Comparing microfluidic performance of three-dimensional (3D) printing platforms

Three-dimensional (3D) printing has emerged as a potential revolutionary technology for the fabrication of microfluidic devices. A direct experimental comparison of the three 3D printing technologies dominating microfluidics was conducted using a Y-junction microfluidic device, the design of which was optimized for each printer: fused deposition molding (FDM), Polyjet, and digital light processing stereolithography (DLP-SLA). Printer performance was evaluated in terms of feature size, accuracy, and suitability for mass manufacturing; laminar flow was studied to assess their suitability for microfluidics. FDM was suitable for microfabrication with minimum features of 321 ± 5 μm, and rough surfaces of 10.97 μm. Microfluidic devices >500 μm, rapid mixing (71% ± 12% after 5 mm, 100 μL/min) was observed, indicating a strength in fabricating micromixers. Polyjet fabricated channels with a minimum size of 205 ± 13 μm, and a surface roughness of 0.99 μm. Compared with FDM, mixing decreased (27% ± 10%), but Polyjet printing is more suited for microfluidic applications where flow splitting is not required, such as cell culture or droplet generators. DLP-SLA fabricated a minimum channel size of 154 ± 10 μm, and 94 ± 7 μm for positive structures such as soft lithography templates, with a roughness of 0.35 μm. These results, in addition to low mixing (8% ± 1%), showed suitability for microfabrication, and microfluidic applications requiring precise control of flow. Through further discussion of the capabilities (and limitations) of these printers, we intend to provide guidance toward the selection of the 3D printing technology most suitable for specific microfluidic applications

Beyond chance? The persistence of performance in online poker

A major issue in the widespread controversy about the legality of poker and the appropriate taxation of winnings is whether poker should be considered a game of skill or a game of chance. To inform this debate we present an analysis into the role of skill in the performance of online poker players, using a large database with hundreds of millions of player-hand observations from real money ring games at three different stakes levels. We find that players whose earlier profitability was in the top (bottom) deciles perform better (worse) and are substantially more likely to end up in the top (bottom) performance deciles of the following time period. Regression analyses of performance on historical performance and other skill-related proxies provide further evidence for persistence and predictability. Simulations point out that skill dominates chance when performance is measured over 1,500 or more hands of play

The development and piloting of the graduate assessment of preparedness for practice (GAPP) questionnaire

Introduction Most new dental graduates in the UK begin their professional career following a year in dental foundation training (DFT). There has been little investigation of how prepared they feel for independent general dental practice across all four domains of the General Dental Council’s curriculum ‘Preparing for practice’. This paper describes the development of the Graduate Assessment of Preparedness for Practice (GAPP) questionnaire to address this. Methodology The GAPP questionnaire was developed and piloted using a cohort of educational supervisors (ESs) and foundation dentists (FDs). The questionnaire comprised three parts, the first of which collected respondent demographic data. The second was based on Preparing for practice and was used to develop 34 ‘competence areas’ and required a tick-box response on a 7‑category Likert Scale. The third comprised free text questions in order to further explore the subject’s responses. Results Pilot feedback was positive, the statements were felt to be clear and unambiguous, allowing them sufficient scope to state their position. The pilot study informed small cosmetic changes to the GAPP questionnaire and inclusion of a ‘comments’ column for respondents to qualify their responses. The pilot results indicated that both FDs and their ESs felt that at ten months of DFT, the FDs were very well prepared for independent general dental practice. Discussion The paper describes the important considerations relating to the reliability and validity of the GAPP questionnaire. Conclusions GAPP appears to be a suitable questionnaire to measure preparedness of new graduates with a degree of reliability and validity. The instrument is designed to be simple to complete and provides a useful analytical instrument for both self-assessment of competence and for wider use within dental education

A Genome-Wide Analysis Reveals No Nuclear Dobzhansky-Muller Pairs of Determinants of Speciation between S. cerevisiae and S. paradoxus, but Suggests More Complex Incompatibilities

