The effect of ultrafine WO3 nanoparticles on the organization of thylakoids enriched in photosystem II and energy transfer in photosystem II complexes

In this work, a new approach to construct self-assembled hybrid systems based on natural PSII-enriched thylakoid membranes (PSII BBY) is demonstrated. Superfine m-WO3 NPs (≈1–2 nm) are introduced into PSII BBY. Transmission electron microscopy (TEM) measurements showed that even the highest concentrations of NPs used did not degrade the PSII BBY membranes. Using atomic force microscopy (AFM), it is shown that the organization of PSII BBY depends strongly on the concentration of NPs applied. This proved that the superfine NPs can easily penetrate the thylakoid membrane and interact with its components. These changes are also related to the modified energy transfer between the external light-harvesting antennas and the PSII reaction center, shown by absorption and fluorescence experiments. The biohybrid system shows stability at pH 6.5, the native operating environment of PSII, so a high rate of O2 evolution is expected. In addition, the light-induced water-splitting process can be further stimulated by the direct interaction of superfine WO3 NPs with the donor and acceptor sides of PSII. The water-splitting activity and stability of this colloidal system are under investigation

Human papillomavirus in head and neck squamous cell carcinoma: A descriptive study of histologically confirmed cases at Kamuzu Central Hospital in Lilongwe, Malawi

Background: Head and neck squamous cell carcinoma (HNSCC) is common in sub-Saharan Africa, but the aetiologic contribution of human papillomavirus (HPV) is not well established.Methods: We assessed HNSCC cases for HPV using p16 immunohistochemistry (IHC) in Malawi. Associations between p16 IHC and tumour site, behavioural risk factors, demographic characteristics, and HIV status were examined.Results: From 2010 to 2014, 77 HNSCC cases were identified. Mean age was 52 years, 50 cases (65%) were male, and 48 (62%) were in the oropharynx (OP) or oral cavity (OC). HIV status was known for 35 patients (45%), with 5 (14%) HIV-infected. Substance use was known for 40 patients (52%), with 38% reporting any tobacco and 31% any alcohol. Forty-two cases (55%) had adequate tissue for p16 IHC, of which seven (17%) were positive, including 22% of OP/OC tumours.Conclusions: Despite high cervical cancer burden, HPV-associated HNSCC is not very common in Malaw

Adapting crowdsourced clinical cancer curation in CIViC to the ClinGen minimum variant level data community-driven standards

Harmonization of cancer variant representation, efficient communication, and free distribution of clinical variant-associated knowledge are central problems that arise with increased usage of clinical next-generation sequencing. The Clinical Genome Resource (ClinGen) Somatic Working Group (WG) developed a minimal variant level data (MVLD) representation of cancer variants, and has an ongoing collaboration with Clinical Interpretations of Variants in Cancer (CIViC), an open-source platform supporting crowdsourced and expert-moderated cancer variant curation. Harmonization between MVLD and CIViC variant formats was assessed by formal field-by-field analysis. Adjustments to the CIViC format were made to harmonize with MVLD and support ClinGen Somatic WG curation activities, including four new features in CIViC: (1) introduction of an assertions feature for clinical variant assessment following the Association of Molecular Pathologists (AMP) guidelines, (2) group-level curation tracking for organizations, enabling member transparency, and curation effort summaries, (3) introduction of ClinGen Allele Registry IDs to CIViC, and (4) mapping of CIViC assertions into ClinVar submission with automated submissions. A generalizable workflow utilizing MVLD and new CIViC features is outlined for use by ClinGen Somatic WG task teams for curation and submission to ClinVar, and provides a model for promoting harmonization of cancer variant representation and efficient distribution of this information

CIViCpy: A Python software evelopment and analysis toolkit for the CIViC knowledgebase

