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Biomedical subjects

L Allison

Publications and source records attributed to L Allison.

15 recordsLinked to original sources
PubMed1995

Long-term efficacy of continuing hepatitis B vaccination in infancy in two Gambian villages.

In 1984, all non-immune children under the age of 5 years in the Gambian villages of Keneba and Manduar were vaccinated against hepatitis B virus (HBV). All children born in these villages since 1984 have been vaccinated in infancy. Despite a rapid fall in antibody concentrations, vaccine efficacy against HBV infection and chronic carriage of HBsAg has increased with time. Overall, vaccine efficacies in 1993 against HBV infection and chronic HBsAg carriage were 94.7% (95% Cl 93.0-96.0) and 95.3% (91.0-97.5), respectively. Breakthrough infections in vaccinated children largely originate from chronic HBsAg carriers. Thus, we tested 261 chronic carriers for HBV DNA and e antigen. The prevalence of these markers of infectivity, and the amount of HBV DNA, decreased greatly with age. Detailed studies of breakthrough infections over two 4-year periods revealed that in the second period there were fewer than half the expected numbers of infections. Our findings suggest that in Keneba and Manduar long-term vaccination is progressively decreasing HBV transmission by chronic carriers, since their infectivity diminishes with time.

Adolescent↗
PubMed1994

The posterior probability distribution of alignments and its application to parameter estimation of evolutionary trees and to optimization of multiple alignments.

How to sample alignments from their posterior probability distribution given two strings is shown. This is extended to sampling alignments of more than two strings. The result is first applied to the estimation of the edges of a given evolutionary tree over several strings. Second, when used in conjunction with simulated annealing, it gives a stochastic search method for an optimal multiple alignment.

Algorithms↗
PubMed1994

Breakthrough infections and identification of a viral variant in Gambian children immunized with hepatitis B vaccine.

Hepatitis B (HB) breakthrough infections, identified by the presence of HB core (c) antibody, were found in 32 of 358 Gambian children vaccinated with plasma-derived HB vaccine. Over 2 years, 15 of these children lost their HBc antibodies. These children had significantly higher HB surface antibody levels before infection than those who retained HBc antibodies. One child, who responded well to the vaccine, had HB viral DNA detected in the presence of HBs antibodies. The S gene sequence of this DNA showed nucleotide changes that resulted in an amino acid substitution at residue 141 (lysine to glutamic acid) of the surface antigen. This finding suggests the child was infected with a variant virus that was not neutralized by antibodies resulting from HB vaccination.

Child↗
PubMed1993

A fast algorithm for the optimal alignment of three strings.

Ukkonen's (pair-wise) string alignment technique is extended to the problem of finding an optimal alignment for three strings. The resulting algorithm has worst-case time-complexity O(nd2) and space-complexity O(d3), where the string lengths are ñ and d is the three-way edit-distance based on tree-costs. In practice, the algorithm usually runs in O(n + d3) time. The algorithm is particularly fast when the strings are similar, in which case, d << n. Three-way alignment is an important special case in string alignment. Each internal node in an unrooted, binary evolutionary-tree has three neighbours. The algorithm presented can be used as an iterative step in a heuristic multiple-alignment program for more than three strings.

Algorithms↗
PubMed1993

Normalization of affine gap costs used in optimal sequence alignment.

It is shown how to normalize the costs of an alignment algorithm that employs affine or linear gap costs. The normalized costs are interpreted as the -log probabilities of the instructions of a finite-state edit-machine. This gives an explicit model relating sequences that can be linked to processes of mutation and evolution.

Animals↗
PubMed1993

Reconstruction of strings past.

A major use of string-alignment algorithms is to compare macromolecules that are thought to have evolved from a common ancestor to estimate the duration of, or the amount of mutation in, their separate evolution and to infer as much as possible about their most recent common ancestor. Minimum message length encoding, a method of inductive inference, is applied to the string-alignment problem. It leads to an alignment method that averages over all alignments in a weighted fashion. Experiments indicates that this method can recover the actual parameters of evolution with high accuracy and over a wide range of values, whereas the use of a single optimal alignment gives biased results.

Algorithms↗
PubMed1992

Finite-state models in the alignment of macromolecules.

Minimum message length encoding is a technique of inductive inference with theoretical and practical advantages. It allows the posterior odds-ratio of two theories or hypotheses to be calculated. Here it is applied to problems of aligning or relating two strings, in particular two biological macromolecules. We compare the r-theory, that the strings are related, with the null-theory, that they are not related. If they are related, the probabilities of the various alignments can be calculated. This is done for one-, three-, and five-state models of relation or mutation. These correspond to linear and piecewise linear cost functions on runs of insertions and deletions. We describe how to estimate parameters of a model. The validity of a model is itself an hypothesis and can be objectively tested. This is done on real DNA strings and on artificial data. The tests on artificial data indicate limits on what can be inferred in various situations. The tests on real DNA support either the three- or five-state models over the one-state model. Finally, a fast, approximate minimum message length string comparison algorithm is described.

