Sub-Hz line width diode lasers by stabilization to vibrationally and thermally compensated ULE Fabry-Perot cavities

We achieved a 0.5 Hz optical beat note line width with ~ 0.1 Hz/s frequency drift at 972 nm between two external cavity diode lasers independently stabilized to two vertically mounted Fabry-Perot (FP) reference cavities. Vertical FP reference cavities are suspended in mid-plane such that the influence of vertical vibrations to the mirror separation is significantly suppressed. This makes the setup virtually immune for vertical vibrations that are more difficult to isolate than the horizontal vibrations. To compensate for thermal drifts the FP spacers are made from Ultra-Low-Expansion (ULE) glass which possesses a zero linear expansion coefficient. A new design using Peltier elements in vacuum allows operation at an optimal temperature where the quadratic temperature expansion of the ULE could be eliminated as well. The measured linear drift of such ULE FP cavity of 63 mHz/s was due to material aging and the residual frequency fluctuations were less than 40 Hz during 16 hours of measurement. Some part of the temperature-caused drift is attributed to the thermal expansion of the mirror coatings. High-frequency thermal fluctuations that cause vibrations of the mirror surfaces limit the stability of a well designed reference cavity. By comparing two similar laser systems we obtain an Allan instability of 2*10-15 between 0.1 and 10 s averaging time, which is close to the theoretical thermal noise limit.Comment: submitted to Applied Physics

Impurity-assisted Andreev reflection at a spin-active half-metal-superconductor interface

The Andreev reflection amplitude at a clean interface between a half-metallic ferromagnet (H) and a superconductor (S) for which the half metal's magnetization has a gradient perpendicular to the interface is proportional to the excitation energy $\varepsilon$ and vanishes at $\varepsilon=0$ [B\'{e}ri {\em et al.}, Phys.\ Rev.\ B {\bf 79}, 024517 (2009)]. Here we show that the presence of impurities at or in the immediate vicinity of the HS interface leads to a finite Andreev reflection amplitude at $\varepsilon=0$. This impurity-assisted Andreev reflection dominates the low-bias conductance of a HS junction and the Josephson current of an SHS junction in the long-junction limit.Comment: 12 pages, 2 figure

Trastuzumab Sensitizes Ovarian Cancer Cells to EGFR-targeted Therapeutics

<p>Abstract</p> <p>Background</p> <p>Early studies have demonstrated comparable levels of HER2/ErbB2 expression in both breast and ovarian cancer. Trastuzumab (Herceptin), a therapeutic monoclonal antibody directed against HER2, is FDA-approved for the treatment of both early and late stage breast cancer. However, clinical studies of trastuzumab in epithelial ovarian cancer (EOC) patients have not met the same level of success. Surprisingly, however, no reports have examined either the basis for primary trastuzumab resistance in ovarian cancer or potential ways of salvaging trastuzumab as a potential ovarian cancer therapeutic.</p> <p>Methods</p> <p>An in vitro model of primary trastuzumab-resistant ovarian cancer was created by long-term culture of HER2-positive ovarian carcinoma-derived cell lines with trastuzumab. Trastuzumab treated vs. untreated parental cells were compared for HER receptor expression, trastuzumab sensitivity, and sensitivity to other HER-targeted therapeutics.</p> <p>Results</p> <p>In contrast to widely held assumptions, here we show that ovarian cancer cells that are not growth inhibited by trastuzumab are still responsive to trastuzumab. Specifically, we show that responsiveness to alternative HER-targeted inhibitors, such as gefitinib and cetuximab, is dramatically potentiated by long-term trastuzumab treatment of ovarian cancer cells. HER2-positive ovarian carcinoma-derived cells are, therefore, not "unresponsive" to trastuzumab as previously assumed, even when they not growth inhibited by this drug.</p> <p>Conclusions</p> <p>Given the recent success of EGFR-targeted therapeutics for the treatment of other solid tumors, and the well-established safety profile of trastuzumab, results presented here provide a rationale for re-evaluation of trastuzumab as an experimental ovarian cancer therapeutic, either in concert with, or perhaps as a "primer" for EGFR-targeted therapeutics.</p

Role of disulphide bond formation in folding, secretion, and assembly of human chorionic gonadotropin subunits.

