Abstract Induced pluripotent stem cells (iPSCs) hold great promise as a cell source for regenerative medicine yet its culture, maintenance of pluripotency and induction of differentiation remain ...challenging. Conversely, graphene (G) and graphene oxide (GO) have captured tremendous interests in the fields of materials science, physics, chemistry and nanotechnology. Here we report on that G and GO can support the mouse iPSCs culture and allow for spontaneous differentiation. Intriguingly, G and GO surfaces led to distinct cell proliferation and differentiation characteristics. In comparison with the glass surface, iPSCs cultured on the G surface exhibited similar degrees of cell adhesion and proliferation while iPSCs on the GO surface adhered and proliferated at a faster rate. Moreover, G favorably maintained the iPSCs in the undifferentiated state while GO expedited the differentiation. The iPSCs cultured on both G and GO surfaces spontaneously differentiated into ectodermal and mesodermal lineages without significant disparity, but G suppressed the iPSCs differentiation towards the endodermal lineage whereas GO augmented the endodermal differentiation. These data collectively demonstrated that the different surface properties of G and GO governed the iPSCs behavior and implicate the potentials of graphene-based materials as a platform for iPSCs culture and diverse applications.
The motion of electrons in a solid has a profound effect on its topological properties and may result in a nonzero Berry's phase, a geometric quantum phase encoded in the system's electronic wave ...function. Despite its ubiquity, there are few experimental observations of Berry's phase of bulk states. Here, we report detection of a nontrivial π Berry's phase in the bulk Rashba semiconductor BiTel via analysis of the Shubnikov-de Haas (SdH) effect. The extremely large Rashba splitting in this material enables the separation of SdH oscillations, stemming from the spin-split inner and outer Fermi surfaces. For both Fermi surfaces, we observe a systematic π-phase shift in SdH oscillations, consistent with the theoretically predicted nontrivial π Berry's phase in Rashba systems.
We present microlensing events in the 2015 Korea Microlensing Telescope Network (KMTNet) data and our procedure for identifying these events. In particular, candidates were detected with a novel ..."completed-event" microlensing event-finder algorithm. The algorithm works by making linear fits to a grid of point-lens microlensing models. This approach is rendered computationally efficient by restricting u0 to just two values (0 and 1), which we show is quite adequate. The implementation presented here is specifically tailored to the commission-year character of the 2015 data, but the algorithm is quite general and has already been applied to a completely different (non-KMTNet) data set. We outline expected improvements for 2016 and future KMTNet data. The light curves of the 660 "clear microlensing" and 182 "possible microlensing" events that were found in 2015 are presented along with our policy for their public release.
We report the discovery of a giant planet in the OGLE-2017-BLG-1522 microlensing event. The planetary perturbations were clearly identified by high-cadence survey experiments despite the relatively ...short event timescale of tE ∼ 7.5 days. The Einstein radius is unusually small, θE = 0.065 mas, implying that the lens system either has very low mass or lies much closer to the microlensed source than the Sun, or both. A Bayesian analysis yields component masses and source-lens distance , implying that this is a brown-dwarf/Jupiter system that probably lies in the Galactic bulge, a location that is also consistent with the relatively low lens-source relative proper motion = 3.2 0.5 mas yr−1. The projected companion-host separation is , indicating that the planet is placed beyond the snow line of the host, i.e., asl ∼ 0.12 au. Planet formation scenarios combined with the small companion-host mass ratio q ∼ 0.016 and separation suggest that the companion could be the first discovery of a giant planet that formed in a protoplanetary disk around a brown-dwarf host.
Current microlensing surveys are sensitive to free-floating planets down to Earth-mass objects. All published microlensing events attributed to unbound planets were identified based on their short ...timescale (below two days), but lacked an angular Einstein radius measurement (and hence lacked a significant constraint on the lens mass). Here, we present the discovery of a Neptune-mass free-floating planet candidate in the ultrashort (tE = 0.320 0.003 days) microlensing event OGLE-2016-BLG-1540. The event exhibited strong finite-source effects, which allowed us to measure its angular Einstein radius of θE = 9.2 0.5 as. There remains, however, a degeneracy between the lens mass and distance. The combination of the source proper motion and source-lens relative proper motion measurements favors a Neptune-mass lens located in the Galactic disk. However, we cannot rule out that the lens is a Saturn-mass object belonging to the bulge population. We exclude stellar companions up to ∼15 au.
Early detection of coagulopathy is important to prevent bleeding during liver transplantation (LT). Rotation thromboelastometry (ROTEM®) provides the earliest parameter of clot amplitudes at 5 min ...(A5). We evaluated whether A5 correlates with platelet count (PLT) and fibrinogen concentration (Fib) and can predict thrombocytopenia and hypofibrinogenaemia in hypocoagulable patients undergoing living-donor LT (LDLT).
A total of 3446 retrospective ROTEM® measurements, including 1139 EXTEM, 1182 INTEM, and 1125 FIBTEM, with simultaneously measured PLT and Fib, were analysed during LDLT in 239 patients. The correlations between A5 and maximum clot firmness (MCF) index, PLT, and Fib were calculated. Receiver operating characteristic analysis with area under the curve (AUC) was used to assess A5 thresholds predictive of PLT and Fib.
