N(1520) 3/2(-) helicity amplitudes from an energy-independent multipole analysis based on new polarization data on photoproduction of neutral pions.

New data on the polarization observables T, P, and H for the reaction γp→pπ(0) are reported. The results are extracted from azimuthal asymmetries when a transversely polarized butanol target and a linearly polarized photon beam are used. The data were taken at the Bonn electron stretcher accelerator ELSA using the CBELSA/TAPS detector. These and earlier data are used to perform a truncated energy-independent partial wave analysis in sliced-energy bins. This energy-independent analysis is compared to the results from energy-dependent partial wave analyses.

Neutron skin of (208)pb from coherent pion photoproduction.

Information on the size and shape of the neutron skin on (208)Pb is extracted from coherent pion photoproduction cross sections measured using the Crystal Ball detector together with the Glasgow tagger at the MAMI electron beam facility. On exploitation of an interpolated fit of a theoretical model to the measured cross sections, the half-height radius and diffuseness of the neutron distribution are found to be c(n)=6.70±0.03(stat.) fm and a(n)=0.55±0.01(stat.)(-0.03)(+0.02)(sys.) fm, respectively, corresponding to a neutron skin thickness Δr(np)=0.15±0.03(stat.)(-0.03)(+0.01)(sys.) fm. The results give the first successful extraction of a neutron skin thickness with an electromagnetic probe and indicate that the skin of (208)Pb has a halo character. The measurement provides valuable new constraints on both the structure of nuclei and the equation of state for neutron-rich matter.

Measurement of the 1H(γ, p)π0 reaction using a novel nucleon spin polarimeter.

We report the first large-acceptance measurement of polarization transfer from a polarized photon beam to a recoiling nucleon. The measurement pioneers a novel polarimetry technique, which can be applied to many other nuclear and hadron physics experiments. The commissioning reaction of 1H(γ, p)π0 in the range 0.4

Photoproduction of π0 mesons off neutrons in the nucleon resonance region.

Precise angular distributions have been measured for the first time for the photoproduction of π0 mesons off neutrons bound in the deuteron. The effects from nuclear Fermi motion have been eliminated by a complete kinematic reconstruction of the final state. The influence of final-state-interaction effects has been estimated by a comparison of the reaction cross section for quasifree protons bound in the deuteron to the results for free protons and then applied as a correction to the quasifree neutron data. The experiment was performed at the tagged photon facility of the Mainz Microtron MAMI with the Crystal Ball and TAPS detector setup for incident photon energies between 0.45 and 1.4 GeV. The results are compared to the predictions from reaction models and partial-wave analyses based on data from other isospin channels. The model predictions show large discrepancies among each other and the present data will provide much tighter constraints. This is demonstrated by the results of a new analysis in the framework of the Bonn-Gatchina coupled-channel analysis which included the present data.

Narrow structure in the excitation function of η photoproduction off the neutron.

The photoproduction of η mesons off nucleons bound in 2H and 3He has been measured in coincidence with recoil protons and recoil neutrons for incident photon energies from threshold up to 1.4 GeV. The experiments were performed at the Mainz MAMI accelerator, using the Glasgow tagged photon facility. Decay photons from the η→2γ and η→3π0 decays and the recoil nucleons were detected with an almost 4π electromagnetic calorimeter combining the Crystal Ball and TAPS detectors. The data from both targets are of excellent statistical quality and show a narrow structure in the excitation function of γn→nη. The results from the two measurements are consistent, taking into account the expected effects from nuclear Fermi motion. The best estimates for position and intrinsic width of the structure are W=(1670±5) MeV and Γ=(30±15) MeV. For the first time precise results for the angular dependence of this structure have been extracted.

Accurate test of chiral dynamics in the γp→π0p reaction.

A precision measurement of the differential cross sections dσ/dΩ and the linearly polarized photon asymmetry Σ≡(dσ⊥-dσ∥)/(dσ⊥+dσ∥) for the γp→π0p reaction in the near-threshold region has been performed with a tagged photon beam and almost 4π detector at the Mainz Microtron. The Glasgow-Mainz photon tagging facility along with the Crystal Ball/TAPS multiphoton detector system and a cryogenic liquid hydrogen target were used. These data allowed for a precise determination of the energy dependence of the real parts of the S- and all three P-wave amplitudes for the first time and provide the most stringent test to date of the predictions of chiral perturbation theory and its energy region of agreement with experiment.

[Preventive bone mineral density measurement in postmenopausal women. Differentiation of treatment of recommendations Guidelines of the Umbrella Organization for Osteology ("Dachverband Osteologie")]. / Präventive Knochendichtemessung bei postmenopausalen Frauen. Differenzierung der Therapieempfehlungen der Leitlinien des Dachverbandes Osteologie (DVO).

