Label-free versus conventional cellular assays: Functional investigations on the human histamine H1 receptor.

A set of histamine H1 receptor (H1R) agonists and antagonists was characterized in functional assays, using dynamic mass redistribution (DMR), electric cell-substrate impedance sensing (ECIS) and various signaling pathway specific readouts (Fura-2 and aequorin calcium assays, arrestin recruitment (luciferase fragment complementation) assay, luciferase gene reporter assay). Data were gained from genetically engineered HEK293T cells and compared with reference data from GTPase assays and radioligand binding. Histamine and the other H1R agonists gave different assay-related pEC50 values, however, the order of potency was maintained. In the luciferase fragment complementation assay, the H1R preferred ß-arrestin2 over ß-arrestin1. The calcium and the impedimetric assay depended on Gq coupling of the H1R, as demonstrated by complete inhibition of the histamine-induced signals in the presence of the Gq inhibitor FR900359 (UBO-QIC). Whereas partial inhibition by FR900359 was observed in DMR and the gene reporter assay, pertussis toxin substantially decreased the response in DMR, but increased the luciferase signal, reflecting the contribution of both, Gq and Gi, to signaling in these assays. For antagonists, the results from DMR were essentially compatible with those from conventional readouts, whereas the impedance-based data revealed a trend towards higher pKb values. ECIS and calcium assays apparently only reflect Gq signaling, whereas DMR and gene reporter assays appear to integrate both, Gq and Gi mediated signaling. The results confirm the value of the label-free methods, DMR and ECIS, for the characterization of H1R ligands. Both noninvasive techniques are complementary to each other, but cannot fully replace reductionist signaling pathway focused assays.

[Evaluation of the Activities of Community Pharmacies during the Annual Campaign with Focus on Diabetes Prevention]. / Evaluation der Aktivitäten öffentlicher Apotheken im Rahmen der Jahresschwerpunktkampagne "Diabetes bewegt uns!".

With its increasing incidence, diabetes is one of the major challenges of the 21th century. Against this background, the Bavarian State Ministry of Public Health and Care Services (BStMGP) started in 2014 the campaign "Diabetes moves us!". The scientific institute for prevention in health care (WIPIG) supported the activities of Bavarian pharmacies and evaluated the extent to which they might be able to contribute towards prevention. Besides additional training of pharmaceutical staff, WIPIG initiated a diabetes prevention network. Pharmacies that were members of the network had the opportunity to order a campaign package including an evaluation questionnaire and to register their activity in the calendar of events of the campaign. A total of 215 pharmacies signed up for the diabetes prevention network and registered 103 events. The WIPIG received 67 completed evaluation questionnaires. Most often (86.6%) the pharmacies conducted a blood glucose screening; 76.1% carried out screening with the diabetes risk questionnaire FINDRISC of the German Diabetes Foundation and 22.4% gave a information lecture on diabetes. During the screening 2,502 persons had their blood sugar checked and 1,765 persons filled in the FINDRISC questionnaire. Overall, 190 persons were advised to visit their physician because of a very high blood glucose level. On the basis of the FINDRISC, 80.2% were advised to change their lifestyle to prevent type 2 diabetes.

Retrospective growth analysis of Atlantic salmon Salmo salar and implications for abundance trends.

Scale archives of Atlantic salmon Salmo salar from Maine, U.S.A., were examined to determine whether ocean conditions affected the long-term trends in S. salar populations in the southern tier of the species' range in North America. To date, scale analyses of southern tier populations have been limited to hatchery fish; previous studies suggest that post-smolt growth does not influence recruitment, with the exception that winter growth may play a role in stock maturation rate. A time series of scales from the Machias and Narraguagus Rivers spanning the years 1946 to 1999 was analysed. Image analysis was used to measure intercirculi spacing, which provided proxy variables of growth rate. Post-smolt growth increment has increased since the early 1990s, as returns have decreased, suggesting that survival factors act on post-smolts independent of growth. The data support the hypothesis of a decoupling between freshwater size and early marine growth. Growth during the second sea winter was independent of post-smolt growth, suggesting that individuals are capable of significant compensatory growth. Southern tier North American stocks exhibit a similar pattern of independence between growth and survival as observed for northern tier North American stocks. These data support the inference that the recruitment of the North American and European subspecies is governed by fundamentally different mechanisms.

Quantized dispersion of two-dimensional magnetoplasmons detected by photoconductivity spectroscopy.

We find that the long-wavelength magnetoplasmon, resistively detected by photoconductivity spectroscopy in high-mobility two-dimensional electron systems, deviates from its well-known semiclassical nature as uncovered in conventional absorption experiments. A clear filling-factor dependent plateau-type dispersion is observed that reveals a so far unknown relation between the magnetoplasmon and the quantum Hall effect.

Fröhlich mass in GaAs-based structures.

The Fröhlich interaction is one of the main electron-phonon intrinsic interactions in polar materials originating from the coupling of one itinerant electron with the macroscopic electric field generated by any longitudinal optical (LO) phonon. Infrared magnetoabsorption measurements of doped GaAs quantum well structures have been carried out in order to test the concept of Fröhlich interaction and polaron mass in such systems. These new experimental results lead one to question the validity of this concept in a real system.

Magneto infrared absorption in high electron density GaAs quantum wells.

Magneto infrared absorption measurements have been performed in a highly doped GaAs quantum well which has been lifted off and bonded to a silicon substrate, in order to study the resonant polaron interaction. It is found that the pinning of the cyclotron energy occurs at an energy close to that of the transverse optical phonon of GaAs. This unexpected result is explained by a model taking into account the full dielectric constant of the quantum well.

Images of the phonon propagation across twist-bonded crystals.

We investigate identical but twist-bonded crystals using phonon imaging techniques. As in homogeneous crystals, very anisotropic flux patterns are observed. However, the shape of the pattern depends dramatically on the respective twist angle. The observed phonon images in wafer bonded GaAs/GaAs and Si/Si samples are essentially consistent with the predictions of the acoustic mismatch model for defect-free interfaces, with the exception of GaAs wafers twist bonded at a 45 degrees angle where modes with large shear stress are missing, which indicates strong dislocation scattering.

Self-starting mode locking of a Nd:glass fiber laser by use of the third-order nonlinearity of low-temperature-grown GaAs.

We present a diode-pumped Nd:glass fiber laser, emitting at 1060 nm, that is passively mode locked by fast nonlinear loss in low-temperature-grown GaAs (LT-GaAs). This new mode-locking mechanism is based on intensity-dependent defocusing in LT-GaAs that occurs after nonresonant generation of free carriers by two-photon absorption. Mode locking is self-starting and produces pulses as short as 4.1 ps.

Clinical indicators to assess the quality of social work services in nursing homes.

Nursing home social work service providers (n = 209) evaluated a proposed set of clinical indicators developed by an NASW Work Group to use in measuring social work performance in that setting. Practitioners rated all of the indicators highly for clarity, relevance, and meaningfulness to service provision. Problems with feasibility of use were identified for two of the indicators. Perceived difficulties in implementation are identified and addressed. A rationale is presented for the utility for nursing home practice of a uniform, professionally validated set of performance indicators as a component of quality improvement efforts.