Definition of Local Spatial Densities in Hadrons.

We show that the matrix element of a local operator between hadronic states can be used to unambiguously define the associated spatial density. As an explicit example, we consider the charge density of a spinless particle and clarify its relationship to the electric form factor. Our results lead to an unconventional interpretation of the spatial densities of local operators and their moments.

Observation of the pη

Data on the beam asymmetry Σ in the photoproduction of η mesons off protons are reported for tagged photon energies from 1130 to 1790 MeV (mass range from W=1748 MeV to W=2045 MeV). The data cover the full solid angle that allows for a precise moment analysis. For the first time, a strong cusp effect in a polarization observable has been observed that is an effect of a branch-point singularity at the pη^{'} threshold [E_{γ}=1447 MeV (W=1896 MeV)]. The latest BnGa partial wave analysis includes the new beam asymmetry data and yields a strong indication for the N(1895)1/2^{-} nucleon resonance, demonstrating the importance of including all singularities for a correct determination of partial waves and resonance parameters.

Precision Nucleon-Nucleon Potential at Fifth Order in the Chiral Expansion.

We present a nucleon-nucleon potential at fifth order in chiral effective field theory. We find a substantial improvement in the description of nucleon-nucleon phase shifts as compared to the fourth-order results utilizing a coordinate-space regularization. This provides clear evidence of the corresponding two-pion exchange contributions with all low-energy constants being determined from pion-nucleon scattering. The fifth-order corrections to nucleon-nucleon observables appear to be of a natural size, which confirms the good convergence of the chiral expansion for nuclear forces. Furthermore, the obtained results provide strong support for the novel way of quantifying the theoretical uncertainty due to the truncation of the chiral expansion proposed by the authors. Our work opens up new perspectives for precision ab initio calculations in few- and many-nucleon systems and is especially relevant for ongoing efforts towards a quantitative understanding of the structure of the three-nucleon force in the framework of chiral effective field theory.

Electric Dipole Moment of the Neutron from 2+1 Flavor Lattice QCD.

We compute the electric dipole moment d(n) of the neutron from a fully dynamical simulation of lattice QCD with 2+1 flavors of clover fermions and nonvanishing θ term. The latter is rotated into a pseudoscalar density in the fermionic action using the axial anomaly. To make the action real, the vacuum angle θ is taken to be purely imaginary. The physical value of dd(n) is obtained by analytic continuation. We find d(n)=-3.9(2)(9)×10(-16) θ e cm, which, when combined with the experimental limit on d(n), leads to the upper bound |θ|≲7.4×10(-11).

Leptin does not induce an inflammatory response in the murine placenta.

Leptin is described as a pro-inflammatory signal in fat tissue, which is released from adipocytes and in turn activates immune cells. Also, leptin levels are known to be increased in pregnancies complicated with enhanced inflammatory processes in the placenta. Hence, we assumed that increased leptin amounts might contribute to inducing an inflammatory response in the placenta. To test this hypothesis, pregnant mice were continuously infused with recombinant murine leptin s. c. from day g13 to g16, resulting in a 3-fold increase of maternal circulating serum leptin levels. Dissected placentas were examined for the expression of pro-inflammatory cytokines IL-6 and TNF-alpha and the anti-inflammatory cytokine IL-10 using qPCR analysis. No changes were found except for TNF-alpha, which was slightly elevated upon leptin stimulation. However, TNF-alpha protein levels were not significantly higher in placentas from leptin treated mice. Also, leukocyte infiltration in the labyrinth section of placentas was not increased. In summary, our data demonstrate for the first time that elevated leptin levels alone do not induce an inflammatory response in the placenta.

Contribution of different placental cells to the expression and stimulation of antimicrobial proteins (AMPs).

The placenta is a major barrier that prevents potentially infectious agents from causing fetal diseases or related complications during pregnancy. Therefore, we postulated that the placenta might express a broad repertoire of antimicrobial proteins as well as inflammatory chemokines and cytokines to combat invading microorganisms. Here we demonstrate that placental cells indeed express a wide range of AMPs (antimicrobial peptides and proteins) including bactericidal/permeability-increasing protein (BPI), secretory leukocyte protease inhibitor (SLPI), human ß-defensin 2 (hBD2), acyloxyacyl hydrolase (AOAH), and cathelicidin (CAP18). In addition, these cells also secrete pro-inflammatory cytokines and chemokines upon stimulation with bacterial ligands. Notably, we show that BPI expression by placental cells could be completely attributed to granulocytes while highly purified placental trophoblasts expressed only a subset of the AMPs like SLPI. Unexpectedly, trophoblast AMPs did not exhibit inducible secretion in response to various TLR ligands and further investigations showed that the unresponsiveness of trophoblasts to lipopolysaccharide (LPS) was due to a lack of TLR4 expression. In summary, we have shown that the expression of different AMPs can be allocated to various cells in the placenta and the repertoire of the AMPs expressed by placental cells is a result of a cooperation of leukocytes as well as cells from embryonic origin.

