Institut für Hochschulforschung

Abstract Neue biologisch aktive Substanzen aus natürlichen Quellen sind für Naturwissenschaftler und Mediziner oft aufregend, stimulierend sowie Herausforderung und Chance zugleich. Erfahrung und Klugheit gebieten die Erforschung ihrer Chemie und das Streben nach ihrer chemischen Synthese, da der Nutzen sowohl für die Chemie als auch für die Medizin groß sein kann. Die Endiin‐Cytostatica/Antibiotica sind eine sich rasch entwickelnde Klasse solcher Verbindungen bakterieller Herkunft. Diese DNA‐spaltenden Verbindungen, die einen einmaligen, außergewöhnlichen Molekülaufbau mit unglaublichen biologischen Aktivitäten und faszinierenden Wirkungsweisen vereinen, betraten in der zweiten Hälfte der achtziger Jahre, als ihre Struktur bekannt wurde, die Szene und rückten rasch in den Mittelpunkt des Geschehens. Heute umfaßt die Familie der Endiine den Neocarzinostatin‐Chromophor, die Calicheamicine, die Esperamicine und die Dynemicine, weitere Familienmitglieder werden sicherlich bald hinzukommen. Diese Moleküle verursachten in chemischen, biologischen und biomedizinischen Kreisen ausgedehnte Forschungsaktivitäten und regten die Entwicklung vieler neue Verbindungen an, um ihre chemischen und biologischen Wirkungen zu untersuchen und nachzuahmen. Um den Anforderungen dieser Moleküle gerecht zu werden, wurden eine neue Synthesetechnik und mehrere neue Synthesestrategien entwickelt. Diese haben bereits die Konzeption und Synthese mehrerer neuer, DNA‐spaltender Verbindungen ermöglicht. Im folgenden werden die Chemie und Biologie der Endiine zusammengefaßt und die zugehörigen mechanistischen, Synthese‐, Molekül‐Design‐ und DNA‐Spaltungs‐Aspekte erörtert.

The new term Flammer syndrome describes a phenotype characterized by the presence of primary vascular dysregulation together with a cluster of symptoms and signs that may occur in healthy people as well as people with disease. Typically, the blood vessels of the subjects with Flammer syndrome react differently to a number of stimuli, such as cold and physical or emotional stress. Nearly all organs, particularly the eye, can be involved. Although the syndrome has some advantages, such as protection against the development of atherosclerosis, Flammer syndrome also contributes to certain diseases, such as normal tension glaucoma. The syndrome occurs more often in women than in men, in slender people than in obese subjects, in people with indoor rather than outdoor jobs, and in academics than in blue collar workers. Affected subjects tend to have cold extremities, low blood pressure, prolonged sleep onset time, shifted circadian rhythm, reduced feeling of thirst, altered drug sensitivity, and increased general sensitivity, including pain sensitivity. The plasma level of endothelin-1 is slightly increased, and the gene expression in lymphocytes is changed. In the eye, the retinal vessels are stiffer and their spatial variability larger; the autoregulation of ocular blood flow is decreased. Glaucoma patients with Flammer syndrome have an increased frequency of the following: optic disc hemorrhages, activated retinal astrocytes, elevated retinal venous pressure, optic nerve compartmentalization, fluctuating diffuse visual field defects, and elevated oxidative stress. Further research should lead to a more concise definition, a precise diagnosis, and tools for recognizing people at risk. This may ultimately lead to more efficient and more personalized treatment.

ABSTRACT Representation on pension fund boards by state officials—often determined by statute decades past—is negatively related to the performance of private equity investments made by the pension fund, despite state officials’ relatively strong financial education and experience. Their underperformance appears to be partly driven by poor investment decisions consistent with political expediency, and is also positively related to political contributions from the finance industry. Boards dominated by elected rank‐and‐file plan participants also underperform, but to a smaller extent and due to these trustees’ lesser financial experience.

