A mutate-and-map protocol for inferring base pairs in structured RNA

Chemical mapping is a widespread technique for structural analysis of nucleic acids in which a molecule's reactivity to different probes is quantified at single-nucleotide resolution and used to constrain structural modeling. This experimental framework has been extensively revisited in the past decade with new strategies for high-throughput read-outs, chemical modification, and rapid data analysis. Recently, we have coupled the technique to high-throughput mutagenesis. Point mutations of a base-paired nucleotide can lead to exposure of not only that nucleotide but also its interaction partner. Carrying out the mutation and mapping for the entire system gives an experimental approximation of the molecules contact map. Here, we give our in-house protocol for this mutate-and-map strategy, based on 96-well capillary electrophoresis, and we provide practical tips on interpreting the data to infer nucleic acid structure.Comment: 22 pages, 5 figure

Interacting Supernovae: Types IIn and Ibn

Supernovae (SNe) that show evidence of strong shock interaction between their ejecta and pre-existing, slower circumstellar material (CSM) constitute an interesting, diverse, and still poorly understood category of explosive transients. The chief reason that they are extremely interesting is because they tell us that in a subset of stellar deaths, the progenitor star may become wildly unstable in the years, decades, or centuries before explosion. This is something that has not been included in standard stellar evolution models, but may significantly change the end product and yield of that evolution, and complicates our attempts to map SNe to their progenitors. Another reason they are interesting is because CSM interaction is an efficient engine for making bright transients, allowing super-luminous transients to arise from normal SN explosion energies, and allowing transients of normal SN luminosities to arise from sub-energetic explosions or low radioactivity yield. CSM interaction shrouds the fast ejecta in bright shock emission, obscuring our normal view of the underlying explosion, and the radiation hydrodynamics of the interaction is challenging to model. The CSM interaction may also be highly non-spherical, perhaps linked to binary interaction in the progenitor system. In some cases, these complications make it difficult to definitively tell the difference between a core-collapse or thermonuclear explosion, or to discern between a non-terminal eruption, failed SN, or weak SN. Efforts to uncover the physical parameters of individual events and connections to possible progenitor stars make this a rapidly evolving topic that continues to challenge paradigms of stellar evolution.Comment: Final draft of a chapter in the "SN Handbook". Accepted. 25 pages, 3 fig

A New Era in the Quest for Dark Matter

There is a growing sense of `crisis' in the dark matter community, due to the absence of evidence for the most popular candidates such as weakly interacting massive particles, axions, and sterile neutrinos, despite the enormous effort that has gone into searching for these particles. Here, we discuss what we have learned about the nature of dark matter from past experiments, and the implications for planned dark matter searches in the next decade. We argue that diversifying the experimental effort, incorporating astronomical surveys and gravitational wave observations, is our best hope to make progress on the dark matter problem.Comment: Published in Nature, online on 04 Oct 2018. 13 pages, 1 figur

Classical Effective Field Theory for Weak Ultra Relativistic Scattering

Inspired by the problem of Planckian scattering we describe a classical effective field theory for weak ultra relativistic scattering in which field propagation is instantaneous and transverse and the particles' equations of motion localize to the instant of passing. An analogy with the non-relativistic (post-Newtonian) approximation is stressed. The small parameter is identified and power counting rules are established. The theory is applied to reproduce the leading scattering angle for either a scalar interaction field or electro-magnetic or gravitational; to compute some subleading corrections, including the interaction duration; and to allow for non-zero masses. For the gravitational case we present an appropriate decomposition of the gravitational field onto the transverse plane together with its whole non-linear action. On the way we touch upon the relation with the eikonal approximation, some evidence for censorship of quantum gravity, and an algebraic ring structure on 2d Minkowski spacetime.Comment: 29 pages, 2 figures. v4: Duration of interaction is determined in Sec 4 and detailed in App C. Version accepted for publication in JHE

Effectiveness of mobile-phone short message service (SMS) reminders for ophthalmology outpatient appointments: Observational study

Abstract Background Non-attendance for hospital outpatient appointments is a significant problem in many countries. It causes suboptimal use of clinical and administrative staff and financial losses, as well as longer waiting times. The use of Short Message Service (SMS) appointment reminders potentially offers a cost-effective and time-efficient strategy to decrease non-attendance and so improve the efficiency of outpatient healthcare delivery. Methods An SMS text message was sent to patients with scheduled appointments between April and September 2006 in a hospital ophthalmology department in London, reminding them of their appointments. This group acted as the intervention group. Controls were patients with scheduled ophthalmology appointments who did not receive an SMS or any alternative reminder. Results During the period of the study, 11.2% (50/447) of patients who received an SMS appointment reminder were non-attenders, compared to 18.1% (1720/9512) who did not receive an SMS reminder. Non-attendance rates were 38% lower in patients who received an SMS reminder than in patients who did not receive a reminder (RR of non-attendance = 0.62; 95% CI = 0.48 – 0.80). Conclusion The use of SMS reminders for ophthalmology outpatient appointments was associated with a reduction of 38% in the likelihood of patients not attending their appointments, compared to no appointment reminder. The use of SMS reminders may also be more cost-effective than traditional appointment reminders and require less labour. These findings should be confirmed with a more rigorous study design before a wider roll-out.</p

SH2 domains serve as lipid binding modules for pTyr-signaling proteins

The Src-homology 2 (SH2) domain is a protein interaction domain that directs myriad phosphotyrosine (pY)-signaling pathways. Genome-wide screening of human SH2 domains reveals that similar to 90% of SH2 domains bind plasma membrane lipids and many have high phosphoinositide specificity. They bind lipids using surface cationic patches separate from pY-binding pockets, thus binding lipids and the pY motif independently. The patches form grooves for specific lipid headgroup recognition or flat surfaces for non-specific membrane binding and both types of interaction are important for cellular function and regulation of SH2 domain-containing proteins. Cellular studies with ZAP70 showed that multiple lipids bind its C-terminal SH2 domain in a spatiotemporally specific manner and thereby exert exquisite spatiotemporal control over its protein binding and signaling activities in T cells. Collectively, this study reveals how lipids control SH2 domain-mediated cellular protein-protein interaction networks and suggest a new strategy for therapeutic modulation of pY-signaling pathways.112620Ysciescopu

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Accreting Black Holes

This chapter provides a general overview of the theory and observations of black holes in the Universe and on their interpretation. We briefly review the black hole classes, accretion disk models, spectral state classification, the AGN classification, and the leading techniques for measuring black hole spins. We also introduce quasi-periodic oscillations, the shadow of black holes, and the observations and the theoretical models of jets.Comment: 41 pages, 18 figures. To appear in "Tutorial Guide to X-ray and Gamma-ray Astronomy: Data Reduction and Analysis" (Ed. C. Bambi, Springer Singapore, 2020). v3: fixed some typos and updated some parts. arXiv admin note: substantial text overlap with arXiv:1711.1025

Analysis of Variation in Total Airborne Bacteria Concentration to Assess the Performance of Biological Safety Cabinets in Microbial Laboratories

Background: The purpose of this study was to compare the concentration of total airborne bacteria (TAB) in biosafety cabinets (BSCs) at universities and hospital microbial laboratories to assess the performance of BSCs. Methods: TAB was determined by using the single-stage Anderson sampler (BioStage Viable Cascade Impactor). The samples were obtained three times (with the BSC turned off and the shield open; with the BSC turned off and the shield closed; and with the BSC tuned on and operating) from the areas in front of 11 BSCs. Results: TAB concentrations of accredited and nonaccredited BSCs were determined. No significant differences were observed in the TAB concentrations of the accredited BSCs and the nonaccredited BSCs for the areas outside the BSCs in the laboratories (p > 0.05). TAB concentrations for the BSCs sampled with the shield open and the instrument turned off showed differences based on the sampling site outside the BSC in each laboratory. Conclusion: These results imply that TAB concentration is not altered by the performance of the BSCs or TAB itself and/or concentration of TAB outside the BSC is not a good index of BSC performance

Bio-Inspired Preparation of Clay–Hexacyanoferrate Composite Hydrogels as Super Adsorbents for Cs+

A facile and low-cost fabrication route, inspired by the adhesive proteins secreted by mussels, has been developed to prepare a clay-based composite hydrogel (DHG(Cu)) containing hexacyanoferrate (HCF) nanoparticles for the selective removal of Cs+ from contaminated water. Initially, montmorillonite was exfoliated prior to coating with a thin layer of polydopamine (PDOPA) via the self-polymerization of dopamine. Mixing the composite (D-clay) with the HCF precursor, followed by the addition of copper ions, led to the self-assembly of the polymer-coated exfoliated clay nanosheets into a three-dimensional network and in situ growth of KCuHCF nanoparticles embedded within the gel structure. Analytical characterization verified the fabrication route and KCuHCF immobilization by a copper–ligand complexation. Rheology testing revealed the composite hydrogel to be elastic under low strain and exhibited reversible, self-healing behavior following high strain deformation, providing a good retention of KCuHCF nanoparticles in the membrane. The adsorbent DHG(Cu) showed a superior Cs+ adsorption capacity (∼173 mg/g), with the performance maintained over a wide pH range, and an excellent selectivity for Cs+ when dispersed in seawater at low concentrations of 0.2 ppm. On the basis of its excellent mechanico-chemical properties, the fabricated hydrogel was tested as a membrane in column filtration, showing excellent removal of Cs+ from Milli-Q water and seawater, with the performance only limited by the fluid residence time. For comparison, the study also considered other composite hydrogels, which were fabricated as intermediates of DHG(Cu) or fabricated with Fe3+ as the cross-linker and reactant for HCF nanoparticle synthesis