An ultraluminous X-ray source powered by an accreting neutron star.

The majority of ultraluminous X-ray sources are point sources that are spatially offset from the nuclei of nearby galaxies and whose X-ray luminosities exceed the theoretical maximum for spherical infall (the Eddington limit) onto stellar-mass black holes. Their X-ray luminosities in the 0.5-10 kiloelectronvolt energy band range from 10(39) to 10(41) ergs per second. Because higher masses imply less extreme ratios of the luminosity to the isotropic Eddington limit, theoretical models have focused on black hole rather than neutron star systems. The most challenging sources to explain are those at the luminous end of the range (more than 10(40) ergs per second), which require black hole masses of 50-100 times the solar value or significant departures from the standard thin disk accretion that powers bright Galactic X-ray binaries, or both. Here we report broadband X-ray observations of the nuclear region of the galaxy M82 that reveal pulsations with an average period of 1.37 seconds and a 2.5-day sinusoidal modulation. The pulsations result from the rotation of a magnetized neutron star, and the modulation arises from its binary orbit. The pulsed flux alone corresponds to an X-ray luminosity in the 3-30 kiloelectronvolt range of 4.9 × 10(39) ergs per second. The pulsating source is spatially coincident with a variable source that can reach an X-ray luminosity in the 0.3-10 kiloelectronvolt range of 1.8 × 10(40) ergs per second. This association implies a luminosity of about 100 times the Eddington limit for a 1.4-solar-mass object, or more than ten times brighter than any known accreting pulsar. This implies that neutron stars may not be rare in the ultraluminous X-ray population, and it challenges physical models for the accretion of matter onto magnetized compact objects.

Rare diseases knowledge management: the contribution of proximity measurements in OntoOrpha and OMIM.

In this paper, we introduce an application of Proxima and define a new measure of proximity between two concepts present in an ontology. The approach is based on the three dimensions of a conceptualization: intention with relations between concepts, expression with terms denoting concepts, and extension with instances of concepts. This preliminary work, in the field of rare diseases, involved the Orphanet Ontology of Rare Diseases (OntoOrpha) and corpus of texts extracted from Online Inheritance in Man (OMIM). The proximity measurements are consistent with an appropriate representation of groups of diseases in the ontology, which are derived from the Orphanet classifications of rare diseases. Other semantic relations are explored and new perspectives in medical knowledge curation are proposed.

[Development of the Saxon Health Target "Active aging - aging in health, autonomy, and participation"]. / Entwicklung des Sächsischen Gesundheitsziels "Aktives Altern - Altern in Gesundheit, Autonomie und Mitverantwortlichkeit."

In Saxony, the consequences of demographic aging are observable already today. To manage the implications on the health sector, the Saxon Health Targets Steering Committee decided in March 2008 to develop a health target "Active Aging - Aging in Health, Autonomy, and Participation". Target development was based on a 7-level approach (fields of action, main goals, target areas, targets, strategies, intervention measures, indicators for evaluation). A quantitative content analysis was used to reveal 10 potential relevant fields of action, three of which were selected for target development. Targets were developed by 53 stakeholders in multiprofessional working groups. Criteria-based analyses were performed to assure appropriate scientific evidence and feasibility of targets and intervention measures. Over a period of 9 months, 24 targets were defined referring to the main goals "needs-based health care structures", "multiprofessional qualification", "self-rated health" and "intergenerational solidarity". Thirteen targets were developed into recommendations for specific intervention measures. Most of the proposed interventions aim to modify health-related structures or psychosocial determinants of health in the elderly. The best recommendations for intervention measures shall be implemented in cooperation with interested decision-makers.

Stellar dynamics. The fastest unbound star in our Galaxy ejected by a thermonuclear supernova.

Hypervelocity stars (HVSs) travel with velocities so high that they exceed the escape velocity of the Galaxy. Several acceleration mechanisms have been discussed. Only one HVS (US 708, HVS 2) is a compact helium star. Here we present a spectroscopic and kinematic analysis of US 708. Traveling with a velocity of ~1200 kilometers per second, it is the fastest unbound star in our Galaxy. In reconstructing its trajectory, the Galactic center becomes very unlikely as an origin, which is hardly consistent with the most favored ejection mechanism for the other HVSs. Furthermore, we detected that US 708 is a fast rotator. According to our binary evolution model, it was spun-up by tidal interaction in a close binary and is likely to be the ejected donor remnant of a thermonuclear supernova.