Chimeric receptors were generated in which structurally defined subdomains of the insulin receptor (IR) and insulin growth factor-I receptor (IGF-1R) alpha-subunits were exchanged between their respective receptor backbone structures. Upon expression in human fibroblasts, nine IR/IGF-1R chimeras were transported to the cell surface, where they formed binding sites with differential properties. One IGF-1R/IR chimera (C3') exhibited to some extent high insulin specificity, demonstrating the presence of major insulin binding determinants within the amino acid 325-524 region of the IR alpha-subunit. Complementation of this region with subdomain 1 (amino acids 1-137) reconstituted full insulin binding potential within an IGF-1R framework. In addition, both the IGF-1R/IR C3' chimera and another chimera (C13') displayed high affinity binding properties for IGF-1, which suggests distinct locations for major insulin and IGF-1 binding determinants in their respective receptors, in agreement with our previous findings (Schumacher, R., Mosthaf, L., Schlessinger, J., Brandenburg, D., and Ullrich, A. (1991) J. Biol. Chem. 266, 19288-19295). The binding characteristics of all receptor chimeras correlated directly with the ability of the ligands to regulate their tyrosine kinase activity in intact cells. These results demonstrate direct coupling of ligand binding affinity and capacity for tyrosine kinase activation.

PURPOSE: To assess the safety and efficacy of one, two, or three trabecular microbypass stents in eyes with primary open-angle glaucoma (OAG) not controlled on ocular hypotensive medication. A total of 119 subjects were followed for 18 months postoperatively. MATERIALS AND METHODS: Subjects with medicated intraocular pressure (IOP) 18-30 mmHg and postmedication-washout baseline IOP 22-38 mmHg were randomized to implantation of one, two, or three stents. Ocular hypotensive medication was to be used if postoperative IOP exceeded 18 mmHg. RESULTS: A total of 38 subjects were implanted with one stent, 41 subjects with two stents, and 40 subjects with three stents. Both month 12 IOP reduction ≥20% without ocular hypotensive medication vs baseline unmedicated IOP and month 12 unmedicated IOP ≤18 mmHg were achieved by 89.2%, 90.2%, and 92.1% of one-, two-, and three-stent eyes, respectively. Furthermore, 64.9%, 85.4%, and 92.1% of the three respective groups achieved unmedicated IOP ≤15 mmHg. Over the 18-month follow-up period, medication was required in seven one-stent subjects, four two-stent subjects, and three three-stent subjects. At 18 months, mean unmedicated IOP was 15.9±0.9 mmHg in one-stent subjects, 14.1±1.0 mmHg in two-stent subjects, and 12.2±1.1 mmHg in three-stent subjects. Month 18 IOP reduction was significantly greater (P<0.001) with implantation of each additional stent, with mean differences in reduction of 1.84 mmHg (95% confidence interval 0.96-2.73) for three-stent vs two-stent groups and 1.73 mmHg (95% confidence interval 0.83-2.64) for two-stent vs one-stent groups. Adverse events through 18 months were limited to cataract progression with best-corrected visual acuity loss and subsequent cataract surgery. CONCLUSION: In this series, implantation of each additional stent resulted in significantly greater IOP reduction with reduced medication use. Titratability of stents as a sole procedure was shown to be effective and safe, with sustained effect through 18 months postoperatively in OAG not controlled with medication.

Abstract Wegen mathematischer Schwierigkeiten werden bei theoretischen Zustandsgleichungen meist nur kugelsymmetrische Potentialansätze zugrunde gelegt. Um spezielle Einflüsse der Molekülstruktur auf die Kompressibilität zu klären, wurden bei Temperaturen zwischen 25 und 80°C die p, V, T ‐Daten von Substanzreihen gemessen, innerhalb derer jeweils nur ein Struktruparameter (Kettenlänge, Zahl der Ringgruppen, Bindungscharakter oder molekularer Verzweigungsgrad) variiert wurde. Mit der beschriebenen Apparatur können Dichten bis zu Drücken von 2000 kp/cm 2 auf vier Stellen genau bestimmt werden. Die erhaltenen p, V, T ‐Daten werden anhand der Zustandsgleichung von Tait erörtert und eine Methode angegeben, mit der p, V, T ‐Daten bei hohen Drücken lediglich aus der Anfangskompressibilität abgeschätzt werden können. Ein Vergleich zwischen der Kompressibilität x und dem Viskositäts‐Druckkoeffizienten α ergibt, daß beide Größen sehr verschieden von den einzelnen Strukturmerkmalen des Moleküls abhängen. x wird im wesentlichen durch die Kettenlänge, α dagegen vor allem durch den molekularen Verzweigungsgrad bestimmt. Flüssigkeiten mit extrem großem α weisen eine extrem niedrige Kompressibilität auf.

