Polarization-based Tests of Gravity with the Stochastic Gravitational-Wave Background

The direct observation of gravitational waves with Advanced LIGO and Advanced Virgo offers novel opportunities to test general relativity in strong-field, highly dynamical regimes. One such opportunity is the measurement of gravitational-wave polarizations. While general relativity predicts only two tensor gravitational-wave polarizations, general metric theories of gravity allow for up to four additional vector and scalar modes. The detection of these alternative polarizations would represent a clear violation of general relativity. The LIGO-Virgo detection of the binary black hole merger GW170814 has recently offered the first direct constraints on the polarization of gravitational waves. The current generation of ground-based detectors, however, is limited in its ability to sensitively determine the polarization content of transient gravitational-wave signals. Observation of the stochastic gravitational-wave background, in contrast, offers a means of directly measuring generic gravitational-wave polarizations. The stochastic background, arising from the superposition of many individually unresolvable gravitational-wave signals, may be detectable by Advanced LIGO at design-sensitivity. In this paper, we present a Bayesian method with which to detect and characterize the polarization of the stochastic background. We explore prospects for estimating parameters of the background, and quantify the limits that Advanced LIGO can place on vector and scalar polarizations in the absence of a detection. Finally, we investigate how the introduction of new terrestrial detectors like Advanced Virgo aid in our ability to detect or constrain alternative polarizations in the stochastic background. We find that, although the addition of Advanced Virgo does not notably improve detection prospects, it may dramatically improve our ability to estimate the parameters of backgrounds of mixed polarization.Comment: 24 pages, 20 figures; Accepted by PRX. This version includes major changes in response to referee comments and corrects an error in Eq. E

Identification of the dynamics of biofouled underwater gliders

Marine growth has been observed to cause a drop in the horizontal and vertical velocities of underwater gliders, thus making them unresponsive and needing immediate recovery. Currently, no strategies exist to correctly identify the onset of marine growth for gliders and only limited datasets of biofouled hulls exist. Here, a field test has been run to investigate the impact of marine growth on the dynamics of underwater gliders. A Slocum glider was deployed first for eight days with drag stimulators to simulate severe biofouling; then the vehicle was redeployed with no additions to the hull for a further 20 days. The biofouling caused a speed reduction due to a significant increase in drag. Additionally, the lower speed causes the steadystate flight stage to last longer and thus a shortening of mission duration. As actual biofouling due to p. pollicipes happened during the deployment, it was possible to develop and test a system that successfully detects and identifies high levels of marine growth on the glider using steady-state flight data. The system will greatly help pilots re-plan missions to safely recover the vehicle if significant biofouling is detected

Climate Action In Megacities 3.0

"Climate Action in Megacities 3.0" (CAM 3.0) presents major new insights into the current status, latest trends and future potential for climate action at the city level. Documenting the volume of action being taken by cities, CAM 3.0 marks a new chapter in the C40-Arup research partnership, supported by the City Leadership Initiative at University College London. It provides compelling evidence about cities' commitment to tackling climate change and their critical role in the fight to achieve global emissions reductions

Prevalence of methicillin-resistant Staphylococcus aureus nasal carriage among hospitalised patients with tuberculosis in rural KwaZulu-Natal

Background. There is little information regarding the presence and characteristics of methicillin-resistant Staphylococcus aureus (MRSA), an important nosocomial pathogen, in rural African hospitals. Objectives. To determine the prevalence of MRSA colonisation in patients admitted to a rural hospital with tuberculosis (TB) in an endemic HIV area and to describe transmission dynamics and resistance patterns among MRSA isolates. Methods. A prospective prevalence survey in the adult TB wards of the Church of Scotland Hospital, a provincial government district hospital in Tugela Ferry, KwaZulu-Natal. Patients were eligible if over the age of 15 and admitted to the TB wards between 15 November and 15 December 2008. Nasal swabs were cultured within 24 hours of admission and repeated at hospital-day 14 or upon discharge. Susceptibility testing was performed with standard disk diffusion. Demographic and clinical information was extracted from medical charts. Results. Of 52 patients with an admission nasal swab, 11 (21%) were positive for MRSA. An additional 4 (10%) of patients with negative admission swabs were positive for MRSA on repeat testing. MRSA carriage on admission was more common among patients with previous hospitalisation, among HIV-infected patients was significantly assciated with lower CD4 counts (p=0.03). All MRSA isolates were resistant to cotrimoxazole, and 74% were resistant to ≥5 classes of antibiotics; all retained susceptibility to vancomycin. Conclusions. A high prevalence of multidrug-resistant MRSA nasal carriage was found. Studies are needed to validate nosocomial acquisition and to evaluate the impact of MRSA on morbidity and mortality among TB patients in similar settings

