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Biomedical subjects

J P Schmidt

Publications and source records attributed to J P Schmidt.

At least 19 recordsLinked to original sources

An algorithm for approximate tandem repeats.

A perfect single tandem repeat is defined as a nonempty string that can be divided into two identical substrings, e.g., abcabc. An approximate single tandem repeat is one in which the substrings are similar, but not identical, e.g., abcdaacd. In this paper we consider two criterions of similarity: the Hamming distance (k mismatches) and the edit distance (k differences). For a string S of length n and an integer k our algorithm reports all locally optimal approximate repeats, r = umacro û, for which the Hamming distance of umacro and û is at most k, in O(nk log (n/k)) time, or all those for which the edit distance of umacro and û is at most k, in O(nk log k log (n/k)) time. This paper concentrates on a more general type of repeat called multiple tandem repeats. A multiple tandem repeat in a sequence S is a (periodic) substring r of S of the form r = u(a)u', where u is a prefix of r and u' is a prefix of u. An approximate multiple tandem repeat is a multiple repeat with errors; the repeated subsequences are similar but not identical. We precisely define approximate multiple repeats, and present an algorithm that finds all repeats that concur with our definition. The time complexity of the algorithm, when searching for repeats with up to k errors in a string S of length n, is O(nka log (n/k)) where a is the maximum number of periods in any reported repeat. We present some experimental results concerning the performance and sensitivity of our algorithm. The problem of finding repeats within a string is a computational problem with important applications in the field of molecular biology. Both exact and inexact repeats occur frequently in the genome, and certain repeats occurring in the genome are known to be related to diseases in the human.

Algorithms↗

Synthesis and evaluation of nitroheterocyclic phosphoramidates as hypoxia-selective alkylating agents.

A series of novel nitroheterocyclic phosphoramidates has been prepared, and the cytotoxicity of these compounds has been evaluated in clonogenic assays against B16, wild-type and cyclophosphamide-resistant MCF-7, and HT-29 cells under aerobic conditions and HT-29 cells under hypoxic conditions. All compounds were comparable in toxicity to wild-type and resistant MCF-7 cells and were also selectively toxic to HT-29 cells under hypoxic conditions (selectivity ratios 1.7 to >20). Analogues lacking the nitro group were not cytotoxic. Electron-withdrawing substituents increased cytotoxicity under aerobic conditions and thereby decreased hypoxic selectivity. In contrast, an electron-donating substituent markedly decreased both aerobic and hypoxic cytotoxicity but enhanced hypoxic selectivity. Chemical reduction of the nitro group resulted in rapid expulsion of the cytotoxic phosphoramide mustard. The most potent of these compounds show significant cytotoxicity under both aerobic and hypoxic conditions.

Animals↗

An information theoretic view of gapped and other alignments.

We use an information theoretical framework to estimate the probability of the score of gapped alignments. With appropriate scaling, the score of a global (and with some adjustments also the score of a local) alignment of two sequences can be viewed as the difference in the number of bits needed to transmit the two sequences T1 and T2 under two different encoding schemes C1 and C2. C1 is an idealized scheme, assumed to achieve an optimal encoding with respect to a distribution p, and the assumption that T1 and T2 are independent. C2 is an alternate scheme, that will transmit T1 and T2 while taking advantage of the optimal alignment between the two. That is under C1, the strings T1 and T2 (with respective probabilities p(T1) and p(T2)), are assumed to be encoded using C1(T1, T2) = log [formula: see text] bits. By slightly modifying a known Theorem we show that the probability (under p) that two independent sequences T1, T2 can be transmitted with an alternate encoding scheme (C2) with no more than C1(T1, T2)-r bits is bounded by 2-r. We then show how to use this bound to derive upper bounds for the probability of gapped alignment scores between two sequences.

Computer Simulation↗

A surface measure for probabilistic structural computations.

