Showing papers by "University of Hamburg published in 1997"

Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas

Abstract: Hereditary papillary renal carcinoma (HPRC) is a recently recognized form of inherited kidney cancer characterized by a predisposition to develop multiple, bilateral papillary renal tumours. The pattern of inheritance of HPRC is consistent with autosomal dominant transmission with reduced penetrance. HPRC is histologically and genetically distinct from two other causes of inherited renal carcinoma, von Hippel-Lindau disease (VHL) and the chromosome translocation (3;8). Malignant papillary renal carcinomas are characterized by trisomy of chromosomes 7, 16 and 17, and in men, by loss of the Y chromosome. Inherited and sporadic clear cell renal carcinomas are characterized by inactivation of both copies of the VHL gene by mutation, and/or by hypermethylation. We found that the HPRC gene was located at chromosome 7q31.1-34 in a 27-centimorgan (cM) interval between D7S496 and D7S1837. We identified missense mutations located in the tyrosine kinase domain of the MET gene in the germline of affected members of HPRC families and in a subset of sporadic papillary renal carcinomas. Three mutations in the MET gene are located in codons that are homologous to those in c-kit and RET, proto-oncogenes that are targets of naturally-occurring mutations. The results suggest that missense mutations located in the MET proto-oncogene lead to constitutive activation of the MET protein and papillary renal carcinomas.

Emergency Room Triage of Patients with Acute Chest Pain by Means of Rapid Testing for Cardiac Troponin T or Troponin I

Abstract: Background Evaluation of patients with acute chest pain in emergency rooms is time-consuming and expensive, and it often results in uncertain diagnoses. We prospectively investigated the usefulness of bedside tests for the detection of cardiac troponin T and troponin I in the evaluation of patients with acute chest pain. Methods In 773 consecutive patients who had had acute chest pain for less than 12 hours without ST-segment elevation on their electrocardiograms, troponin T and troponin I status (positive or negative) was determined at least twice by sensitive, qualitative bedside tests based on the use of specific monoclonal antibodies. Testing was performed on arrival and four or more hours later so that one sample was taken at least six hours after the onset of pain. The troponin T results were made available to the treating physicians. Results Troponin T tests were positive in 123 patients (16 percent), and troponin I tests were positive in 171 patients (22 percent). Among 47 patients with evolving m...

Effect of Danube River dam on Black Sea biogeochemistry and ecosystem structure

Abstract: Rivers contribute significantly to the pollution and eutrophication that have caused drastic changes to the ecosystem of the Black Sea1–3. Although damming is known to affect riverborne nutrient loads, and thus riverine ecosystems, evidence for significant effects in open coastal waters is sparse4–6. Here we present long-term data sets of water and nutrient discharge from the River Danube to the Black Sea. These data reveal a reduction in the dissolved silicate load of the river by about two-thirds since dam constructions in the early 1970s. A concomitant decrease in wintertime dissolved silicate concentrations by more than 60% was observed in central Black Sea surface waters. The consequent changes in silicon to nitrogen ratio of the Black Sea nutrient load appear to be larger than those caused by eutrophication alone, and seem to be responsible for dramatic shifts in phytoplankton species composition from diatoms (siliceous) to coccolithophores and flagellates (non-siliceous). Our results strongly suggest that the damming of the Danube has been instrumental in causing the observed changes in Black Sea surface waters3,7–9, and that the large number of dams in operation around the world today could similarly affect the food web structure and biogeochemical cycling in coastal seas.

Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy.

