iSoMAs: Finding isoform expression and somatic mutation associations in human cancers.

Aberrant alternative splicing, prevalent in cancer, impacts various cancer hallmarks involving proliferation, angiogenesis, and invasion. Splicing disruption often results from somatic point mutations rewiring functional pathways to support cancer cell survival. We introduce iSoMAs (iSoform expression and somatic Mutation Association), an efficient computational pipeline leveraging principal component analysis technique, to explore how somatic mutations influence transcriptome-wide gene expression at the isoform level.

Real-time monitoring of fermentation processes in wine production with benchtop H NMR spectroscopy.

The flexibility, affordability and ease of use of benchtop H NMR spectroscopy makes it potentially very interesting for assessing the quality of wine types and monitoring the fermentation process. However, the low spectral resolution of benchtop H NMR spectroscopy and the complexity of the mixtures hinder the direct quantification of important wine parameters and, thus, prevent its widespread use as an analytical tool in wineries. We show here that these problems can be solved using model-based data processing.

TIGIT inhibitor M6223 as monotherapy or in combination with bintrafusp alfa in patients with advanced solid tumors: a first-in-human, phase 1, dose-escalation trial.

Background: M6223 is an intravenous (IV), Fc-competent, fully human, antagonistic, anti-T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) antibody. Bintrafusp alfa (BA) is a bifunctional fusion protein that simultaneously blocks nonredundant immunosuppressive TGF-β and PD-(L)1 pathways.

Methods: This first-in-human, dose-escalation study in patients with advanced solid tumors (N=58; aged ≥18 years, ECOG PS≤1) evaluated M6223 alone (Part 1A, n=40; M6223 10-2400 mg every 2 weeks, n=32; M6223 2400 mg every 3 weeks, n=8) or with BA (Part 1B, n=18; M6223 300-1600 mg with BA 1200 mg; both every 2 weeks, intravenous).

Time-resolved vacuum-ultraviolet photoelectron spectroscopy of the Ã1Au state of acetylene.

Ultrafast time-resolved photoelectron spectra are reported for the vacuum-ultraviolet (VUV) photoionization of acetylene following excitation to the Ã1Au state via UV absorption at 200 nm. The excitation energy lies above the lowest dissociation threshold to C2H X̃2Σ+ + H, as well as above the threshold for adiabatic dissociation of the Ã1Au state to form C2H (Ã2Π) + H. The time-dependent mass spectra and photoelectron spectra provide insight into the intramolecular decay processes of the Ã1Au state.

Century-long West Antarctic snow accumulation changes induced by tropical teleconnections.

Ice core measurements reveal dipole-like snow accumulation trends over West Antarctica throughout the 20th century, with an increase of >2000 billion metric tons over the Antarctic Peninsula and Ellsworth Land but a decrease of ~500 billion metric tons over Marie Byrd Land. Although atmospheric teleconnections were frequently revealed, linking variability between tropics and higher latitudes on interannual and decadal timescales, centennial-scale teleconnection is absent from literature. Here, using statistical analysis and numerical experiments, we reveal that changes of tropical oceans throughout the 20th century drive the long-term Antarctic snowfall trend.