Search

Using data from the HEGRA air shower array, taken in the period from April 1998 to March 2000, upper limits on the ratio Iγ/ICR of the diffuse photon flux Iγ to the hadronic cosmic ray flux ICR are determined for the energy region 20–100 TeV. The analysis uses a gamma–hadron discrimination which is based on differences in the development of photon- and hadron-induced air showers after the shower maximum. A method which is sensitive only to the non-isotropic component of the diffuse photon flux yields an upper limit of Iγ/ICR (at 54 TeV)

A search for potential point sources of very high energy gamma rays has been carried out on the data taken simul- taneously by the HEGRA AIROBICC and Scintillator arrays from August 1994 to March 2000. The list of sought sources includes supernova remnants, pulsars, AGNs and binary systems. The energy threshold is around 15 TeV. For the Crab Nebula, a modest excess of 2.5 standard deviations above the cosmic ray background has been observed. Flux upper limits (at 90% c.l.) of around 1.3 times the flux of the Crab Nebula are obtained, in average, for the candidate sources. A dierent search procedure has been used for an all-sky search which yields absolute flux upper limits between 4 and 9crabs depending on declination, in the band from= 0t o= 60.

The detection of TeV -rays from the blazar H 1426+428 at an integral flux level of (4 2stat 1syst) 10 12 erg cm 2 s 1 above 1 TeV with the HEGRA imaging atmospheric Cherenkov telescope system is reported. H 1426+428 is located at a redshift of z = 0.129, which makes it the most distant source detected in TeV -rays so far. The TeV radiation is expected to be strongly absorbed by the diuse extragalactic background radiation (DEBRA). The observed energy spectrum of TeV photons is in good agreement with an intrinsic power law spectrum of the source/ E 1:9 corrected for DEBRA absorption. Statistical errors as well as uncertainties about the intrinsic source spectrum, however, do not permit strong statements about the density of the DEBRA infrared photon eld.

Using the HEGRA system of imaging atmospheric Cherenkov telescopes, a region of the Galactic plane ( 10

For distant extragalactic sources of gamma-rays in the PeV (10 15 eV) energy range, interactions of the gamma rays with intergalactic diuse radiation elds will initiate a pair cascade. Depending on the magnetic elds in the vicinity of the source, the cascade can either result in an isotropic halo around an initially beamed source, or remain more or less collimated. Data recorded by the HEGRA system of imaging atmospheric Cherenkov telescopes are used to derive limits on the halo flux from the AGN Mrk 501. This is achieved by comparing the angular distribution of TeV gamma-rays during the 1997 burst phase { where direct photons should dominate { with the distribution during the 1998/99 quiescent state, where a steady-state halo contribution should be most pronounced. The results depend on the assumptions concerning the angular distribution of the halo; limits on the halo flux within 0:5 to 1 from the source range between 0.1% and 1% of the peak burst flux.

Purpose. Lipid-water partitioning of 187 pharmaceuticals has been assessed with solid-supported lipid membranes (TRANSIL) in microwell plates and with multilamellar liposomes for a data comparison. The high-throughput potential of the new approach was evaluated.

Three-month-old female Wistar rats were fed with 20% alcohol in their drinking fluid over 6-17 mo using an interrupted feeding regimen. At different times, pancreatic acini were isolated by mild collagenase digestion. The concentrations of inositol-1,4,5-trisphosphate (1,4,5-IP3) were determined by a specific radioreceptor assay, before and at different times after stimulation with varying concentrations of CCK-8. CCK-induced dynamics of cytoplasmic calcium ([Ca2+]c) was investigated in acinar cells by confocal laser raster microscopy. Acinar alpha-amylase (Aml) secretion was measured as enzyme activity in the medium compared to the total activity in the suspension.In 12-13-mo-old rats, the CCK-stimulated 1,4,5-IP3 formation in acini was found to be decreased compared to young rats (age 4 mo). In rats of the same age fed with ethanol from the age of 3 mo on, 1,4,5-IP3 concentrations in acini were higher and reached values comparable to those in young rats. Correspondingly, the CCK-induced [Ca2+]c dynamics in acini isolated from 9-mo-old rats was impaired compared to that of young rats but normal in aged, chronically alcohol-fed rats. Aml secretion under CCK stimulation, however, which was decreased in aged rats, was additionally impaired after alcohol feeding.Chronic alcohol feeding modifies 1,4,5-IP3 formation, the [Ca2+]c dynamics of, and the Aml secretion of rat pancreatic acini in response to CCK stimulation. Obviously, the age-related impairment of 1,4,5-IP3 formation and [Ca2+]c dynamics is improved. In contrast, the decrease in Aml secretion of acini isolated from aged rats is more pronounced after long-term alcohol-feeding.

