Analysis of 161Tb by radiochemical separation and liquid scintillation counting.

The determination of 161Tb activity is problematic due to its very low fission yield, short half-life, and the complication of its gamma spectrum. At AWE, radiochemically purified 161Tb solution was measured on a PerkinElmer 1220 QuantulusTM Liquid Scintillation Spectrometer. Since there was no 161Tb certified standard solution available commercially, the counting efficiency was determined by the CIEMAT/NIST Efficiency Tracing method. The method was validated during a recent inter-laboratory comparison exercise involving the analysis of a uranium sample irradiated with thermal neutrons. The measured 161Tb result was in excellent agreement with the result using gamma spectrometry and the result obtained by Pacific Northwest National Laboratory.

Directed, Elliptic, and Higher Order Flow Harmonics of Protons, Deuterons, and Tritons in Au+Au Collisions at sqrt[s_{NN}]=2.4 GeV.

Flow coefficients v_{n} of the orders n=1-6 are measured with the High-Acceptance DiElectron Spectrometer (HADES) at GSI for protons, deuterons, and tritons as a function of centrality, transverse momentum, and rapidity in Au+Au collisions at sqrt[s_{NN}]=2.4 GeV. Combining the information from the flow coefficients of all orders allows us to construct for the first time, at collision energies of a few GeV, a multidifferential picture of the angular emission pattern of these particles. It reflects the complicated interplay between the effect of the central fireball pressure on the emission of particles and their subsequent interaction with spectator matter. The high precision information on higher order flow coefficients is a major step forward in constraining the equation of state of dense baryonic matter.

Strong Absorption of Hadrons with Hidden and Open Strangeness in Nuclear Matter.

We present the first observation of K^{-} and ϕ absorption within nuclear matter by means of π^{-}-induced reactions on C and W targets at an incident beam momentum of 1.7 GeV/c studied with HADES at SIS18/GSI. The double ratio (K^{-}/K^{+})_{W}/(K^{-}/K^{+})_{C} is found to be 0.319±0.009(stat)_{-0.012}^{+0.014}(syst) indicating a larger absorption of K^{-} in heavier targets as compared to lighter ones. The measured ϕ/K^{-} ratios in π^{-}+C and π^{-}+W reactions within the HADES acceptance are found to be equal to 0.55±0.04(stat)_{-0.07}^{+0.06}(syst) and to 0.63±0.06(stat)_{-0.11}^{+0.11}(syst), respectively. The similar ratios measured in the two different reactions demonstrate for the first time experimentally that the dynamics of the ϕ meson in nuclear medium is strongly coupled to the K^{-} dynamics. The large difference in the ϕ production off C and W nuclei is discussed in terms of a strong ϕN in-medium coupling. These results are relevant for the description of heavy-ion collisions and the structure of neutron stars.

Anti-FcγRIIB (CD32) Antibodies Differentially Modulate Murine FVIII-Specific Recall Response in vitro.

Fc gamma receptors (FcγRs) for IgG regulate adaptive immune responses by modulating activating and inhibitory signalling pathways within immune cells. Data from a haemophilia A mouse model demonstrate that genetic deletion or blockade of the inhibitory FcγR (CD32) suppresses the formation of antibody-secreting cells (ASCs) in vitro. Mechanisms preventing the FVIII-specific recall response, however, remain unclear. Here, the potential role of CD32 inhibition was studied by differentially modulating receptor activity with selected anti-CD32 monoclonal antibodies (mAbs). Splenocytes from immunized FVIII-/- mice were restimulated with FVIII in the absence or presence of different anti-CD32 mAbs over 6 days. At day 6, cytokine release was quantified from cell culture supernatant and the formation of FVIII-specific ASCs assessed. Binding of FVIII-containing immune complexes (F8-ICs) to bone marrow-derived dendritic cells (BMdDCs) was also investigated. The antagonistic CD32 mAb AT128 suppressed the formation of FVIII-specific ASCs and reduced secretion of IFN-γ and IL-10. In contrast, the agonistic mAbs AT130-2 and AT130-5, and their F(ab')2 fragments, allowed the formation of FVIII-specific ASCs, even though the full IgG of AT130-2 reduced binding of F8-ICs to CD32. Data suggest that an inhibitory signal is transmitted when F8-ICs bind to CD32 and that this signal is required during memory B cell (MBC) activation to support formation of FVIII-specific ASCs. If the inhibitory signal is lacking due to CD32 deletion or blockade with antagonistic anti-CD32 mAbs, FVIII-specific T cell stimulation and ASC formation are suppressed, whereas agonistic stimulation of CD32 restores T cell stimulation and ASC formation.

Subthreshold Ξ

Results on the production of the double strange cascade hyperon Ξ^{-} are reported for collisions of p(3.5 GeV)+Nb, studied with the High Acceptance Di-Electron Spectrometer (HADES) at SIS18 at GSI Helmholtzzentrum for Heavy-Ion Research, Darmstadt. For the first time, subthreshold Ξ^{-} production is observed in proton-nucleus interactions. Assuming a Ξ^{-} phase-space distribution similar to that of Λ hyperons, the production probability amounts to P_{Ξ^{-}}=[2.0±0.4(stat)±0.3(norm)±0.6(syst)]×10^{-4} resulting in a Ξ^{-}/(Λ+Σ^{0}) ratio of P_{Ξ^{-}}/P_{Λ+Σ^{0}}=[1.2±0.3(stat)±0.4(syst)]×10^{-2}. Available model predictions are significantly lower than the measured Ξ^{-} yield.

Potential impact of releases from a new molybdenum-99 production facility on regional measurements of airborne xenon isotopes.

The monitoring of the radioactive xenon isotopes (131m)Xe, (133)Xe, (133m)Xe, and (135)Xe is important for the detection of nuclear explosions. While backgrounds of the xenon isotopes are short-lived, they are constantly replenished from activities dominated by the fission-based production of (99)Mo used for medical procedures. At present, one of the most critical locations on earth for the monitoring of nuclear explosions is the Korean peninsula where the Democratic People's Republic of Korea (DPRK) has announced that it conducted three nuclear tests between 2006 and 2013. This paper explores the backgrounds that would be caused by the medium to large scale production of (99)Mo in the region of the Korean peninsula.

Analysis of data from sensitive U.S. monitoring stations for the Fukushima Dai-ichi nuclear reactor accident.

The March 11, 2011 9.0 magnitude undersea megathrust earthquake off the coast of Japan and subsequent tsunami waves triggered a major nuclear event at the Fukushima Dai-ichi nuclear power station. At the time of the event, units 1, 2, and 3 were operating and units 4, 5, and 6 were in a shutdown condition for maintenance. Loss of cooling capacity to the plants along with structural damage caused by the earthquake and tsunami resulted in a breach of the nuclear fuel integrity and release of radioactive fission products to the environment. Fission products started to arrive in the United States via atmospheric transport on March 15, 2011 and peaked by March 23, 2011. Atmospheric activity concentrations of (131)I reached levels of 3.0×10(-2) Bqm(-3) in Melbourne, FL. The noble gas (133)Xe reached atmospheric activity concentrations in Ashland, KS of 17 Bqm(-3). While these levels are not health concerns, they were well above the detection capability of the radionuclide monitoring systems within the International Monitoring System of the Comprehensive Nuclear-Test-Ban Treaty.

Deep subthreshold Xi;{-} production in Ar + KCl reactions at 1.76A GeV.

We report first results on a deep subthreshold production of the doubly strange hyperon Xi;{-} in a heavy-ion reaction. At a beam energy of 1.76A GeV the reaction Ar + KCl was studied with the High Acceptance Di-Electron Spectrometer at SIS18/GSI. A high-statistics and high-purity Lambda sample was collected, allowing for the investigation of the decay channel Xi;{-} --> Lambdapi;{-}. The deduced Xi;{-}/(Lambda + Sigma;{0}) production ratio of (5.6 +/- 1.2_{-1.7};{+1.8}) x 10;{-3} is significantly larger than available model predictions.

Hepatic failure after injury - a common pathogenesis with sclerosing cholangitis?

