A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies.

Primary cilia organize Hedgehog signaling and shape embryonic development, and their dysregulation is the unifying cause of ciliopathies. We conducted a functional genomic screen for Hedgehog signaling by engineering antibiotic-based selection of Hedgehog-responsive cells and applying genome-wide CRISPR-mediated gene disruption. The screen can robustly identify factors required for ciliary signaling with few false positives or false negatives. Characterization of hit genes uncovered novel components of several ciliary structures, including a protein complex that contains δ-tubulin and ε-tubulin and is required for centriole maintenance. The screen also provides an unbiased tool for classifying ciliopathies and showed that many congenital heart disorders are caused by loss of ciliary signaling. Collectively, our study enables a systematic analysis of ciliary function and of ciliopathies, and also defines a versatile platform for dissecting signaling pathways through CRISPR-based screening

The Diboson Excess: Experimental Situation and Classification of Explanations; A Les Houches Pre-Proceeding

We examine the `diboson' excess at $\sim 2$ TeV seen by the LHC experiments in various channels. We provide a comparison of the excess significances as a function of the mass of the tentative resonance and give the signal cross sections needed to explain the excesses. We also present a survey of available theoretical explanations of the resonance, classified in three main approaches. Beyond that, we discuss methods to verify the anomaly, determining the major properties of the various surpluses and exploring how different models can be discriminated. Finally, we give a tabular summary of the numerous explanations, presenting their main phenomenological features.Comment: 37 pages, 9 Figures, 1 Tabl

The Borrelia afzelii outer membrane protein BAPKO_0422 binds human Factor-H and is predicted to form a membrane-spanning beta-barrel

The deep evolutionary history of the Spirochetes places their branch point early in the evolution of the diderms, before the divergence of the present day Proteobacteria. As a Spirochete, the morphology of the Borrelia cell envelope shares characteristics of both Gram-positive and Gram-negative bacteria. A thin layer of peptidoglycan, tightly associated with the cytoplasmic membrane is surrounded by a more labile outer membrane (OM). This OM is rich in lipoproteins but with few known integral membrane proteins. The OmpA domain is an eight-stranded membrane-spanning β-barrel, highly conserved among the Proteobacteria but so far unknown in the Spirochetes. In the present work we describe the identification of four novel OmpA-like β-barrels from Borrelia afzelii, the most common cause of erythema migrans rash in Europe. Structural characterisation of one these proteins (BAPKO_0422) by small angle X-ray scattering (SAXS) and circular dichroism indicate a compact globular structure rich in β-strand consistent with a monomeric β-barrel. Ab initio molecular envelopes calculated from the scattering profile are consistent with homology models and demonstrate that BAPKO_0422 adopts a peanut shape with dimensions 25 x 45 Å. Deviations from the standard C-terminal signature sequence are apparent; in particular the C-terminal Phe residue commonly found in Proteobacterial OM proteins is replaced by Ile/Leu or Asn. BAPKO_0422 is demonstrated to bind human factor-H and therefore may contribute to immune evasion by inhibition of the complement response. Encoded by chromosomal genes, these proteins are highly conserved between Borrelia subspecies and may be of diagnostic or therapeutic value

Direct detection of Higgs-portal dark matter at the LHC

We consider the process in which a Higgs particle is produced in association with jets and show that monojet searches at the LHC already provide interesting constraints on the invisible decays of a 125 GeV Higgs boson. Using the existing monojet searches performed by CMS and ATLAS, we show the 95% confidence level limit on the invisible Higgs decay rate is of the order of the total Higgs production rate in the Standard Model. This limit could be significantly improved when more data at higher center of mass energies are collected, provided systematic errors on the Standard Model contribution to the monojet background can be reduced. We also compare these direct constraints on the invisible rate with indirect ones based on measuring the Higgs rates in visible channels. In the context of Higgs portal models of dark matter, we then discuss how the LHC limits on the invisible Higgs branching fraction impose strong constraints on the dark matter scattering cross section on nucleons probed in direct detection experiments.Comment: 6 pages, 3 figures; v2: references added; v3: monojet and Higgs data updated, version published in EPJ

Updating Maryland\u27s Sea-level Rise Projections

With its 3,100 miles of tidal shoreline and low-lying rural and urban lands, The Free State is one of the most vulnerable to sea-level rise. Historically, Marylanders have long had to contend with rising water levels along its Chesapeake Bay and Atlantic Ocean and coastal bay shores. Shorelines eroded and low-relief lands and islands, some previously inhabited, were inundated. Prior to the 20th century, this was largely due to the slow sinking of the land since Earth’s crust is still adjusting to the melting of large masses of ice following the last glacial period. Over the 20th century, however, the rate of rise of the average level of tidal waters with respect to land, or relative sea-level rise, has increased, at least partially as a result of global warming. Moreover, the scientific evidence is compelling that Earth’s climate will continue to warm and its oceans will rise even more rapidly. Recognizing the scientific consensus around global climate change, the contribution of human activities to it, and the vulnerability of Maryland’s people, property, public investments, and natural resources, Governor Martin O’Malley established the Maryland Commission on Climate Change on April 20, 2007. The Commission produced a Plan of Action1 that included a comprehensive climate change impact assessment, a greenhouse gas reduction strategy, and strategies for reducing Maryland’s vulnerability to climate change. The Plan has led to landmark legislation to reduce the state’s greenhouse gas emissions and a variety of state policies designed to reduce energy consumption and promote adaptation to climate change

ScreenTrack: Using a Visual History of a Computer Screen to Retrieve Documents and Web Pages

Computers are used for various purposes, so frequent context switching is inevitable. In this setting, retrieving the documents, files, and web pages that have been used for a task can be a challenge. While modern applications provide a history of recent documents for users to resume work, this is not sufficient to retrieve all the digital resources relevant to a given primary document. The histories currently available do not take into account the complex dependencies among resources across applications. To address this problem, we tested the idea of using a visual history of a computer screen to retrieve digital resources within a few days of their use through the development of ScreenTrack. ScreenTrack is software that captures screenshots of a computer at regular intervals. It then generates a time-lapse video from the captured screenshots and lets users retrieve a recently opened document or web page from a screenshot after recognizing the resource by its appearance. A controlled user study found that participants were able to retrieve requested information more quickly with ScreenTrack than under the baseline condition with existing tools. A follow-up study showed that the participants used ScreenTrack to retrieve previously used resources and to recover the context for task resumption.Comment: CHI 2020, 10 pages, 7 figure

Observation of Exclusive Two-Body B Decays to Kaons and Pions

We have studied two-body charmless hadronic decays of B mesons into the final states $\pi\pi$, $K \pi$, and $KK$. Using 3.3 million $B\bar{B}$ pairs collected with the CLEO-II detector, we have made the first observation of the decays $B^0\to K^+\pi^-$, $B^+\to K^0\pi^+$, and the sum of $B^+ \to \pi^+\pi^0$ and $B^+ \to K^+\pi^0$ decays (an average over charge-conjugate states is always implied). We place upper limits on branching fractions for the remaining decay modes.Comment: 9 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Longitudinal maturation of auditory cortical function during adolescence

Cross-sectional studies have demonstrated that the cortical auditory evoked potential (CAEP) changes substantially in amplitude and latency from childhood to adulthood, suggesting that these aspects of the CAEP continue to mature through adolescence. However, no study to date has longitudinally followed maturation of these CAEP measures through this developmental period. Additionally, no study has examined the trial-to-trial variability of the CAEP during adolescence. Therefore, we longitudinally tracked changes in the latency, amplitude, and variability of the P1, N1, P2, and N2 components of the CAEP in 68 adolescents from age 14 years to age 17 years. Latency decreased for N1 and N2, and did not change for P1 or P2. Amplitude decreased for P1 and N2, increased for N1, and did not change for P2. Variability decreased with age for all CAEP components. These findings provide longitudinal support for the view that the human auditory system continues to mature through adolescence. Continued auditory system maturation through adolescence suggests that CAEP neural generators remain plastic during this age range and potentially amenable to experience-based enhancement or deprivation

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured