A non-destructive approach for measuring rice panicle-level photosynthetic responses using 3D-image reconstruction

Our understanding of the physiological response of rice inflorescence (panicle) to environmental stresses is limited by the challenge of accurately determining panicle photosynthetic parameters and their impact on grain yield. This is primarily due to lack of a suitable gas exchange methodology for panicles, as well as non-destructive methods to accurately determine panicle surface area. To address these challenges, we have developed a custom panicle gas exchange cylinder compatible with the LiCor 6800 Infra-red Gas Analyzer. Accurate surface area measurements were determined with a 3D panicle imaging platform to normalize the panicle-level photosynthetic measurements. We observed differential responses in both panicle and flag leaf for two temperate Japonica rice genotypes (accessions, TEJ-1 and TEJ-2) exposed to heat stress during early grain filling. There was a notable divergence in relative photosynthetic contribution of flag leaf and panicles for the genotype tolerant to heat stress (TEJ-2) compared to the less tolerant accession. The novelty of this approach is that it is non-destructive and more accurately determines panicle area and photosynthetic parameters, enabling researchers to monitor temporal changes in panicle physiology during the reproductive development. The method is useful for panicle-level measurements under diverse environmental stresses, and for evaluating genotypic variation for panicle physiology and architecture in other cereals with compact inflorescences

Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma

Abstract: The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy

A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy

The scientific community has avoided using tissue samples from patients that have been exposed to systemic chemotherapy to infer the genomic landscape of a given cancer. Esophageal adenocarcinoma is a heterogeneous, chemoresistant tumor for which the availability and size of pretreatment endoscopic samples are limiting. This study compares whole-genome sequencing data obtained from chemo-naive and chemo-treated samples. The quality of whole-genomic sequencing data is comparable across all samples regardless of chemotherapy status. Inclusion of samples collected post-chemotherapy increased the proportion of late-stage tumors. When comparing matched pre- and post-chemotherapy samples from 10 cases, the mutational signatures, copy number, and SNV mutational profiles reflect the expected heterogeneity in this disease. Analysis of SNVs in relation to allele-specific copy-number changes pinpoints the common ancestor to a point prior to chemotherapy. For cases in which pre- and post-chemotherapy samples do show substantial differences, the timing of the divergence is near-synchronous with endoreduplication. Comparison across a large prospective cohort (62 treatment-naive, 58 chemotherapy-treated samples) reveals no significant differences in the overall mutation rate, mutation signatures, specific recurrent point mutations, or copy-number events in respect to chemotherapy status. In conclusion, whole-genome sequencing of samples obtained following neoadjuvant chemotherapy is representative of the genomic landscape of esophageal adenocarcinoma. Excluding these samples reduces the material available for cataloging and introduces a bias toward the earlier stages of cancer.This study was partly funded by a project grant from Cancer Research UK. R.C.F. is funded by an NIHR Professorship and receives core funding from the Medical Research Council and infrastructure support from the Biomedical Research Centre and the Experimental Cancer Medicine Centre. We acknowledge the support of The University of Cambridge, Cancer Research UK (C14303/A17197) and Hutchison Whampoa Limited

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Systematic Modulation of Quantum (Electron) Tunneling Behavior by Atomic Layer Deposition on Nanoparticulate SnO₂ and TiO₂ Photoanodes

Ultrathin films of TiO₂, ZrO₂, and Al₂O₃ were conformally created on SnO₂ and TiO₂ photoelectrodes via atomic layer deposition (ALD) to examine their influence upon electron transfer (ET) from the electrodes to a representative molecular receptor, I₃^–. Films thicker than 2 Å engender an exponential decrease in ET time with increasing film thickness, consistent with tunneling theory. Increasing the height of the barrier, as measured by the energy difference between the transferring electron and the bottom of the conduction band of the barrier material, results in steeper exponential drops in tunneling rate or probability. The variations are quantitatively consistent with a simple model of quantum tunneling of electrons through square barriers (i.e., barriers of individually uniform energy height) that are characterized by individually uniform physical thickness. The findings demonstrate that ALD is a remarkably uniform and precise method for modifying electrode surfaces and imply that standard tunneling theory can be used as a quantitative guide to intentionally and predictively modulating rates of ET between molecules and electrodes

Thermally Enhancing the Surface Areas of Yamamoto-Derived Porous Organic Polymers

Thermal treatment of highly stable porous organic polymers based upon the Yamamoto polymerization of 2,2′,7,7′-tetrabromo-9,9′-spirobifluorene was done. The polymers are shown to be thermally and chemically stable. Upon thermal treatment the polymers are shown to have BET surface areas of ca. 2,000 m²/g and 2,500 m²/g respectively

