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The development of a safe and reproducible gene delivery system is an essential step toward the clinical application of the hydrodynamic gene delivery (HGD) method. For this purpose, we have developed a novel electric power-driven injection system called the HydroJector-EM, which can replicate various time-pressure curves preloaded into the computer program before injection. The assessment of the reproducibility and safety of gene delivery system in vitro and in vivo demonstrated the precise replication of intravascular time-pressure curves and the reproducibility of gene delivery efficiency. The highest level of luciferase expression (272 pg luciferase per mg of proteins) was achieved safely using the time-pressure curve, which reaches 30 mm Hg in 10 s among various curves tested. Using this curve, the sustained expression of a therapeutic level of human factor IX protein (>500 ng ml−1) was maintained for 2 months after the HGD of the pBS-HCRHP-FIXIA plasmid. Other than a transient increase in liver enzymes that recovered in a few days, no adverse events were seen in rats. These results confirm the effectiveness of the HydroJector-EM for reproducible gene delivery and demonstrate that long-term therapeutic gene expression can be achieved by automatic computer-controlled hydrodynamic injection that can be performed by anyone. [ABSTRACT FROM AUTHOR]

Abstract: The efficiency and accuracy of cortical maps from optical imaging experiments have been improved using periodic stimulation protocols. The resulting data analysis requires the detection and estimation of periodic information in a multivariate dataset. To date, these analyses have relied on discrete Fourier transform (DFT) sinusoid estimates. Multitaper methods have become common statistical tools in the analysis of univariate time series that can give improved estimates. Here, we extend univariate multitaper harmonic analysis methods to the multivariate, imaging context. Given the hypothesis that a coherent oscillation across many pixels exists within a specified bandwidth, we investigate the problem of its detection and estimation in noisy data by constructing Hotelling''s generalized T 2-test. We then extend the investigation of this problem in two contexts, that of standard canonical variate analysis (CVA) and that of generalized indicator function analysis (GIFA) which is often more robust in extracting a signal in spatially correlated noise. We provide detailed information on the fidelities of the mean estimates found with our methods and comparison with DFT estimates. Our results indicate that GIFA provides particularly good estimates of harmonic signals in spatially correlated noise and is useful for detecting small amplitude harmonic signals in applications such as biological imaging measurements where spatially correlated noise is common. We demonstrate the power of our methods with an optical imaging dataset of the periodic response to a periodically rotating oriented drifting grating stimulus experiment in cat visual cortex. [Copyright &y& Elsevier]

Gas desorption rates for several types of B4C resins were investigated using a throughput method. The investigation was particularly focused on determining the out gas composition, effects of dry air, grain size (density) effects on the gas desorption rates. It is found that water is the main component of out gas and that dry air can effectively reduce gas desorption. [ABSTRACT FROM AUTHOR]

Juveniles of two Acentrogobius species collected in a mangrove estuary in Sikao Creek, southern Thailand, were identified by morphological and molecular methods. A total of 1315 Acentrogobius specimens were collected and grouped into types A ( n = 1107, 4·4–12·0 mm standard length, LS) (melanophore absent or indistinct on posterodorsal contour of caudal peduncle; two rows of melanophore blotches on lateral midline) and B ( n = 208, 4·8–12·6 mm LS) (distinct melanophore on posterodorsal contour of caudal peduncle; a single row of melanophore blotches on lateral midline). Based on the reverse series method, the melanophore patterns of larger juveniles were linked with the smallest specimens possessing adult characters. The homogeneities of mitochondrial cytochrome b region sequences between the two juvenile types and adult Acentrogobius species collected in the study area indicated type A to be A. kranjiensis (homogeneity between type A and A. kranjiensis: 99·3–100%), and type B to be A. malayanus (homogeneity between latter 98·1 and 99·7%). No Acentrogobius juveniles were collected from the surf zone outside the creek mouth, both species apparently spending most of their life histories within the estuarine habitat. During their pelagic phase, A. kranjiensis and A. malayanus dispersed in the upper, middle and lower reaches of the creek. On the other hand, occurrence patterns during the benthic phase of A. kranjiensis and A. malayanus differed, the former showing upstream movement and the latter downstream movement with growth. These results emphasize the necessity of analysing early fish life histories at the species level, and the collaboration between morphological and molecular methods should prove valuable in accurately identifying of larvae and juveniles. [ABSTRACT FROM AUTHOR]

