Computational Screening of a Single-Atom Catalyst Supported by Monolayer Nb2S2C for Oxygen Reduction Reaction.

The search for high-performance catalysts to improve the catalytic activity for an oxygen reduction reaction (ORR) is crucial for developing a proton exchange membrane fuel cell. Using the first-principles method, we have performed computational screening on a series of transition metal (TM) atoms embedded in monolayer Nb2S2C to enhance the ORR activity. Through the scaling relationship and volcano plot, our results reveal that the introduction of a single Ni or Rh atom through substitutional doping into monolayer Nb2S2C yields promising ORR catalysts with low overpotentials of 0.52 and 0.42 V, respectively. These doped atoms remain intact on the monolayer Nb2S2C even at elevated temperatures. Importantly, the catalytic activity of the Nb2S2C doped with a TM atom can be effectively correlated with an intrinsic descriptor, which can be computed based on the number of d orbital electrons and the electronegativity of TM and O atoms.

Atomic clock performance enabling geodesy below the centimetre level.

The passage of time is tracked by counting oscillations of a frequency reference, such as Earth's revolutions or swings of a pendulum. By referencing atomic transitions, frequency (and thus time) can be measured more precisely than any other physical quantity, with the current generation of optical atomic clocks reporting fractional performance below the 10-17 level1-5. However, the theory of relativity prescribes that the passage of time is not absolute, but is affected by an observer's reference frame. Consequently, clock measurements exhibit sensitivity to relative velocity, acceleration and gravity potential. Here we demonstrate local optical clock measurements that surpass the current ability to account for the gravitational distortion of space-time across the surface of Earth. In two independent ytterbium optical lattice clocks, we demonstrate unprecedented values of three fundamental benchmarks of clock performance. In units of the clock frequency, we report systematic uncertainty of 1.4 × 10-18, measurement instability of 3.2 × 10-19 and reproducibility characterized by ten blinded frequency comparisons, yielding a frequency difference of [-7 ± (5)stat ± (8)sys] × 10-19, where 'stat' and 'sys' indicate statistical and systematic uncertainty, respectively. Although sensitivity to differences in gravity potential could degrade the performance of the clocks as terrestrial standards of time, this same sensitivity can be used as a very sensitive probe of geopotential5-9. Near the surface of Earth, clock comparisons at the 1 × 10-18 level provide a resolution of one centimetre along the direction of gravity, so the performance of these clocks should enable geodesy beyond the state-of-the-art level. These optical clocks could further be used to explore geophysical phenomena10, detect gravitational waves11, test general relativity12 and search for dark matter13-17.

Proper Management of Amalgam Powder Embedded in the Alveolus.

The presence of foreign bodies in the mandible is not listed as a risk factor or absolute contraindication for implant rehabilitation. However, possible complications caused by foreign bodies, such as infection and cyst formation, could lead to implant failure. The authors report a case of dental implant placed 4 months after the surgical removal of embedded amalgam in the mandibular alveolus using a trephine bur and bone grafting with mineralized freeze-dried bone allograft. Clinical and radiographic evaluations were performed at each appointment to assess factors such as pain, implant mobility, probing depth, and marginal bone loss around the implant. Within 3 years of implant placement, there were no clinical signs and symptoms and no obvious radiographic marginal bone loss. Dental implant installation appears to be safe following the elimination of foreign materials, so long as anatomic and biological factors and appropriate implant choice, are taken into consideration.

The effect of vacancy defects on the electromechanical properties of monolayer NiTe2 from first principles calculations.

The electromechanical properties of monolayer 1-T NiTe2 under charge actuation were investigated using first-principles density functional theory (DFT) calculations. Monolayer 1-T NiTe2 in its pristine form has a work area density per cycle of up to 5.38 MJ m-3 nm upon charge injection and it can generate a strain and a stress of 1.51% and 0.96 N m-1, respectively. We found that defects in the form of vacancies can be exploited to modulate the electromechanical properties of this material. The presence of Ni-vacancies can further enhance the generated stress by 22.5%. On the other hand, with Te-vacancies, it is possible to improve the work area density per cycle by at least 145% and also to enhance the induced strain from 1.51% to 2.92%. The effect of charge polarity on the contraction and expansion of monolayer 1T-NiTe2 was investigated. Due to its excellent environmental stability and good electromechanical properties, monolayer NiTe2 is considered to be a promising electrode material for electroactive polymer (EAP) based actuators.

