Alignment of optical system components using an ADM beam through a null assembly

A system for testing an optical surface includes a rangefinder configured to emit a light beam and a null assembly located between the rangefinder and the optical surface. The null assembly is configured to receive and to reflect the emitted light beam toward the optical surface. The light beam reflected from the null assembly is further reflected back from the optical surface toward the null assembly as a return light beam. The rangefinder is configured to measure a distance to the optical surface using the return light beam

Optical nulling apparatus and method for testing an optical surface

An optical nulling apparatus for testing an optical surface includes an aspheric mirror having a reflecting surface for imaging light near or onto the optical surface under test, where the aspheric mirror is configured to reduce spherical aberration of the optical surface under test. The apparatus includes a light source for emitting light toward the aspheric mirror, the light source longitudinally aligned with the aspheric mirror and the optical surface under test. The aspheric mirror is disposed between the light source and the optical surface under test, and the emitted light is reflected off the reflecting surface of the aspheric mirror and imaged near or onto the optical surface under test. An optical measuring device is disposed between the light source and the aspheric mirror, where light reflected from the optical surface under test enters the optical measuring device. An imaging mirror is disposed longitudinally between the light source and the aspheric mirror, and the imaging mirror is configured to again reflect light, which is first reflected from the reflecting surface of the aspheric mirror, onto the optical surface under test

HmuY Haemophore and Gingipain Proteases Constitute a Unique Syntrophic System of Haem Acquisition by Porphyromonas gingivalis

Haem (iron protoporphyrin IX) is both an essential growth factor and virulence regulator for the periodontal pathogen Porphyromonas gingivalis, which acquires it mainly from haemoglobin via the sequential actions of the R- and K-specific gingipain proteases. The haem-binding lipoprotein haemophore HmuY and its cognate receptor HmuR of P. gingivalis, are responsible for capture and internalisation of haem. This study examined the role of the HmuY in acquisition of haem from haemoglobin and the cooperation between HmuY and gingipain proteases in this process. Using UV-visible spectroscopy and polyacrylamide gel electrophoresis, HmuY was demonstrated to wrest haem from immobilised methaemoglobin and deoxyhaemoglobin. Haem extraction from oxyhaemoglobin was facilitated after oxidation to methaemoglobin by pre-treatment with the P. gingivalis R-gingipain A (HRgpA). HmuY was also capable of scavenging haem from oxyhaemoglobin pre-treated with the K-gingipain (Kgp). This is the first demonstration of a haemophore working in conjunction with proteases to acquire haem from haemoglobin. In addition, HmuY was able to extract haem from methaemalbumin, and could bind haem, either free in solution or from methaemoglobin, even in the presence of serum albumin

The Solute Carrier MFSD1 Decreases the Activation Status of β1 Integrin and Thus Tumor Metastasis

Solute carriers are increasingly recognized as participating in a plethora of pathologies, including cancer. We describe here the involvement of the orphan solute carrier Major Facilitator Superfamily Domain-containing protein 1 (MFSD1) in the regulation of tumor cell migration. Loss of MFSD1 enabled higher levels of metastasis in experimental and spontaneous metastasis mouse models. We identified an increased migratory potential in MFSD1-/- tumor cells which was mediated by increased focal adhesion turnover, reduced stability of mature inactive β1 integrin, and the resulting increased integrin activation index. We show that MFSD1 promoted recycling to the cell surface of endocytosed inactive β1 integrin and thereby protected β1 integrin from proteolytic degradation; this led to dampening of the integrin activation index. Furthermore, downregulation of MFSD1 expression was observed during the early steps of tumorigenesis, and higher MFSD1 expression levels correlate with a better cancer patient prognosis. In sum, we describe a requirement for endolysosomal MFSD1 in efficient β1 integrin recycling to suppress tumor cell dissemination

An increasing number of convolutional neural networks for fracture recognition and classification in orthopaedics:are these externally validated and ready for clinical application?

