Multiplicity of fibronectin-binding alpha V integrin receptors in colorectal cancer.

Current data from in vitro and in vivo animal models indicate that fibronectin-binding integrin receptors expressed by colon cancer cells may regulate tumour growth. While individual members of the beta 1 subfamily of integrins have now been clearly identified in colorectal cancer, little information exists with respect to the alpha V subfamily. In the present study we show that alpha V can associate with multiple and different beta subunits capable of binding fibronectin in this tumour type. This is likely to have functional implications for growth and spread of colorectal cancer

The Anti-Coincidence Detector for the GLAST Large Area Telescope

This paper describes the design, fabrication and testing of the Anti-Coincidence Detector (ACD) for the Gamma-ray Large Area Space Telescope (GLAST) Large Area Telescope (LAT). The ACD is LAT first-level defense against the charged cosmic ray background that outnumbers the gamma rays by 3-5 orders of magnitude. The ACD covers the top and 4 sides of the LAT tracking detector, requiring a total active area of ~8.3 square meters. The ACD detector utilizes plastic scintillator tiles with wave-length shifting fiber readout. In order to suppress self-veto by shower particles at high gamma-ray energies, the ACD is segmented into 89 tiles of different sizes. The overall ACD efficiency for detection of singly charged relativistic particles entering the tracking detector from the top or sides of the LAT exceeds the required 0.9997.Comment: 33 pages, 19 figure

Can two wrongs make a right?:F508del-CFTR ion channel rescue by second-site mutations in its transmembrane domains

Deletion of phenylalanine 508 (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel is the most common cause of cystic fibrosis. The F508 residue is located on nucleotide-binding domain 1 (NBD1) in contact with the cytosolic extensions of the transmembrane helices, in particular intracellular loop 4 (ICL4). To investigate how absence of F508 at this interface impacts the CFTR protein, we carried out a mutagenesis scan of ICL4 by introducing second-site mutations at 11 positions in cis with F508del. Using an image-based fluorescence assay, we measured how each mutation affected membrane proximity and ion-channel function. The scan strongly validated the effectiveness of R1070W at rescuing F508del defects. Molecular dynamics simulations highlighted two features characterizing the ICL4/NBD1 interface of F508del/R1070W-CFTR: flexibility, with frequent transient formation of interdomain hydrogen bonds, and loosely stacked aromatic sidechains (F1068, R1070W, and F1074, mimicking F1068, F508, and F1074 in WT CFTR). F508del-CFTR displayed a distorted aromatic stack, with F1068 displaced toward the space vacated by F508, while in F508del/R1070F-CFTR, which largely retained F508del defects, R1070F could not form hydrogen bonds and the interface was less flexible. Other ICL4 second-site mutations which partially rescued F508del-CFTR included F1068M and F1074M. Methionine side chains allow hydrophobic interactions without the steric rigidity of aromatic rings, possibly conferring flexibility to accommodate the absence of F508 and retain a dynamic interface. These studies highlight how both hydrophobic interactions and conformational flexibility might be important at the ICL4/NBD1 interface, suggesting possible structural underpinnings of F508del-induced dysfunction

Evidence for a Dayside Thermal Inversion and High Metallicity for the Hot Jupiter WASP-18b

We find evidence for a strong thermal inversion in the dayside atmosphere of the highly irradiated hot Jupiter WASP-18b (T$_{eq}=2411K$, $M=10.3M_{J}$) based on emission spectroscopy from Hubble Space Telescope secondary eclipse observations and Spitzer eclipse photometry. We demonstrate a lack of water vapor in either absorption or emission at 1.4$\mu$m. However, we infer emission at 4.5$\mu$m and absorption at 1.6$\mu$m that we attribute to CO, as well as a non-detection of all other relevant species (e.g., TiO, VO). The most probable atmospheric retrieval solution indicates a C/O ratio of 1 and a high metallicity (C/H=$283^{+395}_{-138}\times$ solar). The derived composition and T/P profile suggest that WASP-18b is the first example of both a planet with a non-oxide driven thermal inversion and a planet with an atmospheric metallicity inconsistent with that predicted for Jupiter-mass planets at $>2\sigma$. Future observations are necessary to confirm the unusual planetary properties implied by these results