OBJECTIVE: Hepatic failure after trauma occurs in about 5 - 10 % of multiple injured patients. Mortality rate remains high and liver dysfunction might deteriorate to complete liver failure and contribute to multi organ failure (MOF). Pathogenesis is multifactorial and distinct mechanisms are unknown. METHODS: To get further knowledge about pathogenesis of posttraumatic liver failure we investigated clinical course, inflammatory mediators, ERCP and histologic findings in 7 patients [6 male, 1 female, mean age 45.7 +/- 12.1 years, mean ISS 38.4 +/- 10.8 pts. (range 25-58 pts.)] that evolved hepatic failure after major trauma. Mortality rate was 14 %. RESULTS: All patients presented with a prolonged shock period after trauma and severe respiratory failure requiring differentiated ventilatory support and prone positioning. Onset of significant bilirubinemia (> 2.0 mg/dl) was day 3 to 16 days (median 11 days) after trauma. Past medical history did not reveal any underlying liver disease in all patients. Pro-and anti-inflammatory parameters like WBC, Procalcitonin, IL-4, IL-10, IL-11, IL-12, and IL-18 remained close to healthy control values. CRP was elevated but did not correlate with Bilirubin. Transaminases (ALT, AST) remained close to normal values but increased during the further course, whereas alkaline phosphatase (aP) and gamma-glutamyl transpeptidase (gGT) were already significantly elevated even before Bilirubin (gammaGT: 394 +/- 317 U/l; controls: < 56 U/l; aP 557 +/- 311 U/l; controls: < 127 U/l). Although no cholestasis was proven in ultrasound and CT investigations, all patients underwent ERCP and liver biopsy. Here, all patients presented uniform signs of multiple strictures of the intrahepatic bile ducts and sclerosing cholangitis. CONCLUSIONS: Our data provide evidence that sclerosing cholangitis contributes to liver failure after trauma. The pathomorphologic picture can not distinguish between shock liver and sclerosing cholangitis. Ischemia during posttraumatic shock might be an early trigger of hepatic failure, supported by further contributing factors such as catecholamines, parenteral nutrition, and bacterial translocation. As specific therapy for sclerosing cholangitis does not exist yet, prevention of triggers is central to avoid progressive hepatic failure in those patients. Further prospective studies have to prove whether sclerosing cholangitis is commonly involved in the pathogenesis of liver failure after trauma and shock. If so, one might speculate that early therapy with ursodeoxycholic acid might be effective thus reducing incidence and/or severity of hepatic failure in the future.

Estimation of the mortality risk of surgical intensive care patients based on routine laboratory parameters.

BACKGROUND: In established risk score models the collection and documentation of clinical data is time-consuming, causes labor-related costs, and is dependent on the examiner. MATERIAL AND METHODS: Based on low-cost laboratory parameters that are routinely measured at admission to the intensive care unit, a new score was developed (n = 271, study sample) and validated in an independent group of patients (n = 283, validation sample). Parameters were selected by a stepwise logistic regression analysis. This new score was compared to established risk models (APACHE II, SAPS II). RESULTS: Mean age was 61.3 +/- 1.2 years (study sample) and 63.1 +/- 1.1 years (validation sample), respectively. In-hospital mortality was 24.7% (67/271, study sample) and 23.3% (66/283, validation sample). The following parameters were used to build the new score called Dense Laboratory Whole Blood Applied Risk Estimation (DELAWARE): alanine aminotransferase, C-reactive protein, cholesterol, creatine kinase MB, leukocytes, potassium, thrombocytes, triglycerides, and age. The areas under the curves were 0.853/0.813 (study sample/validation sample). In the study sample DELAWARE correlated with APACHE II (r = 0.586) and SAPS II (r = 0.614; p < 0.001), respectively. CONCLUSIONS: A general admission risk score for surgical intensive care patients solely based on quality controlled low-cost routine laboratory parameters is feasible.

Dielectron production in 12C+12C collisions at 2A GeV with the HADES spectrometer.