Aims: The number of convolutional neural networks (CNN) available for fracture detection and classification is rapidly increasing. External validation of a CNN on a temporally separate (separated by time) or geographically separate (separated by location) dataset is crucial to assess generalizability of the CNN before application to clinical practice in other institutions. We aimed to answer the following questions: are current CNNs for fracture recognition externally valid?; which methods are applied for external validation (EV)?; and, what are reported performances of the EV sets compared to the internal validation (IV) sets of these CNNs? Methods: The PubMed and Embase databases were systematically searched from January 2010 to October 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The type of EV, characteristics of the external dataset, and diagnostic performance characteristics on the IV and EV datasets were collected and compared. Quality assessment was conducted using a seven-item checklist based on a modified Methodologic Index for NOn-Randomized Studies instrument (MINORS). Results: Out of 1,349 studies, 36 reported development of a CNN for fracture detection and/or classification. Of these, only four (11%) reported a form of EV. One study used temporal EV, one conducted both temporal and geographical EV, and two used geographical EV. When comparing the CNN’s performance on the IV set versus the EV set, the following were found: AUCs of 0.967 (IV) versus 0.975 (EV), 0.976 (IV) versus 0.985 to 0.992 (EV), 0.93 to 0.96 (IV) versus 0.80 to 0.89 (EV), and F1-scores of 0.856 to 0.863 (IV) versus 0.757 to 0.840 (EV). Conclusion: The number of externally validated CNNs in orthopaedic trauma for fracture recognition is still scarce. This greatly limits the potential for transfer of these CNNs from the developing institute to another hospital to achieve similar diagnostic performance. We recommend the use of geographical EV and statements such as the Consolidated Standards of Reporting Trials–Artificial Intelligence (CONSORT-AI), the Standard Protocol Items: Recommendations for Interventional Trials–Artificial Intelligence (SPIRIT-AI) and the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis–Machine Learning (TRIPOD-ML) to critically appraise performance of CNNs and improve methodological rigor, quality of future models, and facilitate eventual implementation in clinical practice

The effects of supernovae on the dynamical evolution of binary stars and star clusters

In this chapter I review the effects of supernovae explosions on the dynamical evolution of (1) binary stars and (2) star clusters. (1) Supernovae in binaries can drastically alter the orbit of the system, sometimes disrupting it entirely, and are thought to be partially responsible for `runaway' massive stars - stars in the Galaxy with large peculiar velocities. The ejection of the lower-mass secondary component of a binary occurs often in the event of the more massive primary star exploding as a supernova. The orbital properties of binaries that contain massive stars mean that the observed velocities of runaway stars (10s - 100s km s$^{-1}$) are consistent with this scenario. (2) Star formation is an inherently inefficient process, and much of the potential in young star clusters remains in the form of gas. Supernovae can in principle expel this gas, which would drastically alter the dynamics of the cluster by unbinding the stars from the potential. However, recent numerical simulations, and observational evidence that gas-free clusters are observed to be bound, suggest that the effects of supernova explosions on the dynamics of star clusters are likely to be minimal.Comment: 16 pages, to appear in the 'Handbook of Supernovae', eds. Paul Murdin and Athem Alsabti. This version replaces an earlier version that contained several typo

Administration of Thimerosal to Infant Rats Increases Overflow of Glutamate and Aspartate in the Prefrontal Cortex: Protective Role of Dehydroepiandrosterone Sulfate

