WISP genes are members of the connective tissue growth factor family that are up-regulated in Wnt-1-transformed cells and aberrantly expressed in human colon tumors

Wnt family members are critical to many developmental processes, and components of the Wnt signaling pathway have been linked to tumorigenesis in familial and sporadic colon carcinomas. Here we report the identification of two genes, WISP-1 and WISP-2, that are up-regulated in the mouse mammary epithelial cell line C57MG transformed by Wnt-1, but not by Wnt-4. Together with a third related gene, WISP-3, these proteins define a subfamily of the connective tissue growth factor family. Two distinct systems demonstrated WISP induction to be associated with the expression of Wnt-1. These included (i) C57MG cells infected with a Wnt-1 retroviral vector or expressing Wnt-1 under the control of a tetracyline repressible promoter, and (ii) Wnt-1 transgenic mice. The WISP-1 gene was localized to human chromosome 8q24.1-8q24.3. WISP-1 genomic DNA was amplified in colon cancer cell lines and in human colon tumors and its RNA overexpressed (2- to >30-fold) in 84% of the tumors examined compared with patient-matched normal mucosa. WISP-3 mapped to chromosome 6q22-6q23 and also was overexpressed (4- to >40-fold) in 63% of the colon tumors analyzed. In contrast, WISP-2 mapped to human chromosome 20q12-20q13 and its DNA was amplified, but RNA expression was reduced (2- to >30-fold) in 79% of the tumors. These results suggest that the WISP genes may be downstream of Wnt-1 signaling and that aberrant levels of WISP expression in colon cancer may play a role in colon tumorigenesis

ISO Observations of the dusty quasar BR1202-0725

We present mid- and far-IR photometry of the high-redshift (z=4.69) dusty quasar BR1202-0725. The quasar was detected in the near-IR, at a flux level (0.7+/-0.2 mJy) consistent with an average Radio-Quiet Quasar at it's redshift. Only upper limits for the emission were obtained in the far-IR. These upper limits, when combined with data from ground-based telescopes, are the first direct evidence for a turn-over in the far-IR emission and hence confirm that a black-body dominates the SED at FIR wavelengths. This black-body is most probably cool dust, constrained to have a temperature below 80K, for a beta of 1.5.Comment: 5 pages, one colour figur

Physical model of near-Earth asteroid (1917) Cuyo from ground-based optical and thermal-IR observations

Context: The near-Earth asteroid (1917) Cuyo was subject to radar and lightcurve observations during a close approach in 1989, and observed up until 2008. It was selected as one of our ESO Large Programme targets, aimed at observational detections of the YORP effect through long-term lightcurve monitoring and physical modelling of near-Earth asteroids. Aims: We aimed to constrain physical properties of Cuyo: shape, spin-state, and spectroscopic & thermophysical properties of the surface. Methods: We acquired photometric lightcurves of Cuyo spanning the period between 2010 and 2013, which we combined with published lightcurves from 1989-2008. Our thermal-infrared observations were obtained in 2011. Rotationally-resolved optical spectroscopy data were acquired in 2011 and combined with all available published spectra to investigate any surface material variegation. Results: We developed a convex lightcurve-inversion shape of Cuyo that suggests the presence of an equatorial ridge, typical for an evolved system close to shedding mass due to fast rotation. We determine limits of YORP strength through lightcurve-based spin-state modelling, including both negative and positive acceleration values, between -0.7x10-8 rad day-2 and 1.7x10-8 rad day-2. Thermo-physical modelling with the ATPM provides constraints on the geometric albedo, PV = 0.24 ± 0.07, the effective diameter Deff = 3.15 ± 0.08 km, the thermal inertia, 44 ±- 9 J m-2s-1/2K-1, and a roughness fraction of 0.52 ± 0.26. This enabled a YORP strength prediction of (-6.39 ± 0.96)x10-10 rad day-2. We also see evidence of surface compositional variation. Conclusions: The low value of YORP predicted by means of thermophysical analysis, consistent with the results of the lightcurve study, might be due to the self-limiting properties of rotational YORP, possibly involving movement of sub-surface and surface material. This may also be consistent with the surface compositional variation that we see. The physical model of Cuyo can be used to investigate cohesive forces as a way to explain why some targets survive rotation rates faster than the fission limit

