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Biomedical subjects

A Heger

Publications and source records attributed to A Heger.

At least 19 recordsLinked to original sources

40Ca(alpha, gamma)44Ti reaction in the energy regime of supernova nucleosynthesis.

The 44Ti(t1/2=59 yr) nuclide, an important signature of supernova nucleosynthesis, has recently been observed as live radioactivity by gamma-ray astronomy from the Cas A remnant. We investigate in the laboratory the major 44Ti production reaction 40Ca(alpha, gamma)44Ti (Ec.m. approximately 0.6-1.2 MeV/u by direct off-line counting of 44Ti nuclei. The yield, significantly higher than inferred from previous experiments, is analyzed in terms of a statistical model using microscopic nuclear inputs. The associated stellar rate has important astrophysical consequences, increasing the calculated supernova 44Ti yield by a factor approximately 2 over previous estimates and bringing it closer to Cas A observations.

Journal Article↗

[The pediatric surgeon's role in intensive care].

In contrast to adult surgery, pediatric surgery today is particularly dependent on multidisciplinary cooperation, especially with pediatricians, neonatologists, and pediatric anesthesiologists. This is particularly important in intensive care. Pediatric surgery is not able to manage this challenge on its own because of small numbers of intensive care patients, small staff with few intensive care specialists, and little general interest. The pediatric surgeon's role in interdisciplinary intensive care is to ensure optimal treatment for his patients by helpful cooperation, commitment, and readiness to take on responsibility, together with his own irreplaceable expertise.

Child↗

Stellar (n,gamma) cross section of 62Ni.

The 62Ni(n,gamma)63Ni(t(1/2)=100+/-2 yr) reaction plays an important role in the control of the flow path of the slow neutron-capture (s) nucleosynthesis process. We have measured for the first time the total cross section of this reaction for a quasi-Maxwellian (kT=25 keV) neutron flux. The measurement was performed by fast-neutron activation, combined with accelerator mass spectrometry to detect directly the 63Ni product nuclei. The experimental value of 28.4+/-2.8 mb, fairly consistent with a recent calculation, affects the calculated net yield of 62Ni itself and the whole distribution of nuclei with 62<A<90 produced by the weak s process in massive stars.

Journal Article↗

More for less in structural genomics.

Structural genomics is the idea of covering protein space so that every protein sequence comes within model building distance of a protein of known structure. Unfortunately, reproducing the structural alignment of distantly related proteins is a difficult challenge to existing sequence alignment and motif search software. We have developed a new transitive alignment algorithm (MaxFlow), which generates accurate alignments between proteins deep in the twilight zone of sequence similarity, below 20% sequence identity. In particular, MaxFlow reliably identifies conserved core motifs between proteins which are only indirect PSI-Blast neighbours. Based on MaxFlow alignments, useful 3D models can be generated for all members of a superfamily from as few as a single structural template--despite hundreds of representatives at 40% sequence identity level and patchy detection of homology by PSI-Blast. We propose novel strategies for target prioritization using MaxFlow scores to predict the optimal templates in a superfamily. Our results support an increase in the granularity of covering protein space that has potentially enormous economic implications for planning the transition to the full production phase of structural genomics.

Algorithms↗

Presupernova collapse models with improved weak-interaction rates.

Improved values for stellar weak-interaction rates have been recently calculated based upon a large shell-model diagonalization. Using these new rates (for both beta decay and electron capture), we have examined the presupernova evolution of massive stars in the range (15--40)M(o). Comparing our new models with a standard set of presupernova models by Woosley and Weaver, we find significantly larger values for the electron-to-baryon ratio at the onset of collapse and smaller iron core masses. These changes may have important consequences for nucleosynthesis and the supernova explosion mechanism.

Journal Article↗

A fully automatic evolutionary classification of protein folds: Dali Domain Dictionary version 3.

The Dali Domain Dictionary (http://www.ebi.ac.uk/dali/domain) is a numerical taxonomy of all known structures in the Protein Data Bank (PDB). The taxonomy is derived fully automatically from measurements of structural, functional and sequence similarities. Here, we report the extension of the classification to match the traditional four hierarchical levels corresponding to: (i) supersecondary structural motifs (attractors in fold space), (ii) the topology of globular domains (fold types), (iii) remote homologues (functional families) and (iv) homologues with sequence identity above 25% (sequence families). The computational definitions of attractors and functional families are new. In September 2000, the Dali classification contained 10 531 PDB entries comprising 17 101 chains, which were partitioned into five attractor regions, 1375 fold types, 2582 functional families and 3724 domain sequence families. Sequence families were further associated with 99 582 unique homologous sequences in the HSSP database, which increases the number of effectively known structures several-fold. The resulting database contains the description of protein domain architecture, the definition of structural neighbours around each known structure, the definition of structurally conserved cores and a comprehensive library of explicit multiple alignments of distantly related protein families.

