A Bootstrapping Approach for Generating Maximally Path-Entangled Photon States

We propose a bootstrapping approach to generation of maximally path-entangled states of photons, so called ``NOON states''. Strong atom-light interaction of cavity QED can be employed to generate NOON states with about 100 photons; which can then be used to boost the existing experimental Kerr nonlinearities based on quantum coherence effects to facilitate NOON generation with arbitrarily large number of photons all within the current experimental state of the art technology. We also offer an alternative scheme that uses an atom-cavity dispersive interaction to obtain sufficiently high Kerr-nonlinearity necessary for arbitrary NOON generation

MLA Research Agenda: Appraising the Best Available Evidence

Offers guidelines for the formation and self-governance of autonomous teams as they conduct systematic reviews related to the MLA Research Agenda

A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes

Securin inhibits the protease separase and must be removed before anaphase to ensure timely chromosome segregation. Here, the authors define a mechanism of securin destruction in prometaphase I in mouse oocytes and demonstrate its importance for successful meiotic progression

Discrimination of Methionine Sulfoxide and Sulfone by Human Neutrophil Elastase

Human neutrophil elastase (HNE) is a uniquely destructive serine protease with the ability to unleash a wave of proteolytic activity by destroying the inhibitors of other proteases. Although this phenomenon forms an important part of the innate immune response to invading pathogens, it is responsible for the collateral host tissue damage observed in chronic conditions such as chronic obstructive pulmonary disease (COPD), and in more acute disorders such as the lung injuries associated with COVID-19 infection. Previously, a combinatorially selected activity-based probe revealed an unexpected substrate preference for oxidised methionine, which suggests a link to oxida-tive pathogen clearance by neutrophils. Here we use oxidised model substrates and inhibitors to confirm this observation and to show that neutrophil elastase is specifically selective for the di-oxygenated methionine sulfone rather than the mono-oxygenated methionine sulfoxide. We also posit a critical role for ordered solvent in the mechanism of HNE discrimination between the two oxidised forms methionine residue. Preference for the sulfone form of oxidised methionine is especially significant. While both host and pathogens have the ability to reduce methionine sulfoxide back to methionine, a biological pathway to reduce methionine sulfone is not known. Taken to-gether, these data suggest that the oxidative activity of neutrophils may create rapidly cleaved elas-tase “super substrates” that directly damage tissue, while initiating a cycle of neutrophil oxidation that increases elastase tissue damage and further neutrophil recruitment

Malaysia Airlines flight MH370 search data reveal geomorphology and seafloor processes in the remote southeast Indian Ocean

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Marine Geology 395 (2018): 301-319, doi:10.1016/j.margeo.2017.10.014.A high-resolution multibeam echosounder (MBES) dataset covering over 279,000 km2 was acquired in the southeastern Indian Ocean to assist the search for Malaysia Airlines Flight 370 (MH370) that disappeared on 8 March 2014. The data provided an essential geospatial framework for the search and is the first large-scale coverage of MBES data in this region. Here we report on geomorphic analyses of the new MBES data, including a comparison with the Global Seafloor Geomorphic Features Map (GSFM) that is based on coarser resolution satellite altimetry data, and the insights the new data provide into geological processes that have formed and are currently shaping this remote deepsea area. Our comparison between the new MBES bathymetric model and the latest global topographic/bathymetric model (SRTM15_plus) reveals that 62% of the satellite-derived data points for the study area are comparable with MBES measurements within the estimated vertical uncertainty of the SRTM15_plus model (± 100 m). However, > 38% of the SRTM15_plus depth estimates disagree with the MBES data by > 100 m, in places by up to 1900 m. The new MBES data show that abyssal plains and basins in the study area are significantly more rugged than their representation in the GSFM, with a 20% increase in the extent of hills and mountains. The new model also reveals four times more seamounts than presented in the GSFM, suggesting more of these features than previously estimated for the broader region. This is important considering the ecological significance of high-relief structures on the seabed, such as hosting high levels of biodiversity. Analyses of the new data also enabled sea knolls, fans, valleys, canyons, troughs, and holes to be identified, doubling the number of discrete features mapped. Importantly, mapping the study area using MBES data improves our understanding of the geological evolution of the region and reveals a range of modern sedimentary processes. For example, a large series of ridges extending over approximately 20% of the mapped area, in places capped by sea knolls, highlight the preserved seafloor spreading fabric and provide valuable insights into Southeast Indian Ridge seafloor spreading processes, especially volcanism. Rifting is also recorded along the Broken Ridge – Diamantina Escarpment, with rift blocks and well-bedded sedimentary bedrock outcrops discernible down to 2400 m water depth. Modern ocean floor sedimentary processes are documented by sediment mass transport features, especially along the northern margin of Broken Ridge, and in pockmarks (the finest-scale features mapped), which are numerous south of Diamantina Trench and appear to record gas and/or fluid discharge from underlying marine sediments. The new MBES data highlight the complexity of the search area and serve to demonstrate how little we know about the vast areas of the ocean that have not been mapped with MBES. The availability of high-resolution and accurate maps of the ocean floor can clearly provide new insights into the Earth's geological evolution, modern ocean floor processes, and the location of sites that are likely to have relatively high biodiversity

