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The methods of dynamic programming and generalized cross-validation are used to estimate the acceleration of bone motion using skin-mounted accelerometers. Numerical experiments are performed to demonstrate the usefulness and limitations of the methods.
A dynamic programming filter which provides estimates of the first and second derivative of empirical displacement data is investigated numerically. This filter uses a weighted least squares criteria in estimating the derivatives. The filter equations are presented together with several numerical examples. These examples are taken from references that proposed other techniques.
An image processing system has been developed for a Macintosh II personal computer. It is designed to process sequences of sagittal tongue sections that are digitized in real time and stored in standard tagged image file format (TIFF). The successive processing steps are: (a) a low-pass filter for noise reduction, (b) a resampling of the sector of interest in polar coordinates, (c) a matched filter (vertical differentiator) for the enhancement of the tissue/air interface in the surface region of the tongue, and (d) an extraction of border points by searching for an optimal radial path along the angular dimension. This latter task is achieved by dynamic programming, which has the following advantages. First, due to the use of a global criterion to guide the detection, it is very robust. Second, as a result of certain restrictions of the allowable transitions, the extracted contours are smooth. Finally, the method permits the specification of particular predefined contour points. This system was implemented in a program that can handle image sequences in a fully automatic mode. Results obtained using ultrasound data are presented.
A new computational method (chimeric alignment) has been developed to detect chimeric 16S rRNA artifacts generated during PCR amplification from mixed bacterial populations. In contrast to other nearest-neighbor methods (e.g., CHECK_CHIMERA) that define sequence similarity by k-tuple matching, the chimeric alignment method uses the score from dynamic programming alignments. Further, the chimeric alignments are displayed to the user to assist in sequence classification. The distribution of improvement scores for 500 authentic, nonchimeric sequences and 300 artificial chimeras (constructed from authentic sequences) was used to study the sensitivity and accuracy of both chimeric alignment and CHECK_CHIMERA. At a constant rate of authentic sequence misclassification (5%), chimeric alignment incorrectly classified 13% of the artificial chimeras versus 14% for CHECK_CHIMERA. Interestingly, only 1% of nonchimeras and 10% of chimeras were misclassified by both programs, suggesting that optimum performance is obtained by using the two methods to assign sequences to three classes: high-probability nonchimeras, high-probability chimeras, and sequences that need further study by other means. This study suggests that k-tuple-based matching methods are more sensitive than alignment-based methods when there is significant parental sequence similarity, while the opposite becomes true as the sequences become more distantly related. The software and a World Wide Web-based server are available at http://www-hto.usc.edu/software/mglobal CHI.
Culling dairy cows with clinical mastitis reduces the incidence of the disease in dairy herds, but the costs of such action, in terms of reduced milk production and increased replacement costs, are generally thought to outweigh the benefits. To test this hypothesis a stochastic dynamic programming model was developed to establish the economically optimum time of replacement for dairy cows subject to variable levels of clinical mastitis infection, using average United Kingdom production and price parameters. The optimal stage at which to replace a dairy cow was found to be sensitive to changes in mastitis incidence and in critical price parameters within the bounds of commercial experience. This result indicates that an objective culling policy based on clinical mastitis records in addition to milk production potential may be economically viable.
Despite a multitude of theories describing the mechanics of the intracranial spaces in diseases such as hydrocephalus, little is known about the mechanics of normal CSF flow. A pressure difference is required to drive CSF flow. Knowing that the pressure difference driving fluid through the aqueduct is beyond the resolution of clinically used pressure transducers, a computational fluid dynamics program was used to analyze flow through an aqueduct shape. Flow through this duct was compared with that through a cylinder and through a double hourglass. Both steady and oscillating flows were tested, revealing that only 1.1 Pa of pressure is required to move CSF through the aqueduct. This suggests that normally less than 5% of the total resistance to CSF flow within the CSF pathways occurs in the aqueduct.
We describe a hybrid modeling approach where the parameters of a mode are calculated and modulated by another model, typically a neural network (NN), to avoid both overfitting and underfitting. We develop the approach for the case of Hidden Markov Models (HMMs), by deriving a class of hybrid HMM/NN architectures. These architectures can be trained with unified algorithms that blend HMM dynamic programming with NN backpropagation. In the case of complex data, mixtures of HMMs or modulated HMMs must be used. NNs can then be applied both to the parameters of each single HMM, and to the switching or modulatation of the models, as a function of input or context. Hybrid HMM/NN architectures provide a flexible NN parameterization for the control of model structure and complexity. At the same time, they can capture distributions that, in practice, are inaccessible to single HMMs. The HMM/NN hybrid approach is tested, in its simplest form, by constructing a model of the immunoglobulin protein family. A hybrid model is trained, and a multiple alignment derived, with less than a fourth of the number of parameters used with previous single HMMs.