BACKGROUND: Osteopenia (OP) or osteoporosis (OST) was diagnosed by bone densitometry (DXA) in postmenopausal women free of known skeletal disorders and without acute fracture. DVO guidelines were applied to define therapeutic indication. METHODS: The study included 94 women aged 59-81 years. Fracture or operation ≤12 months, malignant tumor, ovariectomy, and drugs such as cortisone, strontium, fluorides, bisphosphonates, SERMs, estrogens, and steroids were exclusion criteria. The lowest T-score at the spine, femoral neck, or total hip was decisive. The indication for therapy was determined by evaluating age, BMD, and other risk factors. RESULTS: Using the WHO criteria 22.3% (n=21) had normal BMD, 52.1% (n=49) had OP, and 25.6% (n=24) had OST. According to "Dachverband Osteologie" (DVO) guidelines, 28 women (29.8%) of the whole group needed therapy. Of the 28 women receiving therapy, 9 had OP and 19 had OST. Therapy was indicated in 18.4% for OP and 79.2% for OST. CONCLUSION: A preventive measurement of BMD with DXA provides a benefit for postmenopausal women. Combinatory assessment and consideration of other risk factors allows identification of women who might benefit from early treatment.

Collective tumor cell migration in the presence of fibroblasts.

In this work we investigate fibroblast-enhanced tumor cell migration in an idealized tumor setting through a computational model based on a multiphase approach consisting of three phases, namely tumor cells, fibroblasts and interstitial fluid. The interaction between fibroblasts and tumor cells has previously been investigated through this model (Urdal et al., 2019) to comply with reported in vitro experimental results (Shieh et al., 2011). Using the information gained from in vitro single-cell behavior, what will the effect of fibroblast-enhanced tumor cell migration be in a tumor setting? In particular, how will tumor cells migrate in a heterogeneous tumor environment compared to controlled in vitro microfluidic-based experiments? From what we know about the behavior of a tumor, is that collective invasion into adjacent tissue is frequently observed. Here, we want to elucidate how fibroblasts may guide tumor cells towards draining lymphatics to which tumor cells may subsequently intravasate and thus spread to other parts of the body. Fibroblasts can act as leader cells, where they create tracks within the extracellular matrix (ECM) by matrix remodeling and contraction. In addition, a heterotypic mechanical adhesion between fibroblasts and tumor cells also assist the fibroblasts to act as leader cells. Our simulation results show how the interaction between the two cell types yields collective migration of tumor cells outwards from the tumor where fibroblasts dictate the direction of migration. The model also describes how this well-orchestrated invasive behavior is the result of a proper combination of different interaction forces between cell-ECM, fibroblast-ECM, fluid-ECM and cell-fibroblast.

Competing tumor cell migration mechanisms caused by interstitial fluid flow.

In the seminal work by Swartz and collaborators (Shields et al., 2007) it was discovered that autologously secreted or activated (ECM-bound) chemokine forms local pericellular diffusion gradients skewed by fluid convection, and the cells subsequently chemotact up the flow-directed gradient. However, in (Polacheck et al., 2011) Kamm and collaborators found that there is a competing downstream and upstream migration transport mechanism. Their study showed that both mechanisms are present at the same time and the relative strength of these two stimuli governs the directional bias in migration for a cell population and is a function of cell density, interstitial flow rate, and CCR7 receptor availability. The main objective of this work is to give a possible explanation of these two different concurrent cell migration mechanisms by means of a theoretical model. Relying on multiphase modelling, separate momentum balance equations are formulated, respectively, for the cell phase and the interstitial fluid (IF) phase. In order to represent proteolytic activity and autologous chemotaxis a non-moving ECM component is included, as well as proteases secreted by the cancer cells and chemokine that can be released from ECM. The cell and IF momentum balance equations include cell-ECM and fluid-ECM resistance force terms (i.e., classical Darcy's equation terms), but also a cell-fluid interaction term that can account for a more indirect effect that fluid-generated stress may have on cancer cells. We illustrate how the cancer cells can work through this term and effectively avoid being pushed in the flow direction, and even create upstream migration by controlling its magnitude and sign. We think of this as the mathematical interpretation of the experimental observation by Kamm and collaborators that the fluid generated matrix adhesion tension on the upstream side of cells activates integrin adhesion complexes, resulting in activation of focal adhesion (FA) proteins. The model predicts that generally the strength of the upstream migration mechanism is sensitive to the cell volume fraction: a lower density of cells is subject to a weaker upstream migration effect; a higher density of cancer cells can more effectively generate upstream migration. This behavior is a result of the nonlinear coupling between cell-ECM, fluid-ECM, and cell-fluid interaction terms that naturally are involved in the mathematical expression for the net cell velocity.

