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J Engelbrecht

Publications and source records attributed to J Engelbrecht.

15 recordsLinked to original sources
PubMed1995

Analysis of eukaryotic promoter sequences reveals a systematically occurring CT-signal.

A general data study of eukaryotic promoter sequences from widely different species is presented. Mammalian promoters with known transcription initiation sites represented the largest subclass of the data, and for this group neural network algorithms were trained to predict the location of the initiation site in a test set. The prediction accuracy of this local method was higher than what could be expected from the known non-local structure of eukaryotic promoters. Subsequent analysis revealed, besides the consensus of the two known important subregions: the TATA-box TATAAA and the Cap-signal CA, a CT-signal positioned on the average seven nucleotides downstream of the transcription initiation site. The consensus of the CT-signal is CTNCNG. The details of this core promoter element were disclosed using multiple alignment and have earlier only been described in a few isolated examples.

Algorithms↗
PubMed1995

Investigations of Escherichia coli promoter sequences with artificial neural networks: new signals discovered upstream of the transcriptional startpoint.

In this paper we present a novel method for using the learning ability of a neural network as a measure of information in local regions of input data. Using the method to analyze Escherichia coli promoters, we discover all previously described signals, and furthermore find new signals that are regularly spaced along the promoter region. The spacing of all signals correspond to the helical periodicity of DNA, meaning that the signals are all present on the same face of the DNA helix in the promoter region. This is consistent with a model where the RNA polymerase contacts the promoter on one side of the DNA, and suggests that the regions important for promoter recognition may include more positions on the DNA than usually assumed. We furthermore analyze the E. coli promoters by calculating the Kullback Leibler distance, and by constructing sequence logos.

Base Sequence↗
PubMed1995

Periodic sequence patterns in human exons.

We analyse the sequential structure of human exons and their flanking introns by hidden Markov models. Together, models of donor site regions, acceptor site regions and flanked internal exons, show that exons--besides the reading frame--hold a specific periodic pattern. The pattern, which has the consensus: non-T(A/T)G and a minimal periodicity of roughly 10 nucleotides, is not a consequence of the nucleotide statistics in the three codon positions, nor of the well known nucleosome positioning signal. We discuss the relation between the pattern and other known sequence elements responsible for the intrinsic bending or curvature of DNA.

Base Sequence↗
PubMed1995

[Mandatory continued medical education and continuing education accreditation--contributions to quality assurance in medicine?].

Continuing education is seen as one of the most important instruments of medical quality assurance. Therefore, the duty of continuing medical education was put down in the professional rules of German physicians in 1976. It has been demonstrated many times that most of the physicians keep this professional duty. However, it has been repeatedly discussed whether the physician's motivation for continuing education is sufficient or whether it is necessary to introduce a compulsory proof of CME. It is analyzed in this article how the efficacy of compulsory and compulsory proof of is verified scientifically. Further, different tools are introduced which may help to admit a greater obligation. The discussion is based on data from Medline search using the keywords 'Continuing medical education' and 'Quality assurance' for the years 1984-1993. Studies reporting experiences with compulsory CME and considerations of standards were chosen. Further, presentations of the 'European Academy of Medical Education' (EAMF), Cologne March 4-March 5, 1994 as well as the publications of the German Medical Association regarding quality assurance of CME from the years 1993 to 1995 have been taken into account.

Accreditation↗
PubMed1995

Steroid sparing activity of tenidap in patients with polymyalgia rheumatica: a multicenter double blind randomized placebo controlled study.

OBJECTIVE: To determine whether tenidap treatment would allow reduction or replacement of systemic corticosteroid treatment in patients with polymyalgia rheumatica (PMR). METHODS: A 15-week double blind, randomized, multicenter, placebo-controlled study of tenidap sodium (120 mg/day) in patients with symptomatically controlled PMR receiving 10 mg/day prednisone was conducted. After receiving study drug for 3 weeks, prednisone dose was reduced by 2.5 mg/day every 3 weeks. The lowest clinically effective dose of prednisone was recorded as 10, 7.5, 5, 2.5 or 0 mg/day. RESULTS: Thirty-two patients were randomized to tenidap or placebo. As prednisone was reduced more placebo patients experienced an exacerbation of PMR symptoms, elevation of erythrocyte sedimentation rate and increased serum C-reactive protein. Twice as many placebo patients (10 of 16) as tenidap patients (5 of 16) discontinued due to lack of efficacy. The lowest effective dose of prednisone could be determined in 27 of the 32 patients, 11 receiving tenidap and 16 placebo. A significantly (p = 0.027) greater proportion of patients receiving tenidap (5 of 11) than placebo (1 of 16) were able to discontinue prednisone without experiencing a symptomatic flare. CONCLUSION: As prednisone was reduced, symptoms of PMR were controlled better by tenidap than by placebo. Forty-five percent of evaluable patients receiving tenidap were able to discontinue prednisone without a disease flare compared to 6% for placebo.

Aged↗
PubMed1995

[Participation in continuing education by German physicians--exemplified by the Schleswig-Holstein study].

