Proof-of-Principle Experiment for Testing Strong-Field Quantum Electrodynamics with Exotic Atoms: High Precision X-Ray Spectroscopy of Muonic Neon.

To test bound-state quantum electrodynamics (BSQED) in the strong-field regime, we have performed high precision x-ray spectroscopy of the 5g-4f and 5f- 4d transitions (BSQED contribution of 2.4 and 5.2 eV, respectively) of muonic neon atoms in the low-pressure gas phase without bound electrons. Muonic atoms have been recently proposed as an alternative to few-electron high-Z ions for BSQED tests by focusing on circular Rydberg states where nuclear contributions are negligibly small. We determined the 5g_{9/2}- 4f_{7/2} transition energy to be 6297.08±0.04(stat)±0.13(syst) eV using superconducting transition-edge sensor microcalorimeters (5.2-5.5 eV FWHM resolution), which agrees well with the most advanced BSQED theoretical prediction of 6297.26 eV.

Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande.

We report a search for cosmic-ray boosted dark matter with protons using the 0.37 megaton×years data collected at Super-Kamiokande experiment during the 1996-2018 period (SKI-IV phase). We searched for an excess of proton recoils above the atmospheric neutrino background from the vicinity of the Galactic Center. No such excess is observed, and limits are calculated for two reference models of dark matter with either a constant interaction cross section or through a scalar mediator. This is the first experimental search for boosted dark matter with hadrons using directional information. The results present the most stringent limits on cosmic-ray boosted dark matter and exclude the dark matter-nucleon elastic scattering cross section between 10^{-33}cm^{2} and 10^{-27}cm^{2} for dark matter mass from 1 MeV/c^{2} to 300 MeV/c^{2}.

Erratum: Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande [Phys. Rev. Lett. 130, 031802 (2023)].

This corrects the article DOI: 10.1103/PhysRevLett.130.031802.

Cutaneous ischemia-reperfusion injury is exacerbated by IL-36 receptor antagonist deficiency.

BACKGROUND: Loss-of-function homozygous or compound heterozygous mutations in IL36RN, which encodes interleukin-36 receptor antagonist (IL-36Ra), has been implicated in the pathogenesis of skin disorders. However, the pathogenic role of IL-36Ra in cutaneous ischemia-reperfusion (I/R) injury remains unclear. OBJECTIVES: We investigated the role of IL36Ra in cutaneous I/R injury. METHODS: We examined I/R injury in Il36rn-/- mice. The area of wounds, numbers of infiltrated cells, apoptotic cells and neutrophil extracellular trap (NET) formation were assessed. The expression levels of various genes were analysed using real-time RT-PCR. The expression of high mobility group box 1 (HMGB1), an endogenous toll-like receptor (TLR) 4 ligand, was confirmed using immunohistology, and serum HMGB1 levels were measured by ELISA. Cytokine production by stimulated cultured J774A.1 and HaCaT cells was examined. RESULTS: IL-36Ra deficiency resulted in significantly delayed wound healing and increased neutrophil and macrophage infiltration into the wound tissues. Il36rn-/- mice had increased mRNA expression levels of CXCL1, CXCL2, CCL4, TNF-α, TGF-ß, IL-1ß, IL-6 and IL-36γ relative to wild-type mice. Apoptosis was identified in keratinocytes by TUNEL assay. HMGB1 expression in the I/R site was decreased in both keratinocytes and adnexal cells, while serum HMGB1 levels were significantly elevated after reperfusion. The mRNA levels of various cytokines, including IL-1ß, were elevated in J774A.1 cells through TLR4 signalling by HMGB1 stimulation. In addition, HaCaT cells stimulated with IL-1ß showed significantly increased CXCL1, TNF-α, IL-6, IL-36ß and IL-36γ mRNA expression. Furthermore, NET formation was increased by IL-36Ra deficiency. Finally, either the blockade of TLR4 signalling by TAK-242 or inhibition of NET formation by Cl-amidine normalized exacerbated I/R injury in Il36rn-/- mice. CONCLUSIONS: This study indicated that IL-36Ra deficiency exacerbates cutaneous I/R injury due to excessive inflammatory cell recruitment, NET formation, and excessive cytokine and chemokine production via the TLR4 pathway by HMGB1 released from epidermal apoptotic cells.

Deexcitation Dynamics of Muonic Atoms Revealed by High-Precision Spectroscopy of Electronic K X Rays.

We observed electronic K x rays emitted from muonic iron atoms using superconducting transition-edge sensor microcalorimeters. The energy resolution of 5.2 eV in FWHM allowed us to observe the asymmetric broad profile of the electronic characteristic Kα and Kß x rays together with the hypersatellite K^{h}α x rays around 6 keV. This signature reflects the time-dependent screening of the nuclear charge by the negative muon and the L-shell electrons, accompanied by electron side feeding. Assisted by a simulation, these data clearly reveal the electronic K- and L-shell hole production and their temporal evolution on the 10-20 fs scale during the muon cascade process.

Magnon Modes of Microstates and Microwave-Induced Avalanche in Kagome Artificial Spin Ice with Topological Defects.

We investigate spin dynamics of microstates in artificial spin ice (ASI) in Ni_{81}Fe_{19} nanomagnets arranged in an interconnected kagome lattice using microfocus Brillouin light scattering, broadband ferromagnetic resonance, magnetic force microscopy, x-ray photoemission electron microscopy, and simulations. We experimentally reconfigure microstates in ASI using a 2D vector field protocol and apply microwave-assisted switching to intentionally trigger reversal. Our work is key for the creation of avalanches inside the kagome ASI and reprogrammable magnonics based on ASIs.

Daytime Dynamo Electrodynamics With Spiral Currents Driven by Strong Winds Revealed by Vapor Trails and Sounding Rocket Probes.

We investigate the forces and atmosphere-ionosphere coupling that create atmospheric dynamo currents using two rockets launched nearly simultaneously on 4 July 2013 from Wallops Island (USA), during daytime Sq conditions with ΔH of -30 nT. One rocket released a vapor trail observed from an airplane which showed peak velocities of >160 m/s near 108 km and turbulence coincident with strong unstable shear. Electric and magnetic fields and plasma density were measured on a second rocket. The current density peaked near 110 km exhibiting a spiral pattern with altitude that mirrored that of the winds, suggesting the dynamo is driven by tidal forcing. Such stratified currents are obscured in integrated ground measurements. Large electric fields produced a current opposite to that driven by the wind, believed created to minimize the current divergence. Using the observations, we solve the dynamo equation versus altitude, providing a new perspective on the complex nature of the atmospheric dynamo.

Detection of copy number variations in epilepsy using exome data.

Epilepsies are common neurological disorders and genetic factors contribute to their pathogenesis. Copy number variations (CNVs) are increasingly recognized as an important etiology of many human diseases including epilepsy. Whole-exome sequencing (WES) is becoming a standard tool for detecting pathogenic mutations and has recently been applied to detecting CNVs. Here, we analyzed 294 families with epilepsy using WES, and focused on 168 families with no causative single nucleotide variants in known epilepsy-associated genes to further validate CNVs using 2 different CNV detection tools using WES data. We confirmed 18 pathogenic CNVs, and 2 deletions and 2 duplications at chr15q11.2 of clinically unknown significance. Of note, we were able to identify small CNVs less than 10 kb in size, which might be difficult to detect by conventional microarray. We revealed 2 cases with pathogenic CNVs that one of the 2 CNV detection tools failed to find, suggesting that using different CNV tools is recommended to increase diagnostic yield. Considering a relatively high discovery rate of CNVs (18 out of 168 families, 10.7%) and successful detection of CNV with <10 kb in size, CNV detection by WES may be able to surrogate, or at least complement, conventional microarray analysis.

A multi-emitter fitting algorithm for potential live cell super-resolution imaging over a wide range of molecular densities.

Multi-emitter fitting algorithms have been developed to improve the temporal resolution of single-molecule switching nanoscopy, but the molecular density range they can analyse is narrow and the computation required is intensive, significantly limiting their practical application. Here, we propose a computationally fast method, wedged template matching (WTM), an algorithm that uses a template matching technique to localise molecules at any overlapping molecular density from sparse to ultrahigh density with subdiffraction resolution. WTM achieves the localization of overlapping molecules at densities up to 600 molecules µm-2 with a high detection sensitivity and fast computational speed. WTM also shows localization precision comparable with that of DAOSTORM (an algorithm for high-density super-resolution microscopy), at densities up to 20 molecules µm-2 , and better than DAOSTORM at higher molecular densities. The application of WTM to a high-density biological sample image demonstrated that it resolved protein dynamics from live cell images with subdiffraction resolution and a temporal resolution of several hundred milliseconds or less through a significant reduction in the number of camera images required for a high-density reconstruction. WTM algorithm is a computationally fast, multi-emitter fitting algorithm that can analyse over a wide range of molecular densities. The algorithm is available through the website. https://doi.org/10.17632/bf3z6xpn5j.1.