Abstract: Autosomal recessive childhood-onset severe retinal dystrophy (arCSRD) designates a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously1. The most severe cases are termed Leber congenital amaurosis (LCA), while the less aggressive forms are usually considered juvenile retinitis pigmentosa. Recently, mutations in the retinal-specific guanylate cyclase gene were found in patients with LCA2. Disease genes implicated in other forms of arCSRD are expected to encode proteins present in the neuroretina or in the retinal pigment epithelium (RPE). The RPE, a monolayer of cells separating the vascular-rich choroid and the neuroretina, is in intimate contact with the outer segments of rods and cones via the microvilli surrounding the photoreceptors. The RPE expresses a tissue-specific and evolutionary highly conserved 61 kD protein (RPE65) present at high levels in vivo3–6. Although the function of RPE65 is not yet known, an important role in the RPE/photoreceptor vitamin-A cycle is suggested by the fact that RPE65 associates both with serum retinol-binding protein7,8 and with the RPE-specific 11-cis retinol dehydrogenase, an enzyme active in the synthesis of the visual pigment chromophore 11-cis retinal9. Here we report that the analysis of RPE65 in a collection of about 100 unselected retinal-dystrophy patients of different ethnic origin revealed five that are likely to be pathogenic mutations, including a missense mutation (Pro363Thr), two point mutations affecting splicing (912+1G→T and 65+5G→A) and two small re-arrangements (ins144T and 831del8) on a total of nine alleles of five patients with arCSRD. In contrast to other genes whose defects have been implicated in degenerative retinopathies, RPE65 is the first disease gene in this group of inherited disorders that is expressed exclusively in the RPE, and may play a role in vitamin-A metabolism of the retina.

Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen matrix: a new heart muscle model system.

Abstract: A method has been developed for culturing cardiac myocytes in a collagen matrix to produce a coherently contracting 3-dimensional model heart tissue that allows direct measurement of isometric contractile force. Embryonic chick cardiomyocytes were mixed with collagen solution and allowed to gel between two Velcro-coated glass tubes. During culture, the cardiomyocytes formed spontaneously beating cardiac myocyte-populated matrices (CMPMs) anchored at opposite ends to the Velcro-covered tubes through which they could be attached to a force measuring system. Immunohistochemistry and electron microscopy revealed a highly organized tissue-like structure of alpha-actin and alpha-tropomyosin-positive cardiac myocytes exhibiting typical cross-striation, sarcomeric myofilaments, intercalated discs, desmosomes, and tight junctions. Force measurements of paced or unpaced CMPMs were performed in organ baths after 6-11 days of cultivation and were stable for up to 24 h. Force increased with frequency between 0.8 and 2.0 Hz (positive "staircase"), increasing rest length (Starling mechanism), and increasing extracellular calcium. The utility of this system as a test bed for genetic manipulation was demonstrated by infecting the CMPMs with a recombinant beta-galactosidase-carrying adenovirus. Transduction efficiency increased from about 5% (MOI 0.1) to about 50% (MOI 100). CMPMs display more physiological characteristics of intact heart tissue than monolayer cultures. This approach, simpler and faster than generation of transgenic animals, should allow functional consequences of genetic or pharmacological manipulation of cardiomyocytes in vitro to be studied under highly controlled conditions.

Disruption of the mouse L1 gene leads to malformations of the nervous system

Abstract: The adhesion molecule L1 is a member of the immunoglobulin super-family1. L1 is involved in various recognition processes in the CMS and PNS2–3, and binding to L1 can activate signal transduction pathways4,5. Mutations in the human L1 gene are associated with a variable phenotype, including mental retardation and anomalous development of the nervous system, referred to as ‘CRASH’ (corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraplegia, and hydrocephalus)6. We generated an animal model of these conditions by gene targeting. Mutant mice were smaller than wild-type and were less sensitive to touch and pain, and their hind-legs appeared weak and uncoordinated. The size of the corticospinal tract was reduced and, depending on genetic background, the lateral ventricles were often enlarged. Non-myelinating Schwann cells formed processes not associated with axons and showed reduced association with axons. In vitro, neurite outgrowth on an L1 substrate and fasciculation were impaired. The mutant mouse described here will help to elucidate the functions of L1 in the nervous system and how these depend on genetic influences.

