Paceho6402

The photochemistry of pyruvic acid has attracted much scientific interest because it is believed to play critical roles in atmospheric chemistry. However, under most atmospherically relevant conditions, pyruvic acid deprotonates to form its conjugate base, the photochemistry of which is essentially unknown. Here, we present a detailed study of the photochemistry of the isolated pyruvate anion and uncover that it is extremely rich. Using photoelectron imaging and computational chemistry, we show that photoexcitation by UVA light leads to the formation of CO2, CO, and CH3-. The observation of the unusual methide anion formation and its subsequent decomposition into methyl radical and a free electron may hold important consequences for atmospheric chemistry. From a mechanistic perspective, the initial decarboxylation of pyruvate necessarily differs from that in pyruvic acid, due to the missing proton in the anion.Metabolic alterations precede cardiometabolic disease onset. Here we present ceramide- and dihydroceramide-profiling data from a nested case-cohort (type 2 diabetes [T2D, n = 775]; cardiovascular disease [CVD, n = 551]; random subcohort [n = 1137]) in the prospective EPIC-Potsdam study. We apply the novel NetCoupler-algorithm to link a data-driven (dihydro)ceramide network to T2D and CVD risk. Controlling for confounding by other (dihydro)ceramides, ceramides C180 and C220 and dihydroceramides C200 and C222 are associated with higher and ceramide C200 and dihydroceramide C261 with lower T2D risk. Ceramide C160 and dihydroceramide C222 are associated with higher CVD risk. Genome-wide association studies and Mendelian randomization analyses support a role of ceramide C220 in T2D etiology. Our results also suggest that (dh)ceramides partly mediate the putative adverse effect of high red meat consumption and benefits of coffee consumption on T2D risk. Thus, (dihydro)ceramides may play a critical role in linking genetic predisposition and dietary habits to cardiometabolic disease risk.Spin-orbit coupling (SOC), which is the core of many condensed-matter phenomena such as nontrivial band gap and magnetocrystalline anisotropy, is generally considered appreciable only in heavy elements. This is detrimental to the synthesis and application of functional materials. Therefore, amplifying the SOC effect in light elements is crucial. Herein, focusing on 3d and 4d systems, we demonstrate that the interplay between crystal symmetry and electron correlation can significantly enhance the SOC effect in certain partially occupied orbital multiplets through the self-consistently reinforced orbital polarization as a pivot. Thereafter, we provide design principles and comprehensive databases, where we list all the Wyckoff positions and site symmetries in all two-dimensional (2D) and three-dimensional crystals that could have enhanced SOC effect. Additionally, we predict nine material candidates from our selected 2D material pool as high-temperature quantum anomalous Hall insulators with large nontrivial band gaps of hundreds of meV. Our study provides an efficient and straightforward way for predicting promising SOC-active materials, relieving the use of heavy elements for next-generation spin-orbitronic materials and devices.Three-dimensional (3D) structures dictate the functions of RNA molecules in a wide variety of biological processes. However, direct determination of RNA 3D structures in vivo is difficult due to their large sizes, conformational heterogeneity, and dynamics. Here we present a method, Spatial 2'-Hydroxyl Acylation Reversible Crosslinking (SHARC), which uses chemical crosslinkers of defined lengths to measure distances between nucleotides in cellular RNA. Integrating crosslinking, exonuclease (exo) trimming, proximity ligation, and high throughput sequencing, SHARC enables transcriptome-wide tertiary structure contact maps at high accuracy and precision, revealing heterogeneous RNA structures and interactions. SHARC data provide constraints that improves Rosetta-based RNA 3D structure modeling at near-nanometer resolution. Integrating SHARC-exo with other crosslinking-based methods, we discover compact folding of the 7SK RNA, a critical regulator of transcriptional elongation. These results establish a strategy for measuring RNA 3D distances and alternative conformations in their native cellular context.The 53BP1-RIF1 pathway antagonizes resection of DNA broken ends and confers PARP inhibitor sensitivity on BRCA1-mutated tumors. However, it is unclear how this pathway suppresses initiation of resection. Here, we identify ASF1 as a partner of RIF1 via an interacting manner similar to its interactions with histone chaperones CAF-1 and HIRA. ASF1 is recruited to distal chromatin flanking DNA breaks by 53BP1-RIF1 and promotes non-homologous end joining (NHEJ) using its histone chaperone activity. Epistasis analysis shows that ASF1 acts in the same NHEJ pathway as RIF1, but via a parallel pathway with the shieldin complex, which suppresses resection after initiation. Moreover, defects in end resection and homologous recombination (HR) in BRCA1-deficient cells are largely suppressed by ASF1 deficiency. Mechanistically, ASF1 compacts adjacent chromatin by heterochromatinization to protect broken DNA ends from BRCA1-mediated resection. Taken together, our findings identify a RIF1-ASF1 histone chaperone complex that promotes changes in high-order chromatin structure to stimulate the NHEJ pathway for DSB repair.It has become evident that somatic mutations in cancer-associated genes accumulate in the normal endometrium, but spatiotemporal understanding