Abstract: A neutron diffraction study was performed on a single crystal of -moment-free perovskite manganite Eu0.595Y0.405MnO3 to elucidate the relation between the spontaneous ferroelectric polarization and the magnetic structure. Eu0.595Y0.405MnO3 shows an incommensurate magnetic ordering below . The ferroelectric polarization P along the c axis appears below 25K, and it is replaced by P along the a axis below 23K. We have observed the change of magnetic structure at temperatures where the ferroelectric polarization appears and changes its polarization direction. [Copyright &y& Elsevier]

Design and performance of a new chopper spectrometer 4SEASONS, which is under construction for the spallation neutron source at Japan Proton Accelerator Research Complex (J-PARC), are described. This spectrometer has middle energy resolution and two orders higher performance than current state-of-the-art chopper spectrometers by utilizing a unique beam transport design and the repetition rate multiplication (RRM) method. 4SEASONS has a specification optimized for the study of the high critical temperature (Tc) superconductivity, and should be suitable for collecting weak inelastic signals from a single crystal over a wide four-dimensional (4D) Q-ω space. [ABSTRACT FROM AUTHOR]

Abstract: In optical imaging experiments of primary visual cortex, visual stimuli evoke a complicated dynamics. Typically, any stimulus with sufficient contrast evokes a response. Much of the response is the same regardless of which stimulus is presented. For instance, when oriented drifting gratings are presented to the visual system, over 90% of the response is the same from orientation to orientation. Small differences may be seen, however, between the responses to different orientations. A problem in the analysis of optical measurements of the response to stimulus in cortical tissue is the distinction of the ‘global’ or ‘non-specific’ response from the ‘differential’ or ‘stimulus-specific’ response. This problem arises whenever the signal of interest is the difference in response to various stimuli and is evident in many kinds of uni- and multivariate data. To this end, we present enhancements to a frequency-based method that we previously introduced called the periodic stacking method. These enhancements allow us to separately estimate the dynamics of both the average signal across all stimuli (the ‘global’ response) and deviations from the average amongst the various stimuli (the ‘stimulus-specific’ response) evoked in response to a set of stimuli. We also discuss improvements in the signal-to-noise ratio, relative to standard trial averaging methods, that result from the data-adaptive smoothing in our method. [Copyright &y& Elsevier]

Dynamical structures in the vicinity of Q =(π, π) of optimally-doped YBa 2 Cu 3 O 6.9 were measured by means of an inelastic neutron scattering technique utilizing pulsed neutron source. Obtained incommensurability δ of energy transfer at E =36 meV was found to be ∼0.1 [rlu] which is not the value to be expected from the formation of spin-charge stripes. In higher energy above resonance energy (42 meV), a ring structure centered at (π, π) was observed up to 54 meV. Combined with the low energy part of the dynamical structure, the obtained results provide a total picture of the dynamical aspects in the high- T c superconductor YBa 2 Cu 3 O 6.9 . [ABSTRACT FROM AUTHOR]

Focuses on neutron scattering experiments on highly absorbing materials like boron and cadmium. Impact of topical phenomena such as charge orbiting on the demand for neutron scattering studies; Information on the extreme condition epithermal neutron diffractometer; Capabilities of the epithermal neutron diffractometer.

Examines the treatment of IgA nephropathy using novel therapeutic strategy. Preventing nephropathy through local delivery of anti-inflammatory cytokine into glomeruli; Site-specific gene delivery into inflamed glomeruli using a bone marrow-derived cells as vehicle which possesses the ligand of adhesion molecules; Feasibility of the site-specific gene system as therapy for experimental glomerunephritis; Several problems to address before making major investments for clinical use of the site-specific gene system for nephropathy.