We have made low-temperature specific-heat measurements demonstrating tunneling of hydrogen trapped by interstitial nitrogen in niobium.Received 7 November 1977DOI:https://doi.org/10.1103/PhysRevLett.40.947©1978 American Physical Society

SUMMARY Based on self organized growth, a self‐similar geometrical model of rock materials is established. The structural mode of the internal surface is carried over to the three‐dimensional structure of the pore space and solid phase, which can be described as a fractal network. It is characterized by the fractal dimension of surface, which can be measured by physical and stereological methods. From this, the fractal behaviour of other geometrical properties, relevant for physical processes, such as porosity, number of solid connections, tortuosity and constrictivity of the capillary system and of the solid phase can be derived.

Molecules containing short-lived, radioactive nuclei are uniquely positioned to enable a wide range of scientific discoveries in the areas of fundamental symmetries, astrophysics, nuclear structure, and chemistry. Recent advances in the ability to create, cool, and control complex molecules down to the quantum level, along with recent and upcoming advances in radioactive species production at several facilities around the world, create a compelling opportunity to coordinate and combine these efforts to bring precision measurement and control to molecules containing extreme nuclei. In this manuscript, we review the scientific case for studying radioactive molecules, discuss recent atomic, molecular, nuclear, astrophysical, and chemical advances which provide the foundation for their study, describe the facilities where these species are and will be produced, and provide an outlook for the future of this nascent field.

Zusammenfassung Trotz Ausbau und Differenzierung des hçheren Schul- und Hochschulsystems zeichnet sich das deutsche Bildungssystem im internationalen Vergleich durch eine vergleichsweise hohe soziale Selektivität aus. Zwar haben sich im Zuge der Bildungsexpansion neue Zugangswege zu hçherer Bildung aufgetan, es ist allerdings offen, inwieweit dies zu einer hçheren Bildungsbeteiligung der traditionell bildungsfernen Schichten geführt hat. Der vorliegende Beitrag beschäftigt sich dementsprechend mit der Frage, wie sich vor dem Hintergrund der veränderten institutionellen und bildungspolitischen Rahmenbedingungen die herkunftsspezifischen Unterschiede entwickelt haben. Hierbei wird sowohl in theoretischer als auch in methodischer Hinsicht differenziert auf die Entwicklung sozialer Ungleichheiten auf Schul- und Hochschulebene eingegangen und mit der Kombination zweier Datenreihen ein alternativer Weg der Analyse sozialer Ungleichheiten im Zeitverlauf aufgezeigt. Die Analyse macht deutlich, dass an den verschiedenen Bildungsübergängen unterschiedliche Entwicklungen stattfinden und es (auch) eine Frage der methodischen Vorgehensweise ist, zu welchem Ergebnis man hinsichtlich der Ungleichheitsentwicklung gelangt. Während die sozialen Ungleichheiten im Zeitverlauf beim Übergang in die Sekundarstufe II abnehmen, nehmen sie am Übergang ins Studium zu. Diese an beiden Übergängen vorzufindenden gegenläufigen Entwicklungen gleichen sich zum Teil aus, sodass insgesamt aus absoluter Perspektive teilweise von stabilen Ungleichheitsverhältnissen im deutschen Bildungssystem zu berichten ist, während sich aus einer relationalen Perspektive eher eine Abnahme abzeichnet.

We calculate the dressed gluon and ghost propagators of Landau gauge Yang-Mills theory in the complex momentum plane from their Dyson-Schwinger equations. To this end, we develop techniques for a direct calculation such that no mathematically ill-posed inverse problem needs to be solved. We provide a detailed account of the employed ray technique and discuss a range of tools to monitor the stability of the numerical calculation. Within a truncation employing model Ans\"atze for the three-point vertices and neglecting effects due to four-point functions, we find a singularity in the gluon propagator in the second quadrant of the complex ${p}^{2}$ plane. Although the location of this singularity turns out to be strongly dependent on the model for the three-gluon vertex, it always occurs at complex momenta for the range of models considered.

Abstract In a preceding paper the melting- and pour-points of several homologeous series of liquid crystals were measured up to 3 kbar.1 Thereby it was found, that e.g. in the series of benzylidene-butylanilines the pourpoint temperature T c and the slope (dp c/dT c) of the transition curve isotropic/nematic alternate with increasing chainlength, whereas the melting temperature increases continuously.