Algorithms↗
PubMed1990

Minimum message length encoding and the comparison of macromolecules.

A comparison of inductive inference known as minimum message length encoding is applied to string comparison in molecular biology. The question of whether or not two strings are related and, if so, of how they are related and the problem of finding a good theory of string mutation are treated as inductive inference problems. The method allows the posterior odds-ratio of two string alignments or of two models of string mutation to be computed. The connection between models of mutation and existing string alignment algorithms is made explicit. A fast minimum message length alignment algorithm is also described.

Base Sequence↗
PubMed1990

Restriction site mapping for three or more enzymes.

Restriction site mapping requires a generator to put forward possible maps and a constraint checker to reject false maps. Ideally these combine to give an algorithm which calculates a sound and complete solution set. Three algorithms for generation are presented and compared. Two decompose a multi-enzyme problem (greater than or equal to 3) into subproblems. The constraint checker is based on separation theory. Some insights into the extent of constraint checking involved in and feasibility of more checking for three or more enzymes are discussed. The trade-off between computation time and the soundness of the solution set is examined.

Algorithms↗
PubMed1988

Restriction site mapping is in separation theory.

A computer algorithm for restriction-site mapping consists of a generator of partial maps and a consistency checker. This paper examines consistency checking and argues that a method based on separation theory extracts the maximum amount of information from fragment lengths in digest data. It results in the minimum number of false maps being generated.

Algorithms↗
PubMed1985

Mapping of the pattern of DNA replication in polytene chromosome from Chironomus thummi using monoclonal anti-bromodeoxyuridine antibodies.

We present results from a nonautoradiographic study of DNA replication in polytene chromosomes from dipteran larvae. Monoclonal antibodies with specificity for 5-bromodeoxyuridine (BrdUrd) were used to localize by indirect immunofluorescence the sites of BrdUrd incorporation and to follow the dynamics of DNA synthesis in salivary gland cells of 4th instar Chironomus thummi larvae. This technique presents numerous advantages over autoradiographic procedures and allows mapping of DNA synthesis patterns at the level of resolution of one chromosomal band. Several replication patterns were observed, classified according to characteristic features, and tentatively assigned to specific periods of the S-phase. In early S-phase, DNA synthesis is first detectable in puffs and interbands, later in bands. Most chromosomal bands appear to initiate DNA synthesis synchronously; however, in bands within centromeric and heterochromatic regions the start of synthesis is delayed. At mid S-phase, all the bands show uniform staining. Subsequent staining patterns are increasingly differential with the bands displaying characteristic fluorescence intensities. As replication progresses through the late S-phase period, the chromosomes show a decreasing number of fluorescent bands. The last bands to terminate replication are located in centromeric and heterochromatic DNA-rich regions and a few bands of low DNA content in region IIAa-c.

Animals↗
PubMed1985

Thermal inactivation of Pichinde virus.

Detailed information regarding the kinetics of thermal inactivation of Pichinde, an arenavirus, is presented. Inactivation of virus infectivity proceeded as a first order reaction over the temperature range 22-53 degrees C. The determined inactivation rates analysed as a function of absolute temperature revealed that two different reactions were involved. Below 37 degrees C, the energy of activation was determined to be compatible with RNA degradation, whereas at higher temperatures a correspondingly greater value suggests that protein inactivation contributes significantly to loss of infectivity. Both inactivation reactions were retarded in the presence of foetal calf serum to a final concentration of 1%. The relatively short half-life of 12-24 h at 22 degrees C suggests transmission in nature via contaminated foodstuffs and soil may be inefficient.

Arenaviridae↗
PubMed1985

Properties and characterization of monoclonal antibodies to Tacaribe virus.

Monoclonal antibodies prepared against Tacaribe and Junin viruses have been used to define further the serological relationships between arenaviruses of the Tacaribe complex. A close relationship was found between these two viruses and the heterologous Amapari and Machupo viruses, with Pichinde virus and Parana virus being more distantly related. Among the antibodies specific for Tacaribe virus, five were found to react with viral antigens at the surface of infected cells and to neutralize virus infectivity in vitro. These five antibodies could be differentiated by competitive immunoassay as recognizing at least two antigenically distinct epitopes. The kinetics of reaction between antibody and virus were examined for all five neutralizing antibodies. One antibody (2.25.4) effectively neutralized all infectious virus. The remaining four directed against a second epitope gave significant persistent fractions which could be reduced by addition of complement, anti-mouse immunoglobulin, or antibody 2.25.4. Variants of Tacaribe virus resistant to neutralization by antibody 2.25.4 were obtained by growth in the presence of this antibody and neutralization kinetics were reexamined using the heterologous monoclonal neutralizing antibodies. Several different neutralization profiles were obtained, suggesting that point mutations resulted in conformational changes at topographically selected distinct epitopes recognized by the remaining antibodies.

Animals↗