J-PARC, Japan Proton Accelerator Research Complex provides short pulse proton beam at a repetition rate 25 Hz and the maximum power is expected to be 1 MW. Materials and Life Science Experimental Facility (MLF) has 23 neutron beam ports and 21 instruments have already been operated or under construction/commissioning. There are 6 inelastic/quasi-elastic neutron scattering spectrometers and the complementary use of these spectrometers will open new insight for life science. This article is part of a Special Issue entitled “Science for Life” Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo. [ABSTRACT FROM AUTHOR]

Background Abdominal ultrasound fails to detect over one-fourth of hepatocellular carcinoma ( HCC) at an early stage in patients with cirrhosis. Identifying patients in whom ultrasound is of inadequate quality can inform interventions to improve surveillance effectiveness. Aim To evaluate and identify predictors of ultrasound quality in patients with cirrhosis. Methods We performed a retrospective cohort study among patients who underwent ultrasound examination for a cirrhosis-related indication between April 2015 and October 2015. Three fellowship-trained abdominal radiologists collectively reviewed all ultrasound exams and categorised exam quality as definitely adequate, likely adequate, likely inadequate and definitely inadequate to exclude liver lesions. We performed multivariable logistic regression to determine characteristics associated with inadequate ultrasound quality. Results Among 941 patients, 191 (20.3%) ultrasounds were inadequate for excluding HCC- 134 definitely inadequate and 57 likely inadequate. In multivariable analysis, inadequate quality was associated with male gender ( OR 1.68, 95% CI 1.14-2.48), body mass index category ( OR 1.67, 95% CI 1.45-1.93), Child-Pugh B or C cirrhosis ( OR 1.93, 95% CI 1.32-2.81), alcohol-related cirrhosis ( OR 2.11, 95% CI 1.33-3.37), NASH cirrhosis ( OR 2.87, 95% CI 1.71-4.80), and in-patient status ( OR 1.55, 95% CI 1.01-2.37). Ultrasounds were inadequate in over one-third of patients with Child-Pugh C cirrhosis, BMI >35, or NASH cirrhosis. Conclusions One in five ultrasounds in patients with cirrhosis are inadequate for exclusion of HCC, which can contribute to surveillance failure. Alternative surveillance modalities are needed in subgroups prone to inadequate ultrasounds including obese patients, those with Child Pugh B or C cirrhosis, and those with alcohol- or NASH-related cirrhosis. [ABSTRACT FROM AUTHOR]

In this study, we examined the effects of macrophage-colony stimulating factor (M-CSF) on glomerular macrophages in lipopolysaccharide (LPS)-induced murine nephritis. Mice injected intraperitoneally with either M-CSF plus LPS, LPS alone, M-CSF alone or saline every day for 8 days were examined for the degree of urine albumin excretion and lymphocyte-function associated antigen-l-positive (LFA-l+) cells in peripheral blood as well as renal pathology. From our results, LPS or M-CSF combined with LPS emphasized the degree of proteinuria, glomerular deposition of immunoglobulins and mesangial proliferation, associated with accumulation of macrophages in the glomeruli. However, in immunohistological examination of kidneys from these nephritic mice, neither intercellular adhesion molecule-1 (lCAM-1), which may play an important role in the recruitment of macrophages into glomeruli, M-CSF receptor nor the number of LFA-1+ cells in peripheral blood was enhanced by M-CSF. On the other hand, M-CSF alone induced neither proteinuria nor any pathological changes and did not increase the number of glomerular Mac-1+ cells above that in saline-treated controls. These results indicate that M-CSF does not directly cause glomerulonephritis but might participate in accelerating the glomerular inflammatory process by stimulating a potent chemoattractant to recruit monocytes-macrophages into the glomeruli. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Simmons et al and Patel papers. To view these articles visit https://doi.org/10.1111/apt.13841 and https://doi.org/10.1111/apt.13891. [ABSTRACT FROM AUTHOR]

The low-energy spin-wave dispersion in polycrystalline Nd-Fe-B magnets was observed using neutron Brillouin scattering (NBS). Low-energy spin-wave excitations for the lowest acoustic spinwave mode were clearly observed. From the spin-wave dispersion, we were able to determine the spin-wave stiffness constant Dsw (100.0±4.9 meV.Å 2) and the exchange stiffness constant A (6.6 ± 0.3 pJ/m). [ABSTRACT FROM AUTHOR]

The collective spin-wave excitations in the antiferromagnetic state of γ-Fe0.7Mn0.3 were investigated using the inelastic neutron-scattering technique. The spin excitations remain isotropic up to high excitation energy, ħω=78 meV. The excitations gradually become broad and damped above 40 meV. The damping parameter γ reaches 110(16) meV at ħω=78 meV, which is much larger than that for other metallic compounds, e.g., CaFe2As2 (24 meV), La2-2xSr1+2xMn2O7 (52-72 meV), and Mn90Cu10 (88 meV). In addition, the spin-wave dispersion shows a deviation from the relation (ħω)²=c²q²+Δ² above 40 meV. The group velocity above this energy increases to 470(40) meVÅ, which is higher than that at the low energies, c=226(5) meVÅ. These results could suggest that the spin-wave excitations merge with the continuum of the individual particle-hole excitations at 40 meV. [ABSTRACT FROM AUTHOR]

Background Previously, we explored the histopathologic characteristics of medullary ray injury (MRI) inducing interstitial fibrosis and tubular atrophy (IF/TA) to determine its etiologies, which include calcineurin inhibitor (CNI) toxicity and urologic complications. However, we did not examine the effects of these etiologies on long-term kidney allograft prognosis, because biopsy timing differed among cases. Aim We examined the influence of early MRI on kidney allograft prognosis using protocol biopsies taken within a 3-month time frame. Methods We defined early MRI as tubular degeneration with interstitial edema or mild fibrosis localized to the medullary ray. We divided 53 protocol biopsies into 2 groups, with and without early MRI. Early MRI+ cases with isometric vacuolization were classified as CNI toxicity; those with Tamm-Horsfall protein in the interstitium and a thyroidlike appearance were classified as urinary tract system abnormalities; remaining cases were classified as “others.” We compared changes in serum levels of creatinine (sCr) over 3 years and fibrosis extent at 1 year. Results The sCr levels were significantly higher in the MRI+ group than the MRI− group at 3 years ( P = .024). Examining the 3 MRI+ subgroups, only the MRI+ urinary tract system abnormalities group had significantly high sCr levels compared to the MRI− group ( P = .019). The MRI+ group showed significant signs of IF/TA at 1 year. Conclusions Early MRI after kidney transplantation was significantly more likely to develop IF/TA at 1 year and had higher sCr levels at 3 years. In such cases, intervention might preserve graft function over the long term. [ABSTRACT FROM AUTHOR]

We performed inelastic neutron scattering measurements on single crystals of NdFe3(11BO3)4 to explore the magnetic excitations, to establish the underlying Hamiltonian, and to reveal the detailed nature of hybridization between the 4f and 3d magnetism. The observed spectra exhibiting a couple of key features, i.e., anticrossing of Nd and Fe excitations and anisotropy gap at the antiferromagnetic zone center, are explained by the magnetic model including spin interaction in the framework of weakly coupled Fe3+ chains, interaction between the Fe3+ and Nd3+ moments, and single-ion anisotropy derived from the Nd3+ crystal held. The combination of the measurements and calculations reveals that the hybridization between 4f and 3d magnetism propagates the local magnetic anisotropy of the Nd3+ moment to the Fe3+ network, leading to the determination of the bulk structure of both electric polarization and magnetic moment in the multiferroics of the spin-dependent metal-ligand hybridization type. [ABSTRACT FROM AUTHOR]

