Topologically trivial gap-filling in superconducting Fe(Se,Te) by one-dimensional defects.

Structural distortions and imperfections are a crucial aspect of materials science, on the macroscopic scale providing strength, but also enhancing corrosion and reducing electrical and thermal conductivity. At the nanometre scale, multi-atom imperfections, such as atomic chains and crystalline domain walls have conversely been proposed as a route to topological superconductivity, whose most prominent characteristic is the emergence of Majorana Fermions that can be used for error-free quantum computing. Here, we shed more light on the nature of purported domain walls in Fe(Se,Te) that may host 1D dispersing Majorana modes. We show that the displacement shift of the atomic lattice at these line-defects results from sub-surface impurities that warp the topmost layer(s). Using the electric field between the tip and sample, we manage to reposition the sub-surface impurities, directly visualizing the displacement shift and the underlying defect-free lattice. These results, combined with observations of a completely different type of 1D defect where superconductivity remains fully gapped, highlight the topologically trivial nature of 1D defects in Fe(Se,Te).

The association between prenatal oxidative stress levels measured by isoprostanes and offspring neurodevelopmental outcomes at 36 months.

Oxidative stress during pregnancy has been a mechanistic pathway implicated in autism development, yet few studies have examined this association directly. Here, we examined the association of prenatal levels of 8-iso-PGF2α, a widely used measure of oxidative stress, and several neurodevelopmental outcomes related to autism in children. Participants included 169 mother-child pairs from the Early Autism Risk Longitudinal Investigation (EARLI), which enrolled mothers who had an autistic child from a previous pregnancy and followed them through a subsequent pregnancy and until that child reached age 3 years. Maternal urine samples were collected during the second trimester of pregnancy and were later measured for levels of isoprostanes. Child neurodevelopmental assessments included the Mullen Scales of Early Learning (MSEL), the Social Responsiveness Scale (SRS), and the Vineland Adaptive Behavior Scale (VABS), and were conducted around 36 months of age. Primary analyses examined associations between interquartile range (IQR) increases in 8-iso-PGF2α levels, and total composite scores from each assessment using quantile regression. In adjusted analyses, we did not observe statistically significant associations, though estimates suggested modestly lower cognitive scores (ß for MSEL = -3.68, 95% CI: -10.09, 2.70), and minor increases in autism-related trait scores (ß for SRS T score = 1.68, 95% CI: -0.24, 3.60) with increasing 8-iso-PGF2α. These suggestive associations between decreased cognitive scores and increased autism-related traits with increasing prenatal oxidative stress point to the need for continued investigation in larger samples of the role of oxidative stress as a mechanistic pathway in autism and related neurodevelopmental outcomes.

Machine learning in electronic-quantum-matter imaging experiments.

For centuries, the scientific discovery process has been based on systematic human observation and analysis of natural phenomena1. Today, however, automated instrumentation and large-scale data acquisition are generating datasets of such large volume and complexity as to defy conventional scientific methodology. Radically different scientific approaches are needed, and machine learning (ML) shows great promise for research fields such as materials science2-5. Given the success of ML in the analysis of synthetic data representing electronic quantum matter (EQM)6-16, the next challenge is to apply this approach to experimental data-for example, to the arrays of complex electronic-structure images17 obtained from atomic-scale visualization of EQM. Here we report the development and training of a suite of artificial neural networks (ANNs) designed to recognize different types of order hidden in such EQM image arrays. These ANNs are used to analyse an archive of experimentally derived EQM image arrays from carrier-doped copper oxide Mott insulators. In these noisy and complex data, the ANNs discover the existence of a lattice-commensurate, four-unit-cell periodic, translational-symmetry-breaking EQM state. Further, the ANNs determine that this state is unidirectional, revealing a coincident nematic EQM state. Strong-coupling theories of electronic liquid crystals18,19 are consistent with these observations.

In Vivo Evaluation of Teeth Shade Match Capabilities of a Dental Intraoral Scanner.

