First Measurement of Hard Exclusive π

The polarized cross-section ratio σ_{LT^{'}}/σ_{0} from hard exclusive π^{-}Δ^{++} electroproduction off an unpolarized hydrogen target has been extracted based on beam-spin asymmetry measurements using a 10.2 GeV/10.6 GeV incident electron beam and the CLAS12 spectrometer at Jefferson Lab. The study, which provides the first observation of this channel in the deep-inelastic regime, focuses on very forward-pion kinematics in the valence regime, and photon virtualities ranging from 1.5 GeV^{2} up to 7 GeV^{2}. The reaction provides a novel access to the d-quark content of the nucleon and to p→Δ^{++} transition generalized parton distributions. A comparison to existing results for hard exclusive π^{+}n and π^{0}p electroproduction is provided, which shows a clear impact of the excitation mechanism, encoded in transition generalized parton distributions, on the asymmetry.

Multidimensional, High Precision Measurements of Beam Single Spin Asymmetries in Semi-inclusive π

High precision measurements of the polarized electron beam-spin asymmetry in semi-inclusive deep inelastic scattering (SIDIS) from the proton have been performed using a 10.6 GeV incident electron beam and the CLAS12 spectrometer at Jefferson Lab. We report here a high precision multidimensional study of single π^{+} SIDIS data over a large kinematic range in Bjorken x, fractional energy, and transverse momentum of the hadron as well as photon virtualities Q^{2} ranging from 1-7 GeV^{2}. In particular, the structure function ratio F_{LU}^{sinϕ}/F_{UU} has been determined, where F_{LU}^{sinϕ} is a twist-3 quantity that can reveal novel aspects of emergent hadron mass and quark-gluon correlations within the nucleon. The data's impact on the evolving understanding of the underlying reaction mechanisms and their kinematic variation is explored using theoretical models for the different contributing transverse momentum dependent parton distribution functions.

Search for Sub-eV Sterile Neutrinos at RENO.

We report a search result for a light sterile neutrino oscillation with roughly 2200 live days of data in the RENO experiment. The search is performed by electron antineutrino (ν[over ¯]_{e}) disappearance taking place between six 2.8 GW_{th} reactors and two identical detectors located at 294 m (near) and 1383 m (far) from the center of the reactor array. A spectral comparison between near and far detectors can explore reactor ν[over ¯]_{e} oscillations to a light sterile neutrino. An observed spectral difference is found to be consistent with that of the three-flavor oscillation model. This yields limits on sin^{2}2θ_{14} in the 10^{-4}≲|Δm_{41}^{2}|≲0.5 eV^{2} region, free from reactor ν[over ¯]_{e} flux and spectrum uncertainties. The RENO result provides the most stringent limits on sterile neutrino mixing at |Δm_{41}^{2}|≲0.002 eV^{2} using the ν[over ¯]_{e} disappearance channel.

Extraction of Beam-Spin Asymmetries from the Hard Exclusive π

We have measured beam-spin asymmetries to extract the sinϕ moment A_{LU}^{sinϕ} from the hard exclusive e[over →]p→e^{'}nπ^{+} reaction above the resonance region, for the first time with nearly full coverage from forward to backward angles in the center of mass. The A_{LU}^{sinϕ} moment has been measured up to 6.6 GeV^{2} in -t, covering the kinematic regimes of generalized parton distributions (GPD) and baryon-to-meson transition distribution amplitudes (TDA) at the same time. The experimental results in very forward kinematics demonstrate the sensitivity to chiral-odd and chiral-even GPDs. In very backward kinematics where the TDA framework is applicable, we found A_{LU}^{sinϕ} to be negative, while a sign change was observed near 90° in the center of mass. The unique results presented in this Letter will provide critical constraints to establish reaction mechanisms that can help to further develop the GPD and TDA frameworks.

Fuel-Composition Dependent Reactor Antineutrino Yield at RENO.

