Anti-Reflection Coating for Nitrogen-Vacancy Optical Measurements in Diamond

We realize anti-reflection (AR) coatings for optical excitation and fluorescence measurements of nitrogen-vacancy (NV) color centers in bulk diamond by depositing quarter-wavelength thick silica layers on the diamondsurface. These AR coatings improve NV-diamond optical measurements by reducing optical reflection at the diamond-air interface from ≈17% to ≈2%, which allows more effective NV optical excitation and more efficient detection of NV fluorescence. We also show that diamondAR coatings eliminate standing-wave interference patterns of excitation laser intensity within bulk diamond, and thereby greatly reduce spatial variations in NV fluorescence, which can degrade spatially resolved magnetic field sensing using NV centers.Engineering and Applied SciencesPhysic

Hidden negative linear compressibility in lithium L-tartrate†

Development of artificial muscles, next-generation pressure sensors and precision optics relies on advances in materials with anomalous mechanical properties. Negative linear compressibility, NLC, is one such rare, counterintuitive phenomenon, in which a material expands along one axis under hydrostatic pressure. Both classical and recent NLC materials face a pay-off between the active pressure range and magnitude of NLC, and in the vast majority of cases the NLC effect decreases with pressure. By decoupling the mechanical behaviour of building units for the first time in a winerack framework containing two different strut types, we show that lithium L-tartrate exhibits NLC with a maximum value, Kmax = -21 TPa^-1, and an overall NLC capacity, χNLC = 5.1 %, that are comparable to the most exceptional materials to date. Furthermore, the contributions from molecular strut compression and angle opening interplay to give rise to so-called “hidden” negative linear compressibility, in which NLC is absent at ambient pressure, switched on at 2 GPa and sustained up to the limit of our experiment, 5.5 GPa. Analysis of the changes in crystal structure using variable-pressure synchrotron X-ray diffraction reveals new chemical and geometrical design rules to assist the discovery of other materials with exciting hidden anomalous mechanical properties

Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem Cells

Background. Mouse embryonic stem (ES) cells can be differentiated in vitro by aggregation and/or retinoic acid (RA) treatment. The principal differentiation lineage in vitro is extraembryonic primitive endoderm. Dab2, Laminin, GATA4, GATA5, and GATA6 are expressed in embryonic primitive endoderm and play critical roles in its lineage commitment. Results. We found that in the absence of GATA4 or GATA5, RA-induced primitive endoderm differentiation of ES cells was reduced. GATA4 (−/−) ES cells express higher level of GATA5, GATA6, and hepatocyte nuclear factor 4 alpha marker of visceral endoderm lineage. GATA5 (−/−) ES cells express higher level of alpha fetoprotein marker of early liver development. GATA6 (−/−) ES cells express higher level of GATA5 as well as mesoderm and cardiomyocyte markers which are collagen III alpha-1 and tropomyosin1 alpha. Thus, deletion of GATA6 precluded endoderm differentiation but promoted mesoderm lineages. Conclusions. GATA4, GATA5, and GATA6 each convey a unique gene expression pattern and influences ES cell differentiation. We showed that ES cells can be directed to avoid differentiating into primitive endoderm and to adopt unique lineages in vitro by modulating GATA factors. The finding offers a potential approach to produce desirable cell types from ES cells, useful for regenerative cell therapy

Hybrid glasses from strong and fragile metal-organic framework liquids

This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/ncomms9079Hybrid glasses connect the emerging field of metal-organic frameworks (MOFs) with the glass formation, amorphization and melting processes of these chemically versatile systems. Though inorganic zeolites collapse around the glass transition and melt at higher temperatures, the relationship between amorphization and melting has so far not been investigated. Here we show how heating MOFs of zeolitic topology first results in a low density ?perfect? glass, similar to those formed in ice, silicon and disaccharides. This order?order transition leads to a super-strong liquid of low fragility that dynamically controls collapse, before a subsequent order?disorder transition, which creates a more fragile high-density liquid. After crystallization to a dense phase, which can be remelted, subsequent quenching results in a bulk glass, virtually identical to the high-density phase. We provide evidence that the wide-ranging melting temperatures of zeolitic MOFs are related to their network topologies and opens up the possibility of ?melt-casting? MOF glasses.The authors would like to thank Trinity Hall (TDB); HRH Sheikh Saud Bin Saqr Al Qasimi (TDB and AKC); Wuhan University of Science and Technology (YY and GNG), ERC grant number 259619 PHOTO EM (CD); Alexander von Humboldt Foundation (SH); The World Premier International Research Center Initiative on Materials Nanoarchitectronics (WPI-MANA) from MEXT, Japan (HHMY)

Expression and trans-specific polymorphism of self-incompatibility RNases in Coffea (Rubiaceae)

Self-incompatibility (SI) is widespread in the angiosperms, but identifying the biochemical components of SI mechanisms has proven to be difficult in most lineages. Coffea (coffee; Rubiaceae) is a genus of old-world tropical understory trees in which the vast majority of diploid species utilize a mechanism of gametophytic self-incompatibility (GSI). The S-RNase GSI system was one of the first SI mechanisms to be biochemically characterized, and likely represents the ancestral Eudicot condition as evidenced by its functional characterization in both asterid (Solanaceae, Plantaginaceae) and rosid (Rosaceae) lineages. The S-RNase GSI mechanism employs the activity of class III RNase T2 proteins to terminate the growth of "self" pollen tubes. Here, we investigate the mechanism of Coffea GSI and specifically examine the potential for homology to S-RNase GSI by sequencing class III RNase T2 genes in populations of 14 African and Madagascan Coffea species and the closely related self-compatible species Psilanthus ebracteolatus. Phylogenetic analyses of these sequences aligned to a diverse sample of plant RNase T2 genes show that the Coffea genome contains at least three class III RNase T2 genes. Patterns of tissue-specific gene expression identify one of these RNase T2 genes as the putative Coffea S-RNase gene. We show that populations of SI Coffea are remarkably polymorphic for putative S-RNase alleles, and exhibit a persistent pattern of trans-specific polymorphism characteristic of all S-RNase genes previously isolated from GSI Eudicot lineages. We thus conclude that Coffea GSI is most likely homologous to the classic Eudicot S-RNase system, which was retained since the divergence of the Rubiaceae lineage from an ancient SI Eudicot ancestor, nearly 90 million years ago.United States National Science Foundation [0849186]; Society of Systematic Biologists; American Society of Plant Taxonomists; Duke University Graduate Schoolinfo:eu-repo/semantics/publishedVersio