Intraoral scanners were introduced in order to increase patient comfort and improve dentist lab communication. Acquiring optical impressions of the prepared teeth eliminates the need for conventional impression procedures and improves patient comfort. Intraoral scanner software offers since 2017, color shade determination, by analyzing the tooth shade of the obtained 3D model. In this study we tested the accuracy of an intraoral scanner color selection capabilities compared with a dental spectrophotometer, considered as reference. Statistical differences were found between the two system tested when the results were expressed in both Vita Classical and Vita 3D Master shade tabs codification.

The effect of menthol on cigarette smoking behaviors, biomarkers and subjective responses.

BACKGROUND: As part of the Family Smoking Prevention and Tobacco Control Act, the U.S. Food and Drug Administration charged the Tobacco Products Scientific Advisory Committee with developing a report and recommendations about the effect of menthol in cigarettes on the public health. The purpose of this study was to examine smoking behaviors, biomarkers of exposure, and subjective responses when switching from a novel menthol cigarette to a non-menthol cigarette to isolate the effect of menthol and to approximate the effect a menthol ban might have on smokers. METHODS: Thirty-two adult smokers completed this 35-day randomized, open-label, laboratory study. After a 5-day baseline period, participants were randomized to the experimental group (n = 22) where they would smoke menthol Camel crush for 15 days followed by 15 days of non-menthol Camel crush, or the control group (n = 10) where they smoked their own brand cigarette across all periods. Participants attended study visits every 5 days and completed measures of smoking rate, smoking topography, biomarkers of exposure, and subjective responses. RESULTS: Although total puff volume tended to increase when the experimental group switched from menthol to non-menthol (P = 0.06), there were no corresponding increases in cigarette consumption or biomarkers of exposure (P > 0.1). Subjective ratings related to taste and smell decreased during the non-menthol period (P < 0.01), compared with the menthol. CONCLUSIONS: Results suggest menthol has minimal impact on smoking behaviors, biomarkers of exposure, and subjective ratings. IMPACT: When controlling for all other cigarette design features, menthol in cigarettes had minimal effect on outcome measures.

Effects of 21 days of varenicline versus placebo on smoking behaviors and urges among non-treatment seeking smokers.

Varenicline promotes smoking cessation and reduces urges to smoke. However, the mechanisms associated with these effects and their time course are not well characterized. One mechanism may be extinction, but the duration of the current dosing protocol may not be sufficient. We examined the effect of extended pre-treatment with varenicline on smoking behavior among 17 non-treatment seeking adult smokers. Using a within-subjects, double-blind, placebo-controlled crossover design, participants received standard dosing of varenicline for 21 days, followed by a 14-day washout period and 21 days of placebo; order counterbalanced. Cigarettes per day (CPD), smoking topography, smoking urges (QSU), and side effects were assessed every three days. Biomarkers (e.g. nicotine metabolites) were collected on days 1, 7, and 21. There was a significant drug by time interaction indicating a reduction in CPD during varenicline phase (between days 10-21), but no reduction during placebo. Varenicline also led to reductions in nicotine metabolites and urges to smoke. Among this sample of non-treatment seeking smokers, varenicline significantly reduced smoking behavior. Results have important treatment implications because changes in CPD and craving did not occur until after the typical one-week run-up period. This suggests that a longer duration of pre-treatment may be beneficial for some smokers.

Cellular lipid extraction for targeted stable isotope dilution liquid chromatography-mass spectrometry analysis.