Regulation of neuronal survival and morphology by the E3 ubiquitin ligase RNF157.

Neuronal health is essential for the long-term integrity of the brain. In this study, we characterized the novel E3 ubiquitin ligase ring finger protein 157 (RNF157), which displays a brain-dominant expression in mouse. RNF157 is a homolog of the E3 ligase mahogunin ring finger-1, which has been previously implicated in spongiform neurodegeneration. We identified RNF157 as a regulator of survival in cultured neurons and established that the ligase activity of RNF157 is crucial for this process. We also uncovered that independently of its ligase activity, RNF157 regulates dendrite growth and maintenance. We further identified the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65) as an interactor and proteolytic substrate of RNF157 in the control of neuronal survival. Here, the nuclear localization of Fe65 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis. In summary, we described that the E3 ligase RNF157 regulates important aspects of neuronal development.

Functional and protein chemical characterization of the N-terminal domain of the rat corticotropin-releasing factor receptor 1.

Rat corticotropin-releasing factor receptor 1 (rCRFR1) was produced either in transfected HEK 293 cells as a complex glycosylated protein or in the presence of the mannosidase I inhibitor kifunensine as a high mannose glycosylated protein. The altered glycosylation did not influence the biological function of rCRFR1 as demonstrated by competitive binding of rat urocortin (rUcn) or human/rat corticotropin-releasing factor (h/rCRF) and agonist-induced cAMP accumulation. The low production rate of the N-terminal domain of rCRFR1 (rCRFR1-NT) by transfected HEK 293 cells, was increased by a factor of 100 in the presence of kifunensine. The product, rCRFR1-NT-Kif, bound rUcn specifically (K(D) = 27 nM) and astressin (K(I) = 60 nM). This affinity was 10-fold lower than the affinity of full length rCRFR1. However, it was sufficiently high for rCRFR1-NT-Kif to serve as a model for the N-terminal domain of rCRFR1. With protein fragmentation, Edman degradation, and mass spectrometric analysis, evidence was found for the signal peptide cleavage site C-terminally to Thr(23) and three disulfide bridges between precursor residues 30 and 54, 44 and 87, and 68 and 102. Of all putative N-glycosylation sites in positions 32, 38, 45, 78, 90, and 98, all Asn residues except for Asn(32) were glycosylated to a significant extent. No O-glycosylation was observed.

Actions of CRF and its analogs.

Corticotropin-releasing factor (CRF), urocortin, sauvagine and urotensin I form the CRF family. These peptides bind with different affinities to two subtypes of CRF receptor (CRFR), CRFR1 and CRFR2. The latter exists as two splice variants, the neuronal CRFR2a and the peripheral CRFR2b. CRFR is a G protein-dependent receptor which acts mainly through Gs enhancing cAMP production. However, CRFR1 expressed in neutrophils of the spleen in response to immunologic stimulation and psychological stress does not seem to function through Gs, as indicated by the inability of CRF to stimulate the cAMP production of CRFR1+ neutrophils. Besides the two receptors, a 37 kD CRF binding protein (CRF-BP) binds several CRF peptides with high affinity. CRFR and CRF-BP do not share a common amino acid sequence representing the ligand binding site. In view of the unusually slow offrate of CRF-BP, it is proposed that CRF-BP provides an efficient uptake of free extracellular CRF. Thus, the time of exposure of CRFR to CRF or urocortin can be limited. At this time, the fate of the ligand CRF-BP complex is unclear. CRFR1 is not only involved in the hypophyseal stimulation of corticotropin release, but hippocampal CRFR1 mediates enhancement of stress-induced learning. CRFR1 may also be involved in basic anxiety. In contrast, at least in the mouse, CRFR2 of the lateral intermediate septum mediates tonic impairment of learning. In response to stressful stimuli or after local injection of high CRF doses, CRFR2 mediates anxiety. Effects requiring CRFR2 can be blocked specifically by the recently developed peptidic antagonist antisauvagine-30.

Comparative analysis of ribosomal protein L5 sequences from bacteria of the genus Thermus.