The involution of presumptive mesoderm that occurs during amphibian gastrulation is a complex process requiring the coordinated action of a diverse range of cells. We show that cells with distinct morphologies, resembling each of those normally found in the involuting tissue of the Xenopus embryo, are induced in dispersed animal pole cells by different doses of the potent mesoderm-inducing factor activin. Each cell type is induced within a restricted dose range of activin concentrations, the boundaries of which are well demarcated shortly after activin treatment. In contrast, Brachyury and goosecoid, two genes thought to pattern the presumptive mesoderm, and the gene encoding platelet-derived growth factor receptor alpha, which is expressed in the mesoderm of gastrula stage embryos, are induced by broad, overlapping ranges of high activin concentrations at such early times. Similarly, the response of the gene encoding platelet-derived growth factor A, which is expressed normally in ectoderm of gastrula stage embryos, diminishes gradually as the activin concentration increases. Dose windows for the expression of these four genes narrow and become distinct from one another in cell aggregates after several hours in culture, suggesting that activin prompts a dynamic program of gene expression in induced mesoderm.
Conformational analysis of the marine cembranoid sarcophytol A (1a), a potent anti-tumor promoter, was carried out using a newly introduced molecular mechanic and molecular dynamic program Discover. Four minimum-energy conformations were derived, in accordance with a previous results of the epoxidation of 1a, which afforded 7R,8R/7S,8S- and 11R,12R/11S,12S-epoxide pairs. The most stable conformation was the one having C-19 and C-20 directed opposite to C-18, with respect to the average plane of the fourteen-membered ring. X-Ray crystallography of sarcophytol A alpha-methoxy-alpha-trifluoromethylphenylacetate (1c) was carried out simultaneously. This confirmed the 14S absolute configuration of 1a but the conformation of crystalline 1c did not correspond to any of the four minimum-energy conformers of 1a.
Farmers frequently have to decide whether to keep or to replace cows that suffer from clinical mastitis. A dynamic programming model was developed to optimize these decisions for individual cows within the herd, using the hierarchic Markov process technique. This technique provides a method to model a wide variety of cows, differing in age, productive performance, reproductive status, and clinical mastitis occurrence. The model presented was able to support decisions related to 63% of all replacements. Results--for Dutch conditions--showed the considerable impact of mastitis on expected income of affected cows. Nevertheless, in most cases, the optimal decision was to keep and to treat rather than to replace the cow. Clinical mastitis occurring in the previous lactation negligibly influence expected income. Clinical mastitis in current lactation, especially in the current month, however, had a significant effect on expected income. Total losses caused by clinical mastitis were US$83/yr per cow. Farm level treatment, which reduced incidence by 25%, on a farm with 10 clinical quarter cases per 10,000 cow days, may cost at maximum US$27/yr per cow.
Selection indexes have been extensively applied in the estimation of breeding value of dairy cattle for single traits as well as for combinations of traits for selection purposes. Milestones in methodology, such as multiple-trait evaluation procedures by BLUP, (co)variance component estimation, nonlinear models, discounted gene flow, dynamic programming, and international sire evaluations, together with increased computing power and the development of integrated AI and recording schemes, have contributed to efficient implementation of selection indexes and are reviewed in this article. Results of an international survey on evaluation practices and breeding programs are presented, demonstrating wide adoption of index selection for total merit and the need for further applications. Results from a simulation study on the efficiency of index selection for total merit are also presented; when the breeding goal includes, in addition to production traits, functional nonproduction traits such as mastitis resistance and fertility, failure to consider these traits in the selection index decreases efficiency 15 to 25%. Future applications are also discussed in view of advances in the areas of genome mapping, marker detection, and international comparisons. Further research should focus on functional nonproduction traits.
A new method of the homology search between DNA sequences was suggested. This method may be used to find extensive and not strong homologies with point mutations and deletions. The computer time to compare sequences is less than dynamic program algorithms at least by four orders of magnitude. It makes possible to use the method for homology search all over the nucleotide bank by personal computers. Some results of homology search are presented.