UBVRIz Light Curves of 51 Type II Supernovae

We present a compilation of UBV RIz light curves of 51 type II supernovae discovered during the course of four different surveys during 1986 to 2003: the Cerro Tololo Supernova Survey, the Calan/Tololo Supernova Program (C&T), the Supernova Optical and Infrared Survey (SOIRS), and the Carnegie Type II Supernova Survey (CATS). The photometry is based on template-subtracted images to eliminate any potential host galaxy light contamination, and calibrated from foreground stars. This work presents these photometric data, studies the color evolution using different bands, and explores the relation between the magnitude at maximum brightness and the brightness decline parameter (s) from maximum light through the end of the recombination phase. This parameter is found to be shallower for redder bands and appears to have the best correlation in the B band. In addition, it also correlates with the plateau duration, being thus shorter (longer) for larger (smaller) s values.Comment: 110 pages, 9 Figures, 6 Tables, accepted in A

Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers.

Clinical and neuropathological characteristics associated with G4C2 repeat expansions in chromosome 9 open reading frame 72 (C9ORF72), the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, are highly variable. To gain insight on the molecular basis for the heterogeneity among C9ORF72 mutation carriers, we evaluated associations between features of disease and levels of two abundantly expressed "c9RAN proteins" produced by repeat-associated non-ATG (RAN) translation of the expanded repeat. For these studies, we took a departure from traditional immunohistochemical approaches and instead employed immunoassays to quantitatively measure poly(GP) and poly(GA) levels in cerebellum, frontal cortex, motor cortex, and/or hippocampus from 55 C9ORF72 mutation carriers [12 patients with ALS, 24 with frontotemporal lobar degeneration (FTLD) and 19 with FTLD with motor neuron disease (FTLD-MND)]. We additionally investigated associations between levels of poly(GP) or poly(GA) and cognitive impairment in 15 C9ORF72 ALS patients for whom neuropsychological data were available. Among the neuroanatomical regions investigated, poly(GP) levels were highest in the cerebellum. In this same region, associations between poly(GP) and both neuropathological and clinical features were detected. Specifically, cerebellar poly(GP) levels were significantly lower in patients with ALS compared to patients with FTLD or FTLD-MND. Furthermore, cerebellar poly(GP) associated with cognitive score in our cohort of 15 patients. In the cerebellum, poly(GA) levels similarly trended lower in the ALS subgroup compared to FTLD or FTLD-MND subgroups, but no association between cerebellar poly(GA) and cognitive score was detected. Both cerebellar poly(GP) and poly(GA) associated with C9ORF72 variant 3 mRNA expression, but not variant 1 expression, repeat size, disease onset, or survival after onset. Overall, these data indicate that cerebellar abnormalities, as evidenced by poly(GP) accumulation, associate with neuropathological and clinical phenotypes, in particular cognitive impairment, of C9ORF72 mutation carriers

HER2 cancer vaccine optimization by combining Drosophila S2 insect cell manufacturing with a novel VLP-display technology

Breast cancer is a widespread oncology indication affecting more than 1.3 million people worldwide annually, 20%-30% of which are HER2 positive. HER2 is a tyrosine kinase receptor that is frequently overexpressed in several solid-tumor cancers (incl. breast, prostate, gastric, esophageal and osteosarcoma) where it denotes an aggressive phenotype, high metastatic rate, and poor prognosis. In a human context, passive HER2-targeted immunotherapy using monoclonal antibodies (mAb, e.g. Trastuzumab and Pertuzumab) has proven to be an effective treatment modality, which has dramatically improved clinical outcomes. Unfortunately, mAb therapy is very expensive and the repeated injections of high doses can be associated with severe side-effects that reduce efficacy. Vaccines are highly cost-effective, but overall progress in development of anti-cancer vaccines based on cancer-associated antigens (e.g. HER2) has been hampered by inherent immune-tolerogenic mechanisms rendering the immune system incapable of reacting against the body’s own cells/proteins (i.e. self-antigens). Consequently, many attempts to develop anti-cancer vaccines have failed in clinical trials due to insufficient immunogenicity. To circumvent this central issue, we have developed a proprietary virus-like particle (VLP)-based vaccine delivery platform. Notably, the VLP-platform is currently the only available technology to effectively facilitate multivalent “virus-like” display of large/complex vaccine antigens. This is key to overcome immune-tolerance and enable induction of therapeutically potent antibody responses directed against cancer-associated self-antigens. In this talk I will discuss the non-viral Drosophila S2 insect cell production system and how it was applied to the production of hHer2/neu antigen, including using advanced production methods such as perfusion for clinical material manufacture. Furthermore, I will present our data from a transgenic mouse model for spontaneous breast cancer development, where high-density display of the HER2 extracellular domain on the surface of virus-like particles (VLPs) enables induction of therapeutically potent anti-HER2 responses. Split-protein tag/catcher conjugation was used to facilitate directional covalent attachment of HER2 to the surface of icosahedral bacteriophage-derived VLPs, thereby harnessing the VLP platform to effectively overcome B-cell tolerance. Vaccine efficacy was demonstrated both in prevention and therapy of mammary carcinomas in HER2 transgenic mice. Thus, the HER2-VLP vaccine shows promise as a new strategy for treatment of HER2-positive cancer. The modular VLP system may also represent an effective tool for development of self-antigen based vaccines against other non-communicable diseases