The invariant-mass spectrum of e+e- pairs produced in 12C+12C collisions at an incident energy of 2 GeV per nucleon has been measured for the first time. The measured pair production probabilities span over 5 orders of magnitude from the pi(0)-Dalitz to the rho/omega invariant-mass region. Dalitz decays of pi(0) and eta account for all the yield up to 0.15 GeV/c(2), but for only about 50% above this mass. A comparison with model calculations shows that the excess pair yield is likely due to baryon-resonance and vector-meson decays. Transport calculations based on vacuum spectral functions fail, however, to describe the entire mass region.

[Polytrauma with severe lung contusion. Early use of extracorporeal membrane oxygenation]. / Polytrauma mit schwerem Lungenparenchymschaden. Frühzeitiger Einsatz der extrakorporalen Membranoxygenierung.

Extracorporeal membrane oxygenation (ECMO) is a technique for sustaining body oxygenation in case of respiratory failure. Since ECMO technology has undergone improvements resulting in better hemo-compatibility and reduced side effects, venovenous ECMO is a mostly accepted treatment of adult respiratory distress syndrome (ARDS). One should discuss the early initiation of ECMO therapy for post-traumatic respiratory failure. We report about a 23-year-old male and a 15-year-old female patient, who suffered polytrauma and received early treatment with ECMO because of severe lung contusion.

Chromatographic separation and characterization of hydrolyzed Cr(III) species.

Both macroscale and microscale methods to separate hydrolyzed Cr(III) species from acidic to near-neutral pH solutions have been developed. The macroscale approach is based on ion exchange, and involves separating monomeric, dimeric, trimeric, tetrameric, and higher order Cr(III) oligomers from such solutions using a gradient elution with increasing cationic charge. With this approach, the concentration of a given fraction can be maximized, and complete resolution between these species can be achieved. In addition, complete recovery of Cr(III) from the column is achievable. For the microscale approach, capillary electrophoresis with indirect detection is used to isolate and uniquely identify the same smaller oligomers and a fraction of larger Cr(III) species that are not uniquely identified. Capillary electrophoresis also provides indirect structural information for the Cr(III) trimer, suggesting that it exists in a triangular configuration rather than as a linear species. These methods are described in detail, and possible applications are discussed.

Polyarteritis nodosa: spectrum of angiographic findings.

The purpose of this study was to review the positive angiographic findings in patients with polyarteritis nodosa (PAN). The authors reviewed the angiograms of 56 consecutive patients (25 women and 31 men; age range, 18-81 years; mean age, 55 years) with PAN and arterial abnormalities consistent with necrotizing vasculitis. Aneurysms were present in 27 patients and segments of ectasia were present in seven patients, for a total of 34 (61%) of 56 patients with aneurysmal lesions. The remaining 22 (39%) patients had arterial lesions that were occlusive: luminal irregularity, stenosis, or occlusion. All but one of the patients with an aneurysm also had occlusive lesions. Therefore, 55 (98%) of the 56 patients were found to have occlusive lesions. Skeletal muscle arteries were affected in 18 patients, nine in the extremities. The most frequent finding in patients with PAN was occlusive arterial lesions. Although the presence of aneurysms increases specificity for the diagnosis of PAN, many patients have only occlusive lesions. Involvement of skeletal muscle arteries was common.

Trigonal prismatic vs octahedral coordination geometry: syntheses and structural characterization of hexakis(arylthiolato) zirconate complexes.

