Optical dispersion relations for diamondlike carbon films

Ellipsometric measurements on plasma deposited diamondlike amorphous carbon (a-C:H) films were taken in the visible, (E = 1.75 to 3.5 eV). The films were deposited on Si and their properties were varied using high temperature (up to 750 C) anneals. The real (n) and imaginary (k) parts of the complex index of refraction, N, were obtained simultaneously. Following the theory of Forouhi and Bloomer, a least squares fit was used to find the dispersion relations n(E) and k(E). Reasonably good fits were obtained, showing that the theory can be used for a-C:H films. Moreover, the value of the energy gap, Eg, obtained in this way was compared the the Eg value using conventional Tauc plots and reasonably good agreement was obtained

Regulation of Classical Cadherin Membrane Expression and F-Actin Assembly by Alpha-Catenins, during Xenopus Embryogenesis

Alpha (α)-E-catenin is a component of the cadherin complex, and has long been thought to provide a link between cell surface cadherins and the actin skeleton. More recently, it has also been implicated in mechano-sensing, and in the control of tissue size. Here we use the early Xenopus embryos to explore functional differences between two α-catenin family members, α-E- and α-N-catenin, and their interactions with the different classical cadherins that appear as tissues of the embryo become segregated from each other. We show that they play both cadherin-specific and context-specific roles in the emerging tissues of the embryo. α-E-catenin interacts with both C- and E-cadherin. It is specifically required for junctional localization of C-cadherin, but not of E-cadherin or N-cadherin at the neurula stage. α-N-cadherin interacts only with, and is specifically required for junctional localization of, N-cadherin. In addition, α -E-catenin is essential for normal tissue size control in the non-neural ectoderm, but not in the neural ectoderm or the blastula. We also show context specificity in cadherin/ α-catenin interactions. E-cadherin requires α-E-catenin for junctional localization in some tissues, but not in others, during early development. These specific functional cadherin/alpha-catenin interactions may explain the basis of cadherin specificity of actin assembly and morphogenetic movements seen previously in the neural and non-neural ectoderm

A Whole-Genome SNP Association Study of NCI60 Cell Line Panel Indicates a Role of Ca2+ Signaling in Selenium Resistance

Epidemiological studies have suggested an association between selenium intake and protection from a variety of cancer. Considering this clinical importance of selenium, we aimed to identify the genes associated with resistance to selenium treatment. We have applied a previous methodology developed by our group, which is based on the genetic and pharmacological data publicly available for the NCI60 cancer cell line panel. In short, we have categorized the NCI60 cell lines as selenium resistant and sensitive based on their growth inhibition (GI50) data. Then, we have utilized the Affymetrix 125K SNP chip data available and carried out a genome-wide case-control association study for the selenium sensitive and resistant NCI60 cell lines. Our results showed statistically significant association of four SNPs in 5q33–34, 10q11.2, 10q22.3 and 14q13.1 with selenium resistance. These SNPs were located in introns of the genes encoding for a kinase-scaffolding protein (AKAP6), a membrane protein (SGCD), a channel protein (KCNMA1), and a protein kinase (PRKG1). The knock-down of KCNMA1 by siRNA showed increased sensitivity to selenium in both LNCaP and PC3 cell lines. Furthermore, SNP-SNP interaction (epistasis) analysis indicated the interactions of the SNPs in AKAP6 with SGCD as well as SNPs in AKAP6 with KCNMA1 with each other, assuming additive genetic model. These genes were also all involved in the Ca2+ signaling, which has a direct role in induction of apoptosis and induction of apoptosis in tumor cells is consistent with the chemopreventive action of selenium. Once our findings are further validated, this knowledge can be translated into clinics where individuals who can benefit from the chemopreventive characteristics of the selenium supplementation will be easily identified using a simple DNA analysis

A Flow Cytometry-Based FRET Assay to Identify and Analyse Protein-Protein Interactions in Living Cells

Försters resonance energy transfer (FRET) microscopy is widely used for the analysis of protein interactions in intact cells. However, FRET microscopy is technically challenging and does not allow assessing interactions in large cell numbers. To overcome these limitations we developed a flow cytometry-based FRET assay and analysed interactions of human and simian immunodeficiency virus (HIV and SIV) Nef and Vpu proteins with cellular factors, as well as HIV Rev multimer-formation.Amongst others, we characterize the interaction of Vpu with CD317 (also termed Bst-2 or tetherin), a host restriction factor that inhibits HIV release from infected cells and demonstrate that the direct binding of both is mediated by the Vpu membrane-spanning region. Furthermore, we adapted our assay to allow the identification of novel protein interaction partners in a high-throughput format.The presented combination of FRET and FACS offers the precious possibility to discover and define protein interactions in living cells and is expected to contribute to the identification of novel therapeutic targets for treatment of human diseases

Structure of a double ubiquitin-like domain in the talin head: a role in integrin activation