Computing three-dimensional structures from sparse experimental constraints requires method for combining heterogeneous sources of information, such as distances, angles, and measures of total volume, shape, and surface. For some types of information, such as distances between atoms, numerous methods are available for computing structures that satisfy the provided constraints. It is more difficult, however, to use information about the degree to which an atom is on the surface or buried as a useful constraint during structure computations. Surface measures have been used as accept/reject criteria for previously computed structures, but this is not an efficient strategy. In this paper, we investigate the efficacy of applying a surface measure in the computation of molecular structure, using a method of probabilistic least square computations which facilitates the introduction of multiple, noisy, heterogeneous data sources. For this purpose, we introduce a simple purely geometrical measure of surface proximity called maximal conic view (MCV). MCV is efficiently computable and differentiable, and is hence well suited to driving a structural optimization method based, in part, on surface data. As an initial validation, we show that MCV correlates well with known measures for total exposed surface area. We use this measure in our experiments to show that information about surface proximity (derived from theory or experiment, for example) can be added to a set of distance measurements to increase significantly the quality of the computed structure. In particular, when 30 to 50 percent of all possible short-range distances are provided, the addition of surface information improves the quality of the computed structure (as measured by RMS fit) by as much as 80 percent. Our results demonstrate that knowledge of which atoms are on the surface and which are buried can be used as a powerful constraint in estimating molecular structure.

Animals↗

Nitrobenzyl phosphorodiamidates as potential hypoxia-selective alkylating agents.

A series of novel nitrobenzyltetrakis(chloroethyl)phosphorodiamidates has been prepared, and its cytotoxicity has been evaluated against HT-29 cells under aerobic and hypoxic conditions and against murine bone marrow progenitor cells under aerobic conditions. All compounds were selectively toxic to HT-29 cells under hypoxic conditions, and the selectivity ratios varied from 1.6 to > 90. Analogs lacking either the nitro group or the tetrakis(chloroethyl) moiety were not cytotoxic, confirming that the presence of both nitro and incipient alkylating groups are essential for activity. Surprisingly, some analogs were far more toxic to bone marrow progenitors than to HT-29 cells under aerobic conditions, suggesting that other activation mechanisms must exist in these hematopoietic cells. Cytotoxicity increased with increasing depth in the HT-29 spheroid model, consistent with the preferential hypoxic toxicity of these compounds. Alkaline elution experiments showed a greater number of DNA interstrand cross-links under hypoxic compared to aerobic conditions. The extent of cross-linking in hypoxic cells was essentially identical to that produced by an equitoxic dose of melphalan, suggesting that the cytotoxicity of these compounds results from phosphorodiamidate release and alkylation of DNA.

Aerobiosis↗

Factors affecting the survival and growth of bacteria introduced into lake water.

The populations of Pseudomonas sp. B4, Escherichia coli, Klebsiella pneumoniae, Micrococcus flavus, and Rhizobium leguminosarum biovar phaseoli declined rapidly in lake water. The initially rapid decline of the two pseudomonads and R. phaseoli was followed by a period of slow loss of viability, but viable cells of the other species were not found after 10 days. The rapid initial phase of decline was not a result of Bdellovibrio spp., bacteriophages, or toxins in the water since Bdellovibrio spp. were not present and passage of the lake water through filters that should not have removed bacteriophages or soluble toxins led to the elimination of the rapid phase of decline. The addition of 250 micrograms of cycloheximide and 30 micrograms of nystatin per ml eliminated viable protozoa form the lake water, and the population of Pseudomonas sp. B4 did not fall and the decline of E. coli and K. pneumoniae was delayed or slowed under these conditions. Pseudomonas sp. L2 proliferated rapidly in lake water amended with glucose, phosphate, and NH4NO3, but its numbers subsequently fell abruptly; however, in water amended with cycloheximide and nystatin, which killed indigenous protozoa, the population density was higher and the fall in numbers was delayed. Of the nutrients, the chief response was to carbon, but when glucose was added, phosphorus and nitrogen stimulated growth further. Removing other bacteria by filtering the lake water before inoculation with Pseudomonas sp. L2 suggested that competition reduced the extent of response of the pseudomonad to added nutrients.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗

Factorial analysis of the MMPI profiles of low back pain patients.