The determination of partition coefficients is crucial for the biochemical analysis of membrane-based processes, but requires tedious procedures. We have facilitated this analysis using a silica gel coated with a single phospholipid bilayer (TRANSIL) as the membranous phase. We demonstrate the validity of this method using MARCKS-related protein, a 20-kDa member of the MARCKS family (an acronym for myristoylated alanine-rich C kinase substrate). The partition coefficients describing the association of unmyristoylated and myristoylated MARCKS-related protein with membranes of different phospholipid composition are in agreement with previous work with vesicles and show that both the myristoyl moiety and the basic effector domain of MARCKS-related protein mediate the binding. However, no significant cooperativity is observed between these two domains. Interestingly, MARCKS-related protein binds to TRANSIL membranes more strongly at temperatures below their phase-transition temperature. Taking advantage of this property, MARCKS-related protein was purified by phase-transition chromatography, loading Escherichia coli lysates on a TRANSIL column at 4°C and eluting MRP at room temperature. In conclusion, TRANSIL is a versatile tool to determine the affinity of compounds for phospholipid membranes and to purify membrane-bound proteins. TRANSIL should also enable functional studies of protein–ligand and protein–protein interactions at the surface of membranes.

Die Untersuchung zeigt, das die Carbonatgehalte der Wasser aus drei Quellen erhalten werden: 1. biogenes CO2 aus dem Boden, 2. vulkanogenes CO2 aus dem Zechstein-Salz und 3. Carbonat aus Kalk und Dolomit. Das vulkanogene CO2-Gas entstammt ursprunglich den miozanen basaltischen Schmelzen, die bei ihrem Aufstieg die Zechstein-Salze durchbrachen. Das CO2 wurde in Intra- und Intergranularen des Salzgesteins gespeichert und wird bei Zutritt von zirkulierenden meteorischen Wassern freigesetzt. Bei hoher Basalthaufigkeit mit hieraus resultierenden hohen Gehalten an CO2-Gas im Salzgestein reichen schon relativ geringe Mengen von aufgelostem Salz aus, um grose Mengen an „Salz-CO2” fur die Auflosung von Kalk und Dolomit zur Verfugung zu stellen. Aus der Zusammensetzung von carbonatreichen Wassern ergab sich ein δ13C-Wert fur das Salz-CO2 von –1‰ (PDB). Wahrend in diesen Wassern der Anteil von Salz-CO2 gegenuber biogenem CO2 dominiert, nimmt in den carbonatarmen Wassern der Anteil von Salz-CO2 am Carbonatgehalt bis auf etwa 20% ab. Geochemical and 13C/12C-isotopical Investigation of Mineral Waters in Northern Hessia (Germany) and the Origin of their CO2 Content The dissolved carbonate originates from three sources: 1. biogenetic soil-CO2, 2. volcanic CO2 related to the evaporites of the Zechstein formation, and 3. carbonate derived from the dissolution of limestones and dolomites. Miocenic basaltic melts penetrated the evaporites of the Zechstein, and the related CO2 was trapped in the intra- and intergranulars of the salt minerals. Circulating meteoric waters dissolve the salt minerals releasing CO2 gas. Thus, the occurrence of basalt is related to the CO2 contents of the evaporites, and the dissolution of only small amounts of salts rich in CO2 may result in a high concentration of carbonic acid. In waters rich in carbonate, where volcanic CO2 dominates over the other two sources of carbon, a δ13C-value of “salt-CO2” of about –1‰ (PDB) is obtained. Water with less dissolved carbonate species have smaller quantities of salt-CO2 down to about 20%.

The heme-containing enzyme myeloperoxidase (MPO) is mainly expressed in polymorphonuclear leukocytes (PMNs), the most abundant immune cell type in the blood. Accordingly, MPO is classically attributed to the innate immune response against pathogens. Yet, new results also show immune-regulatory functions of the halogenating MPO activity including the formation of anti-inflammatory mediators. In this work we tested the ability of the flavonoid (−)-epicatechin to regenerate this enzymatic activity both in vitro at the isolated MPO–H 2 O 2 –Cl − system and ex vivo in human PMNs. For all experiments the non-fluorescent dye aminophenyl fluorescein (APF) was used. Upon oxidation by the MPO, the halogenation product hypochlorous acid (HOCl) fluorescein is formed which can be detected e.g. by flow cytometry. The in vitro - and ex vivo -results concordantly show that (−)-epicatechin is a suitable substrate to overcome a compound II accumulation of MPO which was experimentally forced by applying excess hydrogen peroxide. Thereby concentration-dependent effects of the flavan-3-ol were found in both cases and confirmed the proposed mode of action of (−)-epicatechin. The results are in accordance with previous stopped-flow kinetic studies which showed a high reactivity of the polyphenol with MPO compound II. The obtained data may contribute to the explanation of the well-known health promoting effects of (−)-epicatechin. Moreover, the presented study provides new insights into the role of MPO during inflammation.