Characterization of glycan substrates accumulating in GM1 Gangliosidosis

Introduction: GM1 gangliosidosis is a rare autosomal recessive genetic disorder caused by the disruption of the GLB1 gene that encodes β-galactosidase, a lysosomal hydrolase that removes β-linked galactose from the non-reducing end of glycans. Deficiency of this catabolic enzyme leads to the lysosomal accumulation of GM1 and its asialo derivative GA1 in β-galactosidase deficient patients and animal models. In addition to GM1 and GA1, there are other glycoconjugates that contain β-linked galactose whose metabolites are substrates for β-galactosidase. For example, a number of N-linked glycan structures that have galactose at their non-reducing end have been shown to accumulate in GM1 gangliosidosis patient tissues and biological fluids. Objective: In this study, we attempt to fully characterize the broad array of GLB1 substrates that require GLB1 for their lysosomal turnover. Results: Using tandem mass spectrometry and glycan reductive isotope labeling with data-dependent mass spectrometry, we have confirmed the accumulation of glycolipids (GM1 and GA1) and N-linked glycans with terminal beta-linked galactose. We have also discovered a novel set of core 1 and 2 O-linked glycan metabolites, many of which are part of structurally-related isobaric series that accumulate in disease. In the brain of GLB1 null mice, the levels of these glycan metabolites increased along with those of both GM1 and GA1 as a function of age. In addition to brain tissue, we found elevated levels of both N-linked and O-linked glycan metabolites in a number of peripheral tissues and in urine. Both brain and urine samples from human GM1 gangliosidosis patients exhibited large increases in steady state levels for the same glycan metabolites, demonstrating their correlation with this disease in humans as well. Conclusions: Our studies illustrate that GLB1 deficiency is not purely a ganglioside accumulation disorder, but instead a broad oligosaccharidosis that include representatives of many β-linked galactose containing glycans and glycoconjugates including glycolipids, N-linked glycans, and various O-linked glycans. Accounting for all β-galactosidase substrates that accumulate when this enzyme is deficient increases our understanding of this severe disorder by identifying metabolites that may drive certain aspects of the disease and may also serve as informative disease biomarkers to fully evaluate the efficacy of future therapies

The potential and value of objective eye tracking in the ophthalmology clinic

Numerous research studies have demonstrated the scope and value of eye movement recording (EMR). There is now potential for EMR to be helpful in a range of clinical contexts and it could be developed as a routine part of the repertoire of clinical investigations offered by the NHS, at least in tertiary centres. We highlight potential uses and challenges below, as a prelude to further development and debat

Rediscovery of the Threatened River Sharks, Glyphis garricki and G. glyphis, in Papua New Guinea

Recent surveys of the shark and ray catches of artisanal fishers in the Western Province of Papua New Guinea (PNG) resulted in the rediscovery of the threatened river sharks, Glyphis garricki and Glyphis glyphis. These represent the first records of both species in PNG since the 1960s and 1970s and highlight the lack of studies of shark biodiversity in PNG. Two individuals of G. garricki and three individuals of G. glyphis were recorded from coastal marine waters of the Daru region of PNG in October and November 2014. The two G. garricki specimens were small individuals estimated to be 100–105 cm and ~113 cm total length (TL). The three G. glyphis specimens were all mature, one a pregnant female and two adult males. These are the first adults of G. glyphis recorded to date providing a more accurate maximum size for this species, i.e. ~260 cm TL. A single pup which was released from the pregnant female G. glyphis, was estimated to be ~65 cm TL. Anecdotal information from the fishers of pregnant females of G. glyphis containing 6 or 7 pups provides the first estimate of litter size for this species. The jaws of the pregnant female G. glyphis were retained and a detailed description of the dentition is provided, since adult dentition has not been previously documented for this species. Genetic analyses confirmed the two species cluster well within samples from these species collected in northern Australia

CD163 versus CD68 in tumor associated macrophages of classical hodgkin lymphoma

Classical Hodgkin lymphoma (CHL) is a B-cell lymphoproliferative disorder with a relatively good prognosis. A small but significant percentage of patients, however, will respond poorly to therapy. A recent gene expression profiling study has identified a macrophage signature which has been correlated with primary treatment failure, and immunohistochemical tissue microarray for CD68 was shown to reflect the gene signature as a potentially clinically useful marker to predict adverse prognosis

Ambient vibration tests of a cross-laminated timber building

Cross-laminated timber has, in the last 6 years, been used for the first time to form shear walls and cores in multi-storey buildings of seven storeys or more. Such buildings can have low mass in comparison to conventional structural forms. This low mass means that, as cross-laminated timber is used for taller buildings still, their dynamic movement under wind load is likely to be a key design parameter. An understanding of dynamic lateral stiffness and damping, which has so far been insufficiently researched, will be vital to the effective design for wind-induced vibration. In this study, an ambient vibration method is used to identify the dynamic properties of a seven-storey cross-laminated timber building in situ. The random decrement method is used, along with the Ibrahim time domain method, to extract the modal properties of the structure from the acceleration measured under ambient conditions. The results show that this output-only modal analysis method can be used to extract modal information from such a building, and that information is compared with a simple structural model. Measurements on two occasions during construction show the effect of non-structural elements on the modal properties of the structure