Integrated Model of Chemical Perturbations of a Biological Pathway Using 18 In Vitro High Throughput Screening Assays for the Estrogen Receptor

We demonstrate a computational network model that integrates 18 in vitro, high-throughput screening assays measuring estrogen receptor (ER) binding, dimerization, chromatin binding, transcriptional activation and ER-dependent cell proliferation. The network model uses activity patterns across the in vitro assays to predict whether a chemical is an ER agonist or antagonist, or is otherwise influencing the assays through a manner dependent on the physics and chemistry of the technology platform (“assay interference”). The method is applied to a library of 1812 commercial and environmental chemicals, including 45 ER positive and negative reference chemicals. Among the reference chemicals, the network model correctly identified the agonists and antagonists with the exception of very weak compounds whose activity was outside the concentration range tested. The model agonist score also correlated with the expected potency class of the active reference chemicals. Of the 1812 chemicals evaluated, 111 (6.1%) were predicted to be strongly ER active in agonist or antagonist mode. This dataset and model were also used to begin a systematic investigation of assay interference. The most prominent cause of false-positive activity (activity in an assay that is likely not due to interaction of the chemical with ER) is cytotoxicity. The model provides the ability to prioritize a large set of important environmental chemicals with human exposure potential for additional in vivo endocrine testing. Finally, this model is generalizable to any molecular pathway for which there are multiple upstream and downstream assays available

Inappropriate p53 Activation During Development Induces Features of CHARGE Syndrome

CHARGE syndrome is a multiple anomaly disorder in which patients present with a variety of phenotypes, including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genitourinary hypoplasia and ear abnormalities. Despite 70-90% of CHARGE syndrome cases resulting from mutations in the gene CHD7, which encodes an ATP-dependent chromatin remodeller, the pathways underlying the diverse phenotypes remain poorly understood. Surprisingly, our studies of a knock-in mutant mouse strain that expresses a stabilized and transcriptionally dead variant of the tumour-suppressor protein p53 (p53(25,26,53,54)), along with a wild-type allele of p53 (also known as Trp53), revealed late-gestational embryonic lethality associated with a host of phenotypes that are characteristic of CHARGE syndrome, including coloboma, inner and outer ear malformations, heart outflow tract defects and craniofacial defects. We found that the p53(25,26,53,54) mutant protein stabilized and hyperactivated wild-type p53, which then inappropriately induced its target genes and triggered cell-cycle arrest or apoptosis during development. Importantly, these phenotypes were only observed with a wild-type p53 allele, as p53(25,26,53,54)(/-) embryos were fully viable. Furthermore, we found that CHD7 can bind to the p53 promoter, thereby negatively regulating p53 expression, and that CHD7 loss in mouse neural crest cells or samples from patients with CHARGE syndrome results in p53 activation. Strikingly, we found that p53 heterozygosity partially rescued the phenotypes in Chd7-null mouse embryos, demonstrating that p53 contributes to the phenotypes that result from CHD7 loss. Thus, inappropriate p53 activation during development can promote CHARGE phenotypes, supporting the idea that p53 has a critical role in developmental syndromes and providing important insight into the mechanisms underlying CHARGE syndrome

The message on the bottle:Rethinking plastic labelling to better encourage sustainable use

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordPlastic pollution continues to worsen globally in volume and complexity. The complexity in plastic production, use and disposal is significant, highlighting the importance of clear communication to consumers. Yet despite this, poor plastic labelling is clear, evident from poor waste management metrics even in the most equipped countries. Plastic labelling must change to contribute to a holistic intervention on global plastic mismanagement. Discussion on this topic leads to three key recommendations: 1. An accurate and clear “sustainability scale” to empower consumers to make decisions informed by environmental and human health implications; 2. Directions for appropriate disposal action in the region of purchase; 3. A comprehensive list of plastic composition, including additives.Natural Environment Research Council (NERC)QUEX InstituteQueensland Health, AustraliaMinderoo Foundation, Australi