Treating [Li(tmeda)]2[Zr(CH3)6] with aryl thiols, HSC6H4-4-R, in a 1:6 stoichiometry in diethyl ether affords excellent yields of [Li(tmeda)]2[Zr(SC6H4-4-R)6], where R = CH3 (1(2-)) or OCH3 (2(2-)) and tmeda denotes N,N,N',N'-tetramethylethylenediamine. These complexes are air-sensitive canary-yellow solids, soluble in hexane, diethyl ether, THF, and acetonitrile, that form yellow single crystals of [Li(tmeda)](2)1 (diethyl ether solution) or [Li(THF)3](2)2 (THF solution) from saturated solutions at -20 degrees C. Both complexes were characterized by X-ray crystallography and consist of a zirconium atom coordinated solely by the sulfur atoms of six aryl thiolate ligands in a nonoctahedral geometry. In each structure the lithium cation coordinates to the three sulfur atoms on the triangular faces of the S6 pseudotrigonal prism. These lithium-sulfur interactions appear to play a role in determining the coordination geometry about the metal center by orienting the sulfur lone pairs of electrons slightly out of the plane defined by the S3 triangular face and tilted away from the zirconium atoms. A likely consequence is the positioning of the sulfur lone pairs of electrons away from orthogonality with the zirconium-sulfur vector, and hence, they are poorly arranged to pi-interact with zirconium. Complex 1(2-) with a twist angle of ca. 9.18 degrees (trigonal prism, 0 degree; octahedron, 60 degrees) agrees with the interpretations of computational studies on d degree complexes, which suggest that a nearly trigonal prismatic geometry is favored when the interaction between metal and ligand is primarily through sigma-bonds. The intrinsically weak pi-donor thiolate ligand is probably converted to a primarily sigma-bonding system by the lithium-sulfur interaction. On the other hand complex 2(2-) with a twist angle of ca. 30.38 degrees is trigonally twisted to the midpoint of the trigonal prismatic-to-octahedral reaction coordinate. In complex 2(2-) the 4-OCH3 group is an electron donor by resonance effects that possibly may lead to the movement away from the expected trigonal prismatic geometry due to either pi-interactions or electrostatics repulsion.

Kavain, dihydrokavain, and dihydromethysticin non-competitively inhibit the specific binding of [3H]-batrachotoxinin-A 20-alpha-benzoate to receptor site 2 of voltage-gated Na+ channels.

The mode of action of the kava pyrones, kavain, dihydrokavain and dihydromethysticin on the specific binding of [3H]-batrachotoxinin-A 20-alpha-benzoate to epitope 2 of voltage-dependent Na+ channels was investigated by performing saturation experiments in the presence and absence of these kava pyrones. The tested compounds significantly decreased the apparent total number of binding sites (Bmax) for [3H]-batrachotoxinin-A 20-alpha-benzoate (control: 0.5 pmol/mg protein, kava pyrones: 0.2-0.27 pmol/mg protein) with little change in the equilibrium constants (KD) for [3H]-batrachotoxin-A 20-alpha-benzoate (control: 28.2 nM, kava pyrones: 24-31 nM). The results indicate for the kava pyrones a non-competitive inhibition of the specific [3H]-batrachotoxinin-A 20-alpha-benzoate binding to receptor site 2 of voltage-gated Na+ channels.

Mode of antinociceptive and toxic action of alkaloids of Aconitum spec..