Clinical impact of the plasminogen activation system in tumor invasion and metastasis : Prognostic relevance and target for therapy

Abstract: Extravasation and intravasation of solid malignant tumors is controlled by attachment of tumor cells to components of the basement membrane and the extracellular matrix, by local proteolysis and tumor cell migration. Strong clinical and experimental evidence has accumulated that the tumor-associated serine protease plasmin, its activator uPA (urokinase-type plasminogen activator), the receptor uPA-R (CD87), and the inhibitors PAI-1 and PAI-2 are linked to cancer invasion and metastasis. In cancer, increase of uPA, uPA-R, and/or PAI-1 is associated with tumor progression and with shortened disease-free and/or overall survival in patients afflicted with malignant solid tumors. uPA and/or its inhibitor PAI-1 appear to be one of the strongest prognostic markers so far described. Strong prognostic value to predict disease recurrence and overall survival has been documented for patients with cancer of the breast, ovary, cervix, endometrium, stomach, colon, lung, bladder, kidney, brain, and soft-tissue. Due to the strong correlation between elevated uPA and/or PAI-1 values in primary cancer tissues and the tumor invasion/ metastasis capacity of cancer cells, proteolytic factors have been selected as targets for therapy. Various very different approaches to interfere with the expression or reactivity of uPA or CD87 at the gene or protein level were successfully tested including antisense oligonucleotides, antibodies, enzyme inhibitors, and recombinant or synthetic uPA and uPA-R analogues.

Mitochondrial footprints of human expansions in Africa.

Abstract: mtDNA studies support an African origin for modern Eurasians, but expansion events within Africa have not previously been investigated. We have therefore analyzed 407 mtDNA control-region sequences from 13 African ethnic groups. A number of sequences (13%) were highly divergent and coalesced on the "mitochondrial Eve" in Africans. The remaining sequences also ultimately coalesced on this sequence but fell into four major clusters whose starlike phylogenies testify to demographic expansions. The oldest of these African expansions dates to approximately 60,000-80,000 years ago. Eurasian sequences are derived from essentially one sequence within this ancient cluster, even though a diverse mitochondrial pool was present in Africa at the time.

Validation of the optic nerve sheath response to changing cerebrospinal fluid pressure: ultrasound findings during intrathecal infusion tests

Abstract: Raised intracranial pressure leads to increased pressure around the optic nerve (ON), which underlies the formation of papilledema and the enlargement of the dural optic nerve sheath (ONS). In clinical practice, the presence of widened ONSs is demonstrable on neuroimaging, but their relationship to cerebrospinal fluid (CSF) pressure remains unknown. The authors investigated the ONS response to pressure during CSF absorption studies in 12 patients undergoing neurological testing. The ONS diameter was evaluated by serial B-mode ultrasound scans of the anterior ON near its entry into the globe. All patients tested showed ONS diameter changes that exhibited covariance with the alteration of lumbar CSF pressure and were completely reversible during the infusion tests. The maximum difference in ONS diameter between baseline and peak pressure conditions was 1.8 mm on average (range 0.7-3.1 mm), corresponding to an average ONS diameter variation of 45% (range 15-89%). Regression analysis yielded a linear covariance between ONS diameter and CSF pressure with different slopes across subjects (0.019-0.071 mm/mm Hg, mean r = 0.78). However, this linear relationship was only present within a CSF pressure interval. This interval differed between patients: ONS dilation commenced at pressure thresholds between 15 mm Hg and 30 mm Hg and in some patients saturation of the response (constant ONS diameter) occurred between 30 mm Hg and 40 mm Hg. With a single exception, definitely enlarged ONS diameters (> 5 mm) were present when CSF pressure exceeded levels of 30 mm Hg. Retrospectively, discrimination between normal and elevated outflow resistance was possible on the basis of the ONS response to intrathecal infusion alone. It is concluded that the human ONS has sufficient elasticity to allow a detectable dilation in response to intracranial hypertension. Because of a variable pressure-diameter relationship, the subarachnoid pressure cannot be predicted exactly by single scans. Therefore, the clinical relevance of this method relies on the demonstration of pathologically enlarged sheaths or ongoing enlargement on serial ultrasonography studies.