The metabolism of fatty acids, such as arachidonic acid (AA) and linoleic acid (LA), results in the formation of oxidized bioactive lipids, including numerous stereoisomers(1,2). These metabolites can be formed from free or esterified fatty acids. Many of these oxidized metabolites have biological activity and have been implicated in various diseases including cardiovascular and neurodegenerative diseases, asthma, and cancer(3-7). Oxidized bioactive lipids can be formed enzymatically or by reactive oxygen species (ROS). Enzymes that metabolize fatty acids include cyclooxygenase (COX), lipoxygenase (LO), and cytochromes P450 (CYPs)(1,8). Enzymatic metabolism results in enantioselective formation whereas ROS oxidation results in the racemic formation of products. While this protocol focuses primarily on the analysis of AA- and some LA-derived bioactive metabolites; it could be easily applied to metabolites of other fatty acids. Bioactive lipids are extracted from cell lysate or media using liquid-liquid (l-l) extraction. At the beginning of the l-l extraction process, stable isotope internal standards are added to account for errors during sample preparation. Stable isotope dilution (SID) also accounts for any differences, such as ion suppression, that metabolites may experience during the mass spectrometry (MS) analysis(9). After the extraction, derivatization with an electron capture (EC) reagent, pentafluorylbenzyl bromide (PFB) is employed to increase detection sensitivity(10,11). Multiple reaction monitoring (MRM) is used to increase the selectivity of the MS analysis. Before MS analysis, lipids are separated using chiral normal phase high performance liquid chromatography (HPLC). The HPLC conditions are optimized to separate the enantiomers and various stereoisomers of the monitored lipids(12). This specific LC-MS method monitors prostaglandins (PGs), isoprostanes (isoPs), hydroxyeicosatetraenoic acids (HETEs), hydroxyoctadecadienoic acids (HODEs), oxoeicosatetraenoic acids (oxoETEs) and oxooctadecadienoic acids (oxoODEs); however, the HPLC and MS parameters can be optimized to include any fatty acid metabolites(13). Most of the currently available bioanalytical methods do not take into account the separate quantification of enantiomers. This is extremely important when trying to deduce whether or not the metabolites were formed enzymatically or by ROS. Additionally, the ratios of the enantiomers may provide evidence for a specific enzymatic pathway of formation. The use of SID allows for accurate quantification of metabolites and accounts for any sample loss during preparation as well as the differences experienced during ionization. Using the PFB electron capture reagent increases the sensitivity of detection by two orders of magnitude over conventional APCI methods. Overall, this method, SID-LC-EC-atmospheric pressure chemical ionization APCI-MRM/MS, is one of the most sensitive, selective, and accurate methods of quantification for bioactive lipids.

Topological defects coupling smectic modulations to intra-unit-cell nematicity in cuprates.

We study the coexisting smectic modulations and intra-unit-cell nematicity in the pseudogap states of underdoped Bi(2)Sr(2)CaCu(2)O(8+δ). By visualizing their spatial components separately, we identified 2π topological defects throughout the phase-fluctuating smectic states. Imaging the locations of large numbers of these topological defects simultaneously with the fluctuations in the intra-unit-cell nematicity revealed strong empirical evidence for a coupling between them. From these observations, we propose a Ginzburg-Landau functional describing this coupling and demonstrate how it can explain the coexistence of the smectic and intra-unit-cell broken symmetries and also correctly predict their interplay at the atomic scale. This theoretical perspective can lead to unraveling the complexities of the phase diagram of cuprate high-critical-temperature superconductors.

Stereospecific reduction of 5ß-reduced steroids by human ketosteroid reductases of the AKR (aldo-keto reductase) superfamily: role of AKR1C1-AKR1C4 in the metabolism of testosterone and progesterone via the 5ß-reductase pathway.

Active sex hormones such as testosterone and progesterone are metabolized to tetrahydrosteroids in the liver to terminate hormone action. One main metabolic pathway, the 5ß-pathway, involves 5ß-steroid reductase (AKR1D1, where AKR refers to the aldo-keto reductase superfamily), which catalyses the reduction of the 4-ene structure, and ketosteroid reductases (AKR1C1-AKR1C4), which catalyse the subsequent reduction of the 3-oxo group. The activities of the four human AKR1C enzymes on 5ß-dihydrotestosterone, 5ß-pregnane-3,20-dione and 20α-hydroxy-5ß-pregnan-3-one, the intermediate 5ß-dihydrosteroids on the 5ß-pathway of testosterone and progesterone metabolism, were investigated. Product characterization by liquid chromatography-MS revealed that the reduction of the 3-oxo group of the three steroids predominantly favoured the formation of the corresponding 3α-hydroxy steroids. The stereochemistry was explained by molecular docking. Kinetic properties of the enzymes identified AKR1C4 as the major enzyme responsible for the hepatic formation of 5ß-tetrahydrosteroid of testosterone, but indicated differential routes and roles of human AKR1C for the hepatic formation of 5ß-tetrahydrosteroids of progesterone. Comparison of the kinetics of the AKR1C1-AKR1C4-catalysed reactions with those of AKR1D1 suggested that the three intermediate 5ß-dihydrosteroids derived from testosterone and progesterone are unlikely to accumulate in liver, and that the identities and levels of 5ß-reduced metabolites formed in peripheral tissues will be governed by the local expression of AKR1D1 and AKR1C1-AKR1C3.

20-HETE mediates ozone-induced, neutrophil-independent airway hyper-responsiveness in mice.

BACKGROUND: Ozone, a pollutant known to induce airway hyper-responsiveness (AHR), increases morbidity and mortality in patients with obstructive airway diseases and asthma. We postulate oxidized lipids mediate in vivo ozone-induced AHR in murine airways. METHODOLOGY/PRINCIPAL FINDINGS: Male BALB/c mice were exposed to ozone (3 or 6 ppm) or filtered air (controls) for 2 h. Precision cut lung slices (PCLS; 250 microm thickness) containing an intrapulmonary airway ( approximately 0.01 mm(2) lumen area) were prepared immediately after exposure or 16 h later. After 24 h, airways were contracted to carbachol (CCh). Log EC(50) and E(max) values were then calculated by measuring the airway lumen area with respect to baseline. In parallel studies, dexamethasone (2.5 mg/kg), or 1-aminobenzotriazol (ABT) (50 mg/kg) were given intraperitoneal injection to naïve mice 18 h prior to ozone exposure. Indomethacin (10 mg/kg) was administered 2 h prior. Cell counts, cytokine levels and liquid chromatography-mass spectrometry (LC-MS) for lipid analysis were assessed in bronchoalveolar lavage (BAL) fluid from ozone exposed and control mice. Ozone acutely induced AHR to CCh. Dexamethasone or indomethacin had little effect on the ozone-induced AHR; while, ABT, a cytochrome P450 inhibitor, markedly attenuated airway sensitivity. BAL fluid from ozone exposed animals, which did not contain an increase in neutrophils or interleukin (IL)-6 levels, increased airway sensitivity following in vitro incubation with a naïve PCLS. In parallel, significant increases in oxidized lipids were also identified using LC-MS with increases of 20-HETE that were decreased following ABT treatment. CONCLUSIONS/SIGNIFICANCE: These data show that ozone acutely induces AHR to CCh independent of inflammation and is insensitive to steroid treatment or cyclooxygenase (COX) inhibition. BAL fluid from ozone exposed mice mimicked the effects of in vivo ozone exposure that were associated with marked increases in oxidized lipids. 20-HETE plays a pivotal role in mediating acute ozone-induced AHR.

Otodental syndrome.

Otodental dysplasia, a form of ectodermal dysplasia, is characterized by abnormal dental crown morphology and sensorineural hearing loss. A variety of dental abnormalities are prominent features of this syndrome--most notably gigantic, bulbous posterior teeth. In this case, a sibling is identifies in a family with otodental syndrome that had been diagnosed earlier. A unique opportunity is provided to view the intact adult dentition and possible complications for dental treatment.

Influence of a dentin bonding agent on the fracture load of Dicor.

The purpose of this investigation was to evaluate the effect of a dentin bonding agent on the fracture resistance of a cast glass-ceramic luted to dentin. Sixty beam-shaped Dicor specimens and 40 bovine dentin specimens of similar dimension were prepared and randomly distributed among three groups of 20 each: Dicor specimens (control); Dicor specimens luted to dentin with Dicor Light-Activated Cement; and Dicor specimens luted to dentin with Prisma Universal Bond 3 dentin bonding agent and Dicor Light-Activated Cement. All samples were thermocycled and loaded to flexural failure with an Instron Universal testing machine. The mean fracture loads of the three groups were all statistically different from one another (P < .05). The use of a dentin bonding agent increased the fracture resistance of the resin-cemented glass-ceramic samples by more than three-fold compared to those luted with resin cement alone. The results of this study suggest that the use of a dentin bonding agent in combination with dual-cure resin cement will increase the fracture resistance of castable glass-ceramic restorations.