Serum vitamin D level correlates with disease activity and health-related quality of life in antineutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND AND OBJECTIVE: The association between vitamin D levels and disease activity has been established in patients with several autoimmune rheumatic diseases. We aimed to examine the association between vitamin D and disease activity of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: Fifty-four AAV patients and 50 age- and sex-matched healthy controls without vitamin D supplements were included. Clinical and laboratory data were evaluated during the assessment of vitamin D levels. Two different forms of vitamin D in the sera-25(OH)D, which is the sum of 25(OH)D2 and 25(OH)D3, and 25(OH)D3, which only includes 25(OH)D in its D3 form-were measured, and the relationship between vitamin D and the obtained data was assessed. Variations in vitamin D levels relative to the season were also evaluated. RESULTS: Patients with AAV demonstrated considerably lower 25(OH)D serum levels than healthy controls (16.0 vs. 20.4 ng/mL, p = 0.016), and the proportion of individuals with vitamin D deficiency was higher in patients with AAV than in healthy controls (68.5% vs. 48.0%, p = 0.035). Both serum 25(OH)D and 25(OH)D3 were positively associated with the 36-item Short-form Health Survey (SF-36) physical component summary and SF-36 mental component summary (MCS) scores. A negative correlation was observed between 25(OH)D and 25(OH)D3 serum levels and Birmingham vasculitis activity score (BVAS), C­reactive protein (CRP), and white blood cell count. Linear regression analysis indicated haemoglobin and 25(OH)D levels to be independently associated with BVAS and CRP and 25(OH)D levels with SF-36 MCS score. No seasonal variations were observed in vitamin D levels. CONCLUSION: The results from this study suggest that vitamin D levels could provide clinically useful information in AAV.

A first-principles study of two-dimensional NbSe2H/g-ZnO van der Waals heterostructures as a water splitting photocatalyst.

Based on first-principles calculations, we propose a new two-dimensional (2D) van der Waals (vdW) heterostructure that can be used as a photocatalyst for water splitting. The heterostructure consists of vertically stacked 2D NbSe2H and graphene-like ZnO (g-ZnO). Depending on the stacking orders, we identified two configurations that have high binding energies with an energy band gap of >2.6 eV. These 2D systems form a type-II heterostructure which enables the separation of photoexcited electrons and holes. The presence of a strong electrostatic potential difference across the 2D NbSe2H and g-ZnO interface is expected to suppress the electron-hole recombination leading to an enhancement in the efficiency of the photocatalytic activity. Our study also shows that the 2D NbSe2H/g-ZnO vdW heterostructure has good thermodynamic properties for water splitting. Furthermore, the optical absorption of the 2D NbSe2H/g-ZnO vdW heterostructure extends into the visible light region. Our results suggest that the 2D NbSe2H/g-ZnO vdW heterostructure is a promising photocatalytic material for water splitting.

Histopathological predictor of the progression from actinic keratosis to squamous cell carcinoma: quantitative computer-aided image analysis.

BACKGROUND: The current histopathological classifications for actinic keratosis (AK) are subjective, and histopathological factors predicting the progression into invasive squamous cell carcinoma (SCC) remain unclear. OBJECTIVES: To quantitatively assess the histopathological findings of AK and to investigate the predisposing factors for malignant transformation of AK. METHODS: A total of 502 AK specimens were retrospectively reviewed. The AK lesions were divided into the atrophic, intermediate, hypertrophic and bowenoid types. Histopathological features were quantitatively analysed using computer-aided image analysis. RESULTS: The epidermal thickness excluding the horny layer increased with statistical significance (P < 0.001) in order of atrophic, intermediate, hypertrophic and bowenoid type. The proportion of keratinocytic atypia was not significantly different among subtypes, except for the bowenoid type. Five of 498 cases were confirmed to develop into SCC. Bowenoid type, epidermal thickening and higher proportion of keratinocytic atypia were significantly associated with progression to invasive SCC in univariate analysis (OR = 12.571, 95% CI: 1.392-113.57; OR = 1.004, 95% CI: 1.001-1.007; OR = 1.069, 95% CI: 1.011-1.130, respectively). In multivariate analysis, only the proportion of keratinocytic atypia was an independent predisposing factor for progression to invasive SCC (OR = 1.069; 95% CI: 1.011-1.130). CONCLUSIONS: Histopathological subtypes based on the essential change of the epidermis well correlated with the actual epidermal thickness excluding the horny layer. The overall severity of keratinocytic atypia might be an independent risk factor for malignant transformation of AK.