Extracts of the plant Aconitum spec. are used in traditional Chinese medicine predominantly as anti-inflammatory and analgesic agents, the latter allegedly equally potent as morphine but without any habit-forming potential. As the only pharmacologically active compounds, the C19 diterpenoid alkaloid aconitine, and some of its derivatives, have been proven to be antinociceptive in different analgesic assays, but the mode of action is unknown. To elucidate the mode of action, ten aconitine-like derivatives were investigated with respect to their affinity for voltage-dependent Na+ channels, the action on synaptosomal Na+ and Ca2+ homoeostasis and their antinociceptive, arrhythmogenic and acute toxic properties. Since aconitine is known to bind to site II of Na+ channels, we determined the affinity of the aconitine-like derivatives in vitro to synaptosomal membranes by the [3H]-batrachotoxinin-binding assay and their properties on intrasynaptosomal concentrations of free Na+ and Ca2+ ([Na+]i and [Ca2+]i), both the latter determined fluorometrically with SBFI and Fura-2 respectively. Furthermore, the alkaloids' arrhythmogenic potential was investigated in guinea-pig isolated atria and the antinociceptive action on formalin-induced hyperalgesia and the acute toxic action estimated in mice. The results show that the alkaloids could be divided into at least three groups. The first is characterized by a high affinity to the site II of Na+ channels (Ki about 1.2 microM), the ability to enhance [Na+]i and [Ca2+]i (EC50 about 3 microM), a strong arrhythmogenic action that starts at about 30 nM, an antinociceptive effect (ED50 about 0.06 mg/kg) and high acute toxicity (LD50 values about 0.15 mg/kg). To this group belong aconitine, 3-acetylaconitine and hypaconitine. The second group, with lappaconitine as the only member, has an affinity to Na+ channels an order of magnitude lower (Ki = 11.5 microM), less acute toxicity (LD50 about 5 mg/kg), and a two orders of magnitude lower antinociceptive action (ED50 about 2.8 mg/kg) and lower cardiotoxicity (bradycardia observed at 3 microM). Additionally, lappaconitine suppresses the increase in [Ca2+]i of aconitine-stimulated synaptosomes and increases the excitation threshold of left atria, indicating an inhibition of Na+ channels. The other derivatives, i.e. delcorine, desoxydelcorine, karakoline, lappaconidine, lappaconine and lycoctonine, belong to the third group, which has hardly any effects. They have a low affinity to Na+ channels with Ki values in the millimolar range, show no effect on synaptosomal [Na+]i and [Ca2+]i, no arrhythmogenic potential up to 100 microM, no antinociceptive activity and low toxicity with LD50 values greater than 50 mg/kg. For the investigated alkaloids we suggest two different antinociceptive-like modes of action. Aconitine, hypaconitine and 3-acetylaconitine may induce a block of neuronal conduction by a permanent cell depolarisation, whereas lappaconitine might act like local anaesthetics. However, because of the low LD50/ED30 quotients of 2-6, the antinociceptive-like action of the Aconitum alkaloids seems to reflect severe intoxication rather than a specific antinociceptive action. The structure/activity relationship shows that alkaloids that activate or block Na+ channels have a benzoyl ester side chain in the C-14 or C-4 positions respectively, whereas the other compounds lack this group.

Protein kinase and phosphatase activity in the lungs of normoxic versus hyperoxic rats.

Studies were designed to examine aspects of phosphorylation and dephosphorylation in rat lung cells in response to hyperoxic exposure. Protein kinase and phosphatase activities were measured in preparations of lungs from normoxic rats, hyperoxia-exposed rats (95% O2 for 60h), and rats recovering in room air for 1 and 3 days. Protein kinase C (PKC) activity immediately postexposure was significantly lower than in normoxic controls (normoxia 127.1 +/- 13 vs. hyperoxia 101.5 +/- 6 pmol/min mg-1) and continued to decline during the recovery period (85.3 +/- 4 and 78.2 +/- 6 pmol/min mg-1 at 1 and 3 days recovery, respectively). The PKC activity did not translocate from cytoplasm to the membranes. In contrast, PKA activity did not change in response to hyperoxia exposure or recovery. Protein phosphatase activity was decreased significantly by hyperoxia exposure (normoxia 30.7 +/- 3 vs. hyperoxia 21.9 +/- 1 pmol/min microgram-1) but returned to normoxic control levels by 1 and 3 days (24.1 +/- and 31.5 +/- 1 pmol/min microgram -1, respectively). Protein phosphatase activity was inhibited by okadaic acid (Ki = 1 nM) and calyculin A (Ki = 0.61 pM), indicating a type 2A protein phosphatase. Enzyme activities in cultured type II alveolar cells paralleled those observed in whole lung preparations. Decreased enzyme activities in the lung may be located to the development of acute lung injury during hyperoxic exposure.

Development of the Abbott AxSYM Free PSA assay: performance characteristics and preliminary clinical evaluation.

The AxSYM Free PSA assay was demonstrated to have good analytical sensitivity and reproducibility. The F/T ratio determinations for 385 men tested during the Prostate Awareness Week who had biopsies due to an elevated total PSA value and/or a suspicious DRE demonstrated that the percentage of free PSA was lower in patients found to have prostate cancer than those that were biopsy negative for the overall group and for all patient categories examined. The optimal strategy for combining PSA values, F/T ratios, DRE and other clinical and diagnostic parameters to improve the early detection of prostate cancer requires additional clinical studies.