Digital Sensing and Molecular Computation by an Enzyme-Free DNA Circuit.

DNA circuits form the basis of programmable molecular systems capable of signal transduction and algorithmic computation. Some classes of molecular programs, such as catalyzed hairpin assembly, enable isothermal, enzyme-free signal amplification. However, current detection limits in DNA amplification circuits are modest, as sensitivity is inhibited by signal leakage resulting from noncatalyzed background reactions inherent to the noncovalent system. Here, we overcome this challenge by optimizing a catalyzed hairpin assembly for single-molecule sensing in a digital droplet assay. Furthermore, we demonstrate digital reporting of DNA computation at the single-molecule level by employing ddCHA as a signal transducer for simple DNA logic gates. By facilitating signal transduction of molecular computation at pM concentration, our approach can improve processing density by a factor of 104 relative to conventional DNA logic gates. More broadly, we believe that digital molecular computing will broaden the scope and efficacy of isothermal amplification circuits within DNA computing, biosensing, and signal amplification in general

Reflecting back and forwards: The ebb and flow of peer-reviewed reflective practice research in sport

Researchers in sport have claimed that reflective practice is important for competent practice. Evidence supporting this claim is sparse, highly theoretical and located within a variety of domains. The aim of this study was to assimilate and analyse the last 12 years of reflective practice literature within the sport domain in order to identify new areas of inquiry, emerging trends with regard to findings or methodology, and to identify implications for future research and practice. A sample of 68 papers published between 2001 and 2012 was examined, and investigated for the research locations, data collection methods utilised, and the professions and communities involved. The paper concludes with some suggestions for future research

Data on a new beta titanium alloy system reinforced with superlattice intermetallic precipitates.

The data presented in this article are related to the research article entitled "a new beta titanium alloy system reinforced with superlattice intermetallic precipitates" (Knowles et al., 2018) [1]. This includes data from the as-cast alloy obtained using scanning electron microscopy (SEM) and x-ray diffraction (XRD) as well as SEM data in the solution heat treated condition. Transmission electron microscopy (TEM) selected area diffraction patterns (SADPs) are included from the alloy in the solution heat treated condition, as well as the aged condition that contained < 100 nm B2 TiFe precipitates [1], the latter of which was found to exhibit double diffraction owing to the precipitate and matrix channels being of a similar width to the foil thickness (Williams and Carter, 2009) [2]. Further details are provided on the macroscopic compression testing of small scale cylinders. Of the micropillar deformation experiment performed in [1], SEM micrographs of focused ion beam (FIB) prepared 2 µm micropillars are presented alongside those obtained at the end of the in-situ SEM deformation as well as videos of the in-situ deformation. Further, a table is included that lists the Schmidt factors of all the possible slip systems given the crystal orientations and loading axis of the deformed micropillars in the solution heat treated and aged conditions

Array-based evolution of DNA aptamers allows modelling of an explicit sequence-fitness landscape

Mapping the landscape of possible macromolecular polymer sequences to their fitness in performing biological functions is a challenge across the biosciences. A paradigm is the case of aptamers, nucleic acids that can be selected to bind particular target molecules. We have characterized the sequence-fitness landscape for aptamers binding allophycocyanin (APC) protein via a novel Closed Loop Aptameric Directed Evolution (CLADE) approach. In contrast to the conventional SELEX methodology, selection and mutation of aptamer sequences was carried out in silico, with explicit fitness assays for 44 131 aptamers of known sequence using DNA microarrays in vitro. We capture the landscape using a predictive machine learning model linking sequence features and function and validate this model using 5500 entirely separate test sequences, which give a very high observed versus predicted correlation of 0.87. This approach reveals a complex sequence-fitness mapping, and hypotheses for the physical basis of aptameric binding; it also enables rapid design of novel aptamers with desired binding properties. We demonstrate an extension to the approach by incorporating prior knowledge into CLADE, resulting in some of the tightest binding sequences

MeerKLASS: MeerKAT Large Area Synoptic Survey

We discuss the ground-breaking science that will be possible with a wide area survey, using the MeerKAT telescope, known as MeerKLASS (MeerKAT Large Area Synoptic Survey). The current specifications of MeerKAT make it a great fit for science applications that require large survey speeds but not necessarily high angular resolutions. In particular, for cosmology, a large survey over $\sim 4,000 \, {\rm deg}^2$ for $\sim 4,000$ hours will potentially provide the first ever measurements of the baryon acoustic oscillations using the 21cm intensity mapping technique, with enough accuracy to impose constraints on the nature of dark energy. The combination with multi-wavelength data will give unique additional information, such as exquisite constraints on primordial non-Gaussianity using the multi-tracer technique, as well as a better handle on foregrounds and systematics. Such a wide survey with MeerKAT is also a great match for HI galaxy studies, providing unrivalled statistics in the pre-SKA era for galaxies resolved in the HI emission line beyond local structures at z > 0.01. It will also produce a large continuum galaxy sample down to a depth of about 5\,$\mu$Jy in L-band, which is quite unique over such large areas and will allow studies of the large-scale structure of the Universe out to high redshifts, complementing the galaxy HI survey to form a transformational multi-wavelength approach to study galaxy dynamics and evolution. Finally, the same survey will supply unique information for a range of other science applications, including a large statistical investigation of galaxy clusters as well as produce a rotation measure map across a huge swathe of the sky. The MeerKLASS survey will be a crucial step on the road to using SKA1-MID for cosmological applications and other commensal surveys, as described in the top priority SKA key science projects (abridged).Comment: Larger version of the paper submitted to the Proceedings of Science, "MeerKAT Science: On the Pathway to the SKA", Stellenbosch, 25-27 May 201

Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues

Personal exome and genome sequencing provides access to loss-of-function and rare deleterious alleles whose interpretation is expected to provide insight into individual disease burden. However, for each allele, accurate interpretation of its effect will depend on both its penetrance and the trait's expressivity. In this regard, an important factor that can modify the effect of a pathogenic coding allele is its level of expression; a factor which itself characteristically changes across tissues. To better inform the degree to which pathogenic alleles can be modified by expression level across multiple tissues, we have conducted exome, RNA and deep, targeted allele-specific expression (ASE) sequencing in ten tissues obtained from a single individual. By combining such data, we report the impact of rare and common loss-of-function variants on allelic expression exposing stronger allelic bias for rare stop-gain variants and informing the extent to which rare deleterious coding alleles are consistently expressed across tissues. This study demonstrates the potential importance of transcriptome data to the interpretation of pathogenic protein-coding variants

Chromium-based bcc-superalloys strengthened by iron supplements

Chromium alloys are being considered for next-generation concentrated solar power applications operating > 800 °C. Cr offers advantages in melting point, cost, and oxidation resistance. However, improvements in mechanical performance are needed. Here, Cr-based body-centred-cubic (bcc) alloys of the type Cr(Fe)-NiAl are investigated, leading to ‘bcc-superalloys’ comprising a bcc-Cr(Fe) matrix (β) strengthened by ordered-bcc NiAl intermetallic precipitates (β’), with iron additions to tailor the precipitate volume fraction and mechanical properties at high temperatures. Computational design using CALculation of PHAse Diagram (CALPHAD) predicts that Fe increases the solubility of Ni and Al, increasing precipitate volume fraction, which is validated experimentally. Nano-scale, highly-coherent B2-NiAl precipitates with lattice misfit ∼ 0.1% are formed in the Cr(Fe) matrix. The Cr(Fe)-NiAl A2-B2 alloys show remarkably low coarsening rate (∼102 nm3/h at 1000 °C), outperforming ferritic-superalloys, cobalt- and nickel-based superalloys. Low interfacial energies of ∼ 40/20 mJ/m2 at 1000/1200 °C are determined based on the coarsening kinetics. The low coarsening rates are principally attributed to the low solubility of Ni and Al in the Cr matrix. The alloys show high compressive yield strength of ∼320 MPa at 1000 °C. The Fe-modified alloy exhibits resistance to age softening, related to the low coarsening rate as well as the relatively stable Orowan strengthening as a function of precipitate radius. Microstructure tailoring with Fe additions offers a new design route to improve the balance of properties in “Cr-superalloys”, accelerating their development as a new class of high-temperature materials

Human peritoneal mesothelial cells display phagocytic and antigen-presenting functions to contribute to intraperitoneal immunity

Mesothelial cells lining the peritoneal cavity are strategically positioned to respond to and counter intraperitoneal infections, cancer cells, and other challenges. We have investigated human peritoneal mesothelial cells (HPMCs) for phagocytic activity, expression of surface MHC Class II and accessory molecules involved in antigen presentation, and the ability to present recall antigens to T cells. Phagocytosis of dextran, latex beads and Escherichia coli was observed by flow cytometry, and internalization was visualised using confocal and electron microscopy. Flow cytometry and/or cellular ELISA showed constitutive expression of ICAM-I, LFA-3, and B7-1, but not B7-2 or MHC II. Interferon-gamma induced MHC II and ICAM-1 expression in a dose- and time-dependent manner. Importantly, HPMCs induced autologous CD3+ T lymphocyte proliferation (3H-incorporation) after pulse with recall antigen. HPMCs equipped with phagocytic and antigen-presenting machinery are anticipated to have an integral role in intraperitoneal immune surveillance

Chromium-based bcc-superalloys strengthened by iron supplements

Chromium alloys are being considered for next-generation concentrated solar power applications operating &gt; 800 °C. Cr offers advantages in melting point, cost, and oxidation resistance. However, improvements in mechanical performance are needed. Here, Cr-based body-centred-cubic (bcc) alloys of the type Cr(Fe)-NiAl are investigated, leading to ‘bcc-superalloys’ comprising a bcc-Cr(Fe) matrix (β) strengthened by ordered-bcc NiAl intermetallic precipitates (β’), with iron additions to tailor the precipitate volume fraction and mechanical properties at high temperatures. Computational design using CALculation of PHAse Diagram (CALPHAD) predicts that Fe increases the solubility of Ni and Al, increasing precipitate volume fraction, which is validated experimentally. Nano-scale, highly-coherent B2-NiAl precipitates with lattice misfit ∼ 0.1% are formed in the Cr(Fe) matrix. The Cr(Fe)-NiAl A2-B2 alloys show remarkably low coarsening rate (∼102 nm3/h at 1000 °C), outperforming ferritic-superalloys, cobalt- and nickel-based superalloys. Low interfacial energies of ∼ 40/20 mJ/m2 at 1000/1200 °C are determined based on the coarsening kinetics. The low coarsening rates are principally attributed to the low solubility of Ni and Al in the Cr matrix. The alloys show high compressive yield strength of ∼320 MPa at 1000 °C. The Fe-modified alloy exhibits resistance to age softening, related to the low coarsening rate as well as the relatively stable Orowan strengthening as a function of precipitate radius. Microstructure tailoring with Fe additions offers a new design route to improve the balance of properties in “Cr-superalloys”, accelerating their development as a new class of high-temperature materials