The influence of two extreme types of lattice distortions on the X‐ray diagram is demonstrated with the help of a simple one‐dimensional model. In the first type the displacements of the lattice points from their original positions are mutually independent, while in the second type of distortion a similar independence applies to the distance between successive lattice points. This second type gives rise to a broadening of reflexions, while the first does not. The theory is further applied to a special type of lattice, viz. that where two lattice periods occur in statistical succession. This type of lattice may occur in many compounds. It is shown that it gives rise to a single interference at a Bragg angle corresponding to the average period defined by equation (17). In other words, the reflexion shows a continuous shift with varying amounts of the two components in the compound; a result which is, for instance, applicable to several examples of “intramicellar swelling”.

BACKGROUND: There has been little systematic research about the extent to which German physicians accept or reject the concept and practice of a) clinical practice guidelines (CPG) and b) evidence based medicine (EBM)The aim of this study was to investigate German office-based physicians' perspective on CPGs and EBM and their application in medical practice. METHODS: Structured national telephone survey of ambulatory care physicians, four thematic blocks with 21 questions (5 point Likert scale). 511 office-based general practitioners and specialists. Main outcome measures were the application of Clinical Practice Guidelines in daily practice, preference for sources of guidelines and degree of knowledge and acceptance of EBM. In the data analysis Pearson's correlation coefficient was used for explorative analysis of correlations. The comparison of groups was performed by Student's t-test. Chi2 test was used to investigate distribution of two or more categorical variables. RESULTS: Of the total study population 55.3% of physicians reported already using guidelines in the treatment of patients. Physicians in group practices (GrP) as well as general practitioners (GP) agreed significantly more with the usefulness of guidelines as a basis for patient care than doctors in single practices (SP) or specialists (S) (Student's t-test mean GP 2.57, S 2.84, p < 0.01; mean GrP 2.55, SP 2.80, p < 0.05). 33.1% of the participants demonstrated a strong rejection to the application of guidelines in patient care. Acceptance of guidelines from a governmental institution was substantially lower than from physician networks or medical societies (36.2% vs. 53.4% vs. 62.0%). 73.8% of doctors interpret EBM as a combination of scientific research and individual medical knowledge; 80% regard EBM as the best basis for patient care. CONCLUSION: Despite a majority of physicians accepting and applying CPGs a large group remains that is critical and opposed to the utilization of CPGs in daily practice and to the concept of EBM in general. Doctors in single practice and specialists appear to be more critical than physicians in group practices and GPs. Future research is needed to evaluate the willingness to acquire necessary knowledge and skills for the promotion and routine application of CPGs.

OBJECTIVE: To generate valid data on attitudes about complementary and alternative medicine (CAM) as well as patterns of use in a large stochastic sample of general practitioner physicians and specialists. DESIGN: Cross-sectional survey in a large random sample of 516 German outpatient care physicians with qualifications in 13 medical fields representative of a basic population of 118,085 statutory health insurance physicians. MATERIALS AND METHODS: Telephone interviews with 36 wide-ranging questions about CAM attitudes and preferred techniques were conducted in November and December 2005 as part of a national healthcare survey. RESULTS: In our sample, 51% were in favor of CAM use (26% were very much in favor, 25% were in favor). The methods most frequently prescribed (combining answers for "very often" and "at times") were physical therapy (71%), phytomedicine (67%), exercise (63%), nutrition and dieting (62%), massage (61%), relaxation techniques (55%), followed by more typical CAM interventions such as homeopathy (38%), acupuncture (37%), and traditional Chinese medicine (18%). Primary care physicians were significantly more inclined to use CAM than were specialists. No striking differences were observed with respect to gender or age. CONCLUSIONS: This survey demonstrates a broader acceptance and practice of CAM by physicians than hitherto believed. Methods traditionally known as "natural medicine" were more frequently used than more typical CAM procedures. Further research should focus on physicians' differing motivations and observed results.

Abstract Auf Grund von Versuchen werden theoretische Vorstellungen über den Mechanismus der Reaktion von Kishner‐Wolff‐Staudinger entwickelt. Dabei wird angenommen, daß primär die Lösung eines Protons aus dem zu spaltenden Hydrazon erfolgt und daß das gleichzeitig gebildete Anion mesomer reagiert. Diese Vorstellungen lassen es verständlich erscheinen, daß unter gewissen konstitutionellen Voraussetzungen eine beträchtliche Erhöhung der Reaktionsgeschwindigkeit stattfindet. Als wesentliche Eigenschaft des Katalysators bei der Reaktion wird seine Eignung als Protonfänger herausgestellt.