In order to evaluate the CME behaviour of the physicians in the state of Schleswig-Holstein, the State Society of Physicians questioned all its members (n = 10,326 and 10,698) regarding the participation in CME activities during the previous year using the same questionnaire in 1991 and 1993. Answers were obtained from 6,329/6,904 physicians where 40.2/42.2% (1991/1993) worked in free practice, 46.9 (44.6)% in hospitals, 6.2 (6.9) % in administrative and scientific institutions, 5.2 (2.9)% in various medical occupations, and 1.6 (3.3)% without medical professions. CME activities were identical in 1990 and 1992, where the study of literature was the most relevant activity (99%). Mean reading time was 5.8/5.6 hours per week (physicians in practice: 5.3/5.3 hpw, in hospital 6.4/6.6 hpw), average of read journals: 3.9/3.9 (practice: 4.3/4.3 hospital: 3.6/3.6). Video-CME was documented with 41.7/44.2% in total (practice: 50.5/52.3%-hospital: 37.2/39.9%). Regarding CME courses and conferences, traditional class-room CME was used most frequently (total: 71.9/72.6%-practice: 69.7/71%-hospital: 73.9/74.9%), followed by workshops (total: 50.3/47.9%-practice: 56.4/54.1%-hospital: 45.6/54.1%) and training in small groups (total: 16.6%-practice: 20.9/19.2%-hospital: 13.2/12%). Physicians participated in CME courses and conferences usually in the evenings (7.6/7.2 times a year), followed by halfdays courses (1.4 times), weekend courses (1.4 times) and conferences lasting several day (1.2/1.3-practice: 0.8/0.9-hospital: 1.6/1.6). This study about CME activities firstly demonstrated both the representativity of systematic questionnaires based on the rules of the medical profession, as well as the continuity of the CME behaviour in Germany. The results proof that repeated questionnaires are of little influence on the answering behaviour of physicians.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Neural network model of the genetic code is strongly correlated to the GES scale of amino acid transfer free energies.

A neural network trained to classify the 61 nucleotide triplets of the genetic code into 20 amino acid categories develops in its internal representation a pattern matching the relative cost of transferring amino acids with satisfied backbone hydrogen bonds from water to an environment of dielectric constant of roughly 2.0. Such environments are typically found in lipid membranes or in the interior of proteins. In learning the mapping between the codons and the categories, the network groups the amino acids according to the scale of transfer free energies developed by Engelman, Goldman and Steitz. Several other scales based on internal preference statistics also agree reasonably well with the network grouping. The network is able to relate the structure of the genetic code to quantifications of amino acid hydrophobicity-hydrophilicity more systematically than the numerous attempts made earlier. Due to its inherent non-linearity, the code is also shown to impose decisive constraints on algorithmic analysis of the protein coding potential of DNA.

Amino Acid Sequence↗
PubMed1992

G+C-rich tract in 5' end of human introns.

Analysis of an artificial neural network trained to classify DNA as coding or non-coding revealed compositional differences between sequence parts translated into protein and those that were not. The 5' end of human introns was found to have a base composition that was non-random to an extent matching the non-randomness in the 3' end that contains the polypyrimidine tract. The prevailing nucleotides in the initial 50 nucleotides of human introns are guanine and cytosine, the trinucleotide GGG was found to occur almost four times as frequently as it would in sequences with a uniform distribution of the nucleotides. The initial part of terminal exons and their associated terminal introns were shown to have a very special base composition deviating strongly from the normal picture in other exons and introns.

Base Composition↗
PubMed1992

Multiple alignment using simulated annealing: branch point definition in human mRNA splicing.

A method for the simultaneous alignment of a very large number of sequences using simulated annealing is presented. The total running time of the algorithm does not depend explicitly on the number of sequences treated. The method has been used for the simultaneous alignment of 1462 human intron sequences upstream of the intron-exon boundary. The consensus sequence of the aligned set together with a calculation of the Shannon information clearly shows that several sequence motives are conserved: (i) a previously undetected guanosine rich region, (ii) the branch point and (iii) the polypyrimidine tract. The nucleotide frequencies at each position of the branch point consensus sequence qualitatively reproduce the frequencies of the experimentally determined branch points.

Algorithms↗
PubMed1991

Prediction of human mRNA donor and acceptor sites from the DNA sequence.

Artificial neural networks have been applied to the prediction of splice site location in human pre-mRNA. A joint prediction scheme where prediction of transition regions between introns and exons regulates a cutoff level for splice site assignment was able to predict splice site locations with confidence levels far better than previously reported in the literature. The problem of predicting donor and acceptor sites in human genes is hampered by the presence of numerous amounts of false positives: here, the distribution of these false splice sites is examined and linked to a possible scenario for the splicing mechanism in vivo. When the presented method detects 95% of the true donor and acceptor sites, it makes less than 0.1% false donor site assignments and less than 0.4% false acceptor site assignments. For the large data set used in this study, this means that on average there are one and a half false donor sites per true donor site and six false acceptor sites per true acceptor site. With the joint assignment method, more than a fifth of the true donor sites and around one fourth of the true acceptor sites could be detected without accompaniment of any false positive predictions. Highly confident splice sites could not be isolated with a widely used weight matrix method or by separate splice site networks. A complementary relation between the confidence levels of the coding/non-coding and the separate splice site networks was observed, with many weak splice sites having sharp transitions in the coding/non-coding signal and many stronger splice sites having more ill-defined transitions between coding and non-coding.

Base Sequence↗
PubMed1990

Neural network detects errors in the assignment of mRNA splice sites.

The use of databanks in genetic research assumes reliability of the information they contain. Currently, error-detection in the manually or electronically entered data contained in the nucleotide sequence databanks at EMBL, Heidelberg and GenBank at Los Alamos is limited. We have used a subset of sequences from these databanks to train neural networks to recognize pre-mRNA splicing signals in human genes. During the training on 33 human genes from the EMBL databank seven genes appeared to disturb the learning process. Subsequent investigation revealed discrepancies from the original published papers, for three genes. In four genes, we found wrongly assigned splicing frames of introns. We believe this to be a reflection of the fact that splicing frames cannot always be unambiguously assigned on the basis of experimental data. Thus incorrect assignment appear both due to mere typographical misprints as well as erroneous interpretation of experiments. Training on 241 human sequences from GenBank revealed nine new errors. We propose that such errors could be detected by computer algorithms designed to check the consistency of data prior to their incorporation in databanks.

Algorithms↗