Pigs with severe combined immunodeficiency (SCID) may provide useful models for regenerative medicine, xenotransplantation, and tumor development and will aid in developing therapies for human SCID ...patients. Using a reporter-guided transcription activator-like effector nuclease (TALEN) system, we generated targeted modifications of recombination activating gene (RAG) 2 in somatic cells at high efficiency, including some that affected both alleles. Somatic-cell nuclear transfer performed with the mutated cells produced pigs with RAG2 mutations without integrated exogenous DNA. Biallelically modified pigs either lacked a thymus or had one that was underdeveloped. Their splenic white pulp lacked B and T cells. Under a conventional housing environment, the biallelic RAG2 mutants manifested a “failure to thrive” phenotype, with signs of inflammation and apoptosis in the spleen compared with age-matched wild-type animals by the time they were 4 wk of age. Pigs raised in a clean environment were healthier and, following injection of human induced pluripotent stem cells (iPSCs), quickly developed mature teratomas representing all three germ layers. The pigs also tolerated grafts of allogeneic porcine trophoblast stem cells. These SCID pigs should have a variety of uses in transplantation biology.
Platinum monolayer electrocatalyst are known to exhibit excellent oxygen reduction reaction (ORR) activity depending on the type of substrate used. Here we demonstrate a relationship between the ORR ...electrocatalytic activity and the surface electronic structure of Pt monolayer shell induced by various IrM bimetallic cores (M=Fe, Co, Ni or Cu). The relationship is rationalized by comparing density functional theory calculations and experimental results. For an efficient Pt monolayer electrocatalyst, the core should induce sufficient contraction to the Pt shell leading to a downshift of the d-band center with respect to the Fermi level. Depending on the structure of the IrM, relative to that of pure Ir, this interaction not only alters the electronic and geometric structure but also induces segregation effects. Combined these effects significantly enhance the ORR activities of the Pt monolayer shell on bimetallic Ir cores electrocatalysts.
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•Core-shell structured IrM nanoparticles are better substrates than alloyed counterparts for Pt monolayer electrocatalyst.•Geometric, electronic, and segregation effects together are crucial to understand the increase in ORR activity.•DFT calculations demonstrate a volcano type behavior with PtMLIrNi/C at the top of the curve.
Kawasaki disease (KD) is an acute febrile vasculitis that causes coronary artery abnormality (CAA) as a complication. In some patients, an association has been noted between elevated liver enzymes or ...an abnormal gallbladder (GB) and hepatobiliary involvement in KD. In this study, we aimed to evaluate clinical, laboratory, and ultrasonographic (USG) risk factors of hepatobiliary involvement for the intravenous immunoglobulin (IVIG) resistance and the development of CAA in children with KD.
From March 2004 through January 2013, clinical features, laboratory data, echocardiographic findings, and USG findings were retrospectively reviewed regarding the response to IVIG treatment and coronary artery complications in 67 children with KD. Acute acalculous cholecystitis (AAC) was diagnosed based on USG criteria.
Among all factors, only the prothrombin time international normalized ratio was significantly different between the IVIG-response and IVIG-resistance groups (p = 0.024). CAA was statistically more frequent in the AAC group (n = 24) than in the non-AAC group (n = 43) (23.3% vs. 58.3%, p = 0.019). Among the laboratory factors, segmented neutrophil percentage, total bilirubin level, and C-reactive protein were significant in children with CAA (p = 0.014, p = 0.009, and p = 0.010). Abnormal GB findings on USG were significantly more frequent in children with CAA than in those without CAA (p = 0.007; OR = 4.620; 95% confidence interval CI: 1.574-13.558). GB distension on USG was the only significant risk factor for CAA (p = 0.001; OR = 7.288; 95% CI: 2.243-23.681) by using multiple logistic regression analysis.
For children in the acute phase of KD, USG findings of the GB, especially GB distension, may be an important risk factor for CAA as a complication.
Objective The purpose of this study was to identify perioperative risk factors for postoperative acute kidney injury (AKI) in patients undergoing esophageal cancer surgery. Design A retrospective ...analysis of the prospectively collected medical data. Setting A tertiary care university hospital. Participants All consecutive adult patients (n = 595) who underwent elective esophageal surgery for cancer between January 2005 and April 2012. Interventions None. Measurements and Main Results AKI was defined by the AKI Network criteria based on serum creatinine changes within the first 48 hours after esophageal cancer surgery. The relationship between perioperative variables and AKI was evaluated using multivariate logistic regression. Postoperative AKI developed in 210 (35.3%) patients. Risk factors for AKI were body mass index (odds ratio OR 1.07; 95% confidence interval CI 1.01-1.14), preoperative serum albumin level (OR 0.52; 95% CI 0.33-0.84), use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (OR 1.35; 95% CI 1.05-1.75), colloid infusion during surgery (OR 1.11; 95% CI 1.06-1.18), and postoperative 2-day C-reactive protein (OR 1.05; 95% CI 1.01-1.09). Postoperative AKI was associated with prolonged length of hospital stay. Conclusions Postoperative AKI is common in patients undergoing esophageal surgery for cancer. Closer evaluation and monitoring in patients with risk factors for AKI may be warranted.
Reactive oxygen species (ROS) are implicated in reperfusion injury after transient focal cerebral ischemia. The antioxidant enzyme Cu,Zn-superoxide dismutase (SOD) is one of the major means by which ...cells counteract the deleterious effects of ROS after ischemia. Recently, we reported that denatured Tat-SOD fusion protein is transduced into cells and skin tissue. Moreover, PEP-1 peptide, which has 21 amino acid residues, is a known carrier peptide that delivers full-length native proteins in vitro and in vivo. In the present study, we investigated the protective effects of PEP-1-SOD fusion protein after ischemic insult. A human SOD gene was fused with PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame PEP-1-SOD fusion protein. The expressed and purified fusion proteins were efficiently transduced both in vitro and in vivo with a native protein structure. Immunohistochemical analysis revealed that PEP-1-SOD injected intraperitoneally (i.p.) into mice can have access into brain neurons. When i.p.-injected into gerbils, PEP-1-SOD fusion proteins prevented neuronal cell death in the hippocampus caused by transient forebrain ischemia. These results suggest that the biologically active intact forms of PEP-1-SOD provide a more efficient strategy for therapeutic delivery in various human diseases related to this antioxidant enzyme or to ROS, including stroke.
Background Melanoma of unknown primary (MUP) is a condition of metastatic melanoma without a primary lesion. Objective We sought to identify the prognosis of MUP compared with melanoma of known ...primary (MKP). Methods We searched for observational studies containing at least 10 patients with MUP from MEDLINE and EMBASE from inception to December 22, 2012. The outcomes of interest were overall and disease-free survival; meta-analyses of hazard ratio stratified by stage using a random effects model were performed. In addition, second systematic review identified risk factors influencing the survival of patients with MUP. Results Eighteen studies including 2084 patients with MUP and 5894 with MKP were included. MUP had a better overall survival compared with MKP in stage III (15 studies; hazard ratio 0.83, 95% confidence interval 0.73-0.96, P = .010) and stage IV (6 studies; hazard ratio 0.85, 95% confidence interval 0.75-0.96, P = .008). Secondly, 22 studies including 3312 patients with MUP were reviewed, and increased stage and old age were the risk factors in patients with MUP. Limitations Diverse observational studies were reviewed, and selection and reporting biases are possible. Conclusions The current meta-analyses suggest better survival outcomes in patients with MUP than those in patients with MKP with the same corresponding tumor stage.
Corrugated organic light emitting diodes are fabricated on photonic crystal substrates patterned using UV nanoimprint lithography process at room-temperature and low-pressure. Forty-nine percentage ...enhancement of light extraction was achieved even with the very low corrugation depth of 50
nm. The power efficiency of the corrugated OLEDs was even further improved by 93% compared to the OLED with a planar structure. Finite difference time domain (FDTD) analyses indicated that the Bragg-reflection by the corrugated metallic mirror plays dominant role in the enhancement of extraction efficiency in the corrugated structure and extraction efficiency can be further improved if corrugation depth is increased to 100
nm.
Photoanodes used in a water-splitting photoelectrochemical cell are almost always paired with an oxygen evolution catalyst (OEC) to efficiently utilize photon-generated holes for water oxidation ...because the surfaces of photoanodes are typically not catalytic for the water oxidation reaction. Suppressing electron–hole recombination at the photoanode/OEC interface is critical for the OEC to maximally utilize the holes reaching the interface for water oxidation. In order to explicitly demonstrate and investigate how the detailed features of the photoanode/OEC interface affect interfacial charge transfer and photocurrent generation for water oxidation, we prepared two BiVO4(010)/FeOOH photoanodes with different Bi:V ratios at the outermost layer of the BiVO4 interface (close to stoichiometric vs Bi-rich) while keeping all other factors in the bulk BiVO4 and FeOOH layers identical. The resulting two photoanodes show striking differences in the photocurrent onset potential and photocurrent density for water oxidation. The ambient pressure X-ray photoelectron spectroscopy results show that these two BiVO4(010)/FeOOH photoanodes show drastically different Fe2+:Fe3+ ratios in FeOOH both in the dark and under illumination with water, demonstrating the immense impact of the interfacial composition and structure on interfacial charge transfer. Using computational studies, we reveal the effect of the surface Bi:V ratio on the hydration of the BiVO4 surface and bonding with the FeOOH layer, which in turn affect the band alignments between BiVO4 and FeOOH. These results explain the atomic origin of the experimentally observed differences in electron and hole transfer and solar water oxidation performance of the two photoanodes having different interfacial compositions.
Abstract A microneedle patch coated with vaccine simplifies vaccination by using a patch-based delivery method and targets vaccination to the skin for superior immunogenicity compared to ...intramuscular injection. Previous studies of microneedles have demonstrated effective vaccination using freshly prepared microneedles, but the issue of long-term vaccine stability has received only limited attention. Here, we studied the long-term stability of microneedles coated with whole inactivated influenza vaccine guided by the hypothesis that crystallization and phase separation of the microneedle coating matrix damages influenza vaccine coated onto microneedles. In vitro studies showed that the vaccine lost stability as measured by hemagglutination activity in proportion to the degree of coating matrix crystallization and phase separation. Transmission electron microscopy similarly showed damaged morphology of the inactivated virus vaccine associated with crystallization. In vivo assessment of immune response and protective efficacy in mice further showed reduced vaccine immunogenicity after influenza vaccination using microneedles with crystallized or phase-separated coatings. This work shows that crystallization and phase separation of the dried coating matrix are important factors affecting long-term stability of influenza vaccine-coated microneedles.
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