Retromer controls planar polarity protein levels and asymmetric localization at intercellular junctions

The coordinated polarization of cells in the plane of a tissue, termed planar polarity, is a characteristic feature of epithelial tissues [1]. In the fly wing, trichome positioning is dependent on the core planar polarity proteins adopting asymmetric subcellular localizations at apical junctions, where they form intercellular complexes that link neighboring cells [1-3]. Specifically, the seven-pass transmembrane protein Frizzled and the cytoplasmic proteins Dishevelled and Diego localize to distal cell ends, the four-pass transmembrane protein Strabismus and the cytoplasmic protein Prickle localize proximally, and the seven-pass transmembrane spanning atypical cadherin Flamingo localizes both proximally and distally. To establish asymmetry, these core proteins are sorted from an initially uniform distribution; however, the mechanisms underlying this polarized trafficking remain poorly understood. Here, we describe the identification of retromer, a master controller of endosomal recycling [4-6], as a key component regulating core planar polarity protein localization in Drosophila. Through generation of mutants, we verify that loss of the retromer-associated Snx27 cargo adaptor, but notably not components of the Wash complex, reduces junctional levels of the core proteins Flamingo and Strabismus in the developing wing. We establish that Snx27 directly associates with Flamingo via its C-terminal PDZ binding motif, and we show that Snx27 is essential for normal Flamingo trafficking. We conclude that Wash-independent retromer function and the Snx27 cargo adaptor are important components in the endosomal recycling of Flamingo and Strabismus back to the plasma membrane and thus contribute to the establishment and maintenance of planar polarization

Quantum Monte Carlo with Directed Loops

We introduce the concept of directed loops in stochastic series expansion and path integral quantum Monte Carlo methods. Using the detailed balance rules for directed loops, we show that it is possible to smoothly connect generally applicable simulation schemes (in which it is necessary to include back-tracking processes in the loop construction) to more restricted loop algorithms that can be constructed only for a limited range of Hamiltonians (where back-tracking can be avoided). The "algorithmic discontinuities" between general and special points (or regions) in parameter space can hence be eliminated. As a specific example, we consider the anisotropic S=1/2 Heisenberg antiferromagnet in an external magnetic field. We show that directed loop simulations are very efficient for the full range of magnetic fields (zero to the saturation point) and anisotropies. In particular for weak fields and anisotropies, the autocorrelations are significantly reduced relative to those of previous approaches. The back-tracking probability vanishes continuously as the isotropic Heisenberg point is approached. For the XY-model, we show that back-tracking can be avoided for all fields extending up to the saturation field. The method is hence particularly efficient in this case. We use directed loop simulations to study the magnetization process in the 2D Heisenberg model at very low temperatures. For LxL lattices with L up to 64, we utilize the step-structure in the magnetization curve to extract gaps between different spin sectors. Finite-size scaling of the gaps gives an accurate estimate of the transverse susceptibility in the thermodynamic limit: chi_perp = 0.0659 +- 0.0002.Comment: v2: Revised and expanded discussion of detailed balance, error in algorithmic phase diagram corrected, to appear in Phys. Rev.

Kaluza-Klein gravitino production with a single photon at e^+ e^- colliders

In a supersymmetric large extra dimension scenario, the production of Kaluza-Klein gravitinos accompanied by a photino at e^+ e^- colliders is studied. We assume that a bulk supersymmetry is softly broken on our brane such that the low-energy theory resembles the MSSM. Low energy supersymmetry breaking is further assumed as in GMSB, leading to sub-eV mass shift in each KK mode of the gravitino from the corresponding graviton KK mode. Since the photino decays within a detector due to its sufficiently large inclusive decay rate into a photon and a gravitino, the process e^+ e^- -> photino + gravitino yields single photon events with missing energy. Even if the total cross section can be substantial at sqrt(s)=500 GeV, the KK graviton background of e^+ e^- -> photon + graviton is kinematically advantageous and thus much larger. It is shown that the observable, sigma(e^-_L)-sigma(e^-_R), can completely eliminate the KK graviton background but retain most of the KK gravitino signal, which provides a unique and robust method to probe the supersymmetric bulk.Comment: Reference added and typos correcte

