Metabolic cutis laxa syndromes

Cutis laxa is a rare skin disorder characterized by wrinkled, redundant, inelastic and sagging skin due to defective synthesis of elastic fibers and other proteins of the extracellular matrix. Wrinkled, inelastic skin occurs in many cases as an acquired condition. Syndromic forms of cutis laxa, however, are caused by diverse genetic defects, mostly coding for structural extracellular matrix proteins. Surprisingly a number of metabolic disorders have been also found to be associated with inherited cutis laxa. Menkes disease was the first metabolic disease reported with old-looking, wrinkled skin. Cutis laxa has recently been found in patients with abnormal glycosylation. The discovery of the COG7 defect in patients with wrinkled, inelastic skin was the first genetic link with the Congenital Disorders of Glycosylation (CDG). Since then several inborn errors of metabolism with cutis laxa have been described with variable severity. These include P5CS, ATP6V0A2-CDG and PYCR1 defects. In spite of the evolving number of cutis laxa-related diseases a large part of the cases remain genetically unsolved. In metabolic cutis laxa syndromes the clinical and laboratory features might partially overlap, however there are some distinct, discriminative features. In this review on metabolic diseases causing cutis laxa we offer a practical approach for the differential diagnosis of metabolic cutis laxa syndromes

The Advanced Virgo+ status

The gravitational wave detector Advanced Virgo+ is currently in the commissioning phase in view of the fourth Observing Run (O4). The major upgrades with respect to the Advanced Virgo configuration are the implementation of an additional recycling cavity, the Signal Recycling cavity (SRC), at the output of the interferometer to broaden the sensitivity band and the Frequency Dependent Squeezing (FDS) to reduce quantum noise at all frequencies. The main difference of the Advanced Virgo + detector with respect to the LIGO detectors is the presence of marginally stable recycling cavities, with respect to the stable recycling cavities present in the LIGO detectors, which increases the difficulties in controlling the interferometer in presence of defects (both thermal and cold defects). This work will focus on the interferometer commissioning, highlighting the control challenges to maintain the detector in the working point which maximizes the sensitivity and the duty cycle for scientific data taking

Mutations in PLOD3, encoding lysyl hydroxylase 3, cause a complex connective tissue disorder including recessive dystrophic epidermolysis bullosa-like blistering phenotype with abnormal anchoring fibrils and type VII collagen deficiency

Epidermolysis bullosa (EB), the paradigm of heritable skin fragility disorders, is associated with mutations in as many as 20 distinct genes. One of the clinical variants, recessive dystrophic EB (RDEB), demonstrates sub-lamina densa blistering accompanied by alterations in anchoring fibrils due to mutations in COL7A1. In this study, we characterized a patient with widespread connective tissue abnormalities, including skin blistering similar to that in RDEB. Whole exome sequencing, combined with genome-wide homozygosity mapping, identified a homozygous missense mutation in PLOD3 encoding lysyl hydroxylase 3 (LH3). No mutations in COL7A1, the gene previously associated with RDEB, were detected. The level of LH3 was dramatically reduced in the skin and fibroblast cultures from the patient. The blistering in the skin occurred below the lamina densa and was associated with variable density and morphology of anchoring fibrils. The level of type VII collagen expression in the skin was markedly reduced. Analysis of hydroxylysine and its glycosylated derivatives (galactosyl-hydroxylysine and glucosyl-galactosyl-hydroxylysine) revealed marked reduction in glycosylated hydroxylysine. Collectively, these findings indicate that PLOD3 mutations can result in a dystrophic EB-like phenotype in the spectrum of connective tissue disorders and add it to the list of candidate genes associated with skin fragility