The Dobzhansky-Muller (D-M) model of speciation by genic incompatibility is widely accepted as the primary cause of interspecific postzygotic isolation. Since the introduction of this model, there have been theoretical and experimental data supporting the existence of such incompatibilities. However, speciation genes have been largely elusive, with only a handful of candidate genes identified in a few organisms. The Saccharomyces sensu stricto yeasts, which have small genomes and can mate interspecifically to produce sterile hybrids, are thus an ideal model for studying postzygotic isolation. Among them, only a single D-M pair, comprising a mitochondrially targeted product of a nuclear gene and a mitochondrially encoded locus, has been found. Thus far, no D-M pair of nuclear genes has been identified between any sensu stricto yeasts. We report here the first detailed genome-wide analysis of rare meiotic products from an otherwise sterile hybrid and show that no classic D-M pairs of speciation genes exist between the nuclear genomes of the closely related yeasts S. cerevisiae and S. paradoxus. Instead, our analyses suggest that more complex interactions, likely involving multiple loci having weak effects, may be responsible for their post-zygotic separation. The lack of a nuclear encoded classic D-M pair between these two yeasts, yet the existence of multiple loci that may each exert a small effect through complex interactions suggests that initial speciation events might not always be mediated by D-M pairs. An alternative explanation may be that the accumulation of polymorphisms leads to gamete inviability due to the activities of anti-recombination mechanisms and/or incompatibilities between the species' transcriptional and metabolic networks, with no single pair at least initially being responsible for the incompatibility. After such a speciation event, it is possible that one or more D-M pairs might subsequently arise following isolation

EXPRES. III. Revealing the stellar activity radial velocity signature of ϵ Eridani with photometry and interferometry

This is the final version. Available from IOP Publishing via the DOI in this record. The distortions of absorption line profiles caused by photospheric brightness variations on the surfaces of cool, main-sequence stars can mimic or overwhelm radial velocity (RV) shifts due to the presence of exoplanets. The latest generation of precision RV spectrographs aims to detect velocity amplitudes ≲ 10 cm s-1, but requires mitigation of stellar signals. Statistical techniques are being developed to differentiate between Keplerian and activity-related velocity perturbations. Two important challenges, however, are the interpretability of the stellar activity component as RV models become more sophisticated, and ensuring the lowest-amplitude Keplerian signatures are not inadvertently accounted for in flexible models of stellar activity. For the K2V exoplanet host Eridani, we separately used ground-based photometry to constrain Gaussian processes for modeling RVs and TESS photometry with a light-curve inversion algorithm to reconstruct the stellar surface. From the reconstructions of TESS photometry, we produced an activity model that reduced the rms scatter in RVs obtained with EXPRES from 4.72 to 1.98 m s-1. We present a pilot study using the CHARA Array and MIRC-X beam combiner to directly image the starspots seen in the TESS photometry. With the limited phase coverage, our spot detections are marginal with current data but a future dedicated observing campaign should allow for imaging, as well as allow the stellar inclination and orientation with respect to the debris disk to be definitively determined. This work shows that stellar surface maps obtained with high-cadence, time-series photometric and interferometric data can provide the constraints needed to accurately reduce RV scatter.European CommissionNSFNSFNASANASA XRPEuropean Research CouncilNASA TESS GIHeising-Simons FoundationAnonymous donor in the Yale alumni communityYale Center for Astronomy and Astrophysics Prize Postdoctoral FellowshipHeising-Simons 51 Pegasi b Postdoctoral Fellowshi

TOI-1634 b: An Ultra-short-period Keystone Planet Sitting inside the M-dwarf Radius Valley

Studies of close-in planets orbiting M dwarfs have suggested that the M dwarf radius valley may be well-explained by distinct formation timescales between enveloped terrestrials, and rocky planets that form at late times in a gas-depleted environment. This scenario is at odds with the picture that close-in rocky planets form with a primordial gaseous envelope that is subsequently stripped away by some thermally-driven mass loss process. These two physical scenarios make unique predictions of the rocky/enveloped transition's dependence on orbital separation such that studying the compositions of planets within the M dwarf radius valley may be able to establish the dominant physics. Here, we present the discovery of one such keystone planet: the ultra-short period planet TOI-1634 b ($P=0.989$ days, $F=121 F_{\oplus}$, $r_p = 1.790^{+0.080}_{-0.081} R_{\oplus}$) orbiting a nearby M2 dwarf ($K_s=8.7$, $R_s=0.45 R_{\odot}$, $M_s=0.50 M_{\odot}$) and whose size and orbital period sit within the M dwarf radius valley. We confirm the TESS-discovered planet candidate using extensive ground-based follow-up campaigns, including a set of 32 precise radial velocity measurements from HARPS-N. We measure a planetary mass of $4.91^{+0.68}_{-0.70} M_{\oplus}$, which makes TOI-1634 b inconsistent with an Earth-like composition at $5.9\sigma$ and thus requires either an extended gaseous envelope, a large volatile-rich layer, or a rocky portion that is not dominated by iron and silicates to explain its mass and radius. The discovery that the bulk composition of TOI-1634 b is inconsistent with that of the Earth favors the gas-depleted formation mechanism to explain the emergence of the radius valley around M dwarfs with $M_s\lesssim 0.5 M_{\odot}$

