Visualizing individual molecules with chemical recognition is a longstanding target in catalysis, molecular nanotechnology and biotechnology. Molecular vibrations provide a valuable 'fingerprint' for ...such identification. Vibrational spectroscopy based on tip-enhanced Raman scattering allows us to access the spectral signals of molecular species very efficiently via the strong localized plasmonic fields produced at the tip apex. However, the best spatial resolution of the tip-enhanced Raman scattering imaging is still limited to 3-15 nanometres, which is not adequate for resolving a single molecule chemically. Here we demonstrate Raman spectral imaging with spatial resolution below one nanometre, resolving the inner structure and surface configuration of a single molecule. This is achieved by spectrally matching the resonance of the nanocavity plasmon to the molecular vibronic transitions, particularly the downward transition responsible for the emission of Raman photons. This matching is made possible by the extremely precise tuning capability provided by scanning tunnelling microscopy. Experimental evidence suggests that the highly confined and broadband nature of the nanocavity plasmon field in the tunnelling gap is essential for ultrahigh-resolution imaging through the generation of an efficient double-resonance enhancement for both Raman excitation and Raman emission. Our technique not only allows for chemical imaging at the single-molecule level, but also offers a new way to study the optical processes and photochemistry of a single molecule.
The hot intra-cluster medium (ICM) permeating galaxy clusters and groups is not pristine, as it has been continuously enriched by metals synthesised in Type Ia (SNIa) and core-collapse (SNcc) ...supernovae since the major epoch of star formation (z ≃ 2–3). The cluster/group enrichment history and mechanisms responsible for releasing and mixing the metals can be probed via the radial distribution of SNIa and SNcc products within the ICM. In this paper, we use deep XMM-Newton/EPIC observations from a sample of 44 nearby cool-core galaxy clusters, groups, and ellipticals (CHEERS) to constrain the average radial O, Mg, Si, S, Ar, Ca, Fe, and Ni abundance profiles. The radial distributions of all these elements, averaged over a large sample for the first time, represent the best constrained profiles available currently. Specific attention is devoted to a proper modelling of the EPIC spectral components, and to other systematic uncertainties that may affect our results. We find an overall decrease of the Fe abundance with radius out to ~0.9 r500 and ~0.6 r500 for clusters and groups, respectively, in good agreement with predictions from the most recent hydrodynamical simulations. The average radial profiles of all the other elements (X) are also centrally peaked and, when rescaled to their average central X/Fe ratios, follow well the Fe profile out to at least ~0.5 r500. As predicted by recent simulations, we find that the relative contribution of SNIa (SNcc) to the total ICM enrichment is consistent with being uniform at all radii, both for clusters and groups using two sets of SNIa and SNcc yield models that reproduce the X/Fe abundance pattern in the core well. In addition to implying that the central metal peak is balanced between SNIa and SNcc, our results suggest that the enriching SNIa and SNcc products must share the same origin and that the delay between the bulk of the SNIa and SNcc explosions must be shorter than the timescale necessary to diffuse out the metals. Finally, we report an apparent abundance drop in the very core of 14 systems (~32% of the sample). Possible origins of these drops are discussed.
Summary
Background
Pemphigus is a group of rare life‐threatening mucocutaneous autoimmune diseases, presenting mainly as two subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Inherited ...predispositions to pemphigus have long been speculated but they remain poorly understood.
Objectives
To identify common and specific nongenetic and genetic factors associated with pemphigus and its subtypes in the Chinese population.
Methods
A genome‐wide association study (GWAS) was performed in 496 unrelated patients with pemphigus (including 365 with PV and 104 with PF) and 1105 controls without pemphigus.
Results
A sex preference was observed only in PV (57·5% female) and not in PF (47·1% female). For male patients only, the mean age at diagnosis was significantly lower for PV than for PF (P < 0·001). The strongest associated single‐nucleotide polymorphisms are in the human leucocyte antigen (HLA) region: rs70993900 (PV; P = 1·5 × 10−45) and rs9469220 (PF; P = 1·1 × 10−8). HLA‐DQB1*05:03 ranks at the top (P = 4·7 × 10−40; odds ratio 12·4) in both subtypes, with significantly different risk allele frequency (RAFPV = 34·2% vs. RAFPF = 18·8% vs. RAFcontrol = 4·4%), whereas HLA‐DRB1*14:01 and HLA‐DRB1*04:06 are PV specific. HLA‐DQB1*03:03 and HLA‐DQB1*03:02 show significant subtype specificity in opposite directions. All of these associations were validated in the replication series with 147 cases of pemphigus and 604 controls. Multiple novel non‐HLA susceptibility loci were also identified in the GWAS.
Conclusions
This study represents the largest GWAS on pemphigus in the Chinese population published to date, and has allowed us to identify HLA haplotypes significantly shared between or specific to the two main subtypes of pemphigus.
What's already known about this topic?
Pemphigus is a group of autoimmune mucocutaneous diseases.
It has multiple subtypes associated with certain human leucocyte antigen (HLA) haplotypes in an ethnicity‐specific manner.
What does this study add?
This is the largest genome‐wide association study published on pemphigus to date.
We identified, for the first time, more than 100 single‐nucleotide polymorphisms (SNPs; six independent) at the HLA locus, with associations reaching genome‐wide significance.
Some of these SNPs are strongly associated with specific subtypes of pemphigus.
What is the translational message?
The identified new haplotypes can potentially serve as genetic markers to improve investigation of the epidemiology and pathogenesis of pemphigus and its specific subtypes.
Linked Comment: Geller. Br J Dermatol 2019; 180:713–714.
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Using the coherent elastic neutrino-nucleus scattering data of the COHERENT experiment, we determine for the first time the average neutron rms radius of ^{133}Cs and ^{127}I. We obtain the ...practically model-independent value R_{n}=5.5_{-1.1}^{+0.9} fm using the symmetrized Fermi and Helm form factors. We also point out that the COHERENT data show a 2.3σ evidence of the nuclear structure suppression of the full coherence.
The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A ...hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.
While many pretreatments attempt to improve the enzymatic digestibility of biomass by removing lignin, this study shows that improving the surface area accessible to cellulase is a more important ...factor for achieving a high sugar yield. Here we compared the pretreatment of switchgrass by two methods, cellulose solvent‐ and organic solvent‐based lignocellulose fractionation (COSLIF) and soaking in aqueous ammonia (SAA). Following pretreatment, enzymatic hydrolysis was conducted at two cellulase loadings, 15 filter paper units (FPU)/g glucan and 3 FPU/g glucan, with and without BSA blocking of lignin absorption sites. The hydrolysis results showed that the lignin remaining after SAA had a significant negative effect on cellulase performance, despite the high level of delignification achieved with this pretreatment. No negative effect due to lignin was detected for COSLIF‐treated substrate. SEM micrographs, XRD crystallinity measurements, and cellulose accessibility to cellulase (CAC) determinations confirmed that COSLIF fully disrupted the cell wall structure, resulting in a 16‐fold increase in CAC, while SAA caused a 1.4‐fold CAC increase. A surface plot relating the lignin removal, CAC, and digestibility of numerous samples (both pure cellulosic substrates and lignocellulosic materials pretreated by several methods) was also developed to better understand the relative impacts of delignification and CAC on glucan digestibility. Biotechnol. Bioeng. 2011; 108:22-30.
Before the industrial revolution, the global economy was largely based on living carbon from plants. Now the economy is mainly dependent on fossil fuels (dead carbon). Biomass is the only sustainable ...bioresource that can provide sufficient transportation fuels and renewable materials at the same time. Cellulosic ethanol production from less costly and most abundant lignocellulose is confronted with three main obstacles: (1) high processing costs ($/gallon of ethanol), (2) huge capital investment ($~4-10/gallon of annual ethanol production capacity), and (3) a narrow margin between feedstock and product prices. Both lignocellulose fractionation technology and effective co-utilization of acetic acid, lignin and hemicellulose will be vital to the realization of profitable lignocellulose biorefineries, since co-product revenues would increase the margin up to 6.2-fold, where all purified lignocellulose co-components have higher selling prices (>~1.0/kg) than ethanol (~0.5/kg of ethanol). Isolation of large amounts of lignocellulose components through lignocellulose fractionation would stimulate R&D in lignin and hemicellulose applications, as well as promote new markets for lignin- and hemicellulose-derivative products. Lignocellulose resource would be sufficient to replace significant fractionations (e.g., 30%) of transportation fuels through liquid biofuels, internal combustion engines in the short term, and would provide 100% transportation fuels by sugar-hydrogen-fuel cell systems in the long term.
Micro-structural evolution and grain refinement in ANSI 304 stainless steel subjected to multiple laser shock processing (LSP) impacts were investigated by means of cross-sectional optical microscopy ...and transmission electron microscopy observations. The plastic strain-induced grain refinement mechanism of the face-centered cubic (fcc) materials with very low stacking fault energy was identified. The micro-structure was obviously refined due to the ultra-high plastic strain induced by multiple LSP impacts. The minimum grain size in the top surface was about 50–200
nm. Multidirectional mechanical twin matrix (MT)–MT intersections led to grain subdivision at the top surface during multiple LSP impacts. Furthermore, a novel structure with submicron triangular blocks was found at the top surface subjected to three LSP impacts. The grain refinement process along the depth direction after multiple LSP impacts can be described as follows: (i) formation of planar dislocation arrays (PDAs) and stacking faults along multiple directions due to the pile up of dislocation lines; (ii) formation of submicron triangular blocks (or irregularly shaped blocks) by the intersection of MT–MT (or MT–PDA or PDA–PDA) along multiple directions; (iii) transformation of MTs into subgrain boundaries; (iv) evolution by continuous dynamic recrystallization of subgrain boundaries to refined grain boundaries. The experimental results and analyses indicate that a high strain with an ultra-high strain rate play a crucial role in the grain refinement process of fcc materials subjected to multiple LSP impacts.
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