Ability of a glycoprotein hormone to fold and assemble correctly is an essential requirement for the attainment of its biological activity . Cells have a quality control system to assure that when proteins of the endoplasmic reticulum mi sfold or fail to assemble correctly they do not exit the cell. But human chorionic gonadotropin (hCG) is an exception to this rule as is illustrated by the following observations. First, both hCG subunits are secreted efficiently as unassembled monomers. Second, some mis(un)folded forms of hCG-β can be efficiently secreted from cells that do not facilitate the secretion of other misfolded proteins. Third, the efficient secretion of an assembly incompetent α-subunit occurs in spite of lacking both of its non-cystine knot disulphide bonds. And fourth, hCG heterodimers that contain misfolded α-subunits as a result of lack ing cystine knot disulphides are also secreted. In this report, we review direct ex perimental evidence demonstrating that the structural requirements necessary for the secretion of hCG subunits differ from the structural requirements necessary for hCG assembly by using disulphide bond formation as an index with which to monitor the folding, assembly, and secretion of hCG and its α - and β-subunits

Colorado Native Plant Society Newsletter, Vol. 4 No. 6, November-December 1980

https://epublications.regis.edu/aquilegia/1155/thumbnail.jp

Dietary supplementation with Bifidobacterium longum subsp. infantis (B. infantis) in healthy breastfed infants: study protocol for a randomised controlled trial.

BackgroundThe development of probiotics as therapies to cure or prevent disease lags far behind that of other investigational medications. Rigorously designed phase I clinical trials are nearly non-existent in the field of probiotic research, which is a contributing factor to this disparity. As a consequence, how to appropriately dose probiotics to study their efficacy is unknown. Herein we propose a novel phase I ascending dose trial of Bifidobacterium longum subsp. infantis (B. infantis) to identify the dose required to produce predominant gut colonisation in healthy breastfed infants at 6&nbsp;weeks of age.Methods/designThis is a parallel-group, placebo-controlled, randomised, double-blind ascending dose phase I clinical trial of dietary supplementation with B. infantis in healthy breastfed infants. The objective is to determine the pharmacologically effective dose (ED) of B. infantis required to produce predominant (&gt;50&nbsp;%) gut colonisation in breastfed infants at 6&nbsp;weeks of age. Successively enrolled infant groups will be randomised to receive two doses of either B. infantis or placebo on days 7 and 14 of life. Stool samples will be used to characterise the gut microbiota at increasing doses of B. infantis.DiscussionProbiotic supplementation has shown promising results for the treatment of a variety of ailments, but evidence-based dosing regimes are currently lacking. The ultimate goal of this trial is to establish a recommended starting dose of B. infantis for further efficacy-testing phase II trials designed to evaluate B. infantis for the prevention of atopic dermatitis and food allergies in at-risk children.Trial registrationClinicaltrials.gov # NCT02286999 , date of trial registration 23 October 2014

Observation and modeling of energetic particles at synchronous orbit on July 29, 1977

In the twelve hours following a worldwide storm, there was a series of at least four magnetospheric substorms, the last and largest of which exhibited an expansion phase onset at approximately 1200 UT. Data from six spacecraft in three general local time groupings (0300, 0700, and 1300 LT) were examined and vector magnetic field data and energetic electron and ion data from approximately 15 keV to 2 MeV were employed

A Frequency Comb calibrated Solar Atlas

The solar spectrum is a primary reference for the study of physical processes in stars and their variation during activity cycles. In Nov 2010 an experiment with a prototype of a Laser Frequency Comb (LFC) calibration system was performed with the HARPS spectrograph of the 3.6m ESO telescope at La Silla during which high signal-to-noise spectra of the Moon were obtained. We exploit those Echelle spectra to study the optical integrated solar spectrum . The DAOSPEC program is used to measure solar line positions through gaussian fitting in an automatic way. We first apply the LFC solar spectrum to characterize the CCDs of the HARPS spectrograph. The comparison of the LFC and Th-Ar calibrated spectra reveals S-type distortions on each order along the whole spectral range with an amplitude of +/-40 m/s. This confirms the pattern found by Wilken et al. (2010) on a single order and extends the detection of the distortions to the whole analyzed region revealing that the precise shape varies with wavelength. A new data reduction is implemented to deal with CCD pixel inequalities to obtain a wavelength corrected solar spectrum. By using this spectrum we provide a new LFC calibrated solar atlas with 400 line positions in the range of 476-530, and 175 lines in the 534-585 nm range. The new LFC atlas improves the accuracy of individual lines by a significant factor reaching a mean value of about 10 m/s. The LFC--based solar line wavelengths are essentially free of major instrumental effects and provide a reference for absolute solar line positions. We suggest that future LFC observations could be used to trace small radial velocity changes of the whole solar photospheric spectrum in connection with the solar cycle and for direct comparison with the predicted line positions of 3D radiative hydrodynamical models of the solar photosphere.Comment: Accept on the 15th of October 2013. 9 pages, 10 figures. ON-lINE data A&A 201