Talin is a 270-kDa protein that activates integrins and couples them to cytoskeletal actin. Talin contains an N-terminal FERM domain comprised of F1, F2 and F3 domains, but it is atypical in that F1 contains a large insert and is preceded by an extra domain F0. Although F3 contains the binding site for β-integrin tails, F0 and F1 are also required for activation of β1-integrins. Here, we report the solution structures of F0, F1 and of the F0F1 double domain. Both F0 and F1 have ubiquitin-like folds joined in a novel fixed orientation by an extensive charged interface. The F1 insert forms a loop with helical propensity, and basic residues predicted to reside on one surface of the helix are required for binding to acidic phospholipids and for talin-mediated activation of β1-integrins. This and the fact that basic residues on F2 and F3 are also essential for integrin activation suggest that extensive interactions between the talin FERM domain and acidic membrane phospholipids are required to orientate the FERM domain such that it can activate integrins

Diazoxide choline extended‐release tablet in people with Prader‐Willi syndrome: results from long‐term open‐label study

Objective: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS). Methods: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Other endpoints included behavioral assessments, body composition, hormonal measures, and safety. Results: DCCR administration resulted in significant improvements in HQ-CT (mean [SE] −9.9 [0.77], p < 0.0001) and greater improvements in those with more severe baseline hyperphagia (HQ-CT > 22). Improvements were seen in aggression, anxiety, and compulsivity (all p < 0.0001). There were reductions in leptin, insulin, and insulin resistance, as well as a significant increase in adiponectin (all p < 0.004). Lean body mass was increased (p < 0.0001). Disease severity was reduced as assessed by clinician and caregiver (both p < 0.0001). Common treatment-emergent adverse events included hypertrichosis, peripheral edema, and hyperglycemia. Adverse events infrequently resulted in discontinuation (7.2%). Conclusions: DCCR administration to people with PWS was well tolerated and associated with broad-ranging improvements in the syndrome. Sustained administration of DCCR has the potential to reduce disease severity and the burden of care for families

Erratum: “Searches for Gravitational Waves from Known Pulsars at Two Harmonics in 2015–2017 LIGO Data” (2019, ApJ, 879, 10)

Due to an error at the publisher, in the published article the number of pulsars presented in the paper is incorrect in multiple places throughout the text. Specifically, "222" pulsars should be "221." Additionally, the number of pulsars for which we have EM observations that fully overlap with O1 and O2 changes from "168" to "167." Elsewhere, in the machine-readable table of Table 1 and in Table 2, the row corresponding to pulsar J0952-0607 should be excised as well. Finally, in the caption for Table 2 the number of pulsars changes from "188" to "187.

Searches for gravitational waves from known pulsars at two harmonics in 2015-2017 LIGO data

International audienceWe present a search for gravitational waves from 222 pulsars with rotation frequencies ≳10 Hz. We use advanced LIGO data from its first and second observing runs spanning 2015–2017, which provides the highest-sensitivity gravitational-wave data so far obtained. In this search we target emission from both the l = m = 2 mass quadrupole mode, with a frequency at twice that of the pulsar’s rotation, and the l = 2, m = 1 mode, with a frequency at the pulsar rotation frequency. The search finds no evidence for gravitational-wave emission from any pulsar at either frequency. For the l = m = 2 mode search, we provide updated upper limits on the gravitational-wave amplitude, mass quadrupole moment, and fiducial ellipticity for 167 pulsars, and the first such limits for a further 55. For 20 young pulsars these results give limits that are below those inferred from the pulsars’ spin-down. For the Crab and Vela pulsars our results constrain gravitational-wave emission to account for less than 0.017% and 0.18% of the spin-down luminosity, respectively. For the recycled millisecond pulsar J0711−6830 our limits are only a factor of 1.3 above the spin-down limit, assuming the canonical value of 1038 kg m2 for the star’s moment of inertia, and imply a gravitational-wave-derived upper limit on the star’s ellipticity of 1.2 × 10−8. We also place new limits on the emission amplitude at the rotation frequency of the pulsars

GW190412: Observation of a Binary-Black-Hole Coalescence with Asymmetric Masses

We report the observation of gravitational waves from a binary-black-hole coalescence during the first two weeks of LIGO’s and Virgo’s third observing run. The signal was recorded on April 12, 2019 at 05∶30∶44 UTC with a network signal-to-noise ratio of 19. The binary is different from observations during the first two observing runs most notably due to its asymmetric masses: a ∼30 M_⊙ black hole merged with a ∼8 M_⊙ black hole companion. The more massive black hole rotated with a dimensionless spin magnitude between 0.22 and 0.60 (90% probability). Asymmetric systems are predicted to emit gravitational waves with stronger contributions from higher multipoles, and indeed we find strong evidence for gravitational radiation beyond the leading quadrupolar order in the observed signal. A suite of tests performed on GW190412 indicates consistency with Einstein’s general theory of relativity. While the mass ratio of this system differs from all previous detections, we show that it is consistent with the population model of stellar binary black holes inferred from the first two observing runs

Open Data from the Third Observing Run of LIGO, Virgo, KAGRA, and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages