Dynamics of immersed molecules in superfluids

The dynamics of a molecule immersed in a superfluid medium are considered. Results are derived using a classical hydrodynamic approach followed by canonical quantization. The classical model, a rigid body immersed in incompressible fluid, permits a thorough analysis; its effective Hamiltonian generalizes the usual rigid-rotor Hamiltonian. In contrast to the free rigid rotor, the immersed body is shown to have chaotic dynamics. Quantization of the classical model leads to new and experimentally verifiable features. It is shown, for instance, that chiral molecules can behave as "quantum propellers": the rotational-translational coupling induced by the superfluid leads to a nonzero linear momentum in the ground state. Hydrogen peroxide is a strong candidate for experimental detection of this effect. The signature is a characteristic splitting of rotational absorption lines. The 1_{01} --> 1_{10} line in hydrogen peroxide, for example, is predicted to split into three lines separated by as much as 0.01 cm^{-1}, which is about the experimental linewidth.Comment: 10 pages, 3 figure

High performance, LED powered, waveguide based total internal reflection microscopy.

Total internal reflection fluorescence (TIRF) microscopy is a rapidly expanding optical technique with excellent surface sensitivity and limited background fluorescence. Commercially available TIRF systems are either objective based that employ expensive special high numerical aperture (NA) objectives or prism based that restrict integrating other modalities of investigation for structure-function analysis. Both techniques result in uneven illumination of the field of view and require training and experience in optics. Here we describe a novel, inexpensive, LED powered, waveguide based TIRF system that could be used as an add-on module to any standard fluorescence microscope even with low NA objectives. This system requires no alignment, illuminates the entire field evenly, and allows switching between epifluorescence/TIRF/bright field modes without adjustments or objective replacements. The simple design allows integration with other imaging systems, including atomic force microscopy (AFM), for probing complex biological systems at their native nanoscale regimes

Structure and permeability of ion-channels by integrated AFM and waveguide TIRF microscopy.

Membrane ion channels regulate key cellular functions and their activity is dependent on their 3D structure. Atomic force microscopy (AFM) images 3D structure of membrane channels placed on a solid substrate. Solid substrate prevents molecular transport through ion channels thus hindering any direct structure-function relationship analysis. Here we designed a ~70 nm nanopore to suspend a membrane, allowing fluidic access to both sides. We used these nanopores with AFM and total internal reflection fluorescence microscopy (TIRFM) for high resolution imaging and molecular transport measurement. Significantly, membranes over the nanopore were stable for repeated AFM imaging. We studied structure-activity relationship of gap junction hemichannels reconstituted in lipid bilayers. Individual hemichannels in the membrane overlying the nanopore were resolved and transport of hemichannel-permeant LY dye was visualized when the hemichannel was opened by lowering calcium in the medium. This integrated technique will allow direct structure-permeability relationship of many ion channels and receptors

A catalog of bright calibrator stars for 200-meter baseline near-infrared stellar interferometry

We present in this paper a catalog of reference stars suitable for calibrating infrared interferometric observations. In the K band, visibilities can be calibrated with a precision of 1% on baselines up to 200 meters for the whole sky, and up to 300 meters for some part of the sky. This work, extending to longer baselines a previous catalog compiled by Borde et al. (2002), is particularly well adapted to hectometric-class interferometers such as the Very Large Telescope Interferometer (VLTI, Glindemann et al. 2003) or the CHARA array (ten Brummelaar et al. 2003) when observing well resolved, high surface brightness objects (K<8). We use the absolute spectro-photometric calibration method introduced by Cohen et al. (1999) to derive the angular diameters of our new set of 948 G8--M0 calibrator stars extracted from IRAS, 2MASS and MSX catalogs. Angular stellar diameters range from 0.6 mas to 1.8 mas (median is 1.1 mas) with a median precision of 1.35%. For both the northern and southern hemispheres, the closest calibrator star is always less than 10 degree away.Comment: 9 pages, 7 figures, submitted to A&A. The full catalog can be found in http://calys.obspm.fr/~merand/Files/MerandEtAlCatalogue.tx

Imaging of Single Antigens, Antibodies, and Specific Immunocomplex Formation by Scanning Force Microscopy

The most sensitive analytical techniques available today for detecting immuno assay complexes are radio or enzyme immuno analytical techniques, by which quantities of 107-108 analyte molecules can be detected. With the introduction of scanning force microscopy, a new method for detecting biological processes became available. Here, we examine the feasibility of using scanning force microscopy as a biosensitive tool. We demonstrate that single or multiple rabbit anti-human serum albumin molecules form complexes with preadsorbed single human serum albumin molecules on mica. However, no interaction is observed between human immunoglobulin G molecules and preadsorbed single albumin molecules; only separate antigens and antibodies are observed at random positions on the mica. This shows the ability of scanning force microscopy to act as a biosensor for detection of immunocomplexes, and to act as a very powerful tool to study molecule-surface interactions in general

Chromosomal instability in untreated primary prostate cancer as an indicator of metastatic potential.

BackgroundMetastatic prostate cancer (PC) is highly lethal. The ability to identify primary tumors capable of dissemination is an unmet need in the quest to understand lethal biology and improve patient outcomes. Previous studies have linked chromosomal instability (CIN), which generates aneuploidy following chromosomal missegregation during mitosis, to PC progression. Evidence of CIN includes broad copy number alterations (CNAs) spanning &gt; 300 base pairs of DNA, which may also be measured via RNA expression signatures associated with CNA frequency. Signatures of CIN in metastatic PC, however, have not been interrogated or well defined. We examined a published 70-gene CIN signature (CIN70) in untreated and castration-resistant prostate cancer (CRPC) cohorts from The Cancer Genome Atlas (TCGA) and previously published reports. We also performed transcriptome and CNA analysis in a unique cohort of untreated primary tumors collected from diagnostic prostate needle biopsies (PNBX) of localized (M0) and metastatic (M1) cases to determine if CIN was linked to clinical stage and outcome.MethodsPNBX were collected from 99 patients treated in the VA Greater Los Angeles (GLA-VA) Healthcare System between 2000 and 2016. Total RNA was extracted from high-grade cancer areas in PNBX cores, followed by RNA sequencing and/or copy number analysis using OncoScan. Multivariate logistic regression analyses permitted calculation of odds ratios for CIN status (high versus low) in an expanded GLA-VA PNBX cohort (n = 121).ResultsThe CIN70 signature was significantly enriched in primary tumors and CRPC metastases from M1 PC cases. An intersection of gene signatures comprised of differentially expressed genes (DEGs) generated through comparison of M1 versus M0 PNBX and primary CRPC tumors versus metastases revealed a 157-gene "metastasis" signature that was further distilled to 7-genes (PC-CIN) regulating centrosomes, chromosomal segregation, and mitotic spindle assembly. High PC-CIN scores correlated with CRPC, PC-death and all-cause mortality in the expanded GLA-VA PNBX cohort. Interestingly, approximately 1/3 of M1 PNBX cases exhibited low CIN, illuminating differential pathways of lethal PC progression.ConclusionsMeasuring CIN in PNBX by transcriptome profiling is feasible, and the PC-CIN signature may identify patients with a high risk of lethal progression at the time of diagnosis

Cost-minimisation analysis of a treat-and-extend regimen with anti-VEGFs in patients with neovascular age-related macular degeneration

PURPOSE: Although intraocular anti-vascular endothelial growth factors (anti-VEGFs) are effective as treatment of neovascular age-related macular degeneration (nAMD), the (economic) burden on the healthcare system is considerable. A treat-and-extend (T&E) regimen is associated with a lower number of injections without compromising the effectiveness and can therefore help optimise nAMD treatment. This study investigates the per-patient costs associated with nAMD treatment, when using aflibercept, bevacizumab, or ranibizumab with a T&E regimen. METHODS: In this cost-minimisation model, the per-patient costs in the Netherlands were modelled using a healthcare payers’ perspective over a 3-year time horizon with the assumption that efficacy of treatments is similar. Additionally, the break-even price of the different anti-VEGFs was calculated relative to the cheapest option and injection frequency. RESULTS: The injection frequency varied from 14.2 for aflibercept to 27.4 for bevacizumab in 3 years. Nonetheless, bevacizumab remains the cheapest treatment option (€14,215), followed by aflibercept (€18,202) and ranibizumab (€31,048). The medication covers the majority of the per-patient costs for aflibercept and ranibizumab, while administration covers the majority of the per-patient costs for bevacizumab. The break-even prices of aflibercept and ranibizumab are respectively €507 and €60.58 per injection. Brolucizumab was included in the scenario analysis and was more expensive than aflibercept (€20,446). Brolucizumab should reduce to 13.8 injections over 3 years to be as costly as aflibercept. CONCLUSION: Bevacizumab is the cheapest anti-VEGF treatment. The list prices of all anti-VEGFs should reduce to be as costly as bevacizumab. Aflibercept is the second-choice treatment and so far brolucizumab is not

Limits on the primordial stellar multiplicity

Most stars - especially young stars - are observed to be in multiple systems. Dynamical evolution is unable to pair stars efficiently, which leads to the conclusion that star-forming cores must usually fragment into \geq 2 stars. However, the dynamical decay of systems with \geq 3 or 4 stars would result in a large single-star population that is not seen in the young stellar population. Additionally, ejections would produce a significant population of hard binaries that are not observed. This leads to a strong constraint on star formation theories that cores must typically produce only 2 or 3 stars. This conclusion is in sharp disagreement with the results of currently available numerical simulations that follow the fragmentation of molecular cores and typically predict the formation of 5--10 seeds per core. In addition, open cluster remnants may account for the majority of observed highly hierarchical higher-order multiple systems in the field.Comment: A&A in press, 5 pages (no figures