Search

DNA methyltransferases and TET enzymes dynamically regulate the DNA methylation-demethylation cycles during mouse embryonic development. DNMT1 maintains cell-specific DNA methylation after DNA replication. However, little is known about the physiological significance of the de novo methylation enzymatic potential of DNMT1, which has attracted much attention. Here, we show that the full-length DNMT1 and a mutant form without the N-terminal necessary for its maintenance activity potentially inhibit the differentiation of mouse pluripotent embryonic stem cells lacking Dnmt1, 3a and 3b into primitive endoderm cells. However, the mutant cells could differentiate into epiblast-like cells and beyond, leading to cell-autonomous mesendoderm differentiation. Strikingly, we found that in response to Nodal signalling and the increased concurrent access of DNMT1 and TET enzymes resulting from chromatin relaxation activated primordial germ cell-specific genes. With the precise target selectivity by its N-terminal region, DNMT1 may be involved in gene regulation leading to germline development.

OBJECTIVES This study aimed to evaluate the efficacy and safety of intraoperative cone-beam computed tomography-guided video-assisted thoracoscopic surgery wedge resection of impalpable small pulmonary nodules. METHODS This was a single-centre phase 2 trial conducted between April 2018 and March 2019. Peripheral small pulmonary nodules, defined as either ground-glass opacity-dominant (>50%) nodules measuring ≤3 cm in diameter (ground-glass opacity-dominant type) or nodules measuring ≤2 cm in diameter located deeper than the nodule diameter from the visceral pleura (deep solid type), were eligible for resection using a cone-beam computed tomography-guided thoracoscopic manner. The primary end-point was macroscopic complete resection, and secondary end-points were: nodule extraction rate, operation time, localization time, marking accuracy, microscopic complete resection and safety. RESULTS Twenty-two nodules, in 9 men and 11 women with a mean age of 64.3 years, were visualized and resected. The nodules were located in the right upper, middle and lower lobes in 3, 1 and 5 patients, respectively, and in the left upper and lower lobes in 5 and 8 patients, respectively. Seven nodules were ground-glass opacity-dominant types, and 15 were deep solid types. Cone-beam computed tomography could clearly image all nodules. The mean time for localization was 17.4 min. The mean operation time was 110.7 min. Macroscopic complete resection was accomplished in 21 nodules (95.5%). Microscopic complete resection was achieved in all nodules (100%). Postoperative air leakage and bleeding were observed in 1 patient (5%). CONCLUSIONS Cone-beam computed tomography might be a safe and useful guide for video-assisted thoracoscopic surgery wedge resection of impalpable peripheral pulmonary nodules. Date and number of IRB approval 15 November 2017, 381. Clinical trial registration number UMIN 000030388.

Background DNA methylation is a significant epigenetic modification that is evolutionarily conserved in various species and often serves as a repressive mark for transcription. DNA methylation levels and patterns are regulated by a balance of opposing enzyme functions, DNA methyltransferases, DNMT1/3A/3B and methylcytosine dioxygenases, TET1/2/3. In mice, the TET enzyme converts DNA cytosine methylation (5mC) to 5-hydroxymethylcytosine (5hmC) at the beginning of fertilisation and gastrulation and initiates a global loss of 5mC, while the 5mC level is increased on the onset of cell differentiation during early embryonic development. Objective Global loss and gain of DNA methylation may be differently regulated in diverged species. Methods Chicken B-cell lymphoma DT40 cells were used as an avian model to compare differences in the overall regulation of DNA modification with mammals. Results We found that DNA methylation is maintained at high levels in DT40 cells through compact chromatin formation, which inhibits TET-mediated demethylation. Human and mouse chromosomes introduced into DT40 cells by cell fusion lost the majority of 5mC, except for human subtelomeric repeats. Conclusion Our attempt to elucidate the differences in the epigenetic regulatory mechanisms between birds and mammals explored the evidence that they share a common chromatin-based regulation of TET–DNA access, while chicken DNMT1 is involved in different target sequence recognition systems, suggesting that factors inducing DNMT–DNA association have already diverged.

Objective:Evaluating the rate of decline in the estimated glomerular filtration rate (eGFR) may help identify patients with occult chronic kidney disease (CKD). We herein report that eGFR fluctuation complicates the assessment of the rate of decline and propose a long-term eGFR plot analysis as a solution., Methods:In 142 patients with persistent eGFR decline in a single hospital, we evaluated the factors influencing the rate of eGFR decline, calculated over the long term (≥3 years) and short term (, Results:The difference between the rate of eGFR decline calculated using short- and long-term plots increased as the time period considered in the short-term plots became shorter. A regression analysis revealed that eGFR fluctuation was the only factor that explained the difference and that the fluctuation exceeded the annual eGFR decline in all participants. Furthermore, the larger the eGFR fluctuation, the more difficult it became to detect eGFR decline using a short-term eGFR analysis. Obesity, a high eGFR at baseline, and faster eGFR decline were associated with larger eGFR fluctuations. To circumvent the issue of eGFR fluctuation in the assessment of the rate of eGFR decline, we developed a system that generates a long-term eGFR plot using all eGFR values for a participant, which enabled the detection of occult CKD, facilitating early therapeutic intervention., Conclusion:The construction of long-term eGFR plots is useful for identifying patients with progressive eGFR decline, as it minimizes the effect of eGFR fluctuation.

Background Regulatory T (Treg) cells play an essential role in peripheral immune tolerance. Bullous pemphigoid (BP) is the most common blistering disease and is caused by autoantibodies to two BP antigens: type XVII collagen and BP230. Recently, we reported that Treg cell dysfunction may cause the production of autoantibodies to BP antigens. Several studies have suggested an association between Treg cells and BP pathogenesis. However, Treg cells are heterogeneous in humans, leading to inconsistent results in previous studies. Objective To assess functional Treg subsets in BP. Methods We examined three distinct Treg subsets in conventional BP (cBP) patients before versus after systemic corticosteroid treatment, dipeptidyl peptidase-4 inhibitor-associated BP (DPP-4i-BP) patients, younger controls and older controls. Results We found that total Treg cells and all Treg cell subsets were increased in cBP patients before treatment and decreased by systemic corticosteroid treatment. In contrast, neither total Treg cells nor all Treg subsets were increased in DPP-4i-BP. Notably, CD45RA− Foxp3hi effector Treg cells positively correlated with disease severity in cBP, whereas CD45RA+Foxp3lo naive Treg cells positively correlated with the disease severity in DPP-4i-BP. Conclusion These findings suggest that Treg cells are differently involved in the pathogeneses of cBP and DPP-4i-BP.

Lung transplantation has become popular in Japan, showing better survival rate than other countries. However, the results are still not satisfactory compared with other solid organ transplantation. One of the reasons for this might be that knowledge on donor-specific antibodies or antibody-related rejection, which has been attracting attention these days, is less than that of kidney or liver transplantation. Our laboratory has continued basic research in this field using rodent lung transplantation model. We have previously shown that type V collagen is associated in chronic rejection as an autoimmune, and that oral administration of type V collagen induces tolerance. The murine chronic rejection model of the minor antigen mismatch was developed, and involvement of the humoral immunity and role of the complement activation were shown. We are now studying the effects of immune checkpoint molecules, which play a central role in the field of cancer therapy, on rejection after lung transplantation. We are also working to verify the effects of anti-complement drugs and molecular targeted drugs in the future treatment on rejection.

Background A pulmonary arteriovenous malformation is an abnormal dilated blood vessel that makes direct communication between a pulmonary artery and pulmonary vein and can be associated with hypoxemia or neurological complications, including brain abscess and cerebral infarction. Treatment of pulmonary arteriovenous malformation includes surgical resection and transcatheter embolotherapy, however the adaptation of therapies should be considered when a patient is in bad condition. Case presentation A 51-year-old man was admitted after developing fever, consciousness disorder, and hypoxemia. Magnetic resonance imaging of the brain showed a brain abscess. Bilateral pulmonary arteriovenous malformations were found by contrast computed tomography. Because of a family history of pulmonary arteriovenous malformation, a history of epistaxis, and the existence of oral mucosa telangiectasia, he was diagnosed with hereditary hemorrhagic telangiectasia and brain abscess caused by intrapulmonary right-to-left shunt. The brain abscess improved with antibiotic treatment; however, the administration of oxygen did not ameliorate his hypoxemia. His hypoxemia was exacerbated by positive pressure ventilation. Considering his systemic and respiratory condition, we considered surgery to involve a high degree of risk. After controlling his brain abscess and pneumonia, transcatheter embolotherapy was performed. This improved his systemic condition, enabling surgical treatment. Conclusions This middle-aged patient suffering from brain abscess and severe hypoxemia with multiple pulmonary arteriovenous malformations was successfully treated by a combination of transcatheter embolotherapy and surgery. The adaptation and combination of therapies, as well as the sequence of treatments, should be considered depending on the patient status and lesions.

Diabetes is associated with mortality and severity of coronavirus disease (COVID-19). Protecting against infection in health care workers at high risk of COVID-19 is critical. This report investigates the usefulness and safety of remote continuous glucose monitoring (CGM) in a patient with diabetes and severe interstitial pneumonia caused by the coronavirus disease. The Dexcom G4 Platinum CGM system® was used to monitor blood glucose (BG) levels from outside the patient's isolation room. Continuous insulin infusion rates and boluses were determined based on the patient's BG levels. Real-time CGM made it possible to track BG trends and prevent dramatic variations in BG, although the rate of insulin infusion changed dynamic. Furthermore, the need for health care workers to enter the isolation room was minimized because the Dexcom G4 Platinum CGM system can evaluate from a distance of up to 6.0 m.

The coronavirus disease of 2019 (COVID-19), which began in Wuhan, China, at the end of 2019, is spreading around the world and causing many deaths, mainly from pneumonia. Currently, there are no specific drugs to treat COVID-19, and existing antiviral drugs are being used as an alternative. One of these is favipiravir, a new type of influenza drug. However, its efficacy, dosage, and duration of administration are still under study. In this case study, we administered favipiravir to patients with COVID-19 and determined the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 pathogen, using semi-quantitative real-time reverse transcription PCR in sputum samples. We report on two patients in whom the viral load increased again after completion of 10 days of favipiravir treatment and a transient relapse of symptoms was observed.

DNA methylation is an essential epigenetic mark that regulates normal mammalian embryonic development. DNA methylation profiles are not always static, especially during germline development. In zygotes, DNA is typically highly methylated but, during preimplantation, DNA methylation is erased globally. Then, at the start of post-implantation development in mouse embryos, DNA again becomes dramatically hypermethylated. Chromatin structure regulates the accessibility of DNA-modifying enzymes to target DNA. Beyond that, however, our understanding of the pathway by which chromatin regulation initiates changes in global DNA methylation during mouse embryonic development remains incomplete. To analyse the relationship between global regulation of DNA methylation and chromatin status, we examined 5-methylcytosine (5mC), modified by the DNA methyltransferase DNMT, and the oxidative derivative 5-hydroxymethylation (5hmC), converted from 5mC by TET-family enzymes, by means of immunofluorescence staining of mitotic chromosomes in mouse embryonic stem cells (ESCs). Our comparison of immunostaining patterns for those epigenetic modifications in wild-type, DNMT-deficient, and TET-deficient ESCs allowed us to visualise cell cycle-mediated DNA methylation changes, especially in euchromatic regions. Our findings suggest that DNA methylation patterns in undifferentiated mouse ESCs are stochastically balanced by the opposing effects of two activities: demethylation by TET and subsequent remethylation by DNMT.

The aim of this study was to evaluate the ability of fluorine-18-fluorodeoxyglucose positron emission tomography coupled with computed tomography (18F-FDG-PET/CT) to predict the WHO malignancy grade, initial staging, and invasive potential of thymic epithelial tumors. We retrospectively reviewed the medical records of 56 patients with thymic epithelial tumors who were evaluated by PET/CT before surgery and underwent surgical resection. We analyzed the relationship of the maximum standardized uptake value (SUVmax) with the WHO histological classification, tumor invasion, TNM classification, and the Masaoka–Koga classification. There were differences of SUVmax of the FDG-PET between thymic carcinoma (9.09 ± 3.34) and thymoma (4.86 ± 2.45; p

In order to predict ash deposition in a pulverized coal combustion process, the fragmentation, detachment, and coalescence behavior of ash particles in coal were quantitatively evaluated to distinguish between excluded and included minerals. The experiments for simulated EM heating and simulated coal combustion were carried out in a drop tube furnace. Change in the numbers of EM and IM particles were measured at different residence times by scanning a sampling probe along the flow direction in the reactor tube. The rate constants of EM fragmentation were estimated from the simulated EM heating experiment. The solution to a system of differential equations that includes the effects of fragmentation, detachment, and coalescence as functions for the numbers of EM and IM was obtained as a kinetic model. These functions were fitted to the experimental results for simulated coal combustion experiment to obtain the rate constants for detachment and coalescence. This method was also applied to previous experimental results using three actual coal samples. The rate constants of detachment and coalescence were mainly affected by char structure during coal combustion.

Although compensatory lung growth (CLG) after lung resection has been reported in various mammalian species, it has generally been thought that the lung cannot regenerate in adult humans. We recently developed a method for evaluating lung weight using a radiologic analysis and demonstrated that the lung was heavier than expected in adult humans after pulmonary resection. In this study, we serially evaluated the morphologic, radiologic, and genomic status during CLG in pneumonectomized mice.The serial changes in morphology and gene expression of the remnant right lung after left pneumonectomy were examined in adult male mice. The alveolar density was determined by the mean linear intercept, and the weight was estimated using the Hounsfield value and volumetric data from micro-computed tomography. The parameters were obtained on days 3, 7, and 30 after left pneumonectomy or thoracotomy only (sham control).After left pneumonectomy, the right lung became significantly progressively larger in volume and weight on postoperative days 3, 7, and 30 in comparison to the sham controls (P 0.01). The estimated weight also significantly increased in association with the real volume on postoperative days 3, 7, and 30 (P 0.01). The cardiac lobe markedly increased in size. During the observation period, the alveolar density was always lower in the pneumonectomized mice than in controls. A microarray analysis revealed that multiple genes related to proliferation (but not specific alveolar development) were initially upregulated until postoperative day 7 and then returned to normal after 1 mo. The morphologic and genomic changes were more evident in the cardiac lobe than in the upper lobe during the observation period.The morphologic, radiologic, and genomic changes during CLG were related to each other in pneumonectomized mice. The present study revealed an association between the radiologically estimated weight and other parameters, indicating a marked CLG reaction of the cardiac lobe.

This is erythema gyratum repens in a man in his 70s with myelodysplastic syndrome (fig1). He presented with persistent, pruritic, generalised erythroderma on the trunk and extremities of …

To predict the spontaneous heating of coal pile by computational fluid dynamics (CFD) is very meaningful for preventing the coal pile from self-ignition. A two-dimensional (2-D) numerical model, which could be simply implemented in FLUENT, was developed in this study. The chemical kinetic parameters of low-temperature oxidation of coal, which were expressed by the outer surface area of particles, were well measured in experiments. The coal piles under different conditions were calculated by using the developed model and measured kinetic parameters, in order to make clear the effects of some important factors. The simulation results indicated the evaporation of moisture from coal played a critical role. The pile height, coal type, wind velocity, and heat loss from bottom have significant effects on the process of spontaneous heating of coal pile. According to these effects, in order to increase the heat loss of pile and then effectively inhibit the self-ignition, the low pile height, good ventilation surrounding the pile, and ground material with high thermal conductivity below the pile should be used. The model developed in this model is expected to become a reliable tool to predict the spontaneous heating of coal pile.

Certain simplified submodels of coal combustion, whose precision can be inadequate for certain situations, are widely used in computational fluid dynamics (CFD) simulations of a pulverized-coal-fired furnace. A large-scale furnace was simulated to explore the effects of certain advanced submodels. Comparing the simulation results in four cases to different submodels shows that the ignitability of burners is closely linked to the amount of H2 generated. In the baseline case, which disregards H2, we obtained very poor ignitability for all burners. Using a four-step mechanism instead of a two-step mechanism for volatile combustion and considering the char gasification (C–H2O) and detailed composition of volatiles are all clearly likely to improve ignitability. Meanwhile, superior ignitability also increases the heat absorbed by walls, reduces gas temperatures at the furnace exit, and reduces CO in the furnace. CO can also be increased by accounting for char gasification (C–CO2) and the detailed composition o...

NH3 co-firing in a commercial 1000 MWe pulverized coal-fired boiler has been considered for reducing CO2 emissions. However, the abundance of fuel-N in NH3 co-firing may cause an increase in NO emissions. The effects of the NH3 co-firing ratio on NO emissions in a commercial boiler are studied through a zero-dimensional numerical calculation with detailed chemistry. A simplified boiler system is composed of a burner zone, an over-fire zone, and two downstream zones. A network of perfectly stirred reactors is used to determine NO emissions in flue gas. The NH3 co-firing ratio is varied from 0 to 80%. NH3 is injected into the flame zone, which is part of the burner zone. As a result of calculation, amount of CO2 emission decreases as an increase in the NH3 co-firing ratio. Since the location where NH3 reacts shifts to the downstream side with an increase in the co-firing ratio, the peak of NO also tends to transfer to the downstream side. Nevertheless, NH3 is almost completely dissociated in the burner zone and unburned NH3 emissions are approximately zero independent of the co-firing ratio. Within the range of 20–60%, NO emissions increase monotonically with the co-firing ratio. However, at 80% co-firing, the NO emission decreases from the value attained at 60% co-firing. With a co-firing ratio higher than 40%, reactions of rich NH3 chemistry, which are characteristic in rich and low-temperature NH3 flame become effective. Due to these reactions, fuel(NH3)–NO production tends to decrease in the location where NH3 reacts.

Background Obliterative bronchiolitis (OB) is a known issue during minor histocompatibility antigen (mHA) disparity during lung transplantation. This study evaluated gene expression in a murine orthotropic lung transplantation model using microarray analysis. Methods Left lungs from C57BL/10(H-2b) donor mice were transplanted into mHA-mismatched C57BL/6(H-2b) recipient mice. Three groups (OB, non-OB, and sham controls) were confirmed pathologically and analyzed. Gene expression changes in the lung grafts were determined by microarray and immunohistochemical staining, and genes were verified by quantitative PCR in the lungs and mediastinal lymph nodes (LNs). Results A total of 1343 genes were upregulated in the OB lungs compared to the sham group. Significant upregulation was observed for genes related to innate, e.g. Tlr2 and CCL3 and adaptive immunity, e.g. H2-ab1 and Il-21. Positive labeling for MHC class II antigen was observed in the bronchial epithelium of OB accompanied with B cells. We found increased Tlr2, Ccl3, H2-ab1, Il-21, Ighg3, Ifng, and Pdcd1 mRNA expression in the OB lung, and increased Il-21, Ighg3, and Pdcd1 expression in the OB LNs. Conclusions Adaptive and innate immune reactions were involved in OB after lung transplantation, and genetic examination of related genes could be used for detection of OB.

Recently, the co-firing ammonia (NH3) with coal in boiler has been paid more and more attention. A computational Fluid Dynamics (CFD) simulation approach was built to investigate the NH3 co-firing in a pulverized coal combustion facility with a single swirling burner. The simulation accuracy was evaluated with the experimental data. The differences between coal firing and NH3 co-firing can be well reproduced with simulation. Then, the effects of NH3 co-firing ratio (CR) on the combustion characteristic and NOx emission were investigated. The flame shape is significantly affected by NH3 CR, due to the changes of momentum of NH3 jet from center of burner. When the NH3 CR exceeds 40 cal.%, the internal recirculation zone is completely penetrated by high velocity NH3 flow, which leads to a long flame and much unreacted NH3 in downstream. As the increase of NH3 CR, the overall trend is that the total heat absorbed slightly decreases due to the decrease of particle radiation, and unburnt carbon in fly ash obviously increases due to decrease of flame temperature. In the case with NH3 CR of 10 cal.%, the NO concentration at exit increases due to the more intense combustion and more fuel-NOx, compared with the case of coal-firing. When the NH3 co-firing ratio exceeds 10 cal.%, the NO concentration at exit decreases monotonously due to the DeNOx effect of unreacted NH3. However, once the NH3 co-firing ratio exceeds 40 cal.%, the unreacted NH3 concentration at exit increases rapidly, which requires careful designs of burner and furnace.

Effects of ammonia (NH3) co-firing on NO emissions in a coal-fired boiler are investigated by zero-dimensional calculation with detailed chemistry. A commercial 1000 MWe boiler system is simplified and expressed as a network of Perfectly Stirred Reactors (PSRs) to calculate emissions in flue gas. The reactor network is composed of burner zone, over-fire zone, and downstream zones. As a result of varied injection positions of NH3, lower NO emission than the coal-fired case was obtained by NH3 injection into flame zone in burner zone. As a result of analysis, NH3 injection causes NH3-rich condition and decrease of temperature in flame zone. Amount of yield of NO including thermal-NO could become relatively less. In addition, since original temperature in flame zone is higher than 2000 K, supplied NH3 is immediately dissociated and converted into NO prior to char oxidation. Since there exists abundance of NO derived from supplied NH3 and more amount of left char, effect of reduction of NO by char becomes greater than the case of coal firing. Supplied NH3 is almost completely consumed, so that it was suggested that decreasing both CO2 and NO emissions in coal-fired boilers could be realized by the NH3 co-firing in a safe way.

Background Bullous pemphigoid (BP) is the most common autoimmune blistering disease. BP180 is the primary autoantigen of BP, and in a portion of BP cases, BP230 is the only target of autoantibodies. Such BP is called BP230-type BP. BP230-type BP tends to show milder clinical phenotypes than conventional BP, but the reason is unclear. The pathogenic roles of autoantibodies and complement activation have been shown in conventional BP, but the distribution of IgG subclasses and the degree of complement deposition in BP230-type BP remain unclear. Objective To compare the distribution of IgG subclasses and the degree of complement deposition in BP230-type BP with those in conventional BP with autoantibodies to BP180 and BP230 (BP180-BP230-type BP). Methods The diagnosis of BP was confirmed by the histopathology of the lesions, the deposition of IgG and complement in the perilesional skin and the presence of circulating autoantibodies to BP180 and BP230. The disease severity was determined by bullous pemphigoid disease area index. The deposition of IgG subclasses and complement deposition were examined by direct immunofluorescence of the perilesional skin in 6 BP230-type BP cases and 11 BP180-BP230-type BP cases. Results Sixty seven percent of BP230-type BP cases show a mild clinical phenotype. All BP230-type BP cases and 82% of BP180-BP230-type BP cases were found to demonstrate the clear deposition of IgG4 at the basement membrane zone of skin specimens. Notably, the deposition of IgG1 and IgG3 was faint or negative in all of the BP230-type BP cases, whereas they were clearly detected in 91% and 64% of the BP180-BP230-type BP cases, respectively. The deposition of complement C3 tended to be weaker in BP230-type BP than in BP180-BP230-type BP. Conclusion The mild clinical phenotype of BP230-type BP may correlate with the weaker deposition of IgG1, IgG3 and complement in the skin lesions.

Punctate palmoplantar keratoderma type 1 (PPKP1) is a rare autosomal dominant disorder of keratinization, clinically characterized by punctate keratotic papules affecting the palmoplantar skin. Loss-of-function mutations in AAGAB have recently been reported as a cause of PPKP1. Despite the discovery of the genetic cause of PPKP1, pathogenesis-based therapies are still unavailable. Moreover, little is known about the effectiveness of treatments for PPKP1. In this study, we analyzed a Japanese woman with PPKP1 and identified a novel frame-shift mutation c.195_198del4 (p.Lys66Phefs*43) in AAGAB. Moreover, low-dose etretinate was effective in improving the PPKP1 lesions in our patient. Our published work review identified only eight cases of PPKP1 with successful response to topical or systemic treatments. Notably, six of the cases were successfully treated with systemic retinoids. Thus, this study clearly provides further evidence that PPKP1 is caused by AAGAB mutations and that systemic retinoids are the most promising current treatment for PPKP1.