1.1 Hintergrund und Ziele Der Tod aus kardialer Ursache ist, wie im Jahresbereicht 2005/2006 der QUASI-Niere mit einer prozentualen Verteilung von 41% bei chronisch niereninsuffizienten Patienten dargelegt, die häufigste Todesursache bei Patienten mit terminaler Niereninsuffizienz (72). Neben Spätkomplikationen in Folge einer im Verlauf der Erkrankung zumeist notwendigen Hämodialyse sind es jedoch auch frühzeitig auftretende Störungen (84), die für diese hohe Mortalität verantwortlich sind. Im Vergleich zu Nierengesunden zeigt sich eine andere Entstehung und Zusammensetzung der atherosklerotischen Plaques (8), die vermehrt Verkalkungen und oxidativen Stress aufweisen. Hyperlipidämien bewirken eine Progression von Gefäßschäden (20). Den HMG- CoA- Reduktasehemmern (Statinen), potenten Hemmern der Cholesterinbiosynthese, konnte in Studien neben ihrer lipidsenkenden Eigenschaft auch zahlreiche Wirkungen auf zellulärer Ebene nachgewiesen werden: Antioxidative Effekte, Entzündungshemmung, Hemmung der Thrombusbildung, Plaquestabilisierung, Aktivierung glatter Muskelzellen und die Schaumzellbildung sowie eine Verbesserung der Endothelfunktion(108), zusammenfassend als pleiotrope Effekte (1, 21) bezeichnet. Ziel der vorliegenden Sekundärpräventionsstudie im ApoE-/- Tiermodell ist es die Auswirkung einer Atorvastatinbehandlung auf atherosklerotische Plaques bei vorbestehender renaler Schädigung nach Uninephrektomie anhand morphometrischer und immunhistochemischer Methoden zu untersuchen. 1.2 Tiermodell und Untersuchungsmethoden Genutzt wurde dafür das Tiermodell der ApoE-/- defizienten Maus. Diese eignen sich auf Grund der spontanen Entwicklung einer Hyperlipidämie mit Ausbildung schwerer atherosklerotischer Läsionen insbesondere im Bereich der Aortenwurzel und des Aortenbogens (15, 19, 63). Diese Läsionen sind mit humanen atherosklerotischen Schäden gut vergleichbar (70). Sechs Monate alte männliche Tiere wurden randomisiert und in 4 Tiergruppen eingeteilt. Um die Effekte einer renalen Schädigung zu beschleunigen, wurde nach einer Adaptionsphase von 2 Wochen bei 2 der Gruppen eine einseitige Nephrektomie (UNX) vorgenommen. Die beiden übrigen Gruppen wurden scheinoperiert. In den folgenden 6 Monaten wurde je eine Gruppe der UNX- (n=9) und eine der scheinoperierten Tiere (n=11) mit Atorvastatin therapiert, die übrigen Tiere (ApoE, n= 10; ApoE+UNX, n=9) blieben unbehandelt. Die atherosklerotischen Veränderungen wurden histologisch anhand von Paraffinschnitten mittels standardisierter Auswertungsverfahren und morphometrischer Methoden quantitativ und qualitativ bestimmt und zwischen den Gruppen verglichen. Die morphologischen Besonderheiten der atherosklerotischen Plaques wurden mit Hilfe immunhistochemischer Untersuchungen bestimmt. 1.3 Ergebnisse und Beobachtungen Die Ergebnisse des Experiments zeigen keine eindeutige Auswirkung der Statinbehandlung auf die Plaquegröße im Bereich der Aorta ascendens im ApoE- Mausmodell. Die Expressionen proinflammatorischer Moleküle wie VCAM oder CD 40 konnten durch Statine signifikant gesenkt werden. Ein einheitlicher Effekt einer Statinbehandlung fand sich jedoch nicht, auch wenn tendenziell die Mehrheit der untersuchten Merkmale in den mit Statinen behandelten Tiergruppen weniger stark ausgeprägt war. Einige Meßwerte wie z.B. Blutdruck und Cholesteringehalt des Blutes zeigten entgegen dieser Tendenz unter Statinbehandlung sogar eine Zunahme. Die milde Nierenfunktionsstörung, die mittels Uninephrektomie erreicht wurde, hatte ebenfalls nur geringe morphologische Auswirkungen. 1.4 Schlussfolgerungen Die Wirksamkeit der Statine als Hemmer einer Plaque-Progression und damit ihr anti-atherosklerotischer Effekt im ApoE- Mausmodell ist insgesamt in dieser Untersuchung nicht sicher belegbar, wenngleich sich signifikante Unterschiede im Bezug auf die Plaquebeschaffenheit finden liessen, die einen anti-inflammatorischen und anti-oxidativen Effekt der Statine andeuten. Eine definitive Klärung, in wie weit dies einer mangelnden Wirksamkeit der HMG- Reduktase- Hemmer bezüglich der gewählten Parameter bei nur milder Nierenschädigung/ geringer Hyperlipidämie zu Schulden ist oder aber aus dem Versuchsaufbau resultiert, kann in diesem Experiment nicht definitiv erbracht werden. Gegebenenfalls könnte eine zusätzliche fettreichere Ernährung der Tiere im Sinne einer „western- type diet“ oder einer alternative Medikamentengabe andere Resultate liefern. Die Uninephrektomie- Operation bei ApoE-/- defizienten Mäusen zur Steigerung der Gefäßveränderungen zeigte entgegen früherer Versuche nur einen geringen Effekt. Um die Auswirkungen einer Statinbehandlung zu überprüfen ist möglicherweise ein alternatives Tiermodell erfolgversprechender (48). 