A Xenon Condenser with a Remote Liquid Storage Vessel

We describe the design and operation of a system for xenon liquefaction in which the condenser is separated from the liquid storage vessel. The condenser is cooled by a pulse tube cryocooler, while the vessel is cooled only by the liquid xenon itself. This arrangement facilitates liquid particle detector research by allowing easy access to the upper and lower flanges of the vessel. We find that an external xenon gas pump is useful for increasing the rate at which cooling power is delivered to the vessel, and we present measurements of the power and efficiency of the apparatus.Comment: 22 pages, 7 figures Corrected typos in authors lis

Impact of germline and somatic missense variations on drug binding sites.

Advancements in next-generation sequencing (NGS) technologies are generating a vast amount of data. This exacerbates the current challenge of translating NGS data into actionable clinical interpretations. We have comprehensively combined germline and somatic nonsynonymous single-nucleotide variations (nsSNVs) that affect drug binding sites in order to investigate their prevalence. The integrated data thus generated in conjunction with exome or whole-genome sequencing can be used to identify patients who may not respond to a specific drug because of alterations in drug binding efficacy due to nsSNVs in the target protein\u27s gene. To identify the nsSNVs that may affect drug binding, protein-drug complex structures were retrieved from Protein Data Bank (PDB) followed by identification of amino acids in the protein-drug binding sites using an occluded surface method. Then, the germline and somatic mutations were mapped to these amino acids to identify which of these alter protein-drug binding sites. Using this method we identified 12 993 amino acid-drug binding sites across 253 unique proteins bound to 235 unique drugs. The integration of amino acid-drug binding sites data with both germline and somatic nsSNVs data sets revealed 3133 nsSNVs affecting amino acid-drug binding sites. In addition, a comprehensive drug target discovery was conducted based on protein structure similarity and conservation of amino acid-drug binding sites. Using this method, 81 paralogs were identified that could serve as alternative drug targets. In addition, non-human mammalian proteins bound to drugs were used to identify 142 homologs in humans that can potentially bind to drugs. In the current protein-drug pairs that contain somatic mutations within their binding site, we identified 85 proteins with significant differential gene expression changes associated with specific cancer types. Information on protein-drug binding predicted drug target proteins and prevalence of both somatic and germline nsSNVs that disrupt these binding sites can provide valuable knowledge for personalized medicine treatment. A web portal is available where nsSNVs from individual patient can be checked by scanning against DrugVar to determine whether any of the SNVs affect the binding of any drug in the database.The Pharmacogenomics Journal advance online publication, 26 January 2016; doi:10.1038/tpj.2015.97

Measurement of the Generalized Forward Spin Polarizabilities of the Neutron

The generalized forward spin polarizabilities $\gamma_0$ and $\delta_{LT}$ of the neutron have been extracted for the first time in a $Q^2$ range from 0.1 to 0.9 GeV$^2$. Since $\gamma_0$ is sensitive to nucleon resonances and $\delta_{LT}$ is insensitive to the $\Delta$ resonance, it is expected that the pair of forward spin polarizabilities should provide benchmark tests of the current understanding of the chiral dynamics of QCD. The new results on $\delta_{LT}$ show significant disagreement with Chiral Perturbation Theory calculations, while the data for $\gamma_0$ at low $Q^2$ are in good agreement with a next-to-lead order Relativistic Baryon Chiral Perturbation theory calculation. The data show good agreement with the phenomenological MAID model.Comment: 5 pages, 2 figures, corrected typo in author name, published in PR

The Q^2 evolution of the generalized Gerasimov-Drell-Hearn integral for the neutron using a He-3 target

We present data on the inclusive scattering of polarized electrons from a polarized He-3 target at energies from 0.862 to 5.06 GeV, obtained at a scattering angle of 15.5 degrees. Our data include measurements from the quasielastic peak, through the resonance region, to the beginning of the deep inelastic regime, and were used to determine the spin difference in the virtual photoabsorption cross section. We extract the extended Gerasimov-Drell-Hearn integral for the neutron in the range of 4-momentum transfer squared Q^2 of 0.1-0.9 GeV.Comment: 14 pages of text when TeXed in preprint format with figures embedded. RevTeX format. Three eps figure