Fokker-Planck and Landau-Lifshitz-Bloch equations for classical ferromagnets

Abstract: A macroscopic equation of motion for the magnetization of a ferromagnet at elevated temperatures should contain both transverse and longitudinal relaxation terms and interpolate between the Landau-Lifshitz equation at low temperatures and the Bloch equation at high temperatures. It is shown that for the classical model where spin-bath interactions are described by stochastic Langevin fields and spin-spin interactions are treated within the mean-field approximation (MFA), such a ``Landau-Lifshitz-Bloch'' (LLB) equation can be derived exactly from the Fokker-Planck equation, if the external conditions change slowly enough. For weakly anisotropic ferromagnets within the MFA the LLB equation can be written in a macroscopic form based on the free-energy functional interpolating between the Landau free energy near ${\mathrm{T}}_{\mathrm{C}}$ and the ``micromagnetic'' free energy, which neglects changes of the magnetization magnitude |M|, at low temperatures.

Evidence for Covalent Modification of the Nuclear Dot–associated Proteins PML and Sp100 by PIC1/SUMO-1

Abstract: PML and Sp100 proteins are associated with nuclear domains, known as nuclear dots (NDs). They were discovered in the context of leukemic transformation and as an autoantigen in primary biliary cirrhosis, respectively. Both proteins are expressed in the form of many COOH-terminally spliced variants, and their expression is enhanced by interferons (IFN). The recent finding that PIC1/SUMO-1, a small ubiquitin-like protein, is covalently linked to the RanGAP1 protein of the nuclear pore complex and also binds PML in yeast cells led us to determine whether PML is covalently modified by PIC1/SUMO-1 and whether the same is true for Sp100. We found an immune reaction of PML and Sp100 proteins with a PIC1/SUMO-1–specific monoclonal antibody by immunoblotting when using cell extracts prepared from stably transfected cells inducibly expressing one isoform of each protein as well as from nontransfected cells. In contrast, both proteins did not react when synthesized in vitro. Immunofluorescence staining showed that PIC1/SUMO-1 colocalized with Sp100 and PML in NDs except in mitotic cells, in which PML and Sp100 are dissociated. Cell fractionation and immunoblotting demonstrated that PIC1/SUMO-1 immunoreactive Sp100 in IFN-treated and untreated cells was exclusively nuclear, whereas nonmodified Sp100 was also found in the cytoplasm. Taken together, these data strongly suggest covalent modification of specific nuclear isoforms of Sp100 and PML by PIC1/SUMO-1. This modification may play a regulatory role in ND structure, composition, and function.

Structural Abnormalities and Deficient Maintenance of Peripheral Nerve Myelin in Mice Lacking the Gap Junction Protein Connexin 32

Abstract: Mutations affecting the connexin 32 (Cx32) gene are associated with the X-linked form of the hereditary peripheral neuropathy Charcot–Marie–Tooth disease (CMTX). We show that Cx32-deficient mice develop a late-onset progressive peripheral neuropathy with abnormalities comparable to those associated with CMTX, thus providing proof of the critical role of Cx32 in the maintenance of peripheral nerve myelin and an animal model for CMTX. Frequently observed features include abnormally thin myelin sheaths, cellular onion bulb formation reflecting myelin degeneration-induced Schwann cell proliferation, and enlarged periaxonal collars while nerve conductance properties are altered only slightly. These observations are consistent with earlier hypotheses suggesting a function of Cx32 as a channel-forming protein that facilitates the communication between the abaxonal and adaxonal aspects of Schwann cell cytoplasm.

A subdivision algorithm for the computation of unstable manifolds and global attractors

Abstract: Each invariant set of a given dynamical system is part of the global attractor. Therefore the global attractor contains all the potentially interesting dynamics, and, in particular, it contains every (global) unstable manifold. For this reason it is of interest to have an algorithm which allows to approximate the global attractor numerically. In this article we develop such an algorithm using a subdivision technique. We prove convergence of this method in a very general setting, and, moreover, we describe the qualitative convergence behavior in the presence of a hyperbolic structure. The algorithm can successfully be applied to dynamical systems of moderate dimension, and we illustrate this fact by several numerical examples.

