Probing sterile neutrino in BB (DD) meson decays at Belle II (BESIII)

We present, how a systematic study of $B \to D\ell N$ ($D \to K \ell N$) decays with $\ell=\mu,\tau$, at Belle II (BESIII) can provide unambiguous signature of a heavy neutrino $N$ and/or constrain its mixing with active neutrinos $\nu_\ell$, which is parameterized by $|U_{\ell N}|^2$. Our constraint on $|U_{\mu N}|^2$ that can be achieved from the full Belle II data is comparable with what can be obtained from the much larger data set of the upgraded LHCb. Additionally, our method offers better constraint on $|U_{\mu N}|^2$ for mass of sterile neutrino $m_N < 2$ GeV. We can also probe the Dirac and Majorana nature of $N$ by observing the sequential decay of $N$, including suppression from observation of a displaced vertex as well as helicity flip, for Majorana $N$.Comment: 9 pages, 6 figures. This is a pre-print of an article published in European Physical Journal C. The final authenticated version is available online at https://doi.org/10.1140/epjc/s10052-020-8310-

Electron−hole separation in ferroelectric oxides for efficient photovoltaic responses

Despite their potential to exceed the theoretical Shockley−Queisser limit, ferroelectric photovoltaics (FPVs) have performed inefficiently due to their extremely low photocurrents. Incorporating Bi₂FeCrO₆(BFCO) as the light absorber in FPVs has recently led to impressively high and record photocurrents [Nechache R, et al. (2015) Nat Photonics 9:61–67], which has revived the FPV field. However, our understanding of this remarkable phenomenon is far from satisfactory. Here, we use first-principles calculations to determine that such excellent performance mainly lies in the efficient separation of electron− hole (e-h) pairs. We show that photoexcited electrons and holes in BFCO are spatially separated on the Fe and Cr sites, respectively. This separation is much more pronounced in disordered BFCO phases, which adequately explains the observed exceptional PV responses. We further establish a design strategy to discover next-generation FPV materials. By exploring 44 additional Bi-based double-perovskite oxides, we suggest five active-layer materials that offer a combination of strong e-h separations and visible-light absorptions for FPV applications. Our work indicates that charge separation is the most important issue to be addressed for FPVs to compete with conventional devices. Keywords: ferroelectrics; double perovskites; photovoltaics; e-h separation; density functional theor

Autophagy Induction Is a Tor- and Tp53-Independent Cell Survival Response in a Zebrafish Model of Disrupted Ribosome Biogenesis

Ribosome biogenesis underpins cell growth and division. Disruptions in ribosome biogenesis and translation initiation are deleterious to development and underlie a spectrum of diseases known collectively as ribosomopathies. Here, we describe a novel zebrafish mutant, titania (tti(s450)), which harbours a recessive lethal mutation in pwp2h, a gene encoding a protein component of the small subunit processome. The biochemical impacts of this lesion are decreased production of mature 18S rRNA molecules, activation of Tp53, and impaired ribosome biogenesis. In tti(s450), the growth of the endodermal organs, eyes, brain, and craniofacial structures is severely arrested and autophagy is up-regulated, allowing intestinal epithelial cells to evade cell death. Inhibiting autophagy in tti(s450) larvae markedly reduces their lifespan. Somewhat surprisingly, autophagy induction in tti(s450) larvae is independent of the state of the Tor pathway and proceeds unabated in Tp53-mutant larvae. These data demonstrate that autophagy is a survival mechanism invoked in response to ribosomal stress. This response may be of relevance to therapeutic strategies aimed at killing cancer cells by targeting ribosome biogenesis. In certain contexts, these treatments may promote autophagy and contribute to cancer cells evading cell death.This research was funded by the National Health and Medical Research Council of Australia through Project grant 433614 (JKH), Program grant 487922 (JKH), a Senior Research Fellowship (JKH), and a Howard Florey Centenary Fellowship (HV). Operational Infrastructure Support was provided by the Victorian Government, Australia. Additional support was from Australian Research Council grant DP0346823 (GJL); NIH grant DK060322 (DYRS); and CDMRP, Department of Defense, USA W81XWH-10-1-0854 (KCE)

Virchow: A Million-Slide Digital Pathology Foundation Model

Computational pathology uses artificial intelligence to enable precision medicine and decision support systems through the analysis of whole slide images. It has the potential to revolutionize the diagnosis and treatment of cancer. However, a major challenge to this objective is that for many specific computational pathology tasks the amount of data is inadequate for development. To address this challenge, we created Virchow, a 632 million parameter deep neural network foundation model for computational pathology. Using self-supervised learning, Virchow is trained on 1.5 million hematoxylin and eosin stained whole slide images from diverse tissue groups, which is orders of magnitude more data than previous works. When evaluated on downstream tasks including tile-level pan-cancer detection and subtyping and slide-level biomarker prediction, Virchow outperforms state-of-the-art systems both on internal datasets drawn from the same population as the pretraining data as well as external public datasets. Virchow achieves 93% balanced accuracy for pancancer tile classification, and AUCs of 0.983 for colon microsatellite instability status prediction and 0.967 for breast CDH1 status prediction. The gains in performance highlight the importance of pretraining on massive pathology image datasets, suggesting pretraining on even larger datasets could continue improving performance for many high-impact applications where limited amounts of training data are available, such as drug outcome prediction