To elucidate the genotypic and phenotypic characteristics of autosomal dominant polycystic kidney disease ( ADPKD) in Japanese populations, we performed a comprehensive search for mutations in PKD1 and PKD2 in 180 Japanese ADPKD patients from 161 unrelated families. We identified 112 (89 PKD1 and 23 PKD2) mutations within 135 families. Patients with PKD2 mutations account for 23.6% of all Japanese ADPKD families in this study. Seventy-five out of the 112 mutations have not been reported previously. The estimated glomerular filtration rate ( eGFR) decline was significantly faster in patients with PKD1 mutations than in those with PKD2 mutations (−3.25 and −2.08 ml min−1 year−1 for PKD1 and PKD2, respectively, p < 0.01). These results indicate that mutations within PKD1 and PKD2 can be linked to most of the cases of Japanese ADPKD, and the renal function decline was faster in patients with PKD1 mutations than in those with PKD2 mutations also in the Japanese ADPKD. We also found that PKD2 mutations were more frequent in Japanese ADPKD than that in European or American ADPKD. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) have been applied to the treatment of various diseases, and MSC administration in marginal donor grafts may help avoid the ischemia–reperfusion injury associated with solid organ transplants. Given the reports of side effects after intravenous MSC administration, local MSC administration to the target organ might be a better approach. We administered adipose tissue–derived MSCs (AT-MSCs) ex vivo to donor rat kidneys obtained after cardiac death (CD). Methods: Using male Lewis rats (8–10 weeks), and a marginal transplant model of 1hr CD plus 1hr sub-normothermic ET-Kyoto solution preservation were conducted. AT-MSCs obtained from double-reporter (luciferase–LacZ) transgenic Lewis rats were injected either systemically (1.0 × 106 cells/0.5 mL) to bilaterally nephrectomized recipient rats that had received a marginal kidney graft (n = 6), or locally via the renal artery (500 μL ET-Kyoto solution containing the same number of AT-MSCs) to marginal kidney grafts, which were then preserved (1 hour; 22°C) before being transplanted into bilaterally nephrectomized recipient rats (n = 8). Serum was collected to assess the therapeutic effects of AT-MSC administration, and the recipients of rats surviving to Day 14 were separately evaluated histopathologically. Follow-up was by in vivo imaging and histological LacZ staining, and tumor formation was evaluated in MSC-injected rats at 3 months. Results: Systemic injection of MSC did not improve recipient survival. In vivo imaging showed MSCs trapped in the lung that later became undetectable. Ex vivo injection of MSCs did show a benefit without adverse effects. At Day 14 after RTx, 75% of the rats in the AT-MSC–injected group (MSC[+]) had survived, whereas 50% of the rats in the AT-MSC–non-injected group (MSC[−]) had died. Renal function in the MSC(+) group was improved compared with that in the MSC(−) group at Day 4. LacZ staining revealed AT-MSCs attached to the renal tubules at 24 hours after RTx that later became undetectable. Histopathologic examination showed little difference in fibrosis between the groups at Day 14. No teratomas or other abnormalities were seen at 3 months. [ABSTRACT FROM AUTHOR]

Abstract: We describe a method of white-beam inelastic neutron scattering for improved measurement efficiency. The method consists of matrix inversion and selective extraction. The former is to resolve each incident energy component from the white-beam data, and the latter eliminates contamination by elastic components, which produce strong backgrounds that otherwise obfuscate the inelastic scattering components. In this method, the optimal experimental condition to obtain high efficiency will strongly depend on the specific aim of the individual experiments. [Copyright &y& Elsevier]

Abstract: In order to improve the stability of high color-purity red phosphors for ultraviolet excitation, we encapsulated an Eu-chelate, Eu(HFA)3(TPPO)2, by sol–gel derived glass networks and studied its thermal stability as well as photoluminescence (PL) characteristics. The PL quantum yield of an encapsulated sample was 14 times higher than that without encapsulation after annealing at 160°C for 2h in air. Three-dimensional glass networks with a sufficient density were shown to reduce thermal quenching of Eu(HFA)3(TPPO)2. Therefore, it is revealed that the surface coating of luminous chelates by sol–gel glasses is an effective way of inorganic and organic hybridization for high-stability of chelate bonding against free oxygen and water. [Copyright &y& Elsevier]

