Nesiritide: Harmful or Harmless?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90328/1/phco.26.10.1465.pd

Protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein

Infections with human respiratory syncytial virus (HRSV) occur globally in all age groups and can have devastating consequences in young infants. We demonstrate that a vaccine based on the extracellular domain (SHe) of the small hydrophobic (SH) protein of HRSV, reduced viral replication in challenged laboratory mice and in cotton rats. We show that this suppression of viral replication can be transferred by serum and depends on a functional IgG receptor compartment with a major contribution of FcRI and FcRIII. Using a conditional cell depletion method, we provide evidence that alveolar macrophages are involved in the protection by SHe-specific antibodies. HRSV-infected cells abundantly express SH on the cell surface and are likely the prime target of the humoral immune response elicited by SHe-based vaccination. Finally, natural infection of humans and experimental infection of mice or cotton rats does not induce a strong immune response against HRSV SHe. Using SHe as a vaccine antigen induces immune protection against HRSV by a mechanism that differs from the natural immune response and from other HRSV vaccination strategies explored to date. Hence, HRSV vaccine candidates that aim at inducing protective neutralizing antibodies or T-cell responses could be complemented with a SHe-based antigen to further improve immune protection

Deep generative modeling for single-cell transcriptomics.

Single-cell transcriptome measurements can reveal unexplored biological diversity, but they suffer from technical noise and bias that must be modeled to account for the resulting uncertainty in downstream analyses. Here we introduce single-cell variational inference (scVI), a ready-to-use scalable framework for the probabilistic representation and analysis of gene expression in single cells ( https://github.com/YosefLab/scVI ). scVI uses stochastic optimization and deep neural networks to aggregate information across similar cells and genes and to approximate the distributions that underlie observed expression values, while accounting for batch effects and limited sensitivity. We used scVI for a range of fundamental analysis tasks including batch correction, visualization, clustering, and differential expression, and achieved high accuracy for each task

Observation of a pairing pseudogap in a two-dimensional Fermi gas

Pairing of fermions is ubiquitous in nature and it is responsible for a large variety of fascinating phenomena like superconductivity, superfluidity of $^3$He, the anomalous rotation of neutron stars, and the BEC-BCS crossover in strongly interacting Fermi gases. When confined to two dimensions, interacting many-body systems bear even more subtle effects, many of which lack understanding at a fundamental level. Most striking is the, yet unexplained, effect of high-temperature superconductivity in cuprates, which is intimately related to the two-dimensional geometry of the crystal structure. In particular, the questions how many-body pairing is established at high temperature and whether it precedes superconductivity are crucial to be answered. Here, we report on the observation of pairing in a harmonically trapped two-dimensional atomic Fermi gas in the regime of strong coupling. We perform momentum-resolved photoemission spectroscopy, analogous to ARPES in the solid state, to measure the spectral function of the gas and we detect a many-body pairing gap above the superfluid transition temperature. Our observations mark a significant step in the emulation of layered two-dimensional strongly correlated superconductors using ultracold atomic gases

Ultra-Sensitive Hot-Electron Nanobolometers for Terahertz Astrophysics

The background-limited spectral imaging of the early Universe requires spaceborne terahertz (THz) detectors with the sensitivity 2-3 orders of magnitude better than that of the state-of-the-art bolometers. To realize this sensitivity without sacrificing operating speed, novel detector designs should combine an ultrasmall heat capacity of a sensor with its unique thermal isolation. Quantum effects in thermal transport at nanoscale put strong limitations on the further improvement of traditional membrane-supported bolometers. Here we demonstrate an innovative approach by developing superconducting hot-electron nanobolometers in which the electrons are cooled only due to a weak electron-phonon interaction. At T<0.1K, the electron-phonon thermal conductance in these nanodevices becomes less than one percent of the quantum of thermal conductance. The hot-electron nanobolometers, sufficiently sensitive for registering single THz photons, are very promising for submillimeter astronomy and other applications based on quantum calorimetry and photon counting.Comment: 19 pages, 3 color figure

Psychometric properties of a prostate cancer radiation late toxicity questionnaire

<p>Abstract</p> <p>Background</p> <p>To construct a short prostate cancer radiation late toxicity (PCRT) questionnaire with health-related quality-of-life (HRQoL) domains.</p> <p>Methods</p> <p>The PCRT was developed by item generation, questionnaire construction (n = 7 experts, n = 8 focus group patients), pilot testing (n = 37), item reduction (n = 100), reliability testing (n = 237), and validity testing (n = 274).</p> <p>Results</p> <p>Reliability of the three item-reduced subscales demonstrated intraclass correlation coefficients (CC) of 0.811 (GU), 0.842 (GI), and 0.740 (sexual). Discriminant validity demonstrated Pearson CC of 0.449 (GU-GI), 0.200 (sexual-GU), and 0.09 (sexual-GI). Content validity correlations between PCRT-PCQoL were 0.35–0.78, PCRT-FACT-G^©were 0.19–0.39, and PCRT-SF-36^®were 0.03–0.34.</p> <p>Conclusion</p> <p>We successfully generated a PCRT HRQoL questionnaire including subscales with very good psychometric properties.</p

Are cells from a snowman realistic? Cryopreserved tissues as a source for single-cell RNA-sequencing experiments

A recently published study in Genome Biology shows that cells isolated from cryopreserved tissues are a reliable source of genetic material for single-cell RNA-sequencing experiments.Please see related Method article: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1171-9