Metallocenes for Polymer Catalysis

Abstract: Metallocenes are very versatile catalysts for the production of polyolefins, polystyrene and copolymers. Some polymers such as syndiotactic polypropene, syndiotactic polystyrene, cycloolefin copolymers, optically active oligomers, and polymethylenecycloalkenes can be produced only by metallocene catalysts. It is possible to tailor the microstructure of polymers by changing the ligand structure of the metallocene. The effect and influence of the ligands can more and more be predicted and understood by molecular modeling and other calculations.

Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia.

Abstract: Antibody-mediated autoimmunity underlies a diverse range of disorders, particularly in the nervous system where the extracellular domains of ion channels and receptors are especially vulnerable targets. We present here a novel means of detecting autoantibodies where the genes of the suspected target proteins are known, and use it to detect specific autoantibodies in acquired neuromyotonia (Isaacs' syndrome), a disorder characterized by hyperexcitable motor nerves and sometimes by central abnormalities. We expressed different human brain voltage-gated potassium channels in Xenopus oocytes by injecting the relevant alpha-subunit complementary RNA, and detected antibody binding by immunohistochemistry on frozen sections. Antibodies were detected to one or more human brain voltage-gated potassium channel in 12 of 12 neuromyotonia patients and none of 18 control subjects. The results establish neuromyotonia as a new antibody-mediated channelopathy and indicate the investigative potential of this molecular immunohistochemical assay.

The H1 detector at HERA

Abstract: General aspects of the H1 detector at the electron-proton storage ring HERA as well as technical descriptions of the magnet, luminosity system, trigger, slow-control, data acquisition and off-line data handling are given. The three major components of the detector, the tracking, calorimeter and muon detectors, will be described in a forthcoming article. The present paper describes the detector that was used from 1992 to the end of 1994. After this a major upgrade of some components was undertaken. Some performance figures from luminosity runs at HERA during 1993 and 1994 are given.

A novel protein with strong homology to the tumor suppressor p53.

Abstract: The p53 tumor suppressor orchestrates a number of important genes involved in cell-cycle control and apoptosis. Mice deficient for p53 show a high incidence of cancer but are developmentally normal suggesting that compensatory mechanisms exist in embryogenesis and differentiation. The new KET protein is the first mammalian protein with strong homology to p53 in all evolutionary conserved regions. This conservation makes a functional redundancy of the two proteins in cell-cycle control possible. KET is expressed during embryonic development and in certain adult tissues. Among all of the known p53 proteins of different species KET is most closely related to that found in squid. The relationship between KET and the invertebrate p53 protein sheds light on the evolutionary origin of p53. KET appears to be an ancestral p53-related protein in vertebrates with a possible role in development and differentiation while the ubiquitously expressed p53 protein attained its general role as 'guardian of the genome' during evolution.

Pulsed laser operation of Yb-doped KY(WO 4 ) 2 and KGd(WO 4 ) 2

Abstract: Spectroscopic properties and laser performance of Yb-doped tungstates at pulsed Ti:sapphire laser pumping are reported. Room-temperature lasing near 1025 nm is demonstrated in Yb:KY(WO4)2 and Yb:KGd(WO4)2, with a slope efficiency as great as 86.9%.

Transmyocardial Laser Revascularization Histological Features in Human Nonresponder Myocardium

Abstract: Background The creation of transmyocardial channels from the epicardium to the left ventricular cavity with the use of a CO2 laser is a modern approach in the treatment of patients with chronic ischemic cardiac disease. The histological features of human myocardium at different times after transmyocardial laser therapy have not been previously described. We had the opportunity to examine hearts from patients who died without clinical evidence of a persistent therapeutic effect at 3, 16, and 150 days after transmyocardial laser revascularization (TMR), respectively. Methods and Results We grossly localized the laser-created channels in unfixed and formalin-fixed tissue. Three ventricular levels were defined for cutting the hearts into four segments. Then, transmural blocks were excised and cut crosswise and lengthwise for histological investigation through the use of established staining methods. On day 3, laser-induced channels were filled with abundant granulocytes and thrombocytes, fibrinous network, an...