1.1 Background and Objectives The 2005/2006 QUASI-kidney annual report places at 41% the rate of cardiac causes of death in patients with chronic renal insufficiency, the most common cause of patient deaths with terminal renal insufficiency.(72) Aside from late complications, derived from hemodialysis, often required in the course of the disease, it is the earlier malfunctions (84) that are responsible for this high mortality rate. Contrary to patients showing no signs of renal dysfunction, a different genesis and composition of atherosclerotic plaques (8) can be found, showing an increased incidence of calcification and oxidative stress. Hyperlipidemias induce a progression of vascular damage.(20) It has been demonstrated in studies that alongside their lipid-reducing qualities, HMG- CoA- reductase inhibitors (Statins), potent obstructers of cholesterol biosynthesis, have numerous effects at the cellular level: Antioxidative effects, antiphlogistic effects, the repression of thrombus formation, the stabilization of plaques, activation of smooth muscle cells and the generation of foam cells as well as an improvement of the endothelial function (108), summed up as pleiotropic effects (1, 21). The objective of the present secondary prevention study in an ApoE / animal model is to examine the effect of a statin therapy on atherosclerotic plaques with pre-existing renal damage following a uninephrectomy on the basis of morphometric and immunohistochemical methods. 1.2 Animal model and methods of examination The ApoE-/- deficient mouse model was used for this study. These animals are suitable because of their spontaneous formation of hyperlipidemia with the creation of severe atherosclerotic lesions, especially in the root and arch regions of the aorta (15, 19, 63). These lesions can well be compared to human atherosclerotic damage (70). Six month old male animals were randomized and divided into 4 groups. To accelerate the effects of renal damage, a uninephrectomy (UNX) was performed with 2 groups following a 2 weeks phase of adaptation. The other groups were sham operated. For the next 6 months, one group of the UNX- (n=9) and one group of animals having received a sham operation (n=11) were treated with Atorvastatin , the other animals (ApoE, n=10; ApoE+UNX, n=9) were left untreated. Using paraffin sections, the atherosclerotic changes were histologically, quantitatively and qualitatively identified and compared from one group to the other using standardized means of analysis and morphometric methods. The morphological particularities of the atherosclerotic plaques were determined with the help of immunohistochemical examinations. 1.3 Results and observations The results of this experiment do not show that statins have a decisive therapeutic effect, in relationship to the size of plaques in the region of the ascending aorta in the ApoE-mouse-model. With statins, it was possible to significantly reduce the expression of pro-inflammatory molecules such as VCAM or CD 40. However, a consistent statin treatment effect could not be discerned, even though, with the majority of the characteristics under examination, there was a tendency to be less expressed in groups treated with statins. But contrary to this tendency, some of the measured data, such as blood pressure and the amount of cholesterol in the blood, showed even an increase during the statin therapy. A mild dysfuntion of the kidneys, attained by uninephrectomy, had also little morphological effect. 1.4 Final conclusions The efficiency of statins, as plaque-progression inhibitors and therefore their anti-atherosclerotic effects in this ApoE-mouse-model, could not be generally confirmed in this study, even though significant differences in characteristics of the plaques could be observed, implying statins' anti-inflammatory and anti-oxidative effect. An ultimate clarification of whether this results from a lack of effectiveness of the HMG-Reductase inhibitors, in regards to the chosen parameters with only mild kidney-dysfunction/ mild hyperlipidemia, or whether this results from the design of the study, cannot be conclusively answered with this experiment. Perhaps an extra fat-enhanced nutrition for the animals, in the sense of a "western- type diet," or an alternative application of the medication could give other results. The uninephrectomy of the ApoE-/- deficient mice, as a means of increasing vascular changes, had only a minor effect, in comparison to earlier studies. An alternative animal-model could possibly prove more promising for verifying the effects of statin therapy (48).