Realization of Harmonic Oscillator Arrays with Graded Semiconductor Quantum Wells.

The harmonic oscillator is a foundational concept in both theoretical and experimental quantum mechanics. Here, we demonstrate harmonic oscillators in a semiconductor platform by faithfully implementing continuously graded alloy semiconductor quantum wells. Unlike current technology, this technique avoids interfaces that can hamper the system and allows for the production of multiwell stacks several micrometers thick. The experimentally measured system oscillations are at 3 THz for two structures containing 18 and 54 parabolic quantum wells. Absorption at room temperature is achieved: this is as expected from a parabolic potential and is unlike square quantum wells that require cryogenic operation. Linewidths below 11% of the central frequency are obtained up to 150 K, with a 5.6% linewidth obtained at 10 K. Furthermore, we show that the system correctly displays an absence of nonlinearity despite electron-electron interactions-analogous to the Kohn theorem. These high-quality structures already open up several new experimental vistas.

Association between ambient air pollution and pregnancy rate in women who underwent IVF.

STUDY QUESTION: Are the concentrations of five criteria air pollutants associated with probabilities of biochemical pregnancy loss and intrauterine pregnancy in women? SUMMARY ANSWER: Increased concentrations of ambient particulate matter (PM10), nitrogen dioxide (NO2), carbon monoxide (CO) during controlled ovarian stimulation (COS) and after embryo transfer were associated with a decreased probability of intrauterine pregnancy. WHAT IS KNOWN ALREADY: Exposure to high ambient air pollution was suggested to be associated with low fertility and high early pregnancy loss in women. STUDY DESIGN, SIZE, DURATION: Using a retrospective cohort study design, we analysed 6621 cycles of 4581 patients who underwent one or more fresh IVF cycles at a fertility centre from January 2006 to December 2014, and lived in Seoul at the time of IVF treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: To estimate patients' individual exposure to air pollution, we computed averages of hourly concentrations of five air pollutants including PM10, NO2, CO, sulphur dioxide (SO2) and ozone (O3) measured at 40 regulatory monitoring sites in Seoul for each of the four exposure periods: period 1 (start of COS to oocyte retrieval), period 2 (oocyte retrieval to embryo transfer), period 3 (embryo transfer to hCG test), and period 4 (start of COS to hCG test). Hazard ratios (HRs) from the time-varying Cox-proportional hazards model were used to estimate probabilities of biochemical pregnancy loss and intrauterine pregnancy for an interquartile range (IQR) increase in each air pollutant concentration during each period, after adjusting for individual characteristics. We tested the robustness of the result using generalised linear mixed model, accounting for within-woman correlation. MAIN RESULTS AND THE ROLE OF CHANCE: Mean age of the women was 35 years. Average BMI was 20.9 kg/m2 and the study population underwent 1.4 IVF cycles on average. Cumulative pregnancy rate in multiple IVF cycles was 51.3% per person. Survival analysis showed that air pollution during periods 1 and 3 was generally associated with IVF outcomes. Increased NO2 (adjusted HR = 0.93, 95% CI: 0.87, 0.99) and CO (0.94, 95% CI: 0.89, 1.00) during period 1 were associated with decreased probability of intrauterine pregnancy. PM10 (0.92, 95% CI: 0.85, 0.99), NO2 (0.93, 95% CI = 0.86, 1.00) and CO (0.93, 95% CI: 0.87, 1.00) levels during period 3 were also inversely associated with intrauterine pregnancy. Both PM10 (1.17, 95% CI: 1.04 1.33) and NO2 (1.18, 95% CI: 1.03, 1.34) during period 3 showed positive associations with biochemical pregnancy loss. LIMITATIONS, REASONS FOR CAUTION: The district-specific ambient air pollution treated as an individual exposure may not represent the actual level of each woman's exposure to air pollution. Smoking, working status, parity or gravidity of women, and semen analysis data were not included in the analysis. WIDER IMPLICATIONS OF THE FINDINGS: This study provided evidence of an association between increased ambient concentrations of PM10, NO2 and CO and reduced probabilities for achieving intrauterine pregnancy using multiple IVF cycle data. Specifically, our results indicated that lower intrauterine pregnancy rates in IVF cycles may be linked to ambient air pollution during COS and the post-transfer period. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013 R1A6A3A04059017, 2016 R1D1A1B03933410 and 2018 R1A2B6004608) and the National Cancer Center of Korea (NCC-1810220-01). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Faraday-Shielded dc Stark-Shift-Free Optical Lattice Clock.

We demonstrate the absence of a dc Stark shift in an ytterbium optical lattice clock. Stray electric fields are suppressed through the introduction of an in-vacuum Faraday shield. Still, the effectiveness of the shielding must be experimentally assessed. Such diagnostics are accomplished by applying high voltage to six electrodes, which are grounded in normal operation to form part of the Faraday shield. Our measurements place a constraint on the dc Stark shift at the 10^{-20} level, in units of the clock frequency. Moreover, we discuss a potential source of error in strategies to precisely measure or cancel nonzero dc Stark shifts, attributed to field gradients coupled with the finite spatial extent of the lattice-trapped atoms. With this consideration, we find that Faraday shielding, complemented with experimental validation, provides both a practically appealing and effective solution to the problem of dc Stark shifts in optical lattice clocks.

Hyperpolarizability and Operational Magic Wavelength in an Optical Lattice Clock.

Optical clocks benefit from tight atomic confinement enabling extended interrogation times as well as Doppler- and recoil-free operation. However, these benefits come at the cost of frequency shifts that, if not properly controlled, may degrade clock accuracy. Numerous theoretical studies have predicted optical lattice clock frequency shifts that scale nonlinearly with trap depth. To experimentally observe and constrain these shifts in an ^{171}Yb optical lattice clock, we construct a lattice enhancement cavity that exaggerates the light shifts. We observe an atomic temperature that is proportional to the optical trap depth, fundamentally altering the scaling of trap-induced light shifts and simplifying their parametrization. We identify an "operational" magic wavelength where frequency shifts are insensitive to changes in trap depth. These measurements and scaling analysis constitute an essential systematic characterization for clock operation at the 10^{-18} level and beyond.

Development of Theoretical Descriptors for Cytotoxicity Evaluation of Metallic Nanoparticles.

Motivated by the recent development of quantitative structure-activity relationship (QSAR) methods in the area of nanotoxicology, we proposed an approach to develop additional descriptors based on results of first-principles calculations. For the evaluation of the biochemical activity of metallic nanoparticles, we consider two processes: ion extraction from the surface of a specimen to aqueous media and water dissociation on the surface. We performed calculations for a set of metals (Al, Fe, Cu, Ag, Au, and Pt). Taking into account the diversity of atomic structures of real metallic nanoparticles, we performed calculations for different models such as (001) and (111) surfaces, nanorods, and two different cubic nanoparticles of 0.6 and 0.3 nm size. Significant energy dependence of the processes from the selected model of nanoparticle suggests that for the correct description we should combine the calculations for several representative models. In addition to the descriptors of chemical activity of the metallic nanoparticles for the two studied processes, we propose descriptors for taking into account the dependence of chemical activity from the size and shape of nanoparticles. Routes to minimization of computational costs for these calculations are also discussed.

Precise observation of C. elegans dynamic behaviours under controlled thermal stimulus using a mobile phone-based microscope.

We investigated the temperature-dependent locomotion of Caenorhabditis elegans by using the mobile phone-based microscope. We developed the customized imaging system with mini incubator and smartphone to effectively control the thermal stimulation for precisely observing the temperature-dependent locomotory behaviours of C. elegans. Using the mobile phone-based microscope, we successfully followed the long-term progress of specimens of C. elegans in real time as they hatched and explored their temperature-dependent locomotory behaviour. We are convinced that the mobile phone-based microscope is a useful device for real time and long-term observations of biological samples during incubation, and can make it possible to carry out live observations via wireless communications regardless of location. In addition, this microscope has the potential for widespread use owing to its low cost and compact design.

Epigenetic memory in induced pluripotent stem cells.

Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.

Effects of low-fat milk consumption on metabolic and atherogenic biomarkers in Korean adults with the metabolic syndrome: a randomised controlled trial.