of the evolution and expansion of mutant clones is limited. To elucidate the timing and mechanism of the clonal expansion of somatic mutations in cancer-associated genes in the normal endometrium, we sequence 1311 endometrial glands from 37 women. By collecting endometrial glands from different parts of the endometrium, we show that multiple glands with the same somatic mutations occupy substantial areas of the endometrium. We demonstrate that "rhizome structures", in which the basal glands run horizontally along the muscular layer and multiple vertical glands rise from the basal gland, originate from the same ancestral clone. Moreover, mutant clones detected in the vertical glands diversify by acquiring additional mutations. These results suggest that clonal expansions through the rhizome structures are involved in the mechanism by which mutant clones extend their territories. Furthermore, we show clonal expansions and copy neutral loss-of-heterozygosity events occur early in life, suggesting such events can be tolerated many years in the normal endometrium. Our results of the evolutionary dynamics of mutant clones in the human endometrium will lead to a better understanding of the mechanisms of endometrial regeneration during the menstrual cycle and the development of therapies for the prevention and treatment of endometrium-related diseases.Machine learning for materials discovery has largely focused on predicting an individual scalar rather than multiple related properties, where spectral properties are an important example. Fundamental spectral properties include the phonon density of states (phDOS) and the electronic density of states (eDOS), which individually or collectively are the origins of a breadth of materials observables and functions. Building upon the success of graph attention networks for encoding crystalline materials, we introduce a probabilistic embedding generator specifically tailored to the prediction of spectral properties. Coupled with supervised contrastive learning, our materials-to-spectrum (Mat2Spec) model outperforms state-of-the-art methods for predicting ab initio phDOS and eDOS for crystalline materials. We demonstrate Mat2Spec's ability to identify eDOS gaps below the Fermi energy, validating predictions with ab initio calculations and thereby discovering candidate thermoelectrics and transparent conductors. Mat2Spec is an exemplar framework for predicting spectral properties of materials via strategically incorporated machine learning techniques.Electron spins in silicon quantum dots are promising qubits due to their long coherence times, scalable fabrication, and potential for all-electrical control. However, charge noise in the host semiconductor presents a major obstacle to achieving high-fidelity single- and two-qubit gates in these devices. In this work, we measure the charge-noise spectrum of a Si/SiGe singlet-triplet qubit over nearly 12 decades in frequency using a combination of methods, including dynamically-decoupled exchange oscillations with up to 512 π pulses during the qubit evolution. The charge noise is colored across the entire frequency range of our measurements, although the spectral exponent changes with frequency. Moreover, the charge-noise spectrum inferred from conductance measurements of a proximal sensor quantum dot agrees with that inferred from coherent oscillations of the singlet-triplet qubit, suggesting that simple transport measurements can accurately characterize the charge noise over a wide frequency range in Si/SiGe quantum dots.Many cellular processes, including ribosome biogenesis, are regulated through post-transcriptional RNA modifications. Here, a genome-wide analysis of the human mitochondrial transcriptome shows that 2'-O-methylation is limited to residues of the mitoribosomal large subunit (mtLSU) 16S mt-rRNA, introduced by MRM1, MRM2 and MRM3, with the modifications installed by the latter two proteins being interdependent. MRM2 controls mitochondrial respiration by regulating mitoribosome biogenesis. In its absence, mtLSU particles (visualized by cryo-EM at the resolution of 2.6 Å) present disordered RNA domains, partial occupancy of bL36m and bound MALSU1L0R8F8mtACP anti-association module, allowing five mtLSU biogenesis intermediates with different intersubunit interface configurations to be placed along the assembly pathway. However, mitoribosome biogenesis does not depend on the methyltransferase activity of MRM2. Disruption of the MRM2 Drosophila melanogaster orthologue leads to mitochondria-related developmental arrest. This work identifies a key checkpoint during mtLSU assembly, essential to maintain mitochondrial homeostasis.The seamless integration of III-V nanostructures on silicon is a long-standing goal and an important step towards integrated optical links. In the present work, we demonstrate scaled and waveguide coupled III-V photodiodes monolithically integrated on Si, implemented as InP/In0.5Ga0.5As/InP p-i-n heterostructures. The waveguide coupled devices show a dark current down to 0.048 A/cm2 at -1 V and a responsivity up to 0.2 A/W at -2 V. Using grating couplers centered around 1320 nm, we demonstrate high-speed detection with a cutoff frequency f3dB exceeding 70 GHz and data reception at 50 GBd with OOK and 4PAM. selleck inhibitor When operated in forward bias as a light emitting diode, the devices emit light centered at 1550 nm. Furthermore, we also investigate the self-heating of the devices using scanning thermal microscopy and find a temperature increase of only ~15 K during the device operation as emitter, in accordance with thermal simulation results.