Thimerosal, a mercury-containing vaccine preservative, is a suspected factor in the etiology of neurodevelopmental disorders. We previously showed that its administration to infant rats causes behavioral, neurochemical and neuropathological abnormalities similar to those present in autism. Here we examined, using microdialysis, the effect of thimerosal on extracellular levels of neuroactive amino acids in the rat prefrontal cortex (PFC). Thimerosal administration (4 injections, i.m., 240 μg Hg/kg on postnatal days 7, 9, 11, 15) induced lasting changes in amino acid overflow: an increase of glutamate and aspartate accompanied by a decrease of glycine and alanine; measured 10–14 weeks after the injections. Four injections of thimerosal at a dose of 12.5 μg Hg/kg did not alter glutamate and aspartate concentrations at microdialysis time (but based on thimerosal pharmacokinetics, could have been effective soon after its injection). Application of thimerosal to the PFC in perfusion fluid evoked a rapid increase of glutamate overflow. Coadministration of the neurosteroid, dehydroepiandrosterone sulfate (DHEAS; 80 mg/kg; i.p.) prevented the thimerosal effect on glutamate and aspartate; the steroid alone had no influence on these amino acids. Coapplication of DHEAS with thimerosal in perfusion fluid also blocked the acute action of thimerosal on glutamate. In contrast, DHEAS alone reduced overflow of glycine and alanine, somewhat potentiating the thimerosal effect on these amino acids. Since excessive accumulation of extracellular glutamate is linked with excitotoxicity, our data imply that neonatal exposure to thimerosal-containing vaccines might induce excitotoxic brain injuries, leading to neurodevelopmental disorders. DHEAS may partially protect against mercurials-induced neurotoxicity

Glycation of Host Proteins Increases Pathogenic Potential of Porphyromonas gingivalis

The non-enzymatic addition of glucose (glycation) to circulatory and tissue proteins is a ubiquitous pathophysiological consequence of hyperglycemia in diabetes. Given the high incidence of periodontitis and diabetes and the emerging link between these conditions, it is of crucial importance to define the basic virulence mechanisms employed by periodontopathogens such as Porphyromonas gingivalis in mediating the disease process. The aim of this study was to determine whether glycated proteins are more easily utilized by P. gingivalis to stimulate growth and promote the pathogenic potential of this bacterium. We analyzed the properties of three commonly encountered proteins in the periodontal environment that are known to become glycated and that may serve as either protein substrates or easily accessible heme sources. In vitro glycated proteins were characterized using colorimetric assays, mass spectrometry, far- and near-UV circular dichroism and UV–visible spectroscopic analyses and SDS-PAGE. The interaction of glycated hemoglobin, serum albumin and type one collagen with P. gingivalis cells or HmuY protein was examined using spectroscopic methods, SDS-PAGE and co-culturing P. gingivalis with human keratinocytes. We found that glycation increases the ability of P. gingivalis to acquire heme from hemoglobin, mostly due to heme sequestration by the HmuY hemophore-like protein. We also found an increase in biofilm formation on glycated collagen-coated abiotic surfaces. We conclude that glycation might promote the virulence of P. gingivalis by making heme more available from hemoglobin and facilitating bacterial biofilm formation, thus increasing P. gingivalis pathogenic potential in vivo

Unilateral versus coordinated effects:comparing the impact on consumer welfare of alternative merger outcomes

The nature of tacitly collusive behaviour often makes coordination unstable, and this may result in periods of breakdown, during which consumers benet from reduced prices. This is allowed for by adding demand uncertainty to the Compte et al. (2002) model of tacit collusion amongst asymmetric rms. Breakdowns occur when a rm cannot exclude the possibility of a deviation by a rival. It is then possible that an outcome with collusive behaviour, subject to long/frequent break downs, can improve consumer welfare compared to an alternative with sustained unilateral conduct. This is illustrated by re-examining the Nestle/Perrier merger analyzed by Compte et al., but now also taking into account the potential for welfare losses arising from unilateral behaviour

Tacit collusion, firm asymmetries and numbers:evidence from EC merger cases

The purpose of this paper is to identify empirically the implicit structural model, especially the roles of size asymmetries and concentration, used by the European Commission to identify mergers with coordinated effects (i.e. collective dominance). Apart from its obvious policy-relevance, the paper is designed to shed empirical light on the conditions under which tacit collusion is most likely. We construct a database relating to 62 candidate mergers and find that, in the eyes of the Commission, tacit collusion in this context virtually never involves more than two firms and requires close symmetry in the market shares of the two firms