We report a fuel-dependent reactor electron antineutrino (ν[over ¯]_{e}) yield using six 2.8 GW_{th} reactors in the Hanbit nuclear power plant complex, Yonggwang, Korea. The analysis uses 850 666 ν[over ¯]_{e} candidate events with a background fraction of 2.0% acquired through inverse beta decay (IBD) interactions in the near detector for 1807.9 live days from August 2011 to February 2018. Based on multiple fuel cycles, we observe a fuel ^{235}U dependent variation of measured IBD yields with a slope of (1.51±0.23)×10^{-43} cm^{2}/fission and measure a total average IBD yield of (5.84±0.13)×10^{-43} cm^{2}/fission. The hypothesis of no fuel-dependent IBD yield is ruled out at 6.6σ. The observed IBD yield variation over ^{235}U isotope fraction does not show significant deviation from the Huber-Mueller (HM) prediction at 1.3 σ. The measured fuel-dependent variation determines IBD yields of (6.15±0.19)×10^{-43} and (4.18±0.26)×10^{-43} cm^{2}/fission for two dominant fuel isotopes ^{235}U and ^{239}Pu, respectively. The measured IBD yield per ^{235}U fission shows the largest deficit relative to the HM prediction. Reevaluation of the ^{235}U IBD yield per fission may mostly solve the reactor antineutrino anomaly (RAA) while ^{239}Pu is not completely ruled out as a possible contributor to the anomaly. We also report a 2.9 σ correlation between the fractional change of the 5 MeV excess and the reactor fuel isotope fraction of ^{235}U.

Measurement of Reactor Antineutrino Oscillation Amplitude and Frequency at RENO.

The RENO experiment reports more precisely measured values of θ_{13} and |Δm_{ee}^{2}| using ∼2200 live days of data. The amplitude and frequency of reactor electron antineutrino (ν[over ¯]_{e}) oscillation are measured by comparing the prompt signal spectra obtained from two identical near and far detectors. In the period between August 2011 and February 2018, the far (near) detector observed 103 212 (850 666) ν[over ¯]_{e} candidate events with a background fraction of 4.8% (2.0%). A clear energy and baseline dependent disappearance of reactor ν[over ¯]_{e} is observed in the deficit of the measured number of ν[over ¯]_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.0896±0.0048(stat)±0.0047(syst) and |Δm_{ee}^{2}|=[2.68±0.12(stat)±0.07(syst)]×10^{-3} eV^{2}.

Differential Cross Section and Photon-Beam Asymmetry for the γ[over →]p → π

Differential cross sections and photon-beam asymmetries for the γ[over →]p→π^{-}Δ^{++}(1232) reaction have been measured for 0.7

Comorbidities Can Predict Mortality of Kidney Transplant Recipients: Comparison With the Charlson Comorbidity Index.

BACKGROUND: Comorbid conditions are important in the survival of kidney transplant recipients. The weights assigned to comorbidities to predict survival may vary based on the type of index disease and advances in the management of comorbidities. We aimed to develop a modified Charlson comorbidity index (CCI) in renal allograft recipients (mCCI-KT), thereby improving risk stratification for mortality. METHODS: A total of 3765 recipients in a multicenter cohort were included to develop a comorbidity score. The weights of the comorbidities, per the CCI, were recalibrated using a Cox proportional hazards model. RESULTS: Peripheral vascular disease, liver disease, myocardial infarction, and diabetes in the CCI were selected from the Cox proportional hazards model. Thus, the mCCI-KT included 4 comorbidities with recalibrated severity weights. Whereas the CCI did not discriminate for survival, the mCCI-KT provided significant discrimination for survival using the Kaplan-Meier method and Cox regression analysis. The mCCI-KT showed modest increases in c-statistics (0.54 vs 0.52, P = .001) and improved net mortality risk reclassification by 16.3% (95% confidence interval, 3.2-29.4; P = .015) relative to the CCI. CONCLUSION: The mCCI-KT stratifies the risk for mortality in renal allograft recipients better than the CCI, suggesting that it may be a preferred index for use in clinical practice.

Sterile Neutrino Search at the NEOS Experiment.

An experiment to search for light sterile neutrinos is conducted at a reactor with a thermal power of 2.8 GW located at the Hanbit nuclear power complex. The search is done with a detector consisting of a ton of Gd-loaded liquid scintillator in a tendon gallery approximately 24 m from the reactor core. The measured antineutrino event rate is 1976 per day with a signal to background ratio of about 22. The shape of the antineutrino energy spectrum obtained from the eight-month data-taking period is compared with a hypothesis of oscillations due to active-sterile antineutrino mixing. No strong evidence of 3+1 neutrino oscillation is found. An excess around the 5 MeV prompt energy range is observed as seen in existing longer-baseline experiments. The mixing parameter sin^{2}2θ_{14} is limited up to less than 0.1 for Δm_{41}^{2} ranging from 0.2 to 2.3 eV^{2} with a 90% confidence level.

Observation of Energy and Baseline Dependent Reactor Antineutrino Disappearance in the RENO Experiment.

The RENO experiment has analyzed about 500 live days of data to observe an energy dependent disappearance of reactor ν[over ¯]_{e} by comparing their prompt signal spectra measured in two identical near and far detectors. In the period between August of 2011 and January of 2013, the far (near) detector observed 31 541 (290 775) electron antineutrino candidate events with a background fraction of 4.9% (2.8%). The measured prompt spectra show an excess of reactor ν[over ¯]_{e} around 5 MeV relative to the prediction from a most commonly used model. A clear energy and baseline dependent disappearance of reactor ν[over ¯]_{e} is observed in the deficit of the observed number of ν[over ¯]_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.082±0.009(stat)±0.006(syst) and |Δm_{ee}^{2}|=[2.62_{-0.23}^{+0.21}(stat)_{-0.13}^{+0.12}(syst)]×10^{-3} eV^{2}.

Note: Near infrared interferometric silicon wafer metrology.

In this investigation, two near infrared (NIR) interferometric techniques for silicon wafer metrology are described and verified with experimental results. Based on the transparent characteristic of NIR light to a silicon wafer, the fiber based spectrally resolved interferometry can measure the optical thickness of the wafer and stitching low coherence scanning interferometry can reconstruct entire surfaces of the wafer.

Treatment Planning and Delivery of Whole Brain Irradiation with Hippocampal Avoidance in Rats.

BACKGROUND: Despite the clinical benefit of whole brain radiotherapy (WBRT), patients and physicians are concerned by the long-term impact on cognitive functioning. Many studies investigating the molecular and cellular impact of WBRT have used rodent models. However, there has not been a rodent protocol comparable to the recently reported Radiation Therapy Oncology Group (RTOG) protocol for WBRT with hippocampal avoidance (HA) which is intended to spare cognitive function. The aim of this study was to develop a hippocampal-sparing WBRT protocol in Wistar rats. METHODS: The technical and clinical challenges encountered in hippocampal sparing during rat WBRT are substantial. Three key challenges were identified: hippocampal localization, treatment planning, and treatment localization. Hippocampal localization was achieved with sophisticated imaging techniques requiring deformable registration of a rat MRI atlas with a high resolution MRI followed by fusion via rigid registration to a CBCT. Treatment planning employed a Monte Carlo dose calculation in SmART-Plan and creation of 0.5 cm thick lead blocks custom-shaped to match DRR projections. Treatment localization necessitated the on-board image-guidance capability of the XRAD C225Cx micro-CT/micro-irradiator (Precision X-Ray). Treatment was accomplished with opposed lateral fields with 225 KVp X-rays at a current of 13 mA filtered through 0.3 mm of copper using a 40x40 mm square collimator and the lead blocks. A single fraction of 4 Gy was delivered (2 Gy per lateral field) with a 41 second beam on time per field at a dose rate of 304.5 cGy/min. Dosimetric verification of hippocampal sparing was performed using radiochromic film. In vivo verification of HA was performed after delivery of a single 4 Gy fraction either with or without HA using γ-H2Ax staining of tissue sections from the brain to quantify the amount of DNA damage in rats treated with HA, WBRT, or sham-irradiated (negative controls). RESULTS: The mean dose delivered to radiochromic film beneath the hippocampal block was 0.52 Gy compared to 3.93 Gy without the block, indicating an 87% reduction in the dose delivered to the hippocampus. This difference was consistent with doses predicted by Monte Carlo dose calculation. The Dose Volume Histogram (DVH) generated via Monte Carlo simulation showed an underdose of the target volume (brain minus hippocampus) with 50% of the target volume receiving 100% of the prescription isodose as a result of the lateral blocking techniques sparing some midline thalamic and subcortical tissue. Staining of brain sections with anti-phospho-Histone H2A.X (reflecting double-strand DNA breaks) demonstrated that this treatment protocol limited radiation dose to the hippocampus in vivo. The mean signal intensity from γ-H2Ax staining in the cortex was not significantly different from the signal intensity in the cortex of rats treated with WBRT (5.40 v. 5.75, P = 0.32). In contrast, the signal intensity in the hippocampus of rats treated with HA was significantly lower than rats treated with WBRT (4.55 v. 6.93, P = 0.012). CONCLUSION: Despite the challenges of planning conformal treatments for small volumes in rodents, our dosimetric and in vivo data show that WBRT with HA is feasible in rats. This study provides a useful platform for further application and refinement of the technique.

Differential modulation of phasic and tonic inhibition underlies serotonergic suppression of long-term potentiation in the rat visual cortex.

GABA receptor type A (GABA(A)R)-mediated inhibition is divided into phasic and tonic inhibition. GABA(A)Rs mediating the two inhibitory modalities exhibit differences in subcellular localization and subunit composition. We previously demonstrated that phasic and tonic inhibition are independently regulated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and protein kinase A (PKA), respectively. Since modulation of GABA(A)Rs by phosphorylation differs depending on subunit composition and protein kinases, phasic and tonic inhibition might be differentially regulated by a single neuromodulator activating multiple protein kinases. However, the neuromodulatory control for phasic and tonic inhibition is largely unknown. Thus, in the present study, we concurrently investigated the serotonin (5-HT) regulation of phasic and tonic inhibition and its functional implication in the pyramidal neurons of the rat visual cortex. Interestingly, 5-HT enhanced phasic inhibition but suppressed tonic inhibition. Increase in phasic inhibition was mediated by 5-HT2 receptor and CaMKII, whereas decrease in tonic inhibition depended on 5-HT1A receptor and PKA. Thus, phasic and tonic inhibition might be independently regulated even by a single neuromodulator. Functionally, the opposite modulation of phasic and tonic inhibition decreased the summation of consecutive excitatory postsynaptic potentials (EPSPs) without affecting the shape of single EPSPs, which might underlie the suppression of the induction of long-term potentiation by 5-HT. These results suggest that the integrative regulation of phasic and tonic inhibition provides mechanisms for elaborate modulation of shape and summation of EPSPs and long-term synaptic plasticity.

Clinically applicable human adipose tissue-derived mesenchymal stem cells delivering therapeutic genes to brainstem gliomas.

Pediatric brainstem glioma is an incurable malignancy because of its inoperability. As a result of their extensive tropism toward cancer and the possibility of autologous transplantation, human adipose-derived mesenchymal stem cells (hAT-MSC) are attractive vehicles to deliver therapeutic genes to brainstem gliomas. In this study, in a good manufacturing practice (GMP) facility, we established clinically applicable hAT-MSCs expressing therapeutic genes and investigated their therapeutic efficacy against brainstem glioma in mice. For feasible clinical applications, (1) primary hAT-MSCs were cultured from human subcutaneous fat to make autologous transplantation possible, (2) hAT-MSCs were genetically engineered to express carboxyl esterase (CE) and (3) a secreted form of the tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) expression vector for synergistic effects was delivered by a gene transfer technology that did not result in genomic integration of the vector. (4) Human CE and sTRAIL sequences were utilized to avoid immunological side effects. The hAT-MSCs expressing CE±sTRAIL showed significant therapeutic effects against brainstem gliomas in vitro and in vivo. However, the simultaneous expression of CE and sTRAIL had no synergistic effects in vivo. The results indicate that non-viral transient single sTRAIL gene transfer to autologous hAT-MSCs is a clinically applicable stem cell-based gene therapy for brainstem gliomas in terms of therapeutic effects and safety.

Longitudinal target-spin asymmetries for deeply virtual compton scattering.

A measurement of the electroproduction of photons off protons in the deeply inelastic regime was performed at Jefferson Lab using a nearly 6 GeV electron beam, a longitudinally polarized proton target, and the CEBAF Large Acceptance Spectrometer. Target-spin asymmetries for ep→e^{'}p^{'}γ events, which arise from the interference of the deeply virtual Compton scattering and the Bethe-Heitler processes, were extracted over the widest kinematics in Q^{2}, x_{B}, t, and ϕ, for 166 four-dimensional bins. In the framework of generalized parton distributions, at leading twist the t dependence of these asymmetries provides insight into the spatial distribution of the axial charge of the proton, which appears to be concentrated in its center. These results also bring important and necessary constraints for the existing parametrizations of chiral-even generalized parton distributions.

Skin dryness in apparently healthy human skin is associated with decreased expression of bleomycin hydrolase in the stratum corneum.

BACKGROUND: Maintenance of water balance in the stratum corneum (SC) is determined by the content of intercellular lipids and natural moisturizing factors (NMFs) in corneocytes. AIM: To investigate the association between the NMFs and (pro)filaggrin and the proteases responsible for the processing of (pro)filaggrin to NMFs in the SC of hydrated and dry skin areas of healthy human subjects. METHODS: The SC hydration state and the transepidermal water loss (TEWL) were measured using a Corneometer and a Tewameter, respectively. Proteases, (pro)filaggrin and NMFs were extracted from SC samples obtained by tape-stripping of the tested skin. Expression levels of (pro)filaggrin were determined by dot blotting and western blotting, and total NMFs by ultra-high performance liquid chromatography. Expression of the proteases caspase-14, calpain-1 and bleomycin hydrolase was measured by western blotting. RESULTS: The levels of (pro)filaggrin were not significantly different between hydrated and dry skin, whereas the level of total NMFs was significantly reduced in dry skin. A negative correlation between (pro)filaggrin and NMFs was found in dry skin (Pearson correlation coefficient r = - 0.57, *P < 0.05). Bleomycin hydrolase expression was significantly decreased in the SC of dry skin. CONCLUSIONS: These results suggest that the low hydration state of dry skin may be due to the reduction in (pro)filaggrin degradation caused by decreased bleomycin hydrolase expression.

Enhanced protection against Clonorchis sinensis induced by co-infection with Trichinella spiralis in rats.

Although co-infection with multiple parasites is a frequent occurrence, changes in the humoral immune response against a pre-existing parasite induced as a result of a subsequent parasitic infection remain undetermined. Here, we utilized enzyme-linked immunosorbent assay (ELISA) to investigate antibody responses, cytokine production and enhanced resistance in Clonorchis sinensis-infected rats (Sprague-Dawley) upon Trichinella spiralis infection. Higher levels of C. sinensis-specific IgG and IgA were elicited upon T. spiralis infection, and these levels remained higher than in rats infected with C. sinensis alone. Upon subsequent infection with T. spiralis, IgG antibodies against C. sinensis appeared to be rapidly boosted at day 3, and IgA antibodies were boosted at day 7. Challenge infection of C. sinensis-infected rats with T. spiralis induced substantial mucosal IgG and IgA responses in the liver and intestine and increases in antibody-secreting plasma cells in the spleen and bone marrow. Subsequent infection also appeared to confer effective control of liver C. sinensis loads, resulting in enhanced resistance. Memory B cells generated in response to C. sinensis infection were rapidly amplified into antibody-secreting cells upon T. spiralis infection. These results indicate that enhanced C. sinensis clearance induced by co-infection is associated with systemic and mucosal IgG and IgA responses.

Characteristic features of ageing in Korean women's hair and scalp.