Going into the groin: Injection into the femoral vein among people who inject drugs in three urban areas of England

Background: There have been increasing concerns about injection into the femoral vein – groin injecting – among people who inject drugs in a number of countries, though most studies have been small. The extent, reasons and harms associated with groin injecting are examined. Method: Participants were recruited using respondent driven sampling (2006–2009). Weighted data was examined using bivariate analyses and logistic regression. Results: The mean age was 32 years; 25% were women (N = 855). During the preceding 28 days, 94% had injected heroin and 13% shared needles/syringes. Overall, 53% reported ever groin injecting, with 9.8% first doing so at the same age as starting to inject. Common reasons given for groin injecting included: “Can’t get a vein elsewhere” (68%); “It is discreet” (18%); and “It is quicker” (14%). During the preceding 28 days, 41% had groin injected, for 77% this was the only body area used (for these “It is discreet” was more frequently given as a reason). In the multivariable analysis, groin injection was associated with: swabbing injection sites; saving filters for reuse; and receiving opiate substitution therapy. It was less common among those injecting into two body areas, and when other people (rather than services) were the main source of needles. Groin injection was more common among those with hepatitis C and reporting ever having deep vein thrombosis or septicaemia. Conclusions: Groin injection was common, often due to poor vascular access, but for some it was out of choice. Interventions are required to reduce injecting risk and this practice

Diagnosis of biliary tract and ampullary carcinomas

Diagnostic methods for biliary tract carcinoma and the efficacy of these methods are discussed. Neither definite methods for early diagnosis nor specific markers are available in this disease. When this disease is suspected on the basis of clinical symptoms and risk factors, hemato-biochemical examination and abdominal ultrasonography are performed and, where appropriate, enhanced computed tomography (CT) and/or magnetic resonance cholangiopancreatography (MRCP) is carried out. Diagnoses of extrahepatic bile duct cancer and ampullary carcinoma are often made based on the presence of obstructive jaundice. Although rare, abdominal pain and pyrexia, as well as abnormal findings of the hepatobiliary system detected by hemato-biochemical examination, serve as a clue to making a diagnosis of these diseases. On the other hand, the early diagnosis of gallbladder cancer is scarcely possible on the basis of clinical symptoms, so when this cancer is found with the onset of abdominal pain and jaundice, it is already advanced at the time of detection, thus making a cure difficult. When gallbladder cancer is suspected, enhanced CT is carried out. Multidetector computed tomography (MDCT), in particular — one of the methods of enhanced CT — is useful for decision of surgical criteria, because MDCT shows findings such as localization and extension of the tumor, and the presence or absence of remote metastasis. Procedures such as magnetic resonance imaging, endoscopic ultrasonography, bile duct biopsy, and cholangioscopy should be carried out taking into account indications for these procedures in individual patients. However, direct biliary tract imaging is necessary for making a precise diagnosis of the horizontal extension of bile duct cancer

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC-2020 March 27 17:00 UTC). We conduct two independent searches: A generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate. © 2022. The Author(s). Published by the American Astronomical Society

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society

Measurement of the gamma ray background in the Davis Cavern at the Sanford Underground Research Facility

Deep underground environments are ideal for low background searches due to the attenuation of cosmic rays by passage through the earth. However, they are affected by backgrounds from γ-rays emitted by 40K and the 238U and 232Th decay chains in the surrounding rock. The LUX-ZEPLIN (LZ) experiment will search for dark matter particle interactions with a liquid xenon TPC located within the Davis campus at the Sanford Underground Research Facility, Lead, South Dakota, at the 4,850-foot level. In order to characterise the cavern background, in-situ γ-ray measurements were taken with a sodium iodide detector in various locations and with lead shielding. The integral count rates (0--3300~keV) varied from 596~Hz to 1355~Hz for unshielded measurements, corresponding to a total flux in the cavern of 1.9±0.4~γ cm−2s−1. The resulting activity in the walls of the cavern can be characterised as 220±60~Bq/kg of 40K, 29±15~Bq/kg of 238U, and 13±3~Bq/kg of 232Th