Amino Acid Motifs↗

Transient pseudohypoaldosteronism secondary to posterior urethral valves--a case report and review of the literature.

In transient pseudohypoaldosteronism (TPHA), renal tubular resistance to aldosterone is thought to be secondary to renal disease. We report a case of TPHA caused by posterior urethral valves associated with urinary tract infection and review 62 cases previously reported. The infant presented with unspecific signs of vomiting and dehydration, so that pyloric stenosis was first suspected. Laboratory data and retroperitoneal sonography led to the diagnosis TPHA. This case illustrates that urine culture and renal ultrasonography should be performed in any infant with electrolyte disturbances to exclude infection or obstructive uropathy.

Aldosterone↗

Picasso: generating a covering set of protein family profiles.

MOTIVATION: Evolutionary classification leads to an economical description of protein sequence data because attributes of function and structure are inherited in protein families. This paper presents Picasso, a procedure for deriving a minimal set of protein family profiles that cover all known protein sequences. RESULTS: Picasso starts from highly overlapping sequence neighbourhoods revealed by all-on-all pairwise Blast alignment. Overlaps are reduced by merging sequences or parts of sequences into multiple alignments. For maximum unification, the multiple alignments must reach into the twilight zone of sequence similarity. Sensitive and selective profile-profile comparison allows unification down to about 15% pairwise sequence identity. Families unified through a short conserved sequence motif are associated with multiple full-length alignments describing different subfamilies. Domains that are mobile modules are identified based on their association with different sets of neighbours. The result is 10000 unified domain families (excluding singletons) representing functionally related proteins and recovering classical prolific domain types in high numbers. The classification is useful, for example, in developing strategies for efficient database searching and for selecting targets to complete the map of all 3-D structures.

Algorithms↗

Rapid automatic detection and alignment of repeats in protein sequences.

Many large proteins have evolved by internal duplication and many internal sequence repeats correspond to functional and structural units. We have developed an automatic algorithm, RADAR, for segmenting a query sequence into repeats. The segmentation procedure has three steps: (i) repeat length is determined by the spacing between suboptimal self-alignment traces; (ii) repeat borders are optimized to yield a maximal integer number of repeats, and (iii) distant repeats are validated by iterative profile alignment. The method identifies short composition biased as well as gapped approximate repeats and complex repeat architectures involving many different types of repeats in the query sequence. No manual intervention and no prior assumptions on the number and length of repeats are required. Comparison to the Pfam-A database indicates good coverage, accurate alignments, and reasonable repeat borders. Screening the Swissprot database revealed 3,000 repeats not annotated in existing domain databases. A number of these repeats had been described in the literature but most were novel. This illustrates how in times when curated databases grapple with ever increasing backlogs, automatic (re)analysis of sequences provides an efficient way to capture this important information.

Algorithms↗

Towards a covering set of protein family profiles.

Evolutionary classification leads to an economical description of the protein sequence universe because attributes of function and structure are inherited in protein families. Efficient strategies of functional and structural genomics therefore target one representative from each family. Enumerating all families and establishing family membership consistently based on sequence similarities are nontrivial computational problems. Emerging concepts and caveats of global sequence clustering are reviewed. Explicit multiple alignments coupled with neighbourhood analysis lead to domain segmentation, and hierarchical unification helps to resolve conflicts and validate clusters. Eventually, every part of every sequence will be assigned to a domain family which is uniquely associated with a fold and a molecular function.

Amino Acid Sequence↗

Estimating the significance of sequence order in protein secondary structure and prediction.

MOTIVATION: How critical is the sequence order information in predicting protein secondary structure segments? We tried to get a rough insight on it from a theoretical approach using both a prediction algorithm and structural fragments from Protein Databank (PDB). RESULTS: Using reverse protein sequences and PDB structural fragments, we theoretically estimated the significance of the order for protein secondary structure and prediction. On average: (1) 79% of protein sequence segments resulted in the same prediction in both normal and reverse directions, which indicated a relatively high conservation of secondary structure propensity in the reverse direction; (2) the reversed sequence prediction alone performed less accurately than the normal forward sequence prediction, but comparably high (2% difference); (3) the commonly predicted regions showed a slightly higher prediction accuracy (4%) than the normal sequences prediction; and (4) structural fragments which have counterparts in reverse direction in the same protein showed a comparable degree of secondary structure conservation (73% identity with reversed structures on average for pentamers). CONTACT: jong@biosophy.org; dietmann@ebi.ac.uk; heger@ebi.ac.uk; holm@ebi.ac.uk

Algorithms↗

RSDB: representative protein sequence databases have high information content.

