Frequency-Dependent Squeezing for Advanced LIGO

The first detection of gravitational waves by the Laser Interferometer Gravitational-wave Observatory (LIGO) in 2015 launched the era of gravitational wave astronomy. The quest for gravitational wave signals from objects that are fainter or farther away impels technological advances to realize ever more sensitive detectors. Since 2019, one advanced technique, the injection of squeezed states of light is being used to improve the shot noise limit to the sensitivity of the Advanced LIGO detectors, at frequencies above $\sim 50$ Hz. Below this frequency, quantum back action, in the form of radiation pressure induced motion of the mirrors, degrades the sensitivity. To simultaneously reduce shot noise at high frequencies and quantum radiation pressure noise at low frequencies requires a quantum noise filter cavity with low optical losses to rotate the squeezed quadrature as a function of frequency. We report on the observation of frequency-dependent squeezed quadrature rotation with rotation frequency of 30Hz, using a 16m long filter cavity. A novel control scheme is developed for this frequency-dependent squeezed vacuum source, and the results presented here demonstrate that a low-loss filter cavity can achieve the squeezed quadrature rotation necessary for the next planned upgrade to Advanced LIGO, known as "A+."Comment: 6 pages, 2 figures, to be published in Phys. Rev. Let

Familial relative risks for breast cancer by pathological subtype: a population-based cohort study.

INTRODUCTION: The risk of breast cancer to first degree relatives of breast cancer patients is approximately twice that of the general population. Breast cancer, however, is a heterogeneous disease and it is plausible that the familial relative risk (FRR) for breast cancer may differ by the pathological subtype of the tumour. The contribution of genetic variants associated with breast cancer susceptibility to the subtype-specific FRR is still unclear. METHODS: We computed breast cancer FRR for subtypes of breast cancer by comparing breast cancer incidence in relatives of breast cancer cases from a population-based series with known estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor 2 (HER2) status with that expected from the general population. We estimated the contribution to the FRR of genetic variants associated with breast cancer susceptibility using subtype-specific genotypic relative risks and allele frequencies for each variant. RESULTS: At least one marker was measured for 4,590 breast cancer cases, who reported 9,014 affected and unaffected first-degree female relatives. There was no difference between the breast cancer FRR for relatives of patients with ER-negative (FRR = 1.78, 95% confidence intervals (CI): 1.44 to 2.11) and ER-positive disease (1.82, 95% CI: 1.67 to 1.98), P = 0.99. There was some suggestion that the breast cancer FRR for relatives of patients with ER-negative disease was higher than that for ER-positive disease for ages of the relative less than 50 years old (FRR = 2.96, 95% CI: 2.04 to 3.87; and 2.05, 95% CI: 1.70 to 2.40 respectively; P = 0.07), and that the breast cancer FRR for relatives of patients with ER-positive disease was higher than for ER-negative disease when the age of the relative was greater than 50 years (FRR = 1.76, 95% CI: 1.59 to 1.93; and 1.41, 95% CI: 1.08 to 1.74 respectively, P = 0.06). We estimated that mutations in BRCA1 and BRCA2 explain 32% of breast cancer FRR for relatives of patients with ER-negative and 9.4% of the breast cancer FRR for relatives of patients with ER-positive disease. Twelve recently identified common breast cancer susceptibility variants were estimated to explain 1.9% and 9.6% of the FRR to relatives of patients with ER-negative and ER-positive disease respectively. CONCLUSIONS: FRR for breast cancer was significantly increased for both ER-negative and ER-positive disease. Including receptor status in conjunction with genetic status may aid risk prediction in women with a family history.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Combining genomics and epidemiology to track mumps virus transmission in the United States.

Unusually large outbreaks of mumps across the United States in 2016 and 2017 raised questions about the extent of mumps circulation and the relationship between these and prior outbreaks. We paired epidemiological data from public health investigations with analysis of mumps virus whole genome sequences from 201 infected individuals, focusing on Massachusetts university communities. Our analysis suggests continuous, undetected circulation of mumps locally and nationally, including multiple independent introductions into Massachusetts and into individual communities. Despite the presence of these multiple mumps virus lineages, the genomic data show that one lineage has dominated in the US since at least 2006. Widespread transmission was surprising given high vaccination rates, but we found no genetic evidence that variants arising during this outbreak contributed to vaccine escape. Viral genomic data allowed us to reconstruct mumps transmission links not evident from epidemiological data or standard single-gene surveillance efforts and also revealed connections between apparently unrelated mumps outbreaks