Effectiveness of a web-based intervention to prevent anxiety in the children of parents with anxiety:Protocol for a Randomized Controlled Trial

BACKGROUND: Anxiety is the most common childhood mental health condition and is associated with impaired child outcomes, including increased risk of mental health difficulties in adulthood. Anxiety runs in families: when a parent has anxiety, their child has a 50% higher chance of developing it themselves. Environmental factors are predominant in the intergenerational transmission of anxiety and, of these, parenting processes play a major role. Interventions that target parents to support them to limit the impact of any anxiogenic parenting behaviors are associated with reduced anxiety in their children. A brief UK-based group intervention delivered to parents within the UK National Health Service led to a 16% reduction in children meeting the criteria for an anxiety disorder. However, this intervention is not widely accessible. To widen access, a 9-module web-based version of this intervention has been developed. This course comprises psychoeducation and home practice delivered through text, video, animations, and practice tasks. OBJECTIVE: This study seeks to evaluate the feasibility of delivering this web-based intervention and assess its effectiveness in reducing child anxiety symptoms. METHODS:  This is the protocol for a randomized controlled trial (RCT) of a community sample of 1754 parents with self-identified high levels of anxiety with a child aged 2-11 years. Parents in the intervention arm will receive access to the web-based course, which they undertake at a self-determined rate. The control arm receives no intervention. Follow-up data collection is at months 6 and months 9-21. Intention-to-treat analysis will be conducted on outcomes including child anxiety, child mental health symptoms, and well-being; parental anxiety and well-being; and parenting behaviors. RESULTS: Funding was received in April 2020, and recruitment started in February 2021 and is projected to end in October 2022. A total of 1350 participants have been recruited as of May 2022. CONCLUSIONS: The results of this RCT will provide evidence on the utility of a web-based course in preventing intergenerational transmission of anxiety and increase the understanding of familial anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT04755933; https://clinicaltrials.gov/ct2/show/NCT04755933 INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/4070

Improved limits on the tensor-to-scalar ratio using BICEP and Planck data

We present constraints on the tensor-to-scalar ratio r using a combination of BICEP/Keck 2018 (BK18) and Planck PR4 data allowing us to fit for r consistently with the six parameters of the ? CDM model. We discuss the sensitivity of constraints on r to uncertainties in the ? CDM parameters as defined by the Planck data. In particular, we are able to derive a constraint on the reionization optical depth ? and thus propagate its uncertainty into the posterior distribution for r . While Planck sensitivity to r is slightly lower than the current ground-based measurements, the combination of Planck with BK18 and baryon-acoustic-oscillation data yields results consistent with r = 0 and tightens the constraint to r < 0.032 at 95% confidence.Planck is a project of the European Space Agency (ESA) with instruments provided by two scientific consortia funded by ESA member states and led by Principal Investigators from France and Italy, telescope reflectors provided through a collaboration between ESA and a scientific consortium led and funded by Denmark, and additional contributions from NASA (USA). We gratefully acknowledge support from the CNRS/IN2P3 Computing Center for providing computing and data-processing resources needed for this work. This research used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02- 05CH11231. Part of the research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (Grant No. 80NM0018D0004)

The Leptonic Higgs as a Messenger of Dark Matter

We propose that the leptonic cosmic ray signals seen by PAMELA and ATIC result from the annihilation or decay of dark matter particles via states of a leptonic Higgs doublet to $\tau$ leptons, linking cosmic ray signals of dark matter to LHC signals of the Higgs sector. The states of the leptonic Higgs doublet are lighter than about 200 GeV, yielding large $\bar{\tau} \tau$ and $\bar{\tau} \tau \bar{\tau} \tau$ event rates at the LHC. Simple models are given for the dark matter particle and its interactions with the leptonic Higgs, for cosmic ray signals arising from both annihilations and decays in the galactic halo. For the case of annihilations, cosmic photon and neutrino signals are on the verge of discovery.Comment: 34 pages, 9 figures, minor typos corrected, references adde