MOTIVATION: Biological sequence databases are highly redundant for two main reasons: 1. various databanks keep redundant sequences with many identical and nearly identical sequences 2. natural sequences often have high sequence identities due to gene duplication. We wanted to know how many sequences can be removed before the databases start losing homology information. Can a database of sequences with mutual sequence identity of 50% or less provide us with the same amount of biological information as the original full database? RESULTS: Comparisons of nine representative sequence databases (RSDB) derived from full protein databanks showed that the information content of sequence databases is not linearly proportional to its size. An RSDB reduced to mutual sequence identity of around 50% (RSDB50) was equivalent to the original full database in terms of the effectiveness of homology searching. It was a third of the full database size which resulted in a six times faster iterative profile searching. The RSDBs are produced at different granularity for efficient homology searching. AVAILABILITY: All the RSDB files generated and the full analysis results are available through internet: ftp://ftp.ebi.ac. uk/pub/contrib/jong/RSDB/http://cyrah.e bi.ac.uk:1111/Proj/Bio/RSDB

Algorithms↗

Atypical hemihepatectomy during primary CDH-repair in a neonate on ECMO.

We report the case of a newborn with a large left-sided congenital diaphragmatic hernia (CDH) who required extra corporeal membrane oxygenation (ECMO) for severe respiratory insufficiency. CDH repair had to be performed on bypass circulation. Intraoperatively, an atypical hemihepatectomy of the herniated lobe was conducted, because reposition of the liver led to a kinking of the vena cava and to a torsion of the right lobe, resulting in ischemia and compromised venous flow. The extraordinary anatomical indication and the potential danger of uncontrollable bleeding are discussed.

Extracorporeal Membrane Oxygenation↗

Appearance of the hymen in newborns.

This study was undertaken to evaluate the genital anatomy of female newborns. Hymenal configuration and the number and location of clefts, bumps, tags, and ridges were observed in 468 neonates; photographs for confirmation were obtained for 449 neonates (96%). Hymenal configurations observed included an annular hymen with a central or ventrally displaced orifice in 80% (372/468) of neonates, a fimbriated hymen in 19% (90/468), and a septated or cribriform hymen in 1% (6/468). Configurations significantly differed by race (P less than .001) but no difference was noted by gestational age or weight. Clefts, which occurred only on the ventral 180 degrees of the rim, were observed in 34% of neonates with an annular hymen. Fifty-six percent of neonates had a longitudinal intravaginal ridge, 87% had an external hymenal ridge, and 13% had a tag extending from the rim or a ridge. Periurethral ligaments were frequently observed. It is concluded that lateral and ventral clefts, intravaginal and external ridges, and periurethral bands are normal anatomical findings in the newborn.

Female↗

The use of the colposcope in the diagnosis of sexual abuse in the pediatric age group.

This brief communication by Woodling and Heger on the use of colposcopy in the assessment of children who may have been sexually exploited raises some interesting and exciting new dimensions to our diagnostic approach. These are presented by the authors as early findings. The readers should note that standards have not yet been established completely, and findings in normal children need to be further delineated, especially for young girls who are athletically inclined, e.g., gymnists as well as victims of accidental genital trauma. Our field urgently awaits these data.

Child Abuse↗

[Experimental neurotraumatology--rotation (author's transl)].

Experimental simulations of motion of the brain at impact were carried out. Rotational accelerations from 2,000 up to 8,000 rad/s2 with durations of 8 to 32 ms were applied to preparations of human skull and brain. The tests were filmed with a high-speed camera with up to 3,000 frames/s. Due to inertia there were relative motion and displacement of the upper part of the brain relative to the skull-cap. Marked displacements (maximum: 2cm) were observed on atrophied brains. Test results are discussed and compared with other investigations.

Acceleration↗

Relationship of child sexual abuse to depression.

Thirty-nine girls aged 6 to 12 participated in this study, each having been referred for evaluation of suspected child sexual abuse. The study investigated the prevalence of depression in the sample as well as the relationship of depressive symptoms to severity of abuse and potential mediator variables. The Child Behaviour Checklist and Child Depression Inventory were used to asses the severity of depression. A composite score for severity of abuse was derived from child disclosure and medical findings. Results indicated that 67% of the children could be classified as experiencing symptoms consistent with a diagnosis of depression. Severity of abuse was not significantly correlated with depression intensity scores. Stepwise regression analyses revealed that a high number of stressful life events and low IQ were significant predictors of depression scores. The clinical implications of these findings are discussed.

Child↗