The genes for the ribosomal 5S rRNA binding protein L5 have been cloned from three extremely thermophilic eubacteria, Thermus flavus, Thermus thermophilus HB8 and Thermus aquaticus (Jahn et al, submitted). Genes for protein L5 from the three Thermus strains display 95% G/C in third positions of codons. Amino acid sequences deduced from the DNA sequence were shown to be identical for T flavus and T thermophilus, although the corresponding DNA sequences differed by two T to C transitions in the T thermophilus gene. Protein L5 sequences from T flavus and T thermophilus are 95% homologous to L5 from T aquaticus and 56.5% homologous to the corresponding E coli sequence. The lowest degrees of homology were found between the T flavus/T thermophilus L5 proteins and those of yeast L16 (27.5%), Halobacterium marismortui (34.0%) and Methanococcus vannielii (36.6%). From sequence comparison it becomes clear that thermostability of Thermus L5 proteins is achieved by an increase in hydrophobic interactions and/or by restriction of steric flexibility due to the introduction of amino acids with branched aliphatic side chains such as leucine. Alignment of the nine protein sequences equivalent to Thermus L5 proteins led to identification of a conserved internal segment, rich in acidic amino acids, which shows homology to subsequences of E coli L18 and L25. The occurrence of conserved sequence elements in 5S rRNA binding proteins and ribosomal proteins in general is discussed in terms of evolution and function.

Pharmacological characterization of recombinant rat corticotropin releasing factor binding protein using different sauvagine analogs.

Little is known on the structural ligand requirements for corticotropin-releasing factor binding protein (CRFBP) of the rat used as an important experimental animal. To obtain such information recombinant rat CRFBP was produced in stably transfected HEK 293 cells. The primary structure and posttranslational processing of purified rat CRFBP was established by peptide mapping using HPLC combined with mass spectrometric analysis. Rat CRFBP was pharmacologically characterized employing a competition binding assay with tritium-labeled rat urocortin. The rank order of declining affinity of various CRF analogs was urotensin-I, human/rat CRF (h/rCRF), rat urocortin, sauvagine (Svg), and ovine CRF in agreement with the rank order found for human CRFBP. In contrast to astressin, the CRF receptor 2-selective antagonist anti-sauvagine-30 did not show any detectable specific binding to rat CRFBP. The significance of residues 10 to 12 and 21 to 24 of Svg for its low affinity binding was established by changing these residues of Svg to those of h/rCRF. The corresponding residues 22 to 25 of h/rCRF represented the ARAE motif determined to be crucial for binding in agreement with reported data on human CRFBP. Residues 11 to 13 of CRF introduced into Svg also enhanced the affinity to rat CRFBP.

[Passive smoking, a risk factor for lung carcinoma?]. / Passivrauchen, ein Lungenkarzinomrisiko?

The established elevated risk of lung cancer in smokers led to the hypothesis that environmental tobacco smoke (ETS) also causes malignancies. The solution of this question is complicated by low exposure levels and dose-response dependence, as well as threshold levels. The differences between the toxins in the main- and side-stream of tobacco smoke and also the lack of significantly elevated risk ratios in epidemiological studies do not permit scientific conclusions endorsing a connection between passive smoking and lung cancer, which has become an emotionalised issue.

[Comparison of 2 field studies (office and food factory)]. / Gegenüberstellung zweier Feldstudien (Büro- und Lebensmittelbetrieb).

The results of a medical investigation of 973 volunteers (632 bank employees and 341 workers in a food factory) are compared: a marked difference exists between the two groups with regard to body-weight distribution. Significantly more persons with elevated levels of serum cholesterol, triglycerides and glucose are registered in the group of food workers; moreover, the incidence of hypertension, bad teeth and varicosis is also higher in this group.

Electromagnetic compatibility of electronic implants--review of the literature.

The aim of the article was to provide an overview of published studies regarding the electromagnetic compatibility (EMC) of electronic implants. The available literature was sorted according to combinations of implant types and sources of interference. Several experiments concerning the susceptibility of pacemakers to mobile phones have been performed. The results of these experiments suggest measures that may be used to prevent the disturbance of pacemakers. For instance, instead of carrying the activated mobile phone in the breast pocket it is recommended that a distance of 30 cm be maintained between the pacemaker and the mobile phone, and that the mobile phone be used on the contralateral side of the pacemaker's location. Similar measures may be recommended for patients with implantable cardioverter defibrillators when using mobile phones. Patients with electronic implants should walk rapidly through anti theft-devices because some of these devices are liable to disturb implants. Patients with cardiac pacemakers should not be subjected to magnetic resonance imaging as far as possible. For a variety of combinations of implants and interference sources, e.g. cardiac pacemakers and base station antennas, no studies were found in the literature. It is strongly recommended that trials be carried out to evaluate the potential risk for patients in these settings.