The median PLT was 47 000 mm−3 and the median Fib was 100 mg dl−1 during LDLT. The A5 parameters of EXTEM (A5EXTEM) and INTEM (A5INTEM) were highly correlated with MCF (r=0.96 and r=0.95, respectively), PLT (r=0.76 and r=0.77, respectively), and Fib (r=0.63 and r=0.64, respectively). A5 of FIBTEM (A5FIBTEM) was also correlated with MCF (r=0.91) and Fib (r=0.75). A5EXTEM thresholds of 15 and 19 mm predicted PLT<30 000 mm−3 (AUC=0.90) and <50 000 mm−3 (AUC=0.87), respectively, whereas A5FIBTEM 4 mm predicted Fib<100 mg dl−1 (AUC=0.86). Biases from A5EXTEM and A5FIBTEM to their MCFs were 16.4 and 1.3 mm, respectively.
A5 as an early variable of clot firmness is effective in detecting critically low PLT and Fib. A5 can therefore be a reliable fast index guiding transfusion therapy in hypocoagulable patients undergoing LDLT.
We report the analysis of the microlensing event OGLE-2018-BLG-0677. A small feature in the light curve of the event leads to the discovery that the lens is a star-planet system. Although there are ...two degenerate solutions that could not be distinguished for this event, both lead to a similar planet-host mass ratio. We perform a Bayesian analysis based on a Galactic model to obtain the properties of the system and find that the planet corresponds to a super-Earth/sub-Neptune with a mass of . The host star has a mass of . The projected separation for the inner and outer solutions are au and au respectively. At , this is by far the lowest Δχ2 for any securely detected microlensing planet to date, a feature that is closely connected to the fact that it is detected primarily via a "dip" rather than a "bump."
Background Sevoflurane is one of the most commonly used volatile anesthetic agents with the fastest onset and offset, replacing isoflurane in modern anesthesiology. Preconditioning and ...postconditioning using volatile anesthetics can attenuate ischemia-reperfusion injury (IRI). However, no previous studies have evaluated the effect of sevoflurane in lung transplantation after cold ischemic injury. We aimed to study the effects of donor and recipient treatment with sevoflurane in a rat lung transplantation model. Methods Lewis rats were allocated to four groups: control, PreC (preconditioning), PostC (postconditioning), and PreC + PostC. Donor rats in the PreC and PreC + PostC groups were exposed to 1.5% sevoflurane for 30 minutes before donor operation. Donor lungs were flushed with Perfadex and stored for 12 hours at 4°C before transplantation. Recipients received orthotopic left lung transplantation. In the PostC and PreC + PostC groups, sevoflurane was initiated 2 minutes before reperfusion and maintained for 30 minutes. Two hours after reperfusion, lung function was evaluated, and samples were collected for histologic, inflammatory, and cell death assessment. Results Preconditioning and postconditioning using sevoflurane significantly improved the oxygenation of lung grafts (partial arterial gas pressure of oxygen: 198 mm Hg in control, 406.5 mm Hg in PreC, 472.4 mm Hg in PostC, and 409.7 mm Hg in PreC + PostC, p < 0.0001) and reduced pulmonary edema. Sevoflurane treatment reduced levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α. Moreover, sevoflurane significantly inhibited apoptotic cells by a decrease in cytochrome c release into cytosol and caspase-3 cleavage. Conclusions Preconditioning or postconditioning of lungs using sevoflurane exhibits a significant protective effect against early phase of ischemia-reperfusion injury in a rat lung transplantation model.
Rapid, chip-scale, and cost-effective single particle detection of biological agents is of great importance to human health and national security. We report real-time, high-throughput detection and ...sizing of individual, low-index polystyrene nanoparticles and H1N1 virus. Our widefield, common path interferometer detects nanoparticles and viruses over a very large sensing area, orders of magnitude larger than competing techniques. We demonstrate nanoparticle detection and sizing down to 70 nm in diameter. We clearly size discriminate nanoparticles with diameters of 70, 100, 150, and 200 nm. We also demonstrate detection and size characterization of hundreds of individual H1N1 viruses in a single experiment.
Abstract Cathepsin K is an osteoclast-derived cysteine protease that has been implicated as playing a major role in bone resorption. A substantial body of evidence indicates that cathepsin K is ...critical in osteoclast-mediated bone resorption and suggests that its pharmacological inhibition should result in inhibition of bone resorption in vivo . Here we report the pharmacological characterization of SB-462795 (relacatib) as a potent and orally bioavailable small molecule inhibitor of cathepsin K that inhibits bone resorption both in vitro in human tissue and in vivo in cynomolgus monkeys. SB-462795 is a potent inhibitor of human cathepsins K, L, and V ( Ki, app = 41, 68, and 53 pM, respectively) that exhibits 39–300-fold selectivity over other cathepsins. SB-462795 inhibited endogenous cathepsin K in situ in human osteoclasts and human osteoclast-mediated bone resorption with IC50 values of ∼ 45 nM and ∼ 70 nM, respectively. The anti-resorptive potential of SB-462795 was evaluated in normal as well as medically ovariectomized (Ovx) female cynomolgus monkeys. Serum levels of the C- and N-terminal telopeptides of Type I collagen (CTx and NTx, respectively) and urinary levels of NTx were monitored as biomarkers of bone resorption. Administration of SB-462795 to medically ovariectomized or normal monkeys resulted in an acute reduction in both serum and urinary markers of bone resorption within 1.5 h after dosing, and this effect lasted up to 48 h depending on the dose administered. Our data indicate that SB-462795 potently inhibits human cathepsin K in osteoclasts, resulting in a rapid inhibition of bone resorption both in vitro and in vivo in the monkey. These studies also demonstrate the therapeutic potential of relacatib in the treatment of postmenopausal osteoporosis and serves to model the planned clinical trials in human subjects.
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