BACKGROUND: The effect of age on hair properties has previously been investigated in white and Japanese women; however, little is known of the age-related characteristic features of hair in Korean women. OBJECTIVES: To determine the ageing features of Korean women's hair by examining physical and biological factors in sufficient numbers of participants. METHODS: In total, 150 healthy Korean women (aged 23-69 years) living in Seoul were allocated to five age-graded groups. Age-related changes of various features of the scalp and hair shaft were measured, including hair density, diameter, tensile strength and lustre, and grey-hair ratio. The hair-shaft compositions of minerals, amino acids and steroid hormones were analysed by high-performance liquid chromatography. RESULTS: Hair-loss parameters (hair density, diameter and tensile strength) and hair lustre decreased significantly with age, beginning in the subjects' 40s. The hair-whiteness value increased significantly with age, beginning in their 60s, due to an increase in the ratio of grey hair. Calcium and magnesium levels greatly exceeded the reference ranges and declined in an age-dependent manner, while potassium and phosphorus levels increased with age. No age-related change of hair-shaft amino acid content was evident. The contents of sterols and their metabolites (cholesterol, desmosterol, lanosterol and pregnenolone) increased significantly with age, but there was no correlation between the examined sex steroids and age. CONCLUSIONS: These results show that intrinsic ageing produces diverse changes in the hair and scalp features of Korean women from their 40s, and the ageing features of Korean women's hair could be partially different from that of women in other countries.

Endocytic processing of adeno-associated virus type 8 vectors for transduction of target cells.

We investigated the transduction of HEK293T cells permissive to adeno-associated virus serotype 8 (AAV8) to understand the mechanisms underlying its endocytic processing. Results showed that AAV8 enters cells through clathrin-mediated endocytosis followed by trafficking through various endosomal compartments. Interestingly, compared to the relatively well-characterized AAV2, a distinct involvement of late endosomes was observed for AAV8 trafficking within the target cell. AAV8 particles were also shown to exploit the cytoskeleton network to facilitate their transport within cells. Moreover, the cellular factors involved during endosomal escape were examined by an in vitro membrane permeabilization assay. Our data demonstrated that an acidic endosomal environment was required for AAV2 penetration through endosomal membranes and that the cellular endoprotease furin could promote AAV2 escape from the early endosomes. In contrast, these factors were not sufficient for AAV8 penetration through endosomal membranes. We further found that the ubiquitin-proteasome system is likely involved in the intracellular transport of AAV8 to nucleus. Taken together, our data have shed some light on the intracellular trafficking pathways of AAV8, which, in turn, could provide insight for potentializing AAV-mediated gene delivery.

Effect of estradiol on the expression of renal sodium transporters in rats.

BACKGROUND: Although estradiol has been thought to perform an important role in blood pressure regulation, the effects of estradiol on the expression of renal sodium transporters are not fully understood. METHODS: Female Sprague-Dawley rats were treated with 17ß-estradiol or vehicle for 10 days after ovariectomy, and after both ovariectomy and adrenalectomy to eliminate the effect of aldosterone. RESULTS: In the ovariectomized (OVX) rats, estradiol decreased the abundance of the Na-K-2Cl cotransporter (NKCC2) (31.5% of control (OVX), p < 0.01), Na-Cl cotransporter (NCC) proteins (40.5% of control (OVX), p < 0.01) and α- and γ-subunits of the epithelial sodium channel (ENaC) (44.7% and 11.0% of control (OVX), p < 0.01). Estradiol also reduced plasma aldosterone levels (OVX + 17ß-estradiol vs. OVX, 116.3 ± 44.4 vs. 184.2 ± 33.4 pmol/l, p < 0.05) and systolic blood pressure (OVX + 17ß-estradiol vs. OVX, 115 ± 4 vs. 132 ± 2 mmHg, p < 0.05). In rats having undergone adrenalectomy and ovariectomy, estradiol did not reduce systolic blood pressure, or the expression of sodium transporters. CONCLUSION: Estradiol decreased systolic blood pressure, plasma aldosterone levels, and the expression of renal sodium transporters. After aldosterone was eliminated, estradiol did not affect blood pressure or the expression of sodium transporters, which indicates that the effect of estradiol on the renal sodium transporters is at least partly influenced by aldosterone.