A High Statistics Search for Ultra-High Energy Gamma-Ray Emission from Cygnus X-3 and Hercules X-1

We have carried out a high statistics (2 Billion events) search for ultra-high energy gamma-ray emission from the X-ray binary sources Cygnus X-3 and Hercules X-1. Using data taken with the CASA-MIA detector over a five year period (1990-1995), we find no evidence for steady emission from either source at energies above 115 TeV. The derived upper limits on such emission are more than two orders of magnitude lower than earlier claimed detections. We also find no evidence for neutral particle or gamma-ray emission from either source on time scales of one day and 0.5 hr. For Cygnus X-3, there is no evidence for emission correlated with the 4.8 hr X-ray periodicity or with the occurrence of large radio flares. Unless one postulates that these sources were very active earlier and are now dormant, the limits presented here put into question the earlier results, and highlight the difficulties that possible future experiments will have in detecting gamma-ray signals at ultra-high energies.Comment: 26 LaTeX pages, 16 PostScript figures, uses psfig.sty to be published in Physical Review

High-throughput imaging assay for drug screening of 3D prostate cancer organoids

First Published June 11, 2021New treatments are required for advanced prostate cancer; however, there are fewer preclinical models of prostate cancer than other common tumor types to test candidate therapeutics. One opportunity to increase the scope of preclinical studies is to grow tissue from patient-derived xenografts (PDXs) as organoid cultures. Here we report a scalable pipeline for automated seeding, treatment and an analysis of the drug responses of prostate cancer organoids. We established organoid cultures from 5 PDXs with diverse phenotypes of prostate cancer, including castrate-sensitive and castrate-resistant disease, as well as adenocarcinoma and neuroendocrine pathology. We robotically embedded organoids in Matrigel in 384-well plates and monitored growth via brightfield microscopy before treatment with poly ADP-ribose polymerase inhibitors or a compound library. Independent readouts including metabolic activity and live-cell imaging-based features provided robust measures of organoid growth and complementary ways of assessing drug efficacy. Single organoid analyses enabled in-depth assessment of morphological differences between patients and within organoid populations and revealed that larger organoids had more striking changes in morphology and composition after drug treatment. By increasing the scale and scope of organoid experiments, this automated assay complements other patient-derived models and will expedite preclinical testing of new treatments for prostate cancer.Nicholas Choo, Susanne Ramm, Jennii Luu, Jean M. Winter, Luke A. Selth, Amy R. Dwyer … et al

Solar Influence on Nuclear Decay Rates: Constraints from the MESSENGER Mission

We have analyzed Cs-137 decay data, obtained from a small sample onboard the MESSENGER spacecraft en route to Mercury, with the aim of setting limits on a possible correlation between nuclear decay rates and solar activity. Such a correlation has been suggested recently on the basis of data from Mn-54 decay during the solar flare of 13 December 2006, and by indications of an annual and other periodic variations in the decay rates of Si-32, Cl-36, and Ra-226. Data from five measurements of the Cs-137 count rate over a period of approximately 5.4 years have been fit to a formula which accounts for the usual exponential decrease in count rate over time, along with the addition of a theoretical solar contribution varying with MESSENGER-Sun separation. The indication of solar influence is then characterized by a non-zero value of the calculated parameter \xi, and we find \xi=(2.8+/-8.1)x10^{-3} for Cs-137. A simulation of the increased data that can hypothetically be expected following Mercury orbit insertion on 18 March 2011 suggests that the anticipated improvement in the determination of \xi could reveal a non-zero value of \xi if present at a level consistent with other data.Comment: Accepted for publication in Astrophysics and Space Science, 2011. 7 pages, 5 figures. Version 2 has corrected Figure 1, since Fig. 1 did not appear correctly in Version