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We put forward a facile one-pot hydrothermal strategy to synthesize the MnX2O4(X = Co, Ni) spinel/graphite nanoflakes (GNF) composites. Note that the physical exfoliation toward GNF frees the method from the complex and expensive conventional chemical treatments. The obtained MnCo2O4/GNF (MCO/GNF) and MnNi2O4/GNF (MNO/GNF) exhibit high specific capacitance (1712 F g−1 for MCO/GNF and 1622 F g−1 for MNO/GNF at 1 A g−1) and good cycling performance (almost 80 % capacitance retention after 3500 cycles at 5 A g−1 for both MCO/GNF and MNO/GNF). Furthermore, the asymmetric supercapacitor (ASC) with MCO/GNF or MNO/GNF as positive electrode and rGO as the negative electrode is assembled. The optimized ASC is able to show high energy density up to 22.5 Wh kg−1. Together with the facile synthetic strategy, such good electrochemical performance may promote the spreading of the next-generation energy storage electrodes.

Purpose: Whether isocitrate dehydrogenase (IDH) gene aberrations affected prognosis of patients with acute myeloid leukemia (AML) was controversial. Here, we conducted a meta-analysis to evaluate their prognostic value. Experimental Design: PubMed, Embase, Cochrane, and Chinese databases were searched to identify studies exploring how IDH gene aberrations affected AML outcome. Pooled HRs and relative risks (RR) were calculated, along with 95% confidence intervals (CI). Results: Thirty-three reports were included. IDH mutations seemed not to affect overall survival (OS: HR, 1.05; 95% CI, 0.89–1.23) and event-free survival (EFS: HR, 0.97; 95% CI, 0.80–1.18) when considered as a single factor, but improved accumulative incidence of relapse (CIR: HR, 1.44; 95% CI, 1.18–1.76) in patients with intermediate-risk karyotypes (IR-AML). However, IDH1 mutation conferred worse OS (HR, 1.17; 95% CI, 1.05–1.31) and EFS (HR, 1.29; 95% CI, 1.07–1.56), especially in patients with normal cytogenetics (OS: HR, 1.21; 95% CI, 1.01–1.46; EFS: HR, 1.56; 95% CI, 1.23–1.98). Prognosis of the IDH1 single-nucleotide polymorphism rs11554137 was also poor (OS: HR, 1.34; 95% CI, 1.03–1.75). IDH2 mutation improved OS (HR, 0.78; 95% CI, 0.66–0.93), particularly in IR-AML patients (OS: HR, 0.65; 95% CI, 0.49–0.86). The IDH2 (R140) mutation was associated with better OS among younger cases (HR, 0.64; 95% CI, 0.49–0.82). Treatment outcome was poor [RR for complete remission rates in IDH1 mutation: 1.21; 95% CI, 1.02–1.44; IDH2 (R172) mutation: 2.14; 95% CI, 1.61–2.85]. Conclusions: Various subtypes of IDH mutations might contribute to different prognosis and be allowed to stratify IR-AML further. Clin Cancer Res; 23(15); 4511–22. ©2017 AACR.

Sodium sulfur (NaS) cell is recognized as a promising candidate for advanced grid-scale large energy storage systems (ESS). In this work, we study the impacts of planar NaS cell container materials on the accumulation of residual stresses in the cell joints and solid electrolyte during the cell assembly and operation processes. Concentration of such thermo-mechanical stress in these vulnerable areas in the modern NaS cells can lead to catastrophic cell failures, which can present a huge challenge for developing large planar NaS cells towards commercial deployment. Here, we employ the finite-element analysis (FEA) computational technique to quantitatively assess the thermo-mechanical stress accumulation using prototype planar NaS cells. Relevant experimental procedures with corresponding thermal cycling conditions for the cell assembly, operation, and