The B allele with a 5·8 kb deletion in intron 1 of the ABO gene is the major allele in Japanese individuals with Bm and A1 Bm phenotypes.

Bm and A1 Bm phenotypes are the most frequent ABO variants in the Japanese population. The B antigen on Bm red blood cells is only detectable by adsorption and elution tests, and plasma B-transferase activity is usually detected at half or less levels compared with that of common B. Recently, a B allele lacking an erythroid cell-specific transcription enhancer in intron 1 of the ABO gene was identified from individuals with Bm and A1 Bm phenotypes, which could explain the unique serologic properties of Bm . In the Japanese Red Cross Society, eight Blood Centers tested blood samples from donors throughout Japan and collected blood samples from 888 Bm and 415 A1 Bm individuals. DNA analysis revealed that 1300 of 1303 (99·77%) individuals had the B allele with a 5·8 kb deletion (c.28 + 5110_10889del), which included the enhancer element.

Screening of furanocoumarin derivatives as cytochrome P450 3A4 inhibitors in citrus.

WHAT IS KNOWN AND OBJECTIVE: Furanocoumarins, such as bergamottin (BG) and 6',7'-dihydroxybergamottin (DHB), isolated from grapefruit juice are clinically active constituents capable of inhibiting cytochrome P450 3A4. Furanocoumarins are also found in hassaku, pummelo and daidai. Several types of hybrid citrus fruits have recently been developed, and these may also contain furanocoumarins because they were produced by cross-breeding pummelo, daidai and other citrus fruits. In this study, we quantified BG and DHB levels in the flesh and peel of hybrid citrus fruits. METHODS: Extracts from flesh and peel were diluted with acetonitrile and analysed using high-performance liquid chromatography. RESULTS AND DISCUSSION: For flesh extracts, lime juice (24.13 µg/mL) contained a greater amount of BG than grapefruit juice (13.61 µg/mL). Lime (13.21 µg/mL) and sour orange (8.08 µg/mL) juices also contained greater amounts of DHB than grapefruit juice (7.54 µg/mL). For peel extracts, lime (1749.15 µg/g), Citrus kawachibankan (308.13 µg/g), lemon (203.44 µg/g) and sour orange (161.95 µg/g) contained greater amounts of BG than grapefruit (white) (78.80 µg/g). The hybrid sweetie (Citrus maxima × Citrus paradise; 173.32 µg/g) contained a greater amount of DHB than grapefruit (white) (85.27 µg/g). WHAT IS NEW AND CONCLUSION: The lime flesh and the sweetie peel contained the greatest amounts of furanocoumarins. Thus, caution is required during the simultaneous use of drugs metabolized by cytochrome P450 3A4 and consumption of these citrus fruits.

Case report of multiple pustules of the bilateral lower limbs caused by a granulocyte colony-stimulating factor-producing solid pseudopapillary tumour of the pancreas.

Here we report a rare case of neutrophilic dermatoses related to a granulocyte colony-stimulating factor (G-CSF)-producing solid pseudopapillary tumour (SPT). The patient was a 39-year-old woman presenting with scattered pustules and crusts of the palms, heels and thighs and plaques of the bilateral lower legs. The skin biopsy revealed dense neutrophil infiltration in the epidermis to the dermis. A pancreatic head tumour was detected using computed tomography. A pathological examination of the resected specimen suggested an SPT. As the skin eruption promptly disappeared after SPT resection, we hypothesized that SPT secretes growth factors including epidermal growth factor (EGF) and G-CSF. The SPT cells stained positive for both EGF and G-CSF tumour cells. The serum levels of interleukin (IL)-6 and IL-10 and tumour necrosis factor-α were within normal limits before and after the SPT resection. In contrast, the serum IL-8, EGF and G-CSF levels decreased after the SPT resection. This is a rare case of neutrophilic dermatoses related to a G-CSF-producing SPT. The present case suggests that physicians should be aware that a G-CSF-producing tumour is a differential diagnosis to consider in patients with unusual aseptic pustulosis.

CYFRA 21-1 as a tumor marker for squamous cell carcinoma of the esophagus.