In order to overcome many limitations of immunoassays, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has the potential to find its place in the clinical laboratory medicine for quantification of steroid hormones. A prerequisite for the application of a new analytical procedure in clinical diagnostics is standardization to minimize analytical intra- and interlaboratory variability and inaccuracy. We evaluate a newly standardized HPLC-MS/MS assay in kit-format, developed for routine determination of 16 steroid hormones in human serum samples. Fifteen metabolites can be measured quantitatively, which include aldosterone, androstenedione, androsterone, corticosterone, cortisol, cortisone, 11-deoxycortisol, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 17β-estradiol (E2), estrone (E1), etiocholanolone, 17α-hydroxyprogesterone (17OHP), progesterone, and testosterone. 11-Deoxycorticosterone is the only compound rated as semi-quantitative in this kit. The sample preparation is performed by solid phase extraction (SPE) on a 96-well plate. The standardized assay has been validated for human serum in terms of lower and upper limit of quantification (LLOQ 0.01-32 ng/mL, ULOQ 5-8000 ng/mL), linear correlation coefficient of calibration (R(2)>0.9966), intra- and inter-day precision (intra-day 1.1-8.8%, inter-day 5.2-14.8% and 8.2-18.6% for 11-deoxycorticosterone), accuracy (intra-day 88.3-115.5% and 109.3-128.2% for 11-deoxycorticosterone, inter-day 91.4-117.2% and 102.3-137.1% for 11-deoxycorticosterone), analytical total error (3.6-17.8%), proficiency test accuracy (85.4-113.4%), recovery (68-99%), and metabolite stability (freeze/thaw stability 95.5-108.1%, short term stability 86.9-107.2%). Inter-assay comparison with a routine reference HPLC-MS/MS assay and seven immunoassays demonstrates the outstanding high performance of this HPLC-MS/MS based kit by improvements in accuracy for progesterone, androstenedione, and 17OHP. Finally, results of two metyrapone tests demonstrate the potential of the standardized HPLC-MS/MS assay for the analysis of a comprehensive steroid hormone profile in clinical diagnostics.

