Teamwork inside the sticky oceanic microscale
MaxDIA is a software platform for analyzing data-independent acquisition (DIA) proteomics data within the MaxQuant software environment. Using spectral libraries, MaxDIA achieves deep proteome coverage with substantially better coefficients of variation in protein quantification than other software. MaxDIA is equipped with accurate false discovery rate (FDR) estimates on both library-to-DIA match and protein levels, including when using whole-proteome predicted spectral libraries. check details This is the foundation of discovery DIA-hypothesis-free analysis of DIA samples without library and with reliable FDR control. MaxDIA performs three- or four-dimensional feature detection of fragment data, and scoring of matches is augmented by machine learning on the features of an identification. MaxDIA's bootstrap DIA workflow performs multiple rounds of matching with increasing quality of recalibration and stringency of matching to the library. Combining MaxDIA with two new technologies-BoxCar acquisition and trapped ion mobility spectrometry-both lead to deep and accurate proteome quantification.Histone exchange between histones carrying position-specific marks and histones bearing general marks is important for gene regulation, but understanding of histone exchange remains incomplete. To overcome the poor time resolution of conventional pulse-chase histone labeling, we present a genetically encoded histone exchange timer sensitive to the duration that two tagged histone subunits co-reside at an individual genomic locus. We apply these sensors to map genome-wide patterns of histone exchange in yeast using single samples. Comparing H3 exchange in cycling and G1-arrested cells suggests that replication-independent H3 exchange occurs at several hundred nucleosomes ( less then 1% of all nucleosomes) per minute, with a maximal rate at histone promoters. We observed substantial differences between the two nucleosome core subcomplexes H2A-H2B subcomplexes undergo rapid transcription-dependent replacement within coding regions, whereas H3-H4 replacement occurs predominantly within promoter nucleosomes, in association with gene activation or repression. Our timers allow the in vivo study of histone exchange dynamics with minute time scale resolution.Porous materials are very promising for the development of cost- and energy-efficient separation processes, such as for the purification of ethylene from ethylene/ethane mixture-an important but currently challenging industrial process. Here we report a microporous hydrogen-bonded organic framework that takes up ethylene with very good selectivity over ethane through a gating mechanism. The material consists of tetracyano-bicarbazole building blocks held together through intermolecular CN···H-C hydrogen bonding interactions, and forms as a threefold-interpenetrated framework with pores of suitable size for the selective capture of ethylene. The hydrogen-bonded organic framework exhibits a gating mechanism in which the threshold pressure required for guest uptake varies with the temperature. Ethylene/ethane separation is validated by breakthrough experiments with high purity of ethylene (99.1%) at 333 K. Hydrogen-bonded organic frameworks are usually not robust, yet this material was stable under harsh conditions, including exposure to strong acidity, basicity and a variety of highly polar solvents.The antagonism between strength and resistance to hydrogen embrittlement in metallic materials is an intrinsic obstacle to the design of lightweight yet reliable structural components operated in hydrogen-containing environments. Economical and scalable microstructural solutions to this challenge must be found. Here, we introduce a counterintuitive strategy to exploit the typically undesired chemical heterogeneity within the material's microstructure that enables local enhancement of crack resistance and local hydrogen trapping. We use this approach in a manganese-containing high-strength steel and produce a high dispersion of manganese-rich zones within the microstructure. These solute-rich buffer regions allow for local micro-tuning of the phase stability, arresting hydrogen-induced microcracks and thus interrupting the percolation of hydrogen-assisted damage. This results in a superior hydrogen embrittlement resistance (better by a factor of two) without sacrificing the material's strength and ductility. The strategy of exploiting chemical heterogeneities, rather than avoiding them, broadens the horizon for microstructure engineering via advanced thermomechanical processing.In 2011, Hanahan and Weinberg added "Deregulating Cellular Energetics" and "Avoiding Immune Destruction" to the six previous hallmarks of cancer. Since this seminal paper, there has been a growing consensus that these new hallmarks are not mutually exclusive but rather interdependent. The following review summarizes how founding genetic events for tumorigenesis ultimately increase tumor cell glycolysis, which not only supports the metabolic demands of malignancy but also provides an immunoprotective niche, promoting malignant cell proliferation, maintenance and progression. The mechanisms by which altered metabolism contributes to immune impairment are multifactorial (1) the metabolic demands of proliferating tumor cells and activated immune cells are similar, thus creating a situation where immune cells may be in competition for key nutrients; (2) the metabolic byproducts of aerobic glycolysis directly inhibit antitumor immunity while promoting a regulatory immune phenotype; and (3) the gene programs associated with the upregulation of glycolysis also result in the generation of immunosuppressive cytokines and metabolites. From this perspective, we shed light on important considerations for the development of new classes of agents targeting cancer metabolism. These types of therapies can impair tumor growth but also pose a significant risk of stifling antitumor immunity.Human technology has evolved in an unparalleled way, allowing us to expand across the globe. One fascinating question is, how do we understand the cognitive origins of this phenomenon, which is known as cumulative technological culture (CTC)? The dominant view posits that CTC results from our unique ability to learn from each other. The cultural niche hypothesis even minimizes the involvement of non-social cognitive skills in the emergence of CTC, claiming that technologies can be optimized without us understanding how they work, but simply through the retention of small improvements over generations. Here we conduct a partial replication of the experimental study of Derex et al. (Nature Human Behaviour, 2019) and show that the improvement of a physical system over generations is accompanied by an increased understanding of it. These findings indicate that technical-reasoning skills (non-social cognitive skills) are important in the acquisition, understanding and improvement of technical content-that is, specific to the technological form of cumulative culture-thereby making social learning a salient source of technical inspiration.