sox9b Is a Key Regulator of Pancreaticobiliary Ductal System Development

The pancreaticobiliary ductal system connects the liver and pancreas to the intestine. It is composed of the hepatopancreatic ductal (HPD) system as well as the intrahepatic biliary ducts and the intrapancreatic ducts. Despite its physiological importance, the development of the pancreaticobiliary ductal system remains poorly understood. The SRY-related transcription factor SOX9 is expressed in the mammalian pancreaticobiliary ductal system, but the perinatal lethality of Sox9 heterozygous mice makes loss-of-function analyses challenging. We turned to the zebrafish to assess the role of SOX9 in pancreaticobiliary ductal system development. We first show that zebrafish sox9b recapitulates the expression pattern of mouse Sox9 in the pancreaticobiliary ductal system and use a nonsense allele of sox9b, sox9bfh313, to dissect its function in the morphogenesis of this structure. Strikingly, sox9bfh313 homozygous mutants survive to adulthood and exhibit cholestasis associated with hepatic and pancreatic duct proliferation, cyst formation, and fibrosis. Analysis of sox9bfh313 mutant embryos and larvae reveals that the HPD cells appear to mis-differentiate towards hepatic and/or pancreatic fates, resulting in a dysmorphic structure. The intrahepatic biliary cells are specified but fail to assemble into a functional network. Similarly, intrapancreatic duct formation is severely impaired in sox9bfh313 mutants, while the embryonic endocrine and acinar compartments appear unaffected. The defects in the intrahepatic and intrapancreatic ducts of sox9bfh313 mutants worsen during larval and juvenile stages, prompting the adult phenotype. We further show that Sox9b interacts with Notch signaling to regulate intrahepatic biliary network formation: sox9b expression is positively regulated by Notch signaling, while Sox9b function is required to maintain Notch signaling in the intrahepatic biliary cells. Together, these data reveal key roles for SOX9 in the morphogenesis of the pancreaticobiliary ductal system, and they cast human Sox9 as a candidate gene for pancreaticobiliary duct malformation-related pathologies

Sfrp5 Modulates Both Wnt and BMP Signaling and Regulates Gastrointestinal Organogensis in the Zebrafish, Danio rerio

Sfrp5 belongs to the family of secreted frizzled related proteins (Sfrp), secreted inhibitors of Wingless-MMTV Integration Site (Wnt) signaling, which play an important role in cancer and development. We selected sfrp5 because of its compelling expression profile in the developing endoderm in zebrafish, Danio rerio. In this study, overexpression of sfrp5 in embryos results in defects in both convergent extension (CE) by inhibition of non-canonical Wnt signaling and defects in dorsoventral patterning by inhibition of Tolloid-mediated proteolysis of the BMP inhibitor Chordin. From 25 hours post fertilization (hpf) to 3 days post fertilization (dpf), both overexpression and knockdown of Sfrp5 decrease the size of the endoderm, significantly reducing liver cell number. At 3 dpf, insulin-positive endodermal cells fail to coalesce into a single pancreatic islet. We show that Sfrp5 inhibits both canonical and non-canonical Wnt signaling during embryonic and endodermal development, resulting in endodermal abnormalities. © 2013 Stuckenholz et al

Taxation and market power

"We analyze the incidence and welfare effects of unit sales taxes in experimental monopoly and Bertrand markets. We find, in line with economic theory, that firms with no market power are able to shift a high share of a tax burden on to consumers, independent of whether buyers are automated or human players. In monopoly markets, a monopolist bears a large share of the burden of a tax increase. With human buyers, however, this share is smaller than with automated buyers as the presence of human buyers constrains the pricing behavior of a monopolist." (author's abstract)"Dieser Artikel untersucht Inzidenz- und Wohlfahrtseffekte einer Mengensteuer in experimentellen Monopol- und Bertrand-Märkten. Im Einklang mit der ökonomischen Theorie sind Firmen ohne Marktmacht in der Lage, einen großen Anteil der Last einer Steuererhöhung an die Konsumenten weiterzugeben. Dies gilt unabhängig davon, ob die Käufer simuliert sind oder die Kaufentscheidungen durch reale Käufer getroffen werden. In Monopolmärkten trägt der Monopolist einen großen Anteil der Last einer Steuererhöhung. Werden die Kaufentscheidungen durch reale Käufer getroffen, ist dieser Anteil jedoch kleiner als mit simulierten Käufern, da reale Käufer im Experiment das Preissetzungsverhalten des Monopolisten einschränken." (Autorenreferat

Genomic Insights Into The Ixodes scapularis Tick Vector Of Lyme Disease

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retrotransposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing B57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick–host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host ‘questing’, prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent