The manipulation of quantum states of light
holds the potential to enhance searches for fundamental physics. Only recently has the maturation of quantum squeezing technology coincided with the ...emergence of fundamental physics searches that are limited by quantum uncertainty
. In particular, the quantum chromodynamics axion provides a possible solution to two of the greatest outstanding problems in fundamental physics: the strong-CP (charge-parity) problem of quantum chromodynamics
and the unknown nature of dark matter
. In dark matter axion searches, quantum uncertainty manifests as a fundamental noise source, limiting the measurement of the quadrature observables used for detection. Few dark matter searches have approached this limit
, and until now none has exceeded it. Here we use vacuum squeezing to circumvent the quantum limit in a search for dark matter. By preparing a microwave-frequency electromagnetic field in a squeezed state and near-noiselessly reading out only the squeezed quadrature
, we double the search rate for axions over a mass range favoured by some recent theoretical projections
. We find no evidence of dark matter within the axion rest energy windows of 16.96-17.12 and 17.14-17.28 microelectronvolts. Breaking through the quantum limit invites an era of fundamental physics searches in which noise reduction techniques yield unbounded benefit compared with the diminishing returns of approaching the quantum limit.
Objective Type-specific prevalence data of human papillomavirus (HPV) DNA in penile carcinoma are needed to determine the potential impact of HPV prophylactic vaccines, assuming demonstrated efficacy ...in men. Methods A review was conducted using search terms including HPV and penile cancer. Studies using polymerase chain reaction (PCR) assays for HPV DNA detection in invasive penile carcinoma were included. Results A total of 1,266 squamous cell carcinoma (SCC) cases contributed data from 30 studies. The number of SCC was similar in Europe (28.2%), North America (27.6%), South America (23.9%) and Asia (20.4%). All SCC were histologically confirmed with biopsies for DNA detection. Most commonly used PCR primers were type-specific (35.2%), and combination PCR (18.2%). HPV prevalence was 47.9%, ranging from 22.4% in verrucous SCC to 66.3% for the basaloid/warty subtypes. HPV16 (30.8%), HPV6 (6.7%) and HPV18 (6.6%) were the most prevalent types. HPV16 and/or HPV 18 prevalence was 36.7%. Conclusions HPV DNA was detected in half of SCC, with HPV16 being the most common type. If proven efficacious in men, prophylactic vaccines targeting carcinogenic types HPV16 and 18 could potentially reduce approximately one-third of incident SCC.
The fetal/neonatal period represents both a unique window of opportunity for interventions as well as vulnerability to a number of viral infections. While
such as herpes simplex virus (HSV) are ...highly prevalent and typically of little consequence among healthy adults, they are among the most consequential infections of early life. Despite treatment with antiviral drugs, neonatal HSV (nHSV) infections can still result in significant mortality and lifelong neurological morbidity. Fortunately, newborns in our pathogen-rich world inherit some of the protection provided by the maternal immune system in the form of transferred antibodies. Maternal seropositivity, resulting in placental transfer of antibodies capable of neutralizing virus and eliciting the diverse effector functions of the innate immune system are associated with dramatically decreased risk of nHSV. Given this clear epidemiological evidence of reduced risk of infection and its sequelae, we present what is known about the ability of monoclonal antibody therapies to treat or prevent HSV infection and explore how effective antibody-based interventions in conjunction with antiviral therapy might reduce early life mortality and long-term morbidity.
Context.
Blazars are the most numerous class of high-energy (HE;
E
∼ 50 MeV−100 GeV) and very high-energy (VHE;
E
∼ 100 GeV−10 TeV) gamma-ray emitters. Currently, a measured spectroscopic redshift is ...available for only about 50% of gamma-ray BL Lacertae objects (BL Lacs), mainly due to the difficulty in measuring reliable redshifts from their nearly featureless continuum-dominated optical spectra. The knowledge of the redshift is fundamental for understanding the emission from blazars, for population studies and also for indirect studies of the extragalactic background light and searches for Lorentz invariance violation and axion-like particles using blazars.
Aims.
This paper is the first in a series of papers that aim to measure the redshift of a sample of blazars likely to be detected with the upcoming Cherenkov Telescope Array (CTA), a ground-based gamma-ray observatory.
Methods.
Monte Carlo simulations were performed to select those hard spectrum gamma-ray blazars detected with the
Fermi
-LAT telescope still lacking redshift measurements, but likely to be detected by CTA in 30 hours of observing time or less. Optical observing campaigns involving deep imaging and spectroscopic observations were organised to efficiently constrain their redshifts. We performed deep medium- to high-resolution spectroscopy of 19 blazar optical counterparts with the Keck II, SALT, and ESO NTT telescopes. We searched systematically for spectral features and, when possible, we estimated the contribution of the host galaxy to the total flux.
Results.
We measured eleven firm spectroscopic redshifts with values ranging from 0.1116 to 0.482, one tentative redshift, three redshift lower limits including one at
z
≥ 0.449 and another at
z
≥ 0.868. Four BL Lacs show featureless spectra.
The central region of the Milky Way is one of the foremost locations to look for dark matter (DM) signatures. We report the first results on a search for DM particle annihilation signals using new ...observations from an unprecedented gamma-ray survey of the Galactic Center (GC) region, i.e., the Inner Galaxy Survey, at very high energies (& GSIM;100 GeV) performed with the H.E.S.S. array of five ground-based Cherenkov telescopes. No significant gamma-ray excess is found in the search region of the 2014-2020 dataset and a profile likelihood ratio analysis is carried out to set exclusion limits on the annihilation cross section (sigma v). Assuming Einasto and Navarro-Frenk-White (NFW) DM density profiles at the GC, these constraints are the strongest obtained so far in the TeV DM mass range. For the Einasto profile, the constraints reach (sigma v) values of 3.7 x 10-26 cm3 s-1 for 1.5 TeV DM mass in the W+W- annihilation channel, and 1.2 x 10-26 cm3 s-1 for 0.7 TeV DM mass in the tau+tau- annihilation channel. With the H.E.S.S. Inner Galaxy Survey, ground-based gamma-ray observations thus probe (sigma v) values expected from thermal-relic annihilating TeV DM particles.
Neonatal herpes simplex virus (nHSV) infections cause devastating morbidity and mortality in infants. Most nHSV cases are associated with primary maternal infection, consistent with the hypothesis ...that maternal immunity is protective. In humans, we found HSV-specific neutralizing antibodies in newborns of immune mothers, indicating that placentally transferred HSV-specific antibody is protective. Using a murine model, we showed that passive administration of HSV-specific antibody to dams prevented disseminated infection and mortality in pups. Maternal immunization with an HSV-2 replication-defective vaccine candidate,
5-29, led to transfer of HSV-specific antibodies into neonatal circulation that protected against nHSV neurological disease and death. Furthermore, we observed considerable anxiety-like behavior in adult mice that had been infected with low doses of HSV as neonates, despite a notable lack of signs of infection. This phenotype suggests that nHSV infection can have an unsuspected and permanent impact on behavior. These behavioral sequelae of nHSV were prevented by maternal immunization with
5-29, demonstrating an unexpected benefit of immunization. These findings also support the general concept that maternal immunization can prevent neurotropic neonatal infections and associated morbidity and mortality.
Elk-1 is a transcription factor that binds together with a dimer of the serum response factor (SRF) to the serum-response element (SRE), a genetic element that connects cellular stimulation with gene ...transcription. Elk-1 plays an important role in the regulation of cellular proliferation and apoptosis, thymocyte development, glucose homeostasis and brain function. The biological function of Elk-1 relies essentially on the interaction with other proteins. Elk-1 binds to SRF and generates a functional ternary complex that is required to activate SRE-mediated gene transcription. Elk-1 is kept in an inactive state under basal conditions via binding of a SUMO-histone deacetylase complex. Phosphorylation by extracellular signal-regulated protein kinase, c-Jun N-terminal protein kinase or p38 upregulates the transcriptional activity of Elk-1, mediated by binding to the mediator of RNA polymerase II transcription (Mediator) and the transcriptional coactivator p300. Strong and extended phosphorylation of Elk-1 attenuates Mediator and p300 recruitment and allows the binding of the mSin3A-histone deacetylase corepressor complex. The subsequent dephosphorylation of Elk-1, catalyzed by the protein phosphatase calcineurin, facilitates the re-SUMOylation of Elk-1, transforming Elk-1 back to a transcriptionally inactive state. Thus, numerous protein–protein interactions control the activation cycle of Elk-1 and are essential for its biological function.
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