Detection of silicone oil leakages in freeze dryers.

As a small leakage from the silicone oil tubes in pharmaceutical freeze dryers may go undetected for several cycles, it provides a major threat to both product safety and the economic performance of such installations. A properly mounted mass spectrometer offers a non-invasive method of detecting the smallest amounts of silicone oil down to 1 ppm. Additionally the system will improve leak testing procedures and can also be used as a process analytical technology tool to improve process control. LAY ABSTRACT: Drugs, and in particular parenterals, need to have a very high level of purity. A production process such as freeze drying carries the inherent risk of contamination by process fluids. This should not happen during routine production, but in the event of a malfunction small amounts of these fluids may contaminate the drug product. The purpose of this paper is to introduce a method which is able to detect such malfunctions before they can develop into a risk for drug purity and ultimately patient safety.

Very early extubation after open-heart surgery in children does not influence cardiac function.

The objective of our study was to evaluate hemodynamic effects and the cardiac function after very early extubation within the first 6 hours after open-heart surgery in children. During a 12-month period, we performed a retrospective study of 50 children (ages 3 months to 7 years) admitted to the pediatric intensive care unit immediately after minor cardiac surgery. All children were extubated within the first 6 hours after their arrival. Arterial blood and central venous pressure were monitored, and arterial blood gas analysis was performed. Cardiac index, stroke volume index, systemic vascular resistance index, and extravascular lung water index were measured by thermodilution. Early extubation of children after minor open-heart surgery with cardiopulmonary bypass is safe and does not affect cardiac functions. A slight decrease of arterial oxygen tension not resulting in respiratory or metabolic acidosis or reintubation was noted. Very early extubation in children after open-heart surgery does not promote cardiodepressive effects. It is a safe procedure that helps to reduce the unnecessary and prolonged mechanical ventilation of children after cardiopulmonary bypass surgery.

Plasmatic [corrected] factor XIII reduces severe pleural effusion in children after open-heart surgery.

Chylous effusions frequently occur after cardiac surgery due to severe damage to the lymphatic system, thus indicating that the insertion of a chest tube may be necessary. Factor XIII (FXIII) is discussed as being essential for wound healing. The aim of this retrospective study was to evaluate whether the application of a single dose of FXIII results in a reduced amount of pleural effusion, leading to an earlier release of patients from the hospital. The cases of 40 children with severe chylous effusions after open-heart surgery were examined. Twenty patients received FXIII and were compared to 20 age- and weight-matched patients who did not receive FXIII. Major parameters included the amount of effusion before and 1 and 3 days after the application of FXIII; the duration of chest tubes; the total amount of fluid loss via drainage; and the period of hospitalization. FXIII levels in plasma showed an inverse correlation with fluid loss. After application of a single dose of FXIII, a significant reduction of pleural effusion within the first 24 hours was detected. However, no difference was observed between the two groups when comparing the total amount of pleural effusions within the first 72 hours. Finally, the duration of hospitalization did not differ between the FXIII-treated and the control group. A single application of FXIII rapidly reduces the amount of chylous effusions in the early period after open-heart surgery. This effect is detectable only for 24 hours after the treatment and does not alter the further clinical outcome. Prospective clinical trials are warranted to determine if repeated application or a higher dose of FXIII may improve the clinical outcome of chylous leakages in children after open-heart surgery.

Comparison of the decameric structure of peroxiredoxin-II by transmission electron microscopy and X-ray crystallography.

The decameric human erythrocyte protein torin is identical to the thiol-specific antioxidant protein-II (TSA-II), also termed peroxiredoxin-II (Prx-II). Single particle analysis from electron micrographs of Prx-II molecules homogeneously orientated across holes in the presence of a thin film of ammonium molybdate and trehalose has facilitated the production of a >/=20 A 3-D reconstruction by angular reconstitution that emphasises the D5 symmetry of the ring-like decamer. The X-ray structure for Prx-II was fitted into the transmission electron microscopic reconstruction by molecular replacement. The surface-rendered transmission electron microscopy (TEM) reconstruction correlates well with the solvent-excluded surface of the X-ray structure of the Prx-II molecule. This provides confirmation that transmission electron microscopy of negatively stained specimens, despite limited resolution, has the potential to reveal a valid representation of surface features of protein molecules. 2-D crystallisation of the Prx-II protein on mica as part of a TEM study resulted in the formation of a p2 crystal form with parallel linear arrays of stacked rings. This latter 2-D form correlates well with that observed from the 2.7 A X-ray structure of Prx-II solved from a new orthorhombic 3-D crystal form.

Three- and four-nucleon systems from chiral effective field theory.