Computational fluid dynamics (CFD) simulations of the oxy-coal combustion in a large-scale furnace were performed by applying different weighted sum of gray-gases models (WSGGMs). Before simulation of the furnace, the different WSGGMs were tested in an enclosed rectangular box containing only gases inside. In both cases of air and oxy-fuel combustion, the calculated radiative sources and wall heat fluxes obtained with gray and non-gray WSGGMs were completely different. Only with the non-gray WSGGMs (i.e., non-gray implementation), the calculated results could well agree with the benchmark data. In the simulation of furnace, three WSGGMs were adopted: Smith’s gray WSGGM (i.e., gray implementation), Johansson’s non-gray-A WSGGM with uniform distribution of radiative energy of particles in each gray band, and Johansson’s non-gray-B WSGGM, in which the radiative energy of particles was distributed using weighting factors. The weighting factors for the particles can be calculated with the same function as that used for gas but using the particle temperature instead of gas temperature, i.e., wp,i = wg,i (Tp). Being different from the rectangular box without particle radiation, in the real furnace, the gas temperature and wall heat flux calculated by gray and non-gray-A WSGGMs almost show no obvious difference. This is attributed to the fact that particle radiation plays a more significant role than gas radiation in the real furnace. However, using the non-gray-B model instead of Smith’s gray model or non-gray-A model can obviously influence the distribution of wall heat flux and total amount of heat absorbed by the walls. This indicates that in the numerical simulation of oxy-fuel combustion, the non-gray WSGGMs should be used by combining with the weighting factors of wp,i = wg,i (Tp) for particles, in order to rigorously describe both the gas and particle radiation during oxy-fuel combustion of coal in real furnace.

Background Regulatory T (Treg) cells play a crucial role in peripheral immune tolerance in multiple organs, including the skin. Thus far, the effect of peripheral immune tolerance failure on autoantibody-related autoimmune reactions to the skin is unclear. Objective We sought to elucidate the target autoantigens in the skin under the condition of Treg cell dysfunction caused by forkhead box P3 (Foxp3) gene mutations in scurfy mice and patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Methods Sera and skin from scurfy mice and sera from patients with IPEX syndrome were analyzed to detect target autoantigens by using immunofluorescence studies, ELISAs, and immunoblotting. The pathogenicity of scurfy IgG was examined by using a passive transfer experiment. CD4+ T cells from scurfy mice were transferred to immunodeficient mice to examine their pathogenicity. Signal transducer and activator of transcription 6 (Stat6)−/− scurfy mice were analyzed to further clarify the molecular pathway of autoantibody production. Follicular helper T-cell counts are measured in Stat6−/− scurfy mice and scurfy mice. Results Scurfy mice spontaneously generated IgG autoantibodies to the dermal-epidermal junction, which had been class-switched from IgM within 12 days after birth. The target autoantigens were murine BP230 and type XVII collagen (COL17). The scurfy polyclonal autoantibodies did not induce skin fragility in neonatal mice. Autoantibody production was induced by CD4+ T cells from scurfy mice and was ameliorated by Stat6 gene knockout in association with a decrease of follicular helper T cells. We also identified autoantibodies to COL17 and BP230 in patients with IPEX syndrome and found an association between production of autoantibodies to COL17 and an eczematous skin phenotype. Conclusions Dysregulation of Treg cells generates autoantibodies to COL17 and BP230 in vivo.

Simplified sub-models for coal combustion are widely used in CFD simulation of pulverized coal fired boiler. A large-scale boiler was simulated to investigate the effects of some advanced sub-models. Through calculating several cases using different sub-models, it is known that the predicted ignitability of burners is closely related with the generation of H2. In the case without taking into account H2, the burners show poor ignitability. Using a multi-step mechanism for gas combustion, including char gasification and detailed compositions of volatile largely improve the ignitability of burners. The good ignitability also leads to more heat absorption in boiler and less CO in furnace. CO can be also increased because of the char gasification and detailed compositions of volatiles. Therefore, it is necessary to using multi-step mechanisms for gas combustion, char gasification, and detailed compositions of volatiles to obtain more accurate simulation results.

A char combustion model was derived by assuming constant intrinsic activation energy for the different chars. The char combustion rates are affected by various diffusion processes within the different char pores. The fractal pore diffusion effects were characterized by three pore structure parameters (porosity, specific surface area, and fractal dimension) and the mean particle diameter. Three-dimensional numerical results for various char particles burned in drop tube furnaces obtained using the model compare well with experimental results to verify the model. The comparisons show that the model has good accuracy for a wide range of char, from lignite to anthracite.