Abstract Frequencies of the normal modes of vibration of cesium iodide at room temperature propagating in certain symmetry directions were determined by means of slow‐neutron inelastic scattering using a triple axis spectrometer. The data are in reasonable agreement with thermal diffuse X‐ray scattering investigations of Eldridge [1]. The shell model was fitted to the frequencies with good results. This 14‐parameter model was used to compute a frequency distribution and related thermodynamic data.

Abstract We provide results for the spectrum of scalar and pseudoscalar glueballs in pure Yang–Mills theory using a parameter-free fully self-contained truncation of Dyson–Schwinger and Bethe–Salpeter equations. The only input, the scale, is fixed by comparison with lattice calculations. We obtain ground state masses of $$1.9\,\text {GeV}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>1.9</mml:mn> <mml:mspace/> <mml:mtext>GeV</mml:mtext> </mml:mrow> </mml:math> and $$2.6\,\text {GeV}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>2.6</mml:mn> <mml:mspace/> <mml:mtext>GeV</mml:mtext> </mml:mrow> </mml:math> for the scalar and pseudoscalar glueballs, respectively, and $$2.6\,\text {GeV}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>2.6</mml:mn> <mml:mspace/> <mml:mtext>GeV</mml:mtext> </mml:mrow> </mml:math> and $$3.9\,\text {GeV}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>3.9</mml:mn> <mml:mspace/> <mml:mtext>GeV</mml:mtext> </mml:mrow> </mml:math> for the corresponding first excited states. This is in very good quantitative agreement with available lattice results. Furthermore, we predict masses for the second excited states at $$3.7\,\text {GeV}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>3.7</mml:mn> <mml:mspace/> <mml:mtext>GeV</mml:mtext> </mml:mrow> </mml:math> and $$4.3\,\text {GeV}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>4.3</mml:mn> <mml:mspace/> <mml:mtext>GeV</mml:mtext> </mml:mrow> </mml:math> . The quality of the results hinges crucially on the self-consistency of the employed input. The masses are independent of a specific choice for the infrared behavior of the ghost propagator providing further evidence that this only reflects a nonperturbative gauge completion.

Abstract Nonperturbative equations of state (EoSs) for two and three quark flavors are constructed with the functional renormalization group (FRG) within a quark-meson model truncation augmented by vector mesons for low temperature and high density. Based on previous FRG studies without repulsive vector meson interactions the influence of isoscalar vector ω - and ϕ -mesons on the dynamical fluctuations of quarks and (pseudo)scalar mesons is investigated. The grand potential as well as vector meson condensates are evaluated as a function of quark chemical potential and the quark matter EoS in β -equilibrium is applied to neutron star (NS) physics. The tidal deformability and mass-radius relations for hybrid stars from combined hadronic and quark matter EoSs are compared for different vector couplings. We observe a significant impact of the vector mesons on the quark matter EoS such that the resulting EoS is sufficiently stiff to support two-solar-mass neutron stars.

BACKGROUND: In 2004, a practice charge for physician visits ('Praxisgebuehr') was implemented in the German health care system, mainly in order to reduce expenditures of sickness funds by reducing outpatient physician visits. In the statutory sickness funds, all adults now have to pay euro 10 at their first physician visit in each 3 month period, except for vaccinations and preventive services. This study looks at the effect of this new patient fee on delaying or avoiding physician visits, with a special emphasis on different income groups. METHODS: Six representative surveys (conducted between 2004 and 2006) of the Bertelsmann Healthcare Monitor were analysed, comprising 7,769 women and men aged 18 to 79 years. The analyses are based on stratified analyses and logistic regression models, including a focus on the subgroup having a chronic disease. RESULTS: Two results can be highlighted. First, avoiding or delaying a physician visit due to this fee is seen most often among younger and healthier adults. Second, those in the lowest income group are much more affected in this way than the better of. The multivariate analysis in the subgroup of respondents having a chronic disease shows, for example, that this reaction is reported 2.45 times more often in the lowest income group than in the highest income group (95% CI: 1.90-3.15). CONCLUSION: The analyses indicate that the effects of the practice charge differ by socio-economic group. It would be important to assess these effects in more detail, especially the effects on health care quality and health outcomes. It can be assumed, however, that avoiding or delaying physician visits jeopardizes both, and that health inequalities are increasing due to the practice charge.