Spatial development is caught somewhere between stability and adaptation to new challenges. The reasons for this are natural risks, as well as dynamic processes of economic and social change, and globalization. In view of increasing risks (cf. Beck, 2007), the resilience of cities and regions is becoming more and more of an issue. The resilience concept, which was originally developed to explain ecological processes, has been further developed and applied to social problems. This has led to links with the social science approach of path theory.

Summary Proteins of healthy pea plants ( Pisum sativum L. cv. Nadja) and of plants infected with red clover mottle virus were examined by one- and two-dimensional electrophoresis. Silver-stained 2-D slab gels revealed more than ten additional protein spots with markedly changed intensity in the extracts from infected plants as compared to extracts from uninfected plants. Two of these spots corresponded to virus proteins (about 38 and 21 kDa).

„Kulturlandschaften“ sollen in dieser Expertise nach ihrem regionalen Entwicklungspotenzial analysiert werden. Dazu ist es von wesentlicher Bedeutung, die institutionengebundenen Wirkungszusammenhänge ihrer Entwicklung zu erkennen. Bei der Ausgestaltung regionaler Steuerungsformen greift aber eine Fokussierung auf formelle Regelungen und deren Umsetzung über planerische Instrumente zu kurz. Vielmehr ist es sinnvoll, sich gleichfalls den (informellen) Interaktionsregeln lokaler und regionaler Akteure mit Einfluss auf die Kulturlandschaftsentwicklung zu widmen und dabei die eng mit Kulturlandschaften zusammenhängenden Images, Ausprägungen regionaler Identitäten, gesellschaftlichen Wertmaßstäbe und Traditionen zu berücksichtigen. So entstehen aus einer Perspektive der sozialwissenschaftlich orientierten Institutionenforschung analytische Aussagen über informelle Institutionen sowie dezentrale Steuerungsformen; sie lassen sich verwenden für künftige Entwicklungs- und Innovationsstrategien. Der als Fallstudie ausgewählte Barnim gehört zu jenen Kulturlandschaften, die ohne eindeutige gemeinsame Identität und charakterisierende Eigenart verschiedene Handlungsräume ausgebildet haben. In Teilregionen des Barnim werden mit dem Naturpark Barnim und dem Regionalpark Barnimer Feldmark zwei kulturlandschaftliche Governanceformen erprobt, deren Prägung durch informelle Institutionen und deren Handlungsformen Gegenstand der Analyse sind. Die Erfahrungen im Barnim zeigen, dass die Mobilisierung kulturlandschaftlicher Entwicklungspotenziale einer Stärkung und Zusammenführung dezentral tätiger Akteure und einer damit einhergehenden Förderung der Rahmenbedingungen gesellschaftlicher Selbstorganisation bedarf. Eine wesentliche Erfolgsvoraussetzung besteht darin, dass die regionale Strategie und die damit verbundene akzentuierte Nutzung der identitäts- und imagebildenden Wirkung der Kulturlandschaft als Potenzial aufgefasst wird. Zur Lösung kulturlandschaftsbezogener Interaktionsprobleme sowie zur Stärkung eines vernetzen projektorientierten Handelns sind Governanceformen entscheidend, die regionale Kooperation sicherstellen und ein Regionalmanagement ermöglichen. Dabei sollten administrative Grenzen stets in Frage gestellt werden, denn Kulturlandschaften konstituieren sich als Handlungsräume stärker über soziale Beziehungen, Images und Identitäten als über formelle Grenzziehungen.

The failure of about half of the drug candidates is associated with poor pharmacokinetic properties leading to a huge loss of time and money [1]. Early profiling of drug like properties provides important information in order to screen out insoluble, poorly absorbed and toxic compounds. Today, large compound libraries have to be screened, and of course the total number of compounds will rise over the next years leading to a growing demand for fully automated assays. A balance between quality, speed, throughput, cost and information content can be accomplished by the careful selection of assays and experimental conditions. Here we describe a novel 384 well format assay for two important ADME related descriptors (lipophilicity and serum protein binding) as input parameters for a precise prediction of fraction absorbed, blood/organ distribution coefficients and permeability, in order to maximize the information about a compound at an early stage of discovery.

Unter Verwendung sozialwissenschaftlicher Ansätze der Güter- und Institutionentheorie werden in diesem Beitrag Gemeinschaftsgutaspekte und Triebkräfte der Kulturlandschaftsentwicklung thematisiert und im Kontext von drei unterschiedlichen Problemstellungen dargestellt: Am Beispiel der Landwirtschaft wird erläutert, wie nutzungsorientierte Institutionensysteme die Kulturlandschaftsentwicklung beeinflussen. Anhand von Seen und ihren Uferzonen werden Konflikte zwischen übergeordneten gesellschaftlichen Ansprüchen und individuellen Nutzungsinteressen erörtert. Die Analyse von Regionalparks als Governance- Form zeigt Möglichkeiten auf, wie neben staatlichen Institutionen, die für die Kulturlandschaft zuständig sind, ein dynamisches Kulturlandschaftsmanagement möglich ist. Zusammenfassend werden Erkenntnisse der Gemeinschaftsgutforschung für den Umgang mit Kulturlandschaften in der Raumordnung abgeleitet. Applying three approaches derived from theories of goods and institutions current in the social sciences, this paper focuses on the aspect of communal assets and on the driving forces underlying the development of cultural landscapes. These are outlined within the context of three different problem areas: agriculture serves to illustrate the way in which the development of cultural landscapes may be influenced by use-oriented institutional systems; lakes and the banks of lakes demonstrate the conflicts over use which exist between the overriding needs of society and the interests of individuals; an analysis of regional parks, as one form of governance, demonstrates a dynamic management concept for cultural landscapes in metropolitan regions to set alongside the public-sector institutions usually responsible for cultural landscapes. In a final summary, lessons are drawn from research into communal assets on how spatial planning should deal with the issue of cultural landscapes.

