Nucleosome Chiral Transition under Positive Torsional Stress in Single Chromatin Fibers

Using magnetic tweezers to investigate the mechanical response of single chromatin fibers, we show that fibers submitted to large positive torsion transiently trap positive turns, at a rate of one turn per nucleosome. A comparison with the response of fibers of tetrasomes (the (H3-H4)2 tetramer bound with ~50 bp of DNA) obtained by depletion of H2A-H2B dimers, suggests that the trapping reflects a nucleosome chiral transition to a metastable form built on the previously documented righthanded tetrasome. In view of its low energy, <8 kT, we propose this transition is physiologically relevant and serves to break the docking of the dimers on the tetramer which in the absence of other factors exerts a strong block against elongation of transcription by the main RNA polymerase.Comment: 33 pages (double spacing), 7 figure

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Broadband tunable hybrid photonic crystal-nanowire light emitter

We integrate about 100 single cadmium selenide semiconductor nanowires in silicon nitride photonic crystal cavities in a single processing run. Room temperature measurements reveal a single and narrow emission linewidth, corresponding to a Q-factor as large as 5000. By varying the structural parameters of the photonic crystal, the peak wavelength is changed, thereby covering the entire emission spectral range of the active material. A very large spectral range could be covered by heterogeneous integration of different active materials.NRF (Natl Research Foundation, S’pore)MOE (Min. of Education, S’pore)Accepted versio

4.7-THz Superconducting hot electron bolometer waveguide mixer

We present the first superconducting hot electron bolometer (HEB) waveguide mixer operating at 4.7 THz. The 5.5-nm-thick, 300-nm-long, and 3600-nm-wide NbN HEB micro-bridge is integrated into a normal metal (Au) planar circuit on a 2 mu m thick silicon substrate. This circuit is integrated in a 24 mu m x 48 mu m x 21 mu m waveguide cavity and a 14 mu m x 7 mu m x 200 mu m substrate channel, which is directly machined into a CuTe alloy block. The power spectrum of the HEB mixer, measured with a Fourier transform spectrometer, is in good agreement with the results of 3-D EM circuit simulation. Measured mixer performance shows a state-of-the-art double sideband noise temperature of 1100 K, averaged over the IF bandwidth of 0.2-3.5 GHz. The 3-dB noise roll-off is 3.5 GHz. This mixer is used in the German REceiver for Astronomy at Terahertz frequencies (GREAT) at the airborne Stratospheric Observatory for Far Infrared Astronomy (SOFIA)