Frequency-Dependent Squeezing for Advanced LIGO

The first detection of gravitational waves by the Laser Interferometer Gravitational-Wave Observatory (LIGO) in 2015 launched the era of gravitational-wave astronomy. The quest for gravitational-wave signals from objects that are fainter or farther away impels technological advances to realize ever more sensitive detectors. Since 2019, one advanced technique, the injection of squeezed states of light, is being used to improve the shot-noise limit to the sensitivity of the Advanced LIGO detectors, at frequencies above ∼50Hz. Below this frequency, quantum backaction, in the form of radiation pressure induced motion of the mirrors, degrades the sensitivity. To simultaneously reduce shot noise at high frequencies and quantum radiation pressure noise at low frequencies requires a quantum noise filter cavity with low optical losses to rotate the squeezed quadrature as a function of frequency. We report on the observation of frequency-dependent squeezed quadrature rotation with rotation frequency of 30 Hz, using a 16-m-long filter cavity. A novel control scheme is developed for this frequency-dependent squeezed vacuum source, and the results presented here demonstrate that a low-loss filter cavity can achieve the squeezed quadrature rotation necessary for the next planned upgrade to Advanced LIGO, known as “A+.

Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients.

Naturally acquired blood-stage infections of the malaria parasite Plasmodium falciparum typically harbour multiple haploid clones. The apparent number of clones observed in any single infection depends on the diversity of the polymorphic markers used for the analysis, and the relative abundance of rare clones, which frequently fail to be detected among PCR products derived from numerically dominant clones. However, minority clones are of clinical interest as they may harbour genes conferring drug resistance, leading to enhanced survival after treatment and the possibility of subsequent therapeutic failure. We deployed new generation sequencing to derive genome data for five non-propagated parasite isolates taken directly from 4 different patients treated for clinical malaria in a UK hospital. Analysis of depth of coverage and length of sequence intervals between paired reads identified both previously described and novel gene deletions and amplifications. Full-length sequence data was extracted for 6 loci considered to be under selection by antimalarial drugs, and both known and previously unknown amino acid substitutions were identified. Full mitochondrial genomes were extracted from the sequencing data for each isolate, and these are compared against a panel of polymorphic sites derived from published or unpublished but publicly available data. Finally, genome-wide analysis of clone multiplicity was performed, and the number of infecting parasite clones estimated for each isolate. Each patient harboured at least 3 clones of P. falciparum by this analysis, consistent with results obtained with conventional PCR analysis of polymorphic merozoite antigen loci. We conclude that genome sequencing of peripheral blood P. falciparum taken directly from malaria patients provides high quality data useful for drug resistance studies, genomic structural analyses and population genetics, and also robustly represents clonal multiplicity

Astrophysically Triggered Searches for Gravitational Waves: Status and Prospects

In gravitational-wave detection, special emphasis is put onto searches that focus on cosmic events detected by other types of astrophysical observatories. The astrophysical triggers, e.g. from gamma-ray and X-ray satellites, optical telescopes and neutrino observatories, provide a trigger time for analyzing gravitational wave data coincident with the event. In certain cases the expected frequency range, source energetics, directional and progenitor information is also available. Beyond allowing the recognition of gravitational waveforms with amplitudes closer to the noise floor of the detector, these triggered searches should also lead to rich science results even before the onset of Advanced LIGO. In this paper we provide a broad review of LIGO's astrophysically triggered searches and the sources they target

Potential opportunities and challenges of deploying next generation sequencing and CRISPR-cas systems to support diagnostics and surveillance towards malaria control and elimination in Africa

Recent developments in molecular biology and genomics have revolutionized biology and medicine mainly in the developed world. The application of next generation sequencing (NGS) and CRISPR-Cas tools is now poised to support endemic countries in the detection, monitoring and control of endemic diseases and future epidemics, as well as with emerging and re-emerging pathogens. Most low and middle income countries (LMICs) with the highest burden of infectious diseases still largely lack the capacity to generate and perform bioinformatic analysis of genomic data. These countries have also not deployed tools based on CRISPR-Cas technologies. For LMICs including Tanzania, it is critical to focus not only on the process of generation and analysis of data generated using such tools, but also on the utilization of the findings for policy and decision making. Here we discuss the promise and challenges of NGS and CRISPR-Cas in the context of malaria as Africa moves towards malaria elimination. These innovative tools are urgently needed to strengthen the current diagnostic and surveillance systems. We discuss ongoing efforts to deploy these tools for malaria detection and molecular surveillance highlighting potential opportunities presented by these innovative technologies as well as challenges in adopting them. Their deployment will also offer an opportunity to broadly build in-country capacity in pathogen genomics and bioinformatics, and to effectively engage with multiple stakeholders as well as policy makers, overcoming current workforce and infrastructure challenges. Overall, these ongoing initiatives will build the malaria molecular surveillance capacity of African researchers and their institutions, and allow them to generate genomics data and perform bioinformatics analysis in-country in order to provide critical information that will be used for real-time policy and decision-making to support malaria elimination on the continent