according to the clinical case at hand. The 3-D location of the fracture as well as the anatomic restrictions for screw placement can be indicated on the screen. Osteosynthesis devices can be indicated in terms of dimensions, number, and material properties.

Biomechanical Phenomena

Multisurface method of pattern separation for medical diagnosis applied to breast cytology.

Multisurface pattern separation is a mathematical method for distinguishing between elements of two pattern sets. Each element of the pattern sets is comprised of various scalar observations. In this paper, we use the diagnosis of breast cytology to demonstrate the applicability of this method to medical diagnosis and decision making. Each of 11 cytological characteristics of breast fine-needle aspirates reported to differ between benign and malignant samples was graded 1 to 10 at the time of sample collection. Nine characteristics were found to differ significantly between benign and malignant samples. Mathematically, these values for each sample were represented by a point in a nine-dimensional space of real variables. Benign points were separated from malignant ones by planes determined by linear programming. Correct separation was accomplished in 369 of 370 samples (201 benign and 169 malignant). In the one misclassified malignant case, the fine-needle aspirate cytology was so definitely benign and the cytology of the excised cancer so definitely malignant that we believe the tumor was missed on aspiration. Our mathematical method is applicable to other medical diagnostic and decision-making problems.

Biopsy, Needle

Uniform depth dose distribution for biological irradiation using negative pions.

A simple, flexible technique has been developed to generate uniform depth dose profiles for the biomedical pion beam at TRIUMF using dynamic momentum control and linear programming. Either the entrance dose or the irradiation time required for a certain dose over the uniform region can be minimised. The dynamic momentum control can operate automatically under computer control even with a highly unstable beam. Cell survival profiles have been obtained for this uniform dose distribution using the gelatin technique. The RBE increases with increasing depth through the uniform dose region.

Animals

Using fragment lengths from incomplete digestion by multiply cleaving enzymes to map antibody binding sites on a protein.

The problem of mapping the positions of the unique binding sites of several monoclonal antibodies on a linear protein structure is considered. Data giving the incidence of binding of individual antibodies to fragments of the protein obtained from it by the incomplete chemical or enzymatic digestion are used to formulate a series of linear programming problems. The solution to these problems shows which orderings of binding sites are possible, and gives upper and lower bounds for the relative positions of the sites.

Algorithms

Detecting and reconstructing breakage-fusion-bridge cycles from long-read sequencing using BFBArchitect.

MOTIVATION: Focal oncogene amplification is a key driver of tumor progression. Remarkably, the increased pathology depends on the context-whether the amplification is extrachromosomal (ecDNA) or intrachromosomal. EcDNA amplifications promote heterogeneity, therapy resistance, and poor prognosis. Focal intrachromosomal amplifications often arise through breakage-fusion-bridge (BFB) cycles, which produce highly rearranged but stable chromosomes. Distinguishing BFB from ecDNA remains challenging due to overlapping genomic signatures. To address this, we present BFBArchitect, a computational method leveraging long-read Oxford Nanopore data to identify BFB sequences consistent with both copy number and structural variations. RESULTS: We provide a novel combinatorial characterization of BFB, which naturally leads to an integer linear programming (ILP) optimization. The ILP optimization generates a BFB sequence that best explains experimentally observed copy numbers and foldback structural variants. We implement this idea in a tool called BFBArchitect, which achieves near-perfect accuracy in distinguishing BFB from non-BFB structures in extensive simulations as well as on 18 validated tumor samples. Moreover, it generates sequence-level BFB reconstructions that provide mechanistic insights into BFB formation, including repair mechanisms with template switching and other structural variants, and recapture of telomere for stabilization. AVAILABILITY AND IMPLEMENTATION: BFBArchitect is available at https://github.com/AmpliconSuite/BFBArchitect.

Sequence Analysis, DNA

A simple method for the computation of first neighbour frequencies of DNAs from CD spectra.

A procedure for the computation of the first neighbour frequencies of DNA's is presented. This procedure is based on the first neighbour approximation of Gray and Tinoco. We show that the knowledge of all the ten elementary CD signals attached to the ten double stranded first neighbour configurations is not necessary. One can obtain the ten frequencies of an unknown DNA with the use of eight elementary CD signals corresponding to eight linearly independent polymer sequences. These signals can be extracted very simply from any eight or more CD spectra of double stranded DNA's of known frequencies. The ten frequencies of a DNA are obtained by least square fit of its CD spectrum with these elementary signals. One advantage of this procedure is that it does not necessitate linear programming, it can be used with CD data digitalized using a large number of wavelengths, thus permitting an accurate resolution of the CD spectra. Under favorable case, the ten frequencies of a DNA (not used as input data) can be determined with an average absolute error < 2%. We have also observed that certain satellite DNA's, those of Drosophila virilis and Callinectes sapidus have CD spectra compatible with those of DNA's of quasi random sequence; these satellite DNA's should adopt also the B-form in solution.

Animals

Evaluating managerial efficiency of Veterans Administration medical centers using Data Envelopment Analysis.

This study applied the methodology of Data Envelopment Analysis (DEA) to the set of VA medical centers to evaluate their relative managerial efficiencies. Each VAMC was viewed as a producer of multiple outputs and a consumer of multiple inputs. DEA uses linear programming to identify resources that were underutilized and services that were inefficiently produced. Managerial strategies based on the dual variables were constructed to indicate the manner in which inefficient VAMCs may be made efficient. The analysis showed that relative inefficiency existed in about one third of the VAMCs nationwide. Elimination of this inefficiency would save the VA over $300 million annually on personnel, equipment, drugs, and supplies, without reducing the level of services provided. A subsequent analysis of co-variance revealed that VAMCs affiliated with a university were generally less efficient than those without such an affiliation. A similar finding was obtained for larger VAMCs relative to smaller medical centers. In neither case, however, should these results be construed to imply that VAMCs should terminate their university affiliations or that VAMCs should be made smaller since factors other than relative efficiency are clearly as or more important in such decisions.

Cost Control

A weighting method for predicting protein structural class from amino acid composition.

A protein is generally classified into one of the following four structural classes: all alpha, all beta, alpha+beta and alpha/beta. In this paper, based on the weighting to the 20 constituent amino acids, a new method is proposed for predicting the structural class of a protein according to its amino acid composition. The 20 weighting parameters, which reflect the different properties of the 20 constituent amino acids, have been obtained from a training set of proteins through the linear-programming approach. The rate of correct prediction for a training set of proteins by means of the new method was 100%, whereas the highest rate of previous methods was 82.8%. Furthermore, the results showed that the more numerous training proteins, the more effective the new method.

Amino Acids