Quantitative analysis of the frictional properties of solid materials at low loads. I. Carbon compounds

Abstract: Load-dependent studies of the frictional properties of the carbon compounds graphite, diamond, amorphous carbon, and C${}_{60}$ were performed by friction force spectroscopy in air and dry argon. During the experiments, the surface was profiled at low loads without wear or plastic deformation. The tips used for profiling were fabricated according to a special production procedure in order to obtain apexes with a well-defined spherical shape and known apex radius. The data obtained were compared with a theoretical model based on the contact mechanical analysis of a Hertzian-type tip/sample contact with small tip radius, low surface energies, but not too low elastic moduli of the tip and sample material. Our experimental results are in excellent agreement with a ${F}_{\mathrm{f}}\ensuremath{\sim}{F}_{\mathrm{n}}^{2/3}$ dependence of the frictional force ${F}_{\mathrm{f}}$ on the normal force ${F}_{\mathrm{n}}$ as predicted for this case. These findings suggest that contact mechanical models, in spite of being based on continuum elasticity theory, are valid for tip radii down to a few nanometers and that the shear stress is constant within the elastic regime. Additionally, it was shown that the friction coefficient $\ensuremath{\mu}{=F}_{\mathrm{f}}{/F}_{\mathrm{n}}$ is not well suited for comparing the tribological behavior of different materials in the case of single-asperity friction. Therefore, an effective friction coefficient for point-contact-like single-asperity friction was introduced for the classification of the microscopic frictional properties of materials. As quantitative results, high microscopic friction was found for C${}_{60}$ thin films, medium friction for amorphous carbon and diamond, and very low friction for graphite.

Angiotensin II stimulates expression of the chemokine RANTES in rat glomerular endothelial cells. Role of the angiotensin type 2 receptor.

Abstract: Glomerular influx of monocytes/macrophages (M/M) occurs in many immune- and non-immune-mediated renal diseases. The mechanisms targeting M/M into the glomerulus are incompletely understood, but may involve stimulated expression of chemokines. We investigated whether angiotensin II (ANG II) induces the chemokine RANTES in cultured glomerular endothelial cells of the rat and in vivo. ANG II stimulated mRNA and protein expression of RANTES in cultured glomerular endothelial cells. The ANG II-induced RANTES protein was chemotactic for human monocytes. Surprisingly, the ANG II-stimulated RANTES expression was transduced by AT2 receptors because the AT2 receptor antagonists PD 123177 and CGP-42112A, but not an AT1 receptor blocker, abolished the induced RANTES synthesis. Intraperitoneal infusion of ANG II (500 ng/h) into naive rats for 4 d significantly stimulated glomerular RANTES mRNA and protein expression compared with solvent-infused controls. Immunohistochemistry revealed induction of RANTES protein mainly in glomerular endothelial cells and small capillaries. Moreover, ANG II- infused animals exhibited an increase in glomerular ED-1- positive cells compared with controls. Oral treatment with PD 123177 (50 mg/liter drinking water) attenuated the glomerular M/M influx without normalizing the slightly elevated systolic blood pressure caused by ANG II infusion, suggesting that the effects on blood pressure and RANTES induction can be separated. We conclude that the vasoactive peptide ANG II may play an important role in glomerular chemotaxis of M/M through local induction of the chemokine RANTES. The observation that the ANG II- mediated induction of RANTES is transduced by AT2 receptors may influence the decision as to which substances might be used for the therapeutic interference with the activity of the renin-angiotensin system.

Molecular dissection of gating in the ClC-2 chloride channel

Abstract: The ClC-2 chloride channel is probably involved in the regulation of cell volume and of neuronal excitability. Site-directed mutagenesis was used to understand ClC-2 activation in response to cell swelling, hyperpolarization and acidic extracellular pH. Similar to equivalent mutations in ClC-0, neutralizing Lys566 at the end of the transmembrane domains results in outward rectification and a shift in voltage dependence, but leaves the basic gating mechanism, including swelling activation, intact. In contrast, mutations in the cytoplasmic loop between transmembrane domains D7 and D8 abolish all three modes of activation by constitutively opening the channel without changing its pore properties. These effects resemble those observed with deletions of an amino-terminal inactivation domain, and suggest that it may act as its receptor. Such a 'ball-and-chain' type mechanism may act as a final pathway in the activation of ClC-2 elicited by several stimuli.