This study assessed the clinical value of CYFRA 21-1 in comparison with squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in patients with esophageal squamous cell carcinoma. In 112 primary cancer patients, the diagnostic sensitivity of CYFRA 21-1 (33.9%) was superior to SCC-Ag (28.6%), CEA (12.5%), and CA19-9 (6.3%). Levels of CYFRA 21-1 were closely correlated with TNM stage and were below the cutoff value in all 21 patients with stage I disease. All 38 patients with a CYFRA 21-1 level over the cutoff value among the 80 patients who underwent esophagectomy had lymph node metastases (pNl). A correlation was found between CYFRA 21-1 levels and clinical response in serial measurements of 21 patients who received chemotherapy or chemo radiotherapy. Our findings suggest that CYFRA 21-1 is not useful for diagnosis, but that it is valuable for monitoring the efficacy of therapy.

Localized NMR Mediated by Electrical-Field-Induced Domain Wall Oscillation in Quantum-Hall-Ferromagnet Nanowire.

We present fractional quantum Hall domain walls confined in a gate-defined wire structure. Our experiments utilize spatial oscillation of domain walls driven by radio frequency electric fields to cause nuclear magnetic resonance. The resulting spectra are discussed in terms of both large quadrupole fields created around the wire and hyperfine fields associated with the oscillating domain walls. This provides the experimental fact that the domain walls survive near the confined geometry despite of potential deformation, by which a localized magnetic resonance is allowed in electrical means.

Campylobacter and Salmonella are prevalent in broiler farms in Kyushu, Japan: results of a 2-year distribution and circulation dynamics audit.

AIM: To elucidate the distribution and circulation dynamics of Campylobacter and Salmonella in Japanese chicken broiler flocks. METHODS AND RESULTS: A 2-year investigation of the distribution of Campylobacter and Salmonella was conducted in 25 broiler flocks at nine farms in Japan from 2013 to 2014. Campylobacter and Salmonella tested positive in 11 (44·0%) and 24 (96·0%) broiler flocks respectively. One hundred and ninety-five Campylobacter and 184 Salmonella isolates were characterized into 12 Campylobacter (including two novel genotypes) and three Salmonella MLST genotypes. Only Salmonella isolation between caecal and environmental samples were significantly correlated. Further, one litter sample tested positive for Salmonella before new chicks were introduced. The Campylobacter strains rapidly lost culturability within 2-18 days; in contrast, the Salmonella strains survived from 64-211 days in artificially inoculated water samples. CONCLUSION: No persistent circulation-mediated Campylobacter contamination was observed. In contrast, circulation of Salmonella in broiler houses was seen, apparently due to the litter excreted from broiler flocks, as well as Salmonella-contaminated water and feed. SIGNIFICANCE AND IMPACT OF THE STUDY: This paper provides the distribution, genotypic data and circulation dynamics of Campylobacter and Salmonella as recently observed in Japanese chicken broiler farms.

Genetic variation of the MHC class II DRB genes in the Japanese weasel, Mustela itatsi, endemic to Japan, compared with the Siberian weasel, Mustela sibirica.

Major histocompatibility complex (MHC) genes encode proteins that play a critical role in vertebrate immune system and are highly polymorphic. To further understand the molecular evolution of the MHC genes, we compared MHC class II DRB genes between the Japanese weasel (Mustela itatsi), a species endemic to Japan, and the Siberian weasel (Mustela sibirica), a closely related species on the continent. We sequenced a 242-bp region of DRB exon 2, which encodes antigen-binding sites (ABS), and found 24 alleles from 31 M. itatsi individuals and 17 alleles from 21 M. sibirica individuals, including broadly distributed, species-specific and/or geographically restricted alleles. Our results suggest that pathogen-driven balancing selection have acted to maintain the diversity in the DRB genes. For predicted ABS, nonsynonymous substitutions exceeded synonymous substitutions, also indicating positive selection, which was not seen at non-ABS. In a Bayesian phylogenetic tree, two M. sibirica DRB alleles were basal to the rest of the sequences from mustelid species and may represent ancestral alleles. Trans-species polymorphism was evident between many mustelid DRB alleles, especially between M. itatsi and M. sibirica. These two Mustela species divided about 1.7 million years ago, but still share many MHC alleles, indicative of their close phylogenetic relationship.

Pressure-induced valence crossover and novel metamagnetic behavior near the antiferromagnetic quantum phase transition of YbNi_{3}Ga_{9}.

We report electrical resistivity, ac magnetic susceptibility, and x-ray absorption spectroscopy measurements of intermediate valence YbNi_{3}Ga_{9} under pressure and magnetic field. We have revealed a characteristic pressure-induced Yb valence crossover within the temperature-pressure phase diagram, and a first-order metamagnetic transition is found below P_{c}∼9 GPa where the system undergoes a pressure-induced antiferromagnetic transition. As a possible origin of the metamagnetic behavior, a critical valence fluctuation emerging near the critical point of the first-order valence transition is discussed on the basis of the temperature-field-pressure phase diagram.

Verruciform xanthoma: report of three patients with comparative dermoscopic study.

We report three cases of verruciform xanthoma (VX) in male patients aged 82, 88 and 39 years, respectively. The clinical appearance was of a mulberry-like area consisting of small papillae, which is typical of and specific to VX, and the diagnosis were histologically confirmed in all cases. Dermoscopy revealed that each surface papilla contained linear or hairpin vessels, which were surrounded by a marginal whitish rim. These structures are thought to correspond to dilated vessels in dermal papillae and papillated acanthotic epidermis, respectively. Furthermore, observation under compression (similar to diascopy) revealed yellow dots and debris, reflecting lipid-laden foam cells. In order to compare these findings with those of other disorders with similar findings, two patients with xanthogranuloma, six with sebaceous naevus, and three with senile sebaceous hyperplasia were examined. The dermoscopic findings in these patients were not similar to those of VX. Therefore, we believe that the above dermoscopic findings are specific to VX and could be helpful in diagnosis.

Root surface strain during canal shaping and its influence on apical microcrack development: a preliminary investigation.

AIM: To determine the root surface strain (RSS) generated during root canal shaping and its effects on apical microcrack development. METHODOLOGY: Twenty-five extracted human mandibular premolars were selected and decoronated. The teeth were instrumented with either the ProTaper (PT) or WaveOne (WO) (Dentsply Maillefer) NiTi rotary systems (n = 10 per group) or used as controls (n = 5). Instrumented root canals were enlarged to ProTaper F4 (size 40, 0.06 taper) or using WaveOne LARGE (size 40, 0.08 taper) instruments according to the manufacturer's instructions. An electrical strain gage (KFG02-120-C1-16, Kyowa Dengyo, Tokyo, Japan) was fixed on the proximal root surface and connected to a strain amplifier via a bridge box in order to measure RSS. During canal shaping, the strain output of the amplifier was recorded. The instantaneous RSS induced by each instrument and the maximum RSSs were determined. All teeth were then stained with contrast media and imaged with micro-computed tomography (micro-CT) at an isotropic resolution of 10 µm to detect microcracks. The mean maximum RSS values (microstrain) and mean number of microcracks recorded for both groups were tested for statistical significance using Mann-Whitney U-test. Presence/absence of microcracks in both groups was compared by chi-square tests. RESULTS: Increased baseline RSS from strain accumulation during canal shaping was observed, with similar maximum RSS (mean ± SD) for PT (416.6 ± 185.1 µstrain) and WO (398.2 ± 163.8 µstrain) (P = 0.94). The interevaluator reliability for microcrack detection using micro-CT had a kappa value of 0.998. Compared to the PT group, there was a trend for fewer samples with microcracks in the WO group (P = 0.051). On the micro-CT images, apical microcracks were detected in 20 PT and 11 WO samples (P = 0.10). The microcracks were observed in the buccolingual direction in all WO and 81% of PT samples. No vertical root fractures were found. The maximum RSS obtained during canal shaping was poorly correlated with the number of microcracks found (R(2)  = 0.093). CONCLUSIONS: Based on these preliminary data, canal shaping appears to cause apical microcracks regardless of the type of rotary instrument motion. Contrast-enhanced micro-CT was able to identify microcracks in roots.

Generation of α-1,3-Galactosyltransferase-Deficient Porcine Embryonic Fibroblasts by CRISPR/Cas9-Mediated Knock-in of a Small Mutated Sequence and a Targeted Toxin-Based Selection System.

The CRISPR/Cas9 system has enabled the editing of mammalian genomes; however, its applicability and efficiency in the pig genome has not been studied in depth. The α-gal epitope synthesized by α-1,3-galactosyltransferase gene (GGTA1) is known as a xenoantigen obtained upon pig-to-human xenotransplantation. We here employed the CRISPR/Cas9 system-mediated knock-in of endogenous GGTA1 via targeted homologous recombination (HR). Linearized donors with ~800-bp homology flanking the CRISPR/Cas9 target site [exon 4 (containing ATG) of GGTA1] served as a template for gene targeting by HR. Using a targeted toxin strategy to select clones lacking α-gal epitope expression, we successfully obtained several knock-in clones within 3 weeks of initial transfection. These results suggest that the use of CRISPR/Cas9-mediated HR to knock-in a mutated fragment at defined loci represents an efficient strategy to achieve the rapid modulation of genes of interest in swine cells and is a promising tool for the creation of KO piglets.