Perfect Reflection of Light by an Oscillating Dipole

We show theoretically that a directional dipole wave can be perfectly reflected by a single point-like oscillating dipole. Furthermore, we find that in the case of a strongly focused plane wave up to 85 % of the incident light can be reflected by the dipole. Our results hold for the full spectrum of the electromagnetic interactions and have immediate implications for achieving strong coupling between a single propagating photon and a single quantum emitter.Comment: 3 figure

Azimuthally polarized spatial dark solitons: exact solutions of Maxwell's equations in a Kerr medium

Spatial Kerr solitons, typically associated with the standard paraxial nonlinear Schroedinger equation, are shown to exist to all nonparaxial orders, as exact solutions of Maxwell's equations in the presence of vectorial Kerr effect. More precisely, we prove the existence of azimuthally polarized, spatial, dark soliton solutions of Maxwell's equations, while exact linearly polarized (2+1)-D solitons do not exist. Our ab initio approach predicts the existence of dark solitons up to an upper value of the maximum field amplitude, corresponding to a minimum soliton width of about one fourth of the wavelength.Comment: 4 pages, 4 figure

A mid-term astrometric and photometric study of Trans-Neptunian Object (90482) Orcus

From CCD observations of a fixed and large star field that contained the binary TNO Orcus, we have been able to derive high-precision relative astrometry and photometry of the Orcus system with respect to background stars. The RA residuals of an orbital fit to the astrometric data revealed a periodicity of 9.7+-0.3 days, which is what one would expect to be induced by the known Orcus companion. The residuals are also correlated with the theoretical positions of the satellite with regard to the primary. We therefore have revealed the presence of Orcus' satellite in our astrometric measurements. The photocenter motion is much larger than the motion of Orcus around the barycenter, and we show here that detecting some binaries through a carefully devised astrometric technique might be feasible with telescopes of moderate size. We also analyzed the system's mid-term photometry to determine whether the rotation could be tidally locked to the satellite's orbital period. We found that a photometric variability of 9.7+-0.3 days is clear in our data, and is nearly coincident with the orbital period of the satellite. We believe this variability might be induced by the satellite's rotation. There is also a slight hint for an additional small variability in the 10 hr range that was already reported in the literature. This short-term variability would indicate that the primary is not tidally locked and therefore the system would not have reached a double synchronous state. Implications for the basic physical properties of the primary and its satellite are discussed. From angular momentum considerations we suspect that the Orcus satellite might have formed from a rotational fission. This requires that the mass of the satellite would be around 0.09 times that of the primary, close to the value that one derives by using an albedo of 0.12 for the satellite and assuming equal densities for both objects.Comment: in Press at A&

Evolution of Streptococcus pneumoniae Serotype 3 in England and Wales: A Major Vaccine Evader.

Despite its inclusion in pneumococcal conjugate vaccine 13 (PCV13), Streptococcus pneumoniae serotype 3 remains a major cause of invasive pneumococcal disease in England and Wales. Previous studies have indicated that there are distinct lineages within serotype 3 clonal complex 180 and the clade distributions have shifted in recent years with the emergence of clade II. We undertook whole genome sequencing and genomic analysis of 616 serotype 3 isolates from England and Wales between 2003 and 2018, including invasive and carriage isolates. Our investigations showed that clade II has expanded since 2014 and now represents 50% of serotype 3 invasive pneumococcal disease (IPD) isolates in England and Wales. Genomic analysis of antibiotic resistance and protein antigen genes showed that distinct profiles are present within the clades which could account for the recent emergence of this clade. This investigation highlights the importance and utility of routine whole genome sequencing and its ability to identify new and emerging variation at the single nucleotide level which informs surveillance and will impact future vaccine development