An improved composite surface model for the radar backscattering cross section of the ocean surface 1. Theory of the model and optimization/validation by scatterometer data

Abstract: An improved composite surface model for the calculation of the normalized radar backscattering cross section (NRCS) of the ocean surface at moderate incidence angles is presented. The model is based on Bragg scattering theory. A Taylor expansion of the NRCS in the two-dimensional surface slope yields nonzero second-order terms which represent a first approximation for the effect of the geometric and hydrodynamic modulation of the Bragg scattering facets by all waves that are long compared to these facets. The corresponding expectation value of the NRCS varies with the wave height spectral density of all these waves, and it depends in a well-defined way on frequency, polarization, incidence angle, and azimuthal look direction of the radar. We show that measured NRCS values at frequencies ranging from 1 GHz (L band) through 34 GHz (Ka band) and wind speeds between 2 and 20 m/s can be well reproduced by the proposed model after some reasonable tuning of the input ocean wave spectrum. Also, polarization effects and upwind/downwind differences of the NRCS appear to be relatively well represented. The model can thus be considered as an advanced wind scatterometer model which is based on physical principles rather than on empirical relationships. The most promising field of application, however, will be the calculation of NRCS variations associated with local distortions of the wave spectrum by surface current gradients or wind effects.

Identification of cyclone-track regimes in the North Atlantic

Abstract: A Langrangian-type climatology of North Atlantic cyclones is established based on the high-resolution European Centre for Medium-Range Weather Forecasts data-set of the 1000 hPa height-field. First, an algorithm is introduced to identify mid-latitude cyclones and cyclone paths with as few constraints as possible. Cluster analysis of relative cyclone displacements yields three types of cyclone tracks characterizing stationary-, north-eastward-and zonally-travelling storms. the internal Lagrangian statistics of these cyclone-track types reveal representative life-cycles for central pressure and geopotential-height gradients and a power-law scaling behaviour of cyclone displacements. Finally, a basic climatology of North Atlantic cyclone-track regimes is deduced in terms of a time-series and circulation statistics.

Germline dinucleotide mutation in codon 883 of the RET proto-oncogene in multiple endocrine neoplasia type 2B without codon 918 mutation

Abstract: The autosomal dominant multiple endocrine neoplasia type 2 syndromes (MEN 2) comprise three clinically distinct entities, MEN 2A, familial medullary thyroid carcinoma and MEN 2B, which share a common clinical feature: medullary thyroid carcinoma (MTC). MEN 2B is considered to have the most aggressive form of MTC. Therefore, early detection of MEN 2B in order to prevent potentially lethal MTC is important. More than 95% of all MEN 2B cases are caused by germline mutation at codon 918 (M918T) in exon 16 of the RET proto-oncogene. In this study, we demonstrate the presence of germline codon 883 mutation (A883F) in 2 of 3 unrelated MEN 2B cases without codon 918 mutation. Our data demonstrate a novel etiologic event which may have roles in predisposition to MEN 2B when present in the germline and in the pathogenesis of sporadic MTC when somatic.

CW laser performance of Yb and Er,Yb doped tungstates

Abstract: Room temperature cw laser action of Yb3+-doped KY(WO4)2 and KGd(WO4)2 crystals at 1.025 μm and Er, Yb : KY(WO4)2 at 1.54 μm has been demonstrated under pumping by both Ti-sapphire laser and InGaAs laser diodes. A slope efficiency of Yb-lasers up to 78% has been obtained.

Strategic Choice of Quality When Quality is Costly: The Persistence of the High-Quality Advantage

Abstract: In a two-firm, two-stage model of vertical product differentiation, I show that for every convex fixed-cost function of quality, the firm that chooses the higher quality at the first stage earns the higher profits. The result holds for the pure-strategy equilibrium in the simultaneous-quality game, and it holds as well if firms choose their qualities in sequential order.