Using the HEGRA system of imaging atmospheric Cherenkov telescopes, one quarter of the Galactic plane (-2 deg < l < 85 deg) was surveyed for TeV gamma-ray emission from point sources and moderately extended sources (diameter, 10 pages, 5 figures, 4 tables, accepted for publication in A&A

Lipid-water partitioning of 187 pharmaceuticals has been assessed with solid-supported lipid membranes (TRANSIL) in microwell plates and with multilamellar liposomes for a data comparison. The high-throughput potential of the new approach was evaluated.Drugs were incubated at pH 7.4 with egg yolk lecithin membranes either on a solid support (TRANSIL beads) or in the form of multilamellar liposomes. Phase separation of lipid and water phase was achieved by ultracentrifugation in case of liposomes or by a short filtration step in case of solid-supported lipid membranes.Lipid-water partitioning data of both approaches correlate well without systematic deviations in the investigated lipophilicity range. The solid-supported lipid membrane approach provides high-precision data in an automated microwell-plate setup. The lipid composition of the solid-supported lipid membranes was varied to study the influence of membrane change on lipid-water partitioning. In addition, pH-dependent measurements have been performed with minimal experimental effort.Solid-supported lipid membranes represent a valuable tool to determine physiologically relevant lipid-water partitioning data of pharmaceuticals in an automated setup and is well suited for high-throughput data generation in lead optimization programs.

Data taken with the HEGRA system of imaging atmospheric Cherenkov telescopes during the 1997 flares of Mkn 501 are reanalyzed using an algorithm providing improved energy resolution. A resolution of 10% to 12% is obtained by accounting for the variation of the Cherenkov light yield with the height of the shower maximum in the atmosphere. The improved energy resolution is particularly relevant for the study of the high-energy cutoff in the spectrum, which might be caused by interactions with the intergalactic infrared background radiation. The reanalysis presented here confirms the results obtained in the previous analysis, but hints a steeper slope of the spectrum in the region around 20 TeV., 6 Pages, 4 figures; A&A, in press

Preliminary evidence suggests that genetic polymorphisms in certain enzymes involved in xenobiotic metabolism and chemical defense could modify a susceptibility to prostate cancer. In the present study, two recently described phenol sulphotransferase SULT1A1 alleles (SULT1A1*1, SULT1A1*2) were investigated using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. Genotyping was performed on DNA isolated from white blood cells from 134 patients with prostate cancer and 184 healthy control subjects. Both the prostate cancer patients and the controls demonstrated similar frequencies of the variant allele SULT1A1*2 (35.1% vs 39.1%). Homozygosity for the variant allele was slightly less frequent in cancer patients than controls (12.7% vs 17.4%). Our study does not support the hypothesis that the phenol sulphotransferase variant allele SULT1A1*2 with a G/A transition at nucleotide 638 is a risk modifier for prostate cancer in the Caucasian population.

The energy spectrum of the Blazar type galaxy Markarian 501 (Mrk 501) as measured by the High-Energy-Gamma-Ray Astronomy (HEGRA) air Cerenkov telescopes extends beyond 16 TeV and constitutes the most energetic photons observed from an extragalactic object. A fraction of the emitted spectrum is possibly absorbed in interactions with low energy photons of the diffuse extragalactic infrared radiation, which in turn offers the unique possibility to measure the diffuse infrared radiation density by TeV spectroscopy. The upper limit on the density of the extragalactic infrared radiation derived from the TeV observations imposes constraints on models of galaxy formation and stellar evolution. One of the recently published ideas to overcome severe absorption of TeV photons is based upon the assumption that sources like Mrk 501 could produce Bose-Einstein condensates of coherent photons. The condensates would have a higher survival probability during the transport in the diffuse radiation field and could mimic TeV air shower events. The powerful stereoscopic technique of the HEGRA air Cerenkov telescopes allows to test this hypothesis by reconstructing the penetration depths of TeV air shower events: Air showers initiated by Bose-Einstein condensates are expected to reach the maximum of the shower development in the atmosphere earlier than single photon events. By comparing the energy-dependent penetration depths of TeV photons from Mrk 501 with those from the TeV standard-candle Crab Nebula and simulated air shower events, we can reject the hypothesis that TeV photons from Mrk 501 are pure Bose-Einstein condensates., 9 pages, 2 figures, published by ApJ Letters, revised version (simulation results added)