Recently developed chiral nucleon-nucleon (NN) forces at next-to-leading order (NLO), that describe NN phase shifts up to about 100 MeV fairly well, have been applied to 3N and 4N systems. Faddeev-Yakubovsky equations have been solved rigorously. The resulting 3N and 4N binding energies are in the same range as found using standard NN potentials. In addition, low-energy 3N scattering observables are very well reproduced as for standard NN forces. The long-standing A(y) puzzle is absent at NLO. The cutoff dependence of the scattering observables is rather weak.

A soluble form of the murine common gamma chain is present at high concentrations in vivo and suppresses cytokine signaling.

The common gamma-chain (gammac) is a component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15 and is essential for their signal transduction. Western blotting and a newly established enzyme-linked immunosorbent assay detected substantial constitutive levels (50-250 ng/mL) of soluble gammac (sgammac) in sera of murine inbred strains. It was demonstrated that purified immune cells, such as T, B, and natural killer cells, and macrophages released this protein after activation. Transfection experiments with cDNA encoding the full-length gammac showed that shedding of the transmembrane receptor led to the release of sgammac. The shedding enzymes, however, appeared to be distinct from those cleaving other cytokine receptors because inhibitors of metalloproteases (eg, TAPI) did not influence sgammac release. In vivo, superantigen-induced stimulation of T cells enhanced sgammac serum concentrations up to 10-fold within 6 hours. Because these findings demonstrated regulated expression of a yet unknown molecule in the immune response, further experiments were performed to assess the possible function(s) of sgammac. A physiological role of sgammac was indicated by its capacity to specifically inhibit cell growth induced by gammac-dependent cytokines. Mutational analysis revealed that the C-terminus and the WSKWS motif are essential for the cytokine inhibitory effect of the sgammac and for binding of the molecule to cytokine receptor-expressing cells. Thus, competitive displacement of the transmembrane gammac by excess sgammac is the most likely mechanism of cell growth inhibition. It was implied that naturally produced sgammac is a negative modulator of gammac-dependent cytokines.

Marine tumor vaccine carriers: structure of the molluscan hemocyanins KLH and htH.

Keyhole limpet hemocyanin (KLH) is a well-established immune stimulant and hapten carrier, and Haliotis tuberculata hemocyanin (HtH) is a related product. Biologically, KLH and HtH are blue copper proteins which serve as oxygen carriers in the blood of the keyhole limpet Megathura crenulata and the abalone H. tuberculata, respectively, two marine gastropods. Both hemocyanins occur as two distinct isoforms, termed KLH1 KLH2, HtH1, and HtH2. Each of these molecules is based on a very large polypeptide chain, the subunit (molecular mass ca 400 kDa), which is folded into a series of eight globular functional units (molecular mass ca 50 kDa each). Twenty copies of this subunit form a cylindrical quaternary structure (molecular mass ca 8 MDa). This article reviews the recent data on the biosynthesis, quaternary structure, subunit architecture, amino acid sequence, gene structure, and recombinant production of KLH and HtH.

Structure of a molluscan hemocyanin didecamer (HtH1 from Haliotis tuberculata) at 12 A resolution by cryoelectron microscopy.

A 12 A resolution three-dimensional density map of the Haliotis tuberculata hemocyanin type 1 (HtH1) didecamer has been obtained by cryoelectron microscopy of unstained molecules and angular reconstitution. The dyad symmetry of the 8 MDa D5 HtH1 didecamer, formed by the pairing of two asymmetric 4 MDa ring-like C5 decamers, is emphasised. The major and minor surface helical grooves of the didecamer are well defined, in agreement with earlier data on molluscan hemocyanins. The location of the obliquely orientated repeating unit, a subunit dimer, within the decamer has been defined. Following interactive extraction of this dimer, several new structural features of the dimer and of the subunit have now emerged with improved detail. The subunit dimer possesses pseudo 2-fold symmetry, resulting from the steric arrangement of the wall domains/functional units (FUs-abcdef) of the two subunits. The arc and collar FUs (g and h) depart from this inherent 2-fold symmetry and are thereby responsible for the asymmetry of the C5 decamer, with the internalised collar/arc complex at one edge of the decamer. The FU heterodimers forming the wall morphological units have a hollow centre, and thus create a series of repeating channels that extend within the wall through all three tiers of the decamer. The connections between the wall and the arc are defined with improved clarity, and evidence is provided to indicate that the arc and collar FU pairs have a homodimeric composition (gg and hh, respectively). Two possibilities for the subunit path within the subunit dimer are presented, which correlate with the available structural, immunolabelling and protease cleavage data from HtH1 and other molluscan hemocyanins.

[Addition osteotomy of the head of the tibia with joint repair. Indications--technic--results]. / Die Tibiakopf-Additionsosteotomie mit Gelenktoilette. Indikation--Technik--Ergebnisse.

The study presents the results of our high tibial osteotomy which combine joint-toilet and wedge addition in 71 knees. In spite of a partly far advanced compartment-arthrosis could a joint replacement also by an unfavourable course (28% of the cases) in means 4.5 years be put off. In 50% could maybe get a satisfying condition over 5 years.