The significance of early diagnosis in the management of testicular tumour patients.

Surveying the therapeutic results of 16 testicular tumour patients treated in the recent 5 years, the authors stress, beside the generally accepted and use complex treatment, the importance of recognizing the disease in its early stage.

[Diagnostic difficulties in space-reducing kidney processes]. / Diagnostische Schwierigkeiten bei raumbeengenden Nierenprozessen.

With the discussion of four cases the authors draw attention to the diagnostic difficulties which arise in the diagnosis of space reducing renal processes. They disapprove of the application of percutaneous puncture of the renal cyst as a therapeutic procedure, and emphasize, in doubtful cases, the importance of intraoperative histological examination. With two of their cases which were diagnosed only at the time of the second hospitalization of the patient, the authors wish to stress the need for a still wider use of angiographic examinations.

[Priapism]. / Zur Frage des Priapismus

The data of patients treated for priapism in the Department of Urology of Semmelveis University Medical School between 1951 and 1971 are analyzed. Eleven patients were hospitalized and three were outpatients. After a brief survey of the literature, mechanism, aetiology and treatment of the condition are discussed. In the majority of the patients after the cessation of priapism sexual libido returned as a rule without the appearance of erection. Three cases are briefly described. In four patients after some time partial erection and orgasm was experienced under mechanical influence. Two of these patients had married and have children.

[Treatment of bladder tumors]. / Uber die Therapie der Blasentumoren.

Experience with surgical and combined treatment of bladder tumours are reported. 587 patients were subjected to operation only, 71 received complex therapy. The patients were classified according to the TNM system, assessment of the results was based on five-year survival. In the group in which the tumour involved only the mucous membrane and did not infiltrate the bladder wall, the results were favourable (85%), while in the group when the bladder wall was deeply infiltrated, there was no five-year survival irrespective of the treatment having been purely surgical or surgical combined with cytostatic or X-ray therapy.

Plasticity and steric strain in a parallel beta-helix: rational mutations in the P22 tailspike protein.

By means of genetic screens, a great number of mutations that affect the folding and stability of the tailspike protein from Salmonella phage P22 have been identified. Temperature-sensitive folding (tsf) mutations decrease folding yields at high temperature, but hardly affect thermal stability of the native trimeric structure when assembled at low temperature. Global suppressor (su) mutations mitigate this phenotype. Virtually all of these mutations are located in the central domain of tailspike, a large parallel beta-helix. We modified tailspike by rational single amino acid replacements at three sites in order to investigate the influence of mutations of two types: (1) mutations expected to cause a tsf phenotype by increasing the side-chain volume of a core residue, and (2) mutations in a similar structural context as two of the four known su mutations, which have been suggested to stabilize folding intermediates and the native structure by the release of backbone strain, an effect well known for residues that are primarily evolved for function and not for stability or folding of the protein. Analysis of folding yields, refolding kinetics and thermal denaturation kinetics in vitro show that the tsf phenotype can indeed be produced rationally by increasing the volume of side chains in the beta-helix core. The high-resolution crystal structure of mutant T326F proves that structural rearrangements only take place in the remarkably plastic lumen of the beta-helix, leaving the arrangement of the hydrogen-bonded backbone and thus the surface of the protein unaffected. This supports the notion that changes in the stability of an intermediate, in which the beta-helix domain is largely formed, are the essential mechanism by which tsf mutations affect tailspike folding. A rational design of su mutants, on the other hand, appears to be more difficult. The exchange of two residues in the active site expected to lead to a drastic release of steric strain neither enhanced the folding properties nor the stability of tailspike. Apparently, side-chain interactions in these cases overcompensate for backbone strain, illustrating the extreme optimization of the tailspike protein for conformational stability. The result exemplifies the view arising from the statistical analysis of the distribution of backbone dihedral angles in known three-dimensional protein structures that the adoption of straight phi/psi angles other than the most favorable ones is often caused by side-chain interactions. Proteins 2000;39:89-101.