Advanced Virgo Plus: Future Perspectives

While completing the commissioning phase to prepare the Virgo interferometer for the next joint Observation Run (O4), the Virgo collaboration is also finalizing the design of the next upgrades to the detector to be employed in the following Observation Run (O5). The major upgrade will concern decreasing the thermal noise limit, which will imply using very large test masses and increased laser beam size. But this will not be the only upgrade to be implemented in the break between the O4 and O5 observation runs to increase the Virgo detector strain sensitivity. The paper will cover the challenges linked to this upgrade and implications on the detector's reach and observational potential, reflecting the talk given at 12th Cosmic Ray International Seminar - CRIS 2022 held in September 2022 in Napoli

Frequency-Dependent Squeezed Vacuum Source for the Advanced Virgo Gravitational-Wave Detector

In this Letter, we present the design and performance of the frequency-dependent squeezed vacuum source that will be used for the broadband quantum noise reduction of the Advanced Virgo Plus gravitational-wave detector in the upcoming observation run. The frequency-dependent squeezed field is generated by a phase rotation of a frequency-independent squeezed state through a 285 m long, high-finesse, near-detuned optical resonator. With about 8.5 dB of generated squeezing, up to 5.6 dB of quantum noise suppression has been measured at high frequency while close to the filter cavity resonance frequency, the intracavity losses limit this value to about 2 dB. Frequency-dependent squeezing is produced with a rotation frequency stability of about 6 Hz rms, which is maintained over the long term. The achieved results fulfill the frequency dependent squeezed vacuum source requirements for Advanced Virgo Plus. With the current squeezing source, considering also the estimated squeezing degradation induced by the interferometer, we expect a reduction of the quantum shot noise and radiation pressure noise of up to 4.5 dB and 2 dB, respectively

Frequency-Dependent Squeezed Vacuum Source for the Advanced Virgo Gravitational-Wave Detector

In this Letter, we present the design and performance of the frequency-dependent squeezed vacuum source that will be used for the broadband quantum noise reduction of the Advanced Virgo Plus gravitational-wave detector in the upcoming observation run. The frequency-dependent squeezed field is generated by a phase rotation of a frequency-independent squeezed state through a 285 m long, high-finesse, near-detuned optical resonator. With about 8.5 dB of generated squeezing, up to 5.6 dB of quantum noise suppression has been measured at high frequency while close to the filter cavity resonance frequency, the intracavity losses limit this value to about 2 dB. Frequency-dependent squeezing is produced with a rotation frequency stability of about 6 Hz rms, which is maintained over the long term. The achieved results fulfill the frequency dependent squeezed vacuum source requirements for Advanced Virgo Plus. With the current squeezing source, considering also the estimated squeezing degradation induced by the interferometer, we expect a reduction of the quantum shot noise and radiation pressure noise of up to 4.5 dB and 2 dB, respectively

Search for continuous gravitational waves from known pulsars in the first part of the fourth LIGO-Virgo-KAGRA observing run

Continuous gravitational waves (CWs) emission from neutron stars carries information about their internal structure and equation of state, and it can provide tests of general relativity. We present a search for CWs from a set of 45 known pulsars in the first part of the fourth LIGO–Virgo–KAGRA observing run, known as O4a. We conducted a targeted search for each pulsar using three independent analysis methods considering single-harmonic and dual-harmonic emission models. We find no evidence of a CW signal in O4a data for both models and set upper limits on the signal amplitude and on the ellipticity, which quantifies the asymmetry in the neutron star mass distribution. For the single-harmonic emission model, 29 targets have the upper limit on the amplitude below the theoretical spin-down limit. The lowest upper limit on the amplitude is 6.4 × 10−27 for the young energetic pulsar J0537−6910, while the lowest constraint on the ellipticity is 8.8 × 10−9 for the bright nearby millisecond pulsar J0437−4715. Additionally, for a subset of 16 targets, we performed a narrowband search that is more robust regarding the emission model, with no evidence of a signal. We also found no evidence of nonstandard polarizations as predicted by the Brans–Dicke theory

A search using GEO600 for gravitational waves coincident with fast radio bursts from SGR 1935+2154