Terminal differentiation can be induced in cultured basal cells by either increasing the Ca2+ level in the medium from 0.05 to 1.4 mM or by exposure to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). If Ca2+ and TPA act by a common mechanism, then a common pattern of protein synthesis and/or phosphorylation would be expected. Computer-assisted analysis of radioactively labeled polypeptides separated by two-dimensional-polyacrylamide gel electrophoresis was utilized to study protein synthesis and phosphorylation. Within 1 h of increasing the Ca2+ level in the medium, the synthesis of 57 polypeptides was altered by 2-fold or more. Similarly, exposure to TPA for 1 h affected the synthesis of 106 polypeptides. Sixteen polypeptides were affected by both Ca2+ and TPA; the synthesis of nine was increased and seven was decreased, with changes in the same direction for both effectors. By 4 h, the synthesis of 32 polypeptides was similarly modulated by both Ca2+ and TPA. Only one polypeptide which was increased at 1 h was still elevated at 4 h. These results suggest that a common dynamic program of protein synthesis, likely to be related to terminal keratinocyte differentiation, is induced by both Ca2+ and TPA. Overall phosphorylation of epidermal proteins was increased after 30 min of TPA treatment, but was not increased by Ca2+ at this time. Keratin polypeptides were heavily phosphorylated in low Ca2+ medium, but the level or pattern of phosphorylation of these proteins was not altered by either Ca2+ or TPA. Although phosphorylation of a minor polypeptide (pI 5.1/Mr 45,000) was increased 2-3-fold by both Ca2+ and TPA, most of the specific protein phosphorylation changes induced in keratinocytes by Ca2+ and TPA appear to be unique. Thus, if protein phosphorylation is an early signal for epidermal differentiation by each effector, only a single apparent common substrate is involved and multiple kinases are activated. Alternatively, substrate specificity of a single kinase may be differentially altered by each effector.
Changes in intrahepatic arterial blood flow after intraarterial injection of degradable starch microspheres (DSM) were studied in four patients undergoing hepatic arterial chemotherapy. All four livers contained metastases, three from colorectal cancer and one from melanoma. Using a CT scanner with a dynamic program, 8 mm liver sections were studied in each patient before and after the DSM infusion (180(-6) in 3 min). Density plots were obtained from 12 tumoral and 12 parenchymal areas after 5 ml push arterial injections of nonionic contrast medium. The areas under the curves (ID) were calculated. The ID after DSM infusion was reduced by 94% in a single hyperdense colorectal metastasis and by a mean of c. 82% in ten parenchymal areas. By contrast, nine hypodense colorectal metastases showed an average ID decrease of c. 156%. The ID of two melanoma metastases was reduced after DSM (-48% and -68%), while the ID of two matched parenchymal areas showed an approximately similar degree of increase (+36% and +64%). Since ID after contrast injection can be assumed to be a function of blood volume, mutual changes of parenchymal and tumoral blood flow appear to take place in metastases-bearing liver after arterial infusion of DSM. This phenomenon may be of diagnostic and therapeutic value for intraarterial chemotherapy of liver tumors.
The paper describes certain cases of using mathematical methods in the planning of biological experiments. The paper presents an algorithm of the distribution of the experimental data based on dynamic programming. The paper discusses an application of computer-aided calculations for the formation of homogeneous groups of experimental and control tests.
We propose in this paper a modular learning environment for protein modeling. In this system, the protein modeling problem is tackled in two successive phases. First, partial structural informations are determined via numerical learning techniques. Then, in the second phase, the multiple available informations are combined in pattern matching searches via dynamic programming. It is shown on real problems that various protein structure predictions can be improved in this way, such as secondary structure prediction, alignment of weakly homologous protein sequences or protein model evaluations.
The minimal-length encoding approach is applied to define concept of sequence similarity. A sequence is defined to be similar to another sequence or to a set of keywords if it can be encoded in a small number of bits by taking advantage of common subwords. Minimal-length encoding of a sequence is computed in linear time, using a data compression algorithm that is based on a dynamic programming strategy and the directed acyclic word graph data structure. No assumptions about common word ("k-tuple") length are made in advance, and common words of any length are considered. The newly proposed algorithmic significance method provides an exact upper bound on the probability that sequence similarity has occurred by chance, thus eliminating the need for any arbitrary choice of similarity thresholds. Preliminary experiments indicate that a small number of keywords can positively identify a DNA sequence, which is extremely relevant in the context of partial sequencing by hybridization.
A key issue in managing today's large amounts of genetic data is the availability of efficient, accurate, and selective techniques for detecting homologies (similarities) between newly discovered and already stored sequences. A common characteristic of today's most advanced algorithms, such as FASTA, BLAST, and BLAZE is the need to scan the contents of the entire database, in order to find one or more matches. This design decision results in either excessively long search times or, as is the case of BLAST, in a sharp trade-off between the achieved accuracy and the required amount of computation. The homology detection algorithm presented in this paper, on the other hand, is based on a probabilistic indexing framework. The algorithm requires minimal access to the database in order to determine matches. This minimal requirement is achieved by using the sequences of interest to generate a highly redundant number of very descriptive tuples; these tuples are subsequently used as indices in a table look-up paradigm. In addition to the description of the algorithm, theoretical and experimental results on the sensitivity and accuracy of the suggested approach are provided. The storage and computational requirements are described and the probability of correct matches and false alarms is derived. Sensitivity and accuracy are shown to be close to those of dynamic programming techniques. A prototype system has been implemented using the described ideas. It contains the full Swiss-Prot database rel 25 (10 MR) and the genome of E. Coli (2 MR). The system is currently being expanded to include the complete Genbank database.(ABSTRACT TRUNCATED AT 250 WORDS)