A New Mixed-Backbone Oligonucleotide against Glucosylceramide Synthase Sensitizes Multidrug-Resistant Tumors to Apoptosis

Enhanced ceramide glycosylation catalyzed by glucosylceramide synthase (GCS) limits therapeutic efficiencies of antineoplastic agents including doxorubicin in drug-resistant cancer cells. Aimed to determine the role of GCS in tumor response to chemotherapy, a new mixed-backbone oligonucleotide (MBO-asGCS) with higher stability and efficiency has been generated to silence human GCS gene. MBO-asGCS was taken up efficiently in both drug-sensitive and drug-resistant cells, but it selectively suppressed GCS overexpression, and sensitized drug-resistant cells. MBO-asGCS increased doxorubicin sensitivity by 83-fold in human NCI/ADR-RES, and 43-fold in murine EMT6/AR1 breast cancer cells, respectively. In tumor-bearing mice, MBO-asGCS treatment dramatically inhibited the growth of multidrug-resistant NCI/ADR-RE tumors, decreasing tumor volume to 37%, as compared with scrambled control. Furthermore, MBO-asGCS sensitized multidrug-resistant tumors to chemotherapy, increasing doxorubicin efficiency greater than 2-fold. The sensitization effects of MBO-asGCS relied on the decreases of gene expression and enzyme activity of GCS, and on the increases of C18-ceramide and of caspase-executed apoptosis. MBO-asGCS was accumulation in tumor xenografts was greater in other tissues, excepting liver and kidneys; but MBO-asGCS did not exert significant toxic effects on liver and kidneys. This study, for the first time in vivo, has demonstrated that GCS is a promising therapeutic target for cancer drug resistance, and MBO-asGCS has the potential to be developed as an antineoplastic agent

Mycobacteria Attenuate Nociceptive Responses by Formyl Peptide Receptor Triggered Opioid Peptide Release from Neutrophils

In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly downregulate postoperative as well as arthritic pain. In rats, inflammatory pain is induced by intraplantar injection of heat inactivated Mycobacterium butyricum, a component of complete Freund's adjuvant. We hypothesized that mycobacterially derived formyl peptide receptor (FPR) and/or toll like receptor (TLR) agonists could activate neutrophils, leading to opioid peptide release and inhibition of inflammatory pain. In complete Freund's adjuvant-induced inflammation, thermal and mechanical nociceptive thresholds of the paw were quantified (Hargreaves and Randall-Selitto methods, respectively). Withdrawal time to heat was decreased following systemic neutrophil depletion as well as local injection of opioid receptor antagonists or anti-opioid peptide (i.e. Met-enkephalin, β-endorphin) antibodies indicating an increase in pain. In vitro, opioid peptide release from human and rat neutrophils was measured by radioimmunoassay. Met-enkephalin release was triggered by Mycobacterium butyricum and formyl peptides but not by TLR-2 or TLR-4 agonists. Mycobacterium butyricum induced a rise in intracellular calcium as determined by FURA loading and calcium imaging. Opioid peptide release was blocked by intracellular calcium chelation as well as phosphoinositol-3-kinase inhibition. The FPR antagonists Boc-FLFLF and cyclosporine H reduced opioid peptide release in vitro and increased inflammatory pain in vivo while TLR 2/4 did not appear to be involved. In summary, mycobacteria activate FPR on neutrophils, resulting in tonic secretion of opioid peptides from neutrophils and in a decrease in inflammatory pain. Future therapeutic strategies may aim at selective FPR agonists to boost endogenous analgesia