PURPOSE: Precision oncology depends on the matching of tumor variants to relevant knowledge describing the clinical significance of those variants. We recently developed the Clinical Interpretations for Variants in Cancer (CIViC; civicdb.org) crowd-sourced, expert-moderated, and open-access knowledgebase. CIViC provides a structured framework for evaluating genomic variants of various types (eg, fusions, single-nucleotide variants) for their therapeutic, prognostic, predisposing, diagnostic, or functional utility. CIViC has a documented application programming interface for accessing CIViC records: assertions, evidence, variants, and genes. Third-party tools that analyze or access the contents of this knowledgebase programmatically must leverage this application programming interface, often reimplementing redundant functionality in the pursuit of common analysis tasks that are beyond the scope of the CIViC Web application. METHODS: To address this limitation, we developed CIViCpy (civicpy.org), a software development kit for extracting and analyzing the contents of the CIViC knowledgebase. CIViCpy enables users to query CIViC content as dynamic objects in Python. We assess the viability of CIViCpy as a tool for advancing individualized patient care by using it to systematically match CIViC evidence to observed variants in patient cancer samples. RESULTS: We used CIViCpy to evaluate variants from 59,437 sequenced tumors of the American Association for Cancer Research Project GENIE data set. We demonstrate that CIViCpy enables annotation of \u3e 1,200 variants per second, resulting in precise variant matches to CIViC level A (professional guideline) or B (clinical trial) evidence for 38.6% of tumors. CONCLUSION: The clinical interpretation of genomic variants in cancers requires high-throughput tools for interoperability and analysis of variant interpretation knowledge. These needs are met by CIViCpy, a software development kit for downstream applications and rapid analysis. CIViCpy is fully documented, open-source, and available free online

Bayesian Optimization of High‐Entropy Alloy Compositions for Electrocatalytic Oxygen Reduction**

Active, selective and stable catalysts are imperative for sustainable energy conversion, and engineering materials with such properties are highly desired. High-entropy alloys (HEAs) offer a vast compositional space for tuning such properties. Too vast, however, to traverse without the proper tools. Here, we report the use of Bayesian optimization on a model based on density functional theory (DFT) to predict the most active compositions for the electrochemical oxygen reduction reaction (ORR) with the least possible number of sampled compositions for the two HEAs Ag-Ir-Pd-Pt-Ru and Ir-Pd-Pt-Rh-Ru. The discovered optima are then scrutinized with DFT and subjected to experimental validation where optimal catalytic activities are verified for Ag-Pd, Ir-Pt, and Pd-Ru binary systems. This study offers insight into the number of experiments needed for exploring the vast compositional space of multimetallic alloys which has been determined to be on the order of 50 for ORR on these HEAs

Surface potential and roughness controlled cell adhesion and collagen formation in electrospun PCL fibers for bone regeneration

Surface potential of biomaterials is a key factor regulating cell responses, driving their adhesion and signaling in tissue regeneration. In this study we compared the surface and zeta potential of smooth and porous electrospun polycaprolactone (PCL) fibers, as well as PCL films, to evaluate their significance in bone regeneration. The ' surface potential of the fibers was controlled by applying positive and negative voltage polarities during the electrospinning. The surface properties of the different PCL fibers and films were measured using X-ray photoelectron spectroscopy (XPS) and Kelvin probe force microscopy (KPFM), and the zeta potential was measured using the electrokinetic technique. The effect of surface potential on the morphology of bone cells was examined using advanced microcopy, including 3D reconstruction based on a scanning electron microscope with a focused ion beam (FIB-SEM). Initial cell adhesion and collagen formation were studied using fluorescence microscopy and Sirius Red assay respectively, while calcium mineralization was confirmed with energy-dispersive x-ray (EDX) and Alzarin Red staining. These studies revealed that cell adhesion is driven by both the surface potential and morphology of PCL fibers. Furthermore, the ability to tune the surface potential of electrospun PCL scaffolds provides an essential electrostatic handle to enhance cell-material interaction and cellular activity, leading to controllable morphological changes