4SEASONS is designed to utilize the multiple incident energies (MIE) selected by a special Fermi chopper and enhance the measurement efficiency. Chopper opening time determined by a conventional Fermi chopper is inevitably constant, and thus we cannot realize the optimal experimental condition for each incident energy. Therefore, a new concept of Fermi chopper is required for the success of MIE measurement at 4SEASONS. In this paper, we present a new concept of supermirror-coated Fermi chopper (MAGIC chopper) specialized for MIE measurement at 4SEASONS. MAGIC chopper increases the effective opening time at lower incident energies, and consequently the energy dependence of effective opening time gets close to that of moderator pulse width. In addition to the matching of experimental condition, MAGIC chopper also realizes almost constant energy resolution in the wide range of incident energy. [ABSTRACT FROM AUTHOR]

Presents a study which examined the use of genetically modified bone marrow-derived vehicle cells to deliver anti-inflammatory cytokines to inflamed interstitium. Cytokines involved in the development of interstitial injury and fibrosis; Methodology; Results and discussion.

New superionic glasses (CuI) x (AgPO 3 ) 1-x with x =0.1, 0.2 and 0.3 have been prepared by rapid quenching method. Neutron diffraction experiments have been performed by a HIT-II spectrometer at the Neutron Spallation Source, KEK, Japan. A small first diffraction peak at low Q around 0.8 Å was observed in the structure factor for x =0.2 and x =0.3, but for x =0.1 it shows only a shoulder that is similar to the undoped glass AgPO 3 . Three new peaks appear at the radial distribution function of (CuI) x (AgPO 3 ) 1-x at &nvsim; 1.9, 2.7 and 3.4 Å, that may correspond to the Cu-O, Cu-I and Cu-Cu pair correlations, respectively. Those peaks increase with the amount of CuI. These results indicate that there are two different kinds of Cu atoms. Cu-I bond in the glass is very similar to that in crystalline α-CuI, and Cu-O bond is very similar to that in Cu 2 O insulating crystal. [ABSTRACT FROM AUTHOR]

We report on a wide angle neutron spin analyzer for neutron energies up to 40 meV (λ = 1.4 Å) that was recently realized in collaboration with Tohoku University and KEK, Japan (Ohoyama et al., 2014; Yokoo et al., 2014). Curved polarizing Fe/Si supermirrors with m = 5.5/1.5 (Schanzer et al., 2016) are arranged radially around the sample covering an angular range of 40° if all channels are equipped with supermirrors. The mirrors are saturated by a vertical permanent magnetic field B ≃ 40 mT generated by NdFeB magnets. It was optimized using finite element analysis. The polarization and transmission of the spin filter have been determined at the beamline BOA at the Swiss spallation neutron source (SINQ) to be P = (0. 975 ± 0. 01) and T u p = T = (0. 55 ± 0. 017) for spin-up neutrons at λ = 3 Å (E = 9 meV), respectively. The transmission is excellent considering that approximately one third of the neutrons hit the front faces of the polarizing blades. The experimental results are in good agreement with Monte Carlo simulations using the software package McStas. [ABSTRACT FROM AUTHOR]

Abstract: Multi-grid-type microstrip gas chambers (M-MSGCs) are being developed for the next-generation pulsed neutron source. Two new concepts, a global–local-grouping (GLG) method and a graded cathode pattern readout method, were applied to the M-MSGC design for realizing higher counting rate than traditional 3He proportional counters. One-dimensional detectors with 700mm-long test plates were fabricated and tested with X-ray and neutron beams, which demonstrated position detection capability based on these concepts. [Copyright &y& Elsevier]

Examines the role of osteopontin (OPN) expression in proximal tubular cells in the long-term prognosis of IgA nephropathy. Study method; Analysis of incidence of end-stage renal disease (ESRD); Association of the OPN expression in proximal tubular cells with progression.