The Crab Nebula has been observed by the HEGRA (High-Energy Gamma-Ray Astronomy) stereoscopic system of imaging air Cherenkov telescopes (IACTs) for a total of about 200 hrs during two observational campaigns: from September 1997 to March 1998 and from August 1998 to April 1999. The recent detailed studies of system performance give an energy threshold and an energy resolution for gamma-rays of 500 GeV and ~ 18%, respectively. The Crab energy spectrum was measured with the HEGRA IACT system in a very broad energy range up to 20 TeV, using observations at zenith angles up to 65 degrees. The Crab data can be fitted in the energy range from 1 to 20 TeV by a simple power-law, which yields dJg/dE = (2.79+/-0.02 +/- 0.5) 10^{-7} E^{-2.59 +/- 0.03 +/- 0.05}, ph m^{-2} s^{-1} TeV^{-1} The Crab Nebula energy spectrum, as measured with the HEGRA IACT system, agrees within 15% in the absolute scale and within 0.1 units in the power law index with the latest measurements by the Whipple, CANGAROO and CAT groups, consistent within the statistical and systematic errors quoted by the experiments. The pure power-law spectrum of TeV gamma-rays from the Crab Nebula constrains the physics parameters of the nebula environment as well as the models of photon emission., to appear in ApJ, 29 pages, 6 figures

The HEGRA system of 4 Imaging Atmospheric Cherenkov Telescopes (IACTs) has been used to determine the flux and the spectrum of cosmic ray protons over a limited energy range around 1.5 TeV. Although the IACT system is designed for the detection of gamma-rays with energies above 500 GeV, it has also a large detection area of $ \simeq 10^6 m^2 \cdot 3 msr$ for primary protons of energies above 1 TeV and the capability to reconstruct the primary proton energy with a reasonable accuracy $\Delta$E/E of 50% near this threshold. Furthermore, the principle of stereoscopic detection of air showers permits the effective suppression of air showers induced by heavier primaries already on the trigger level, and in addition on the software level by analysis of the stereoscopic images. The combination of both capabilities permits a determination of the proton spectrum almost independently of the cosmic ray chemical composition. The accuracy of our estimate of the spectral index at 1.5 TeV is limited by systematic uncertainties and is comparable to the accuracy achieved with recent balloon and space borne experiments. In this paper we describe in detail the analysis tools, namely the detailed Monte Carlo simulation, the analysis procedure and the results. We determine the local (i.e. in the range of 1.5 to 3 TeV) differential spectral index to be $\gamma_p = 2.72\pm 0.02_{stat.}{\pm 0.15}_{syst.}$ and obtain an integral flux above 1.5 TeV of $F(> 1.5 TeV) =3.1\pm 0.6_{stat.}\pm 1.2_{syst.} 10^{-2}/s sr m^2$., Comment: 39 pages, 13 figures, 10 tables, prepared with REVtex. accepted by Physical Review D, in press

Using air showers induced by TeV gamma-rays from Mrk 501, the radial distribution of Cherenkov light is investigated. The shower geometry is reconstructed from the stereoscopic shower images obtained with the telescopes of the HEGRA IACT system. We observe a change in the shape of the light pool with shower energy, and with zenith angle. Data are well reproduced by Monte-Carlo air shower simulations., Comment: 15 Pages, 8 figures, Latex

The time profiles of Cherenkov images of cosmic-ray showers and of gamma-ray showers are investigated, using data gathered with the HEGRA system of imaging atmospheric Cherenkov telescopes during the 1997 outbursts of Mrk 501. Photon arrival times are shown to vary across the shower images. The dominant feature is a time gradient along the major axis of the images. The gradient varies with the distance between the telescope and the shower core, and is maximal for large distances. The time profiles of cosmic-ray showers and of gamma-ray showers differ in a characteristic fashion. The main features of the time profiles can be understood in terms of simple geometrical models. Use of the timing information towards improved shower reconstruction and cosmic-ray suppression is discussed., Comment: 25 Pages, 16 figures, Latex

During the period March-April 1997, a high flux level of TeV γ-rays was observed from Mkn 501, using the HEGRA stereoscopic system of four imaging atmospheric Cherenkov telescopes (IACTs). The almost background-free detection of γ-rays with a rate exceeding in average 100 h−1, coupled with good energy resolution of the instrument ⩽25% allowed a study of the flux variation on time scales between 5 min and days, and measurements of the differential energy spectrum of the source for selected periods. Here we briefly discuss the results of observations with emphasis on the measurements of temporal and spectral characteristics of the source at 3 subsequent periods in April when the average flux of the source showed a remarkable increase of the flux from about one to eight times the flux observed from the Crab Nebula.