BACKGROUND: Previous studies of the health effects of low-fat milk or dairy consumption on the metabolic syndrome have yielded inconsistent results. The present study aimed to investigate the effects of low-fat milk consumption on traits associated with the metabolic syndrome, as well as inflammatory and atherogenic biomarkers, in Korean adults with the metabolic syndrome. METHODS: Overweight Koreans with the metabolic syndrome (n = 58) were recruited and randomly assigned to either the low-fat milk or control group. The low-fat milk group was instructed to consume two packs of low-fat milk per day (200 mL twice daily) for 6 weeks, and the control group was instructed to maintain their habitual diet. Clinical investigations were conducted during the screening visit, on study day 0, and after 6 weeks. RESULTS: No significant differences in changes in body mass index, blood pressure, lipid profile and adiponectin levels, as well as levels of inflammatory markers, oxidative stress markers and atherogenic markers, were found between the low-fat milk and control groups. However, compared to the controls, significant favourable decreases in serum soluble vascular adhesion molecule-1 and endothelin-1 levels were found in the 12 subjects with high blood pressure and in the 18 subjects with hypertriglyceridaemia in the low-fat milk group. CONCLUSIONS: The present study did not demonstrate an overall beneficial effect of low-fat milk consumption in subjects with the metabolic syndrome. However, low-fat milk consumption may have a favourable effect on atherogenic markers in subjects with high blood pressure or hypertriglyceridaemia.

Identification of 1-{2-[4-chloro-1'-(2,2-dimethylpropyl)-7-hydroxy-1,2-dihydrospiro[indole-3,4'-piperidine]-1-yl]phenyl}-3-{5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-yl}urea, a potent, efficacious and orally bioavailable P2Y(1) antagonist as an antiplatelet agent.

Spiropiperidine indoline-substituted diaryl ureas had been identified as antagonists of the P2Y1 receptor. Enhancements in potency were realized through the introduction of a 7-hydroxyl substitution on the spiropiperidinylindoline chemotype. SAR studies were conducted to improve PK and potency, resulting in the identification of compound 3e, a potent, orally bioavailable P2Y1 antagonist with a suitable PK profile in preclinical species. Compound 3e demonstrated a robust antithrombotic effect in vivo and improved bleeding risk profile compared to the P2Y12 antagonist clopidogrel in rat efficacy/bleeding models.

Brucella melitensis sternal osteomyelitis following median sternotomy.

Human brucellosis, a zoonotic infection, may present with a range of symptoms but is rarely described as a cause of surgical site infections. We present the first reported case of Brucella melitensis causing sternal osteomyelitis of a midline sternotomy for a coronary artery bypass graft. The operation was performed in a non-endemic country but the patient had travelled to Syria immediately before surgery, where the infection was assumed to have been acquired. The infection resolved following treatment with doxycycline, rifampicin and gentamicin. We review the literature for surgical site infections related to Brucella species and discuss the infection control implications. Human brucellosis has the potential to cause surgical site infections and it should be in the differential diagnosis of any patient with a relevant exposure history presenting with a febrile illness and musculoskeletal findings.

Proton pump inhibitors as a possible cause of vitiligo: an in vivo and in vitro study.

BACKGROUND: Vitiligo is an acquired depigmentation disorder of melanocytes. Recently, some clinical reports have suggested that proton pump inhibitors (PPIs) may worsen vitiligo, but their effects on melanocytes have yet to be elucidated. OBJECTIVE: We investigated the effect of PPIs on melanogenesis in vivo and in vitro. METHODS: We examined the effect of PPIs on melanogenesis in B16 murine melanoma cells by measuring melanin content and tyrosinase (TYR) activity. TYR and tyrosinase-related protein-1 (TRP-1) were monitored by western blotting. Finally, a PPI was applied to zebrafish embryos to investigate its in vivo effect on pigmentation. RESULTS: In agreement with our clinical experience of worsened vitiligo after PPI treatment, PPIs decreased both melanin content and TYR activity. Western blotting showed that PPIs decreased TYR and TRP-1 protein levels. In the zebrafish test, PPIs inhibited body pigmentation in a dose-dependent manner. CONCLUSION: These results suggest that the functional inhibition of melanization by PPIs may induce or aggravate vitiligo lesions in genetically predisposed patients.

Immature teratoma of the parapharyngeal space presenting with airway obstruction in an infant.

Teratoma is the most common germ cell tumour in childhood. Teratoma typically arises in the sacrococcygeal region, gonads and mediastinum. The head and neck region is seldom involved. Teratomas of the neck region represent one of the most unusual causes of respiratory distress during the neonatal period. We present a case of an immature teratoma in the parapharyngeal space presenting with airway obstruction in an infant. Surgeons should consider the possibility of immature teratoma in the head and neck region in the differential diagnosis of respiratory distress in an infant, even if the patient does not have an external deformity.