Initial Development toward Non-Invasive Drug Monitoring via Untargeted Mass Spectrometric Analysis of Human Skin.

Drug monitoring is crucial for providing accurate and effective care; however, current methods (e.g., blood draws) are inconvenient and unpleasant. We aim to develop a non-invasive method for the detection and monitoring of drugs via human skin. The initial development toward this aim required information about which drugs, taken orally, can be detected via the skin. Untargeted liquid chromatography-mass spectrometry (LC-MS) was used as it was unclear if drugs, known drug metabolites, or other transformation products were detectable. In accomplishing our aim, we analyzed samples obtained by swabbing the skin of 15 kidney transplant recipients in five locations (forehead, nasolabial area, axillary, backhand, and palm), bilaterally, on two different clinical visits. Untargeted LC-MS data were processed using molecular networking via the Global Natural Products Social Molecular Networking platform. Herein, we report the qualitative detection and location of drugs and drug metabolites. For example, escitalopram/citalopram and diphenhydramine, taken orally, were detected in forehead, nasolabial, and hand samples, whereas N-acetyl-sulfamethoxazole, a drug metabolite, was detected in axillary samples. In addition, chemicals associated with environmental exposure were also detected from the skin, which provides insight into the multifaceted chemical influences on our health. The proof-of-concept results presented support the finding that the LC-MS and data analysis methodology is currently capable of the qualitative assessment of the presence of drugs directly via human skin

Hybrid-Electric and Distributed Propulsion Technologies for Large Commercial Transports: A NASA Perspective

Develop and demonstrate technologies that will revolutionize commercial transport aircraft propulsion and accelerate development of all-electric aircraft architectures. Enable radically different propulsion systems that can meet national environmental and fuel burn reduction goals for subsonic commercial aircraft. Focus on future large regional jets and single-aisle twin (Boeing 737- class) aircraft for greatest impact on fuel burn, noise and emissions. Research horizon is long-term but with periodic spinoff of technologies for introduction in aircraft with more- and all-electric architectures. Research aligned with new NASA Aeronautics strategic R&T thrusts in areas of transition to low-carbon propulsion and ultra-efficient commercial transports

Spatial modulation of dark versus bright stimulus responses in the mouse visual system

A fundamental task of the visual system is to respond to both increases and decreases of luminance with action potentials (ON and OFF responses1–4). OFF responses are stronger, faster, and more salient than ON responses in primary visual cortex (V1) of both cats5,6 and primates,7,8 but in ferrets9 and mice,10 ON responses can be stronger, weaker,11 or balanced12 in comparison to OFF responses. These discrepancies could arise from differences in species, experimental techniques, or stimulus properties, particularly retinotopic location in the visual field, as has been speculated;9 however, the role of retinotopy for ON/OFF dominance has not been systematically tested across multiple scales of neural activity within species. Here, we measured OFF versus ON responses across large portions of visual space with silicon probe and whole-cell patch-clamp recordings in mouse V1 and lateral geniculate nucleus (LGN). We found that OFF responses dominated in the central visual field, whereas ON and OFF responses were more balanced in the periphery. These findings were consistent across local field potential (LFP), spikes, and subthreshold membrane potential in V1, and were aligned with spatial biases in ON and OFF responses in LGN. Our findings reveal that retinotopy may provide a common organizing principle for spatial modulation of OFF versus ON processing in mammalian visual systems

Reproducibility in high-throughput density functional theory: a comparison of AFLOW, Materials Project, and OQMD

A central challenge in high throughput density functional theory (HT-DFT) calculations is selecting a combination of input parameters and post-processing techniques that can be used across all materials classes, while also managing accuracy-cost tradeoffs. To investigate the effects of these parameter choices, we consolidate three large HT-DFT databases: Automatic-FLOW (AFLOW), the Materials Project (MP), and the Open Quantum Materials Database (OQMD), and compare reported properties across each pair of databases for materials calculated using the same initial crystal structure. We find that HT-DFT formation energies and volumes are generally more reproducible than band gaps and total magnetizations; for instance, a notable fraction of records disagree on whether a material is metallic (up to 7%) or magnetic (up to 15%). The variance between calculated properties is as high as 0.105 eV/atom (median relative absolute difference, or MRAD, of 6%) for formation energy, 0.65 {\AA}$^3$/atom (MRAD of 4%) for volume, 0.21 eV (MRAD of 9%) for band gap, and 0.15 $\mu_{\rm B}$/formula unit (MRAD of 8%) for total magnetization, comparable to the differences between DFT and experiment. We trace some of the larger discrepancies to choices involving pseudopotentials, the DFT+U formalism, and elemental reference states, and argue that further standardization of HT-DFT would be beneficial to reproducibility.Comment: Authors VIH and CKHB contributed equally to this wor

Effect of Dopant Ions on the Electrical Conductivity and Microstructure of Polyaniline (Emeraldine Salt)

Samples of polyaniline (emeraldine salt) were prepared with different protonic acid dopants, namely, hydrochloric acid (HCl), nitric acid (HNO3), perchloric acid (HClO4), sulfuric acid (H2SO4), and hydroiodic acid (HI). Using the two-point probe method, it was found that the samples had ohmic behaviors in which high linear coefficients were found in the range 0.9686–0.9997. On the other hand, the electrical conductivities were measured using the Van der Pauw method. The undoped sample had a conductivity of 5x10–4 S/cm. The highest conductivity of 109.04 S/cm was observed for the HClO4-doped sample, while the lowest value (0.02 S/cm) was obtained for the HI-doped sample. These conductivities were compared with the computed energy gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) where it was found that they are inversely proportional to each other. Scanning electron microscopy revealed significant differences among the samples in terms of shapes and morphologies

Breadwinners and Homemakers: Migration and Changing Conjugal Expectations in Rural Bangladesh

The literature on marriage norms and aspirations across societies largely sees the institution as static – a tool for the assertion of masculinities and subordination of women. The changing meanings of marriage and conjugality in the contemporary context of globalisation have received scant attention. Based on research in rural Bangladesh, this article questions the usefulness of notions of autonomy and dependence in understanding conjugal relations and expectations in a context of widespread migration for extended periods, especially to overseas destinations, where mutuality is crucial for social reproduction, though in clearly genderdemarcated domains

Severe pulmonary arterial hypertension is characterized by increased neutrophil elastase and relative elafin deficiency

BACKGROUND: Preclinical evidence implicates neutrophil elastase (NE) in PAH pathogenesis, and the NE inhibitor elafin is under early therapeutic investigation. RESEARCH QUESTION: Are circulating NE and elafin levels abnormal in PAH and associated with clinical severity? STUDY DESIGN/METHODS: . In an observational Stanford University PAH cohort (N=249), plasma NE and elafin were measured in comparison to healthy controls (N=106) then related to clinical features and relevant ancillary biomarkers. Cox regression models were fitted with cubic spline functions to associate NE and elafin with survival. To validate prognostic relationships, we analyzed two United Kingdom cohorts (N=75, N=357). Mixed effects models evaluated NE and elafin changes during disease progression. Finally, we studied effects of NE/elafin balance on pulmonary artery endothelial cells (PAECs) from PAH patients. RESULTS: Relative to controls, patients had increased NE (205.1 [123.6-387.3] vs. 97.6 [74.4-126.6] ng/mL, P168.5 ng/mL portended increased mortality risk after adjustment for known clinical predictors (HR 2.52, CI 1.36-4.65, P=0.003) or prognostic cytokines (HR 2.63, CI 1.42-4.87, P=0.001), and NE added incremental value to established PAH risk scores. Similar prognostic thresholds were identified in validation cohorts. Longitudinal NE changes tracked with clinical trends and outcomes. PAH-PAECs exhibited increased apoptosis and attenuated angiogenesis when exposed to NE at the level observed in patients' blood. Elafin rescued PAEC homeostasis, yet the required dose exceeded levels found in patients. INTERPRETATION: NE is increased and elafin deficient across PAH subtypes. NE associates with disease severity and outcomes, and this target-specific biomarker could facilitate therapeutic development of elafin

A panchromatic view of infrared quasars: excess star formation and radio emission in the most heavily obscured systems

To understand the active galactic nuclei (AGNs) phenomenon and their impact on the evolution of galaxies, a complete AGN census is required; however, finding heavily obscured AGNs is observationally challenging. Here we use the deep and extensive multiwavelength data in the COSMOS field to select a complete sample of 578 infrared (IR) quasars (LAGN,IR > 1045 erg s−1) at z < 3, with minimal obscuration bias, using detailed UV-to-far-IR spectral energy distribution (SED) fitting. We complement our SED constraints with X-ray and radio observations to further investigate the properties of the sample. Overall, 322 of the IR quasars are detected by Chandra and have individual X-ray spectral constraints. From a combination of X-ray stacking and L2−10 kev – L6 μm analyses, we show that the majority of the X-ray faint and undetected quasars are heavily obscured (many are likely Compton thick), highlighting the effectiveness of the mid-IR band to find obscured AGNs. We find that 355 (≈61 per cent) IR quasars are obscured (NH > 1022 cm−2) and identify differences in the average properties between the obscured and unobscured quasars: (1) obscured quasars have star formation rates ≈3 times higher than unobscured systems for no significant difference in stellar mass and (2) obscured quasars have stronger radio emission than unobscured systems, with a radio-loudness parameter ≈ 0.2 dex higher. These results are inconsistent with a simple orientation model but in general agreement with either extreme host-galaxy obscuration towards the obscured quasars or a scenario where obscured quasars are an early phase in the evolution of quasars