Q^2 Evolution of the Neutron Spin Structure Moments using a He-3 Target

We have measured the spin structure functions $g_1$ and $g_2$ of $^3$He in a double-spin experiment by inclusively scattering polarized electrons at energies ranging from 0.862 to 5.07 GeV off a polarized $^3$He target at a 15.5$^{\circ}$ scattering angle. Excitation energies covered the resonance and the onset of the deep inelastic regions. We have determined for the first time the $Q^2$ evolution of $\Gamma_1(Q^2)=\int_0^{1} g_1(x,Q^2) dx$, $\Gamma_2(Q^2)=\int_0^1 g_2(x,Q^2) dx$ and $d_2 (Q^2) = \int_0^1 x^2[ 2g_1(x,Q^2) + 3g_2(x,Q^2)] dx$ for the neutron in the range 0.1 GeV$^2$ $\leq Q^2 \leq$ 0.9 GeV$^2$ with good precision. $\Gamma_1(Q^2)$ displays a smooth variation from high to low $Q^2$. The Burkhardt-Cottingham sum rule holds within uncertainties and $d_2$ is non-zero over the measured range.Comment: 5 pages, 2 figures, submitted to Phys. Rev. Lett.. Updated Hermes data in Fig. 2 (top panel) and their corresponding reference. Updated the low x extrapolation error Fig. 2 (middle panel). Corrected references to ChiPT calculation

A xenon gas purity monitor for EXO

We discuss the design, operation, and calibration of two versions of a xenon gas purity monitor (GPM) developed for the EXO double beta decay program. The devices are sensitive to concentrations of oxygen well below 1 ppb at an ambient gas pressure of one atmosphere or more. The theory of operation of the GPM is discussed along with the interactions of oxygen and other impurities with the GPM's tungsten filament. Lab tests and experiences in commissioning the EXO-200 double beta decay experiment are described. These devices can also be used on other noble gases.Comment: 41 pages, 26 figure

^3He spin-dependent cross sections and sum rules

We present a measurement of the spin-dependent cross sections for the ^3He(e,e) X reaction in the quasielastic and resonance regions at a four-momentum transfer 0:1 ≤ Q^2 ≤ 0:9 GeV^2. The spin-structure functions have been extracted and used to evaluate the nuclear Burkhardt-Cottingham and extended Gerasimov-Drell-Hearn sum rules for the first time. The data are also compared to an impulse approximation calculation and an exact three-body Faddeev calculation in the quasielastic region

Dynamics of the 16^{16}O(e,e'p) cross section at high missing energies

We measured the cross section and response functions (R_L, R_T, and R_LT) for the 16O(e,e'p) reaction in quasielastic kinematics for missing energies 25 60 MeV and P_miss > 200 MeV/c, the cross section is relatively constant. Calculations which include contributions from pion exchange currents, isobar currents and short-range correlations account for the shape and the transversity but only for half of the magnitude of the measured cross section

Pharmacokinetic evaluation of a transdermal anastrozole-in-adhesive formulation

Ralf Regenthal,1,* Margarita Voskanian,2,* Frank Baumann,1 Jens Teichert,1 Christian Brätter,2 Achim Aigner,1 Getu Abraham31Rudolf-Boehm-Institute of Pharmacology and Toxicology, Clinical Pharmacology, Faculty of Medicine, University of Leipzig, Leipzig, Germany; 2Department Pharmaceutical Development, Formula GmbH, Pharmaceutical and Chemical Development Company, Berlin, Germany; 3Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany*These authors contributed equally to this workBackground and objective: Anastrozole is a well-established active pharmaceutical ingredient (API) used for the treatment of hormone-sensitive breast cancer (BC) in postmenopausal women. However, treatment with the only available oral formulation is often associated with concentration-dependent serious side effects such as hot flashes, fatigue, muscle and joint pain, nausea, diarrhea, headache, and others. In contrast, a sustained-release system for the local application of anastrozole should minimize these serious adverse drug reactions.Methods: Anastrozole-in-adhesive transdermal drug delivery systems (TDDS) were developed offering efficient loading, avoidance of inhomogeneity or crystallization of the drug, the desired controlled release kinetics, storage stability, easy handling, mechanical stability, and sufficient stickiness on the skin. In vitro continuous anastrozole release profiles were studied in Franz diffusion cells. In vivo, consecutive drug plasma kinetics from the final anastrozole transdermal system was tested in beagle dogs. For drug analysis, a specific validated liquid chromatography–mass spectrometry method using fragment ion detection was developed and validated.Results: After efficient drug loading, a linear and sustained 65% drug release from the TDDS over 48 h was obtained. In vivo data showed a favorable anastrozole plasma concentration–time course, avoiding side effect-associated peak concentrations as obtained after oral administration but matching therapeutic plasma levels up to 72 h.Conclusion: These results provide the basis for establishing the transdermal application of anastrozole with improved pharmacokinetics and drug safety as novel therapeutic approach and promising option to treat human BC by decreasing the high burden of unwanted side effects.Keywords: anastrozole, breast cancer, transdermal drug delivery system, pharmacokinetics, Franz diffusion cell