To examine the interrelationships of MMPI scale scores among low back pain patients, 50 profiles were scored on the traditional 13 scales, Hanvik's Lb scale and seven subscales derived from Scales 1 and 3. The profiles were randomly divided into two equal samples and factor analyzed. Comparison of the two samples yielded three common factors. The first factor measured severity of the symptoms, the second assessed the level of anger and aggression and the third assessed the psychogenic components of the syndrome. The implications of the factors are discussed.

Back Pain↗

Issues in psychiatric day-care programs in non-urban areas: a case study.

As community mental health continues to grow in credibility, it has expanded, not only into new areas of treatment (e.g., child abuse), but also into new geographical areas, such as rural Canada. However, transplantation of urban-based community mental health models into the rural community poses major problems. To illustrate such problems as well as possible solutions, this paper describes a day-care program in a non-urban area, the overall settings of the program, a description of its structure and the issues facing it, as well as some of the ways we have dealt with them. We then discuss some recent changes we made in the program and how we evaluated these, to illustrate how such a program can institute an ongoing program evaluation. Finally, some data on the outcome of the program is presented.

Adolescent↗

A behavioral approach to patient compliance.

A behavioral program for increasing a patient's compliance with a drug regimen can be administered by a physician or by trained health care personnel. The program focuses first on the development of a strong external cue to the timing of medication and then on helping the patient to have realistic expectations and to establish an appropriate self-reward for compliance. Monitoring of degree of compliance is essential to the success of the program, as is development of a cooperative, rather than authoritatian, relationship between physician and patient.

Behavior↗

The interactive effects of instructional set, field dependence, and extraversion on the Holtzman Inkblot Technique.

Studied the interactive effects of examiner, instructional set, field dependence, and extraversion on the reactions of 81 males and 39 females to five Holtzman Inkblot Technique factor scores. Half of the Ss were told that the HIT was a measure of mental health and half that it was experimental in nature, which produced two instructional sets. Field dependence was measured with the Embedded Figures Test and extraversion by the Eysenck Personality Inventory. Subjective anxiety was tapped via the State-Trait Anxiety Inventory. Results revealed no differences among five examiners. However, three of the five HIT factors and the STAI were affected significantly by the instructional set. The effects, while significant, were not massive. Field dependence interacted with instructional set; field dependent Ss reacted with generally more changes in scores than did field independent S. Unlike field dependence, extraversion appeared unrelated to instructional set effects. The results are discussed in terms of how the factor scores interacted with the field dependence and instructional set in psychologically meaningful ways.

Adult↗

Factorial relationships of measures of perceived level of psychopathology and sociometric choice.

Studied the relationship of diagnosis, age, length of hospitalization, and various measures of perceived level of psychopathology, perceived appropriateness of hospitalization, and sociometric choice among 39 adolescent psychiatric inpatients. Factor analysis revealed two factors, one that was apparently a measure of perceived level of psychopathology and another that was apparently a measure of sociometric choice. Perceptions of an individual's level of psychopathology appear to be shared across staff and patient boundaries. Appropriateness of hospitalization had a strong positive relationship to perceived level of psychopathology and a weak negative relationship to sociometric standing. The relative lack of relationship between sociometric standing and perceived level of psychopathology is discussed in light of past research and methodological design issues.

Adolescent↗

Further studies on the influence of steroids on viral infection in mice.

Certain steroids have been reported to enhance experimental viral infections, whereas others have little or no effect. Interference with the interferon system has been suggested as a possible mechanism for the viral infection-enhancing (VIE) activity of hormones. In the present study, steroids (prednisolone, progesterone, testosterone) which had no effect on MM virus infection demonstrated VIE activity against Mayaro virus infection. It is suggested that the VIE activity of a hormone may be dependent on the viral agent used for challenge. Data are also presented which suggest that, in addition to interference with the interferon system, the VIE activity of steroid hormones may be the result of at least two other actions: (i) alteration of cell membranes; (ii) stimulation of initial viral replication.

Animals↗