Barrier-Layer-Mediated Electron Transfer from Semiconductor Electrodes to Molecules in Solution: Sensitivity of Mechanism to Barrier-Layer Thickness

Electron transfer (ET) phenomena at and near semiconductor/molecule interfaces are of fundamental significance for applications involving liquid-junction photovoltaics, organic photovoltaics, and electrochemical heterogeneous catalysis. To probe mechanisms of electron delivery through barrier layers at such interfaces, we make use of atomic layer deposition to deposit ultrathin films of TiO₂ conformally onto SnO₂ electrodes. In the presence of TiO₂ films (i.e., barrier layers) up to 10 Å thick, electrons are delivered from the electrode to molecules in solution by tunneling through the layers, as evidenced, in part, by an exponential decrease in ET rate with layer thickness. For films thicker than 10 Å, there is little change in ET rate as a function of TiO₂ thickness. To our surprise, thermally annealing a 55 Å layer of TiO₂ on SnO₂ yielded a 10-fold decrease in ET rate compared to that imposed by the as-deposited layer. At applied potentials near the conduction-band edge of SnO₂, and significantly below the band edge of TiO₂, electrochemical impedance spectroscopy with nominally flat, as-deposited TiO₂ indicates the presence of nearly twice the density of electronic states as found with air-annealed samples. These and related observations point to a barrier-layer-thickness-dependent change in the mechanism of electron delivery, from the underlying electrode to solution species, from one based on tunneling to one entailing trap-facilitated hopping. The findings have design implications for the application of interfacial barrier layers to electrochemical and photoelectrochemical problems

Porphyrins as Templates for Site-Selective Atomic Layer Deposition: Vapor Metalation and in Situ Monitoring of Island Growth

Examinations of enzymatic catalysts suggest one key to efficient catalytic activity is discrete size metallo clusters. Mimicking enzymatic cluster systems is synthetically challenging because conventional solution methods are prone to aggregation or require capping of the cluster, thereby limiting its catalytic activity. We introduce site-selective atomic layer deposition (ALD) on porphyrins as an alternative approach to grow isolated metal oxide islands that are spatially separated. Surface-bound tetra-acid free base porphyrins (H₂TCPP) may be metalated with Mn using conventional ALD precursor exposure to induce homogeneous hydroxide synthetic handles which acts as a nucleation point for subsequent ALD MnO island growth. Analytical fitting of in situ QCM mass uptake reveals island growth to be hemispherical with a convergence radius of 1.74 nm. This growth mode is confirmed with synchrotron grazing-incidence small-angle X-ray scattering (GISAXS) measurements. Finally, we extend this approach to other ALD chemistries to demonstrate the generality of this route to discrete metallo island materials

Atomic Layer Deposition of Ultrathin Nickel Sulfide Films and Preliminary Assessment of Their Performance as Hydrogen Evolution Catalysts

Transition metal sulfides show great promise for applications ranging from catalysis to electrocatalysis to photovoltaics due to their high stability and conductivity. Nickel sulfide, particularly known for its ability to electrochemically reduce protons to hydrogen gas nearly as efficiently as expensive noble metals, can be challenging to produce with certain surface site compositions or morphologies, e.g., conformal thin films. To this end, we employed atomic layer deposition (ALD), a preeminent method to fabricate uniform and conformal films, to construct thin films of nickel sulfide (NiS_<i>x</i>) using bis­(<i>N</i>,<i>N</i>′-di-<i>tert</i>-butyl­acetamidinato)­nickel­(II) (Ni­(amd)₂) vapor and hydrogen sulfide gas. Effects of experimental conditions such as pulse and purge times and temperature on the growth of NiS_<i>x</i> were investigated. These revealed a wide temperature range, 125–225 °C, over which self-limiting NiS_<i>x</i> growth can be observed. <i>In situ</i> quartz crystal microbalance (QCM) studies revealed conventional linear growth behavior for NiS_<i>x</i> films, with a growth rate of 9.3 ng/cm² per cycle being obtained. The ALD-synthesized films were characterized using X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) methods. To assess the electrocatalyitic activity of NiS_<i>x</i> for evolution of molecular hydrogen, films were grown on conductive-glass supports. Overpotentials at a current density of 10 mA/cm² were recorded in both acidic and pH 7 phosphate buffer aqueous reaction media and found to be 440 and 576 mV, respectively, with very low NiS_<i>x</i> loading. These results hint at the promise of ALD-grown NiS_<i>x</i> materials as water-compatible electrocatalysts