The magnetar SGR 1935+2154 is the only known Galactic source of fast radio bursts (FRBs). FRBs from SGR 1935+2154 were first detected by the Canadian Hydrogen Intensity Mapping Experiment (CHIME)/FRB and the Survey for Transient Astronomical Radio Emission 2 in 2020 April, after the conclusion of the LIGO, Virgo, and KAGRA Collaborations' O3 observing run. Here, we analyze four periods of gravitational wave (GW) data from the GEO600 detector coincident with four periods of FRB activity detected by CHIME/FRB, as well as X-ray glitches and X-ray bursts detected by NICER and NuSTAR close to the time of one of the FRBs. We do not detect any significant GW emission from any of the events. Instead, using a short-duration GW search (for bursts ≤1 s) we derive 50% (90%) upper limits of 1048 (1049) erg for GWs at 300 Hz and 1049 (1050) erg at 2 kHz, and constrain the GW-to-radio energy ratio to ≤1014−1016. We also derive upper limits from a long-duration search for bursts with durations between 1 and 10 s. These represent the strictest upper limits on concurrent GW emission from FRBs

Search for subsolar-mass black hole binaries in the second part of Advanced LIGO's and Advanced Virgo's third observing run

We describe a search for gravitational waves from compact binaries with at least one component with mass 0.2 $M_\odot$ -- $1.0 M_\odot$ and mass ratio $q \geq 0.1$ in Advanced LIGO and Advanced Virgo data collected between 1 November 2019, 15:00 UTC and 27 March 2020, 17:00 UTC. No signals were detected. The most significant candidate has a false alarm rate of 0.2 $\mathrm{yr}^{-1}$. We estimate the sensitivity of our search over the entirety of Advanced LIGO's and Advanced Virgo's third observing run, and present the most stringent limits to date on the merger rate of binary black holes with at least one subsolar-mass component. We use the upper limits to constrain two fiducial scenarios that could produce subsolar-mass black holes: primordial black holes (PBH) and a model of dissipative dark matter. The PBH model uses recent prescriptions for the merger rate of PBH binaries that include a rate suppression factor to effectively account for PBH early binary disruptions. If the PBHs are monochromatically distributed, we can exclude a dark matter fraction in PBHs $f_\mathrm{PBH} \gtrsim 0.6$ (at 90% confidence) in the probed subsolar-mass range. However, if we allow for broad PBH mass distributions we are unable to rule out $f_\mathrm{PBH} = 1$. For the dissipative model, where the dark matter has chemistry that allows a small fraction to cool and collapse into black holes, we find an upper bound $f_{\mathrm{DBH}} < 10^{-5}$ on the fraction of atomic dark matter collapsed into black holes.Comment: https://dcc.ligo.org/P220013

Swift-BAT GUANO follow-up of gravitational-wave triggers in the Third LIGO–Virgo–KAGRA Observing Run

We present results from a search for X-ray/gamma-ray counterparts of gravitational-wave (GW) candidates from the third observing run (O3) of the LIGO–Virgo–KAGRA network using the Swift Burst Alert Telescope (Swift-BAT). The search includes 636 GW candidates received with low latency, 86 of which have been confirmed by the offline analysis and included in the third cumulative Gravitational-Wave Transient Catalogs (GWTC-3). Targeted searches were carried out on the entire GW sample using the maximum-likelihood Non-imaging Transient Reconstruction and Temporal Search pipeline on the BAT data made available via the GUANO infrastructure. We do not detect any significant electromagnetic emission that is temporally and spatially coincident with any of the GW candidates. We report flux upper limits in the 15–350 keV band as a function of sky position for all the catalog candidates. For GW candidates where the Swift-BAT false alarm rate is less than 10−3 Hz, we compute the GW–BAT joint false alarm rate. Finally, the derived Swift-BAT upper limits are used to infer constraints on the putative electromagnetic emission associated with binary black hole mergers