Measuring ligand efficacy at the mu-opioid receptor using a conformational biosensor.

The intrinsic efficacy of orthosteric ligands acting at G-protein-coupled receptors (GPCRs) reflects their ability to stabilize active receptor states (R*) and is a major determinant of their physiological effects. Here, we present a direct way to quantify the efficacy of ligands by measuring the binding of a R*-specific biosensor to purified receptor employing interferometry. As an example, we use the mu-opioid receptor (µ-OR), a prototypic class A GPCR, and its active state sensor, nanobody-39 (Nb39). We demonstrate that ligands vary in their ability to recruit Nb39 to µ-OR and describe methadone, loperamide, and PZM21 as ligands that support unique R* conformation(s) of µ-OR. We further show that positive allosteric modulators of µ-OR promote formation of R* in addition to enhancing promotion by orthosteric agonists. Finally, we demonstrate that the technique can be utilized with heterotrimeric G protein. The method is cell-free, signal transduction-independent and is generally applicable to GPCRs

Biochip sensors for the rapid and sensitive detection of viral disease

Recent advances in DNA and protein microarray methodology and the emerging technology of cell-based sensors have massively increased the speed and sensitivity with which we can detect viral infections. The advantages of the multi-parameter microarray technologies could be combined with the speed and sensitivity of cell-based systems to give 'cell-omic' sensors

Quiet Sun magnetic fields from simultaneous inversions of visible and infrared spectropolarimetric observations

We study the quiet Sun magnetic fields using spectropolarimetric observations of the infrared and visible Fe I lines at 6301.5, 6302.5, 15648 and 15653 A. Magnetic field strengths and filling factors are inferred by the simultaneous fit of the observed Stokes profiles under the MISMA hypothesis. The observations cover an intra-network region at the solar disk center. We analyze 2280 Stokes profiles whose polarization signals are above noise in the two spectral ranges, which correspond to 40% of the field of view. Most of these profiles can be reproduced only with a model atmosphere including 3 magnetic components with very different field strengths, which indicates the co-existence of kG and sub-kG fields in our 1.5" resolution elements. We measure an unsigned magnetic flux density of 9.6 G considering the full field of view. Half of the pixels present magnetic fields with mixed polarities in the resolution element. The fraction of mixed polarities increases as the polarization weakens. We compute the probability density function of finding each magnetic field strength. It has a significant contribution of kG field strengths, which concentrates most of the observed magnetic flux and energy. This kG contribution has a preferred magnetic polarity, while the polarity of the weak fields is balanced.Comment: 16 pages and 14 figure

Phase Separation in Ti-6Al-4V Alloys with Boron Additions for Biomedical Applications: Scanning Kelvin Probe Force Microscopy Investigation of Microgalvanic Couples and Corrosion Initiation

To investigate the effect of boron additions on the corrosion behavior of Ti-6Al-4V for potential use in biomedical implants and devices, cast samples of Ti-6Al-4V were alloyed with 0.01% to 1.09% boron by weight and subjected to hot isostatic pressing. Subsequent analysis via scanning Kelvin probe force microscopy and scanning electron microscopy/energy-dispersive spectroscopy revealed the presence of both alpha (α) and beta (β) phase titanium, enriched in aluminum and vanadium, respectively. At all concentrations, boron additions affected the grain structure and were dispersed throughout both phases, but above the solubility limit, needle-like TiB structures also formed. The TiB needles and β phase exhibited similar surface potentials, whereas that of the α phase was found to be significantly lower. Nevertheless, when subjected to high applied electrochemical potentials in saline solutions, corrosion initiation was observed exclusively within the more noble β phase

Epidemiology of and surveillance for postpartum infections.

We screened automated ambulatory medical records, hospital and emergency room claims, and pharmacy records of 2,826 health maintenance organization (HMO) members who gave birth over a 30-month period. Full-text ambulatory records were reviewed for the 30-day postpartum period to confirm infection status for a weighted sample of cases. The overall postpartum infection rate was 6.0%, with rates of 7.4% following cesarean section and 5.5% following vaginal delivery. Rehospitalization; cesarean delivery; antistaphylococcal antibiotics; diagnosis codes for mastitis, endometritis, and wound infection; and ambulatory blood or wound cultures were important predictors of infection. Use of automated information routinely collected by HMOs and insurers allows efficient identification of postpartum infections not detected by conventional surveillance

Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process

Physics Performance Report for PANDA Strong Interaction Studies with Antiprotons

To study fundamental questions of hadron and nuclear physics in interactions of antiprotons with nucleons and nuclei, the universal PANDA detector will be build. Gluonic excitations, the physics of strange and charm quarks and nucleon structure studies will be performed with unprecedented accuracy thereby allowing high-precision tests of the strong interaction. The proposed PANDA detector is a state-of-the-art internal target detector at the HESR at FAIR allowing the detection and identifcation of neutral and charged particles generated within the relevant angular and energy range. This report presents a summary of the physics accessible at PANDA and what performance can be expected

Technical Design Report for PANDA Electromagnetic Calorimeter (EMC)

This document presents the technical layout and the envisaged performance of the Electromagnetic Calorimeter (EMC) for the PANDA target spectrometer. The EMC has been designed to meet the physics goals of the PANDA experiment. The performance figures are based on extensive prototype tests and radiation hardness studies. The document shows that the EMC is ready for construction up to the front-end electronics interface

Technical Design Report for the PANDA Micro Vertex Detector

This document illustrates the technical layout and the expected performance of the Micro Vertex Detector (MVD) of the PANDA experiment. The MVD will detect charged particles as close as possible to the interaction zone. Design criteria and the optimisation process as well as the technical solutions chosen are discussed and the results of this process are subjected to extensive Monte Carlo physics studies. The route towards realisation of the detector is outlined

Hysteresis and Avalanches in the Random Anisotropy Ising Model

The behaviour of the Random Anisotropy Ising model at T=0 under local relaxation dynamics is studied. The model includes a dominant ferromagnetic interaction and assumes an infinite anisotropy at each site along local anisotropy axes which are randomly aligned. Two different random distributions of anisotropy axes have been studied. Both are characterized by a parameter that allows control of the degree of disorder in the system. By using numerical simulations we analyze the hysteresis loop properties and characterize the statistical distribution of avalanches occuring during the metastable evolution of the system driven by an external field. A disorder-induced critical point is found in which the hysteresis loop changes from displaying a typical ferromagnetic magnetization jump to a rather smooth loop exhibiting only tiny avalanches. The critical point is characterized by a set of critical exponents, which are consistent with the universal values proposed from the study of other simpler models.Comment: 40 pages, 21 figures, Accepted for publication in Phys. Rev.