Developing the principles of chair based exercise for older people: a modified Delphi study

Background Chair based exercise (CBE) is suggested to engage older people with compromised health and mobility in an accessible form of exercise. A systematic review looking at the benefits of CBE for older people identified a lack of clarity regarding a definition, delivery, purpose and benefits. This study aimed to utilise expert consensus to define CBE for older people and develop a core set of principles to guide practice and future research. Methods The framework for consensus was constructed through a team workshop identifying 42 statements within 7 domains. A four round electronic Delphi study with multi-disciplinary health care experts was undertaken. Statements were rated using a 5 point Likert scale of agreement and free text responses. A threshold of 70% agreement was used to determine consensus. Free text responses were analysed thematically. Between rounds a number of strategies (e.g., amended wording of statements, generation and removal of statements) were used to move towards consensus. Results 16 experts agreed on 46 statements over four rounds of consultation (Round 1: 22 accepted, 3 removed, 5 new and 17 modified; Round 2: 16 accepted, 0 removed, 4 new and 6 modified; Round 3: 4 accepted, 2 removed, 0 new and 4 modified; Round 4: 4 accepted, 0 removed, 0 new, 0 modified). Statements were accepted in all seven domains: the definition of CBE (5), intended users (3), potential benefits (8), structure (12), format (8), risk management (7) and evaluation (3). The agreed definition of CBE had five components: 1. CBE is primarily a seated exercise programme; 2. The purpose of using a chair is to promote stability in both sitting and standing; 3. CBE should be considered as part of a continuum of exercise for frail older people where progression is encouraged; 4. CBE should be used flexibly to respond to the changing needs of frail older people; and 5. Where possible CBE should be used as a starting point to progress to standing programmes. Conclusions Consensus has been reached on a definition and a set of principles governing CBE for older people; this provides clarity for implementation and future research about CBE

Cryopreservation of human cancers conserves tumour heterogeneity for single-cell multi-omics analysis

Background: High throughput single-cell RNA sequencing (scRNA-Seq) has emerged as a powerful tool for exploring cellular heterogeneity among complex human cancers. scRNA-Seq studies using fresh human surgical tissue are logistically difficult, preclude histopathological triage of samples, and limit the ability to perform batch processing. This hindrance can often introduce technical biases when integrating patient datasets and increase experimental costs. Although tissue preservation methods have been previously explored to address such issues, it is yet to be examined on complex human tissues, such as solid cancers and on high throughput scRNA-Seq platforms. Methods: Using the Chromium 10X platform, we sequenced a total of ~ 120,000 cells from fresh and cryopreserved replicates across three primary breast cancers, two primary prostate cancers and a cutaneous melanoma. We performed detailed analyses between cells from each condition to assess the effects of cryopreservation on cellular heterogeneity, cell quality, clustering and the identification of gene ontologies. In addition, we performed single-cell immunophenotyping using CITE-Seq on a single breast cancer sample cryopreserved as solid tissue fragments. Results: Tumour heterogeneity identified from fresh tissues was largely conserved in cryopreserved replicates. We show that sequencing of single cells prepared from cryopreserved tissue fragments or from cryopreserved cell suspensions is comparable to sequenced cells prepared from fresh tissue, with cryopreserved cell suspensions displaying higher correlations with fresh tissue in gene expression. We showed that cryopreservation had minimal impacts on the results of downstream analyses such as biological pathway enrichment. For some tumours, cryopreservation modestly increased cell stress signatures compared to freshly analysed tissue. Further, we demonstrate the advantage of cryopreserving whole-cells for detecting cell-surface proteins using CITE-Seq, which is impossible using other preservation methods such as single nuclei-sequencing. Conclusions: We show that the viable cryopreservation of human cancers provides high-quality single-cells for multiomics analysis. Our study guides new experimental designs for tissue biobanking for future clinical single-cell RNA sequencing studies

Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia.

Non-genetic drug resistance is increasingly recognised in various cancers. Molecular insights into this process are lacking and it is unknown whether stable non-genetic resistance can be overcome. Using single cell RNA-sequencing of paired drug naïve and resistant AML patient samples and cellular barcoding in a unique mouse model of non-genetic resistance, here we demonstrate that transcriptional plasticity drives stable epigenetic resistance. With a CRISPR-Cas9 screen we identify regulators of enhancer function as important modulators of the resistant cell state. We show that inhibition of Lsd1 (Kdm1a) is able to overcome stable epigenetic resistance by facilitating the binding of the pioneer factor, Pu.1 and cofactor, Irf8, to nucleate new enhancers that regulate the expression of key survival genes. This enhancer switching results in the re-distribution of transcriptional co-activators, including Brd4, and provides the opportunity to disable their activity and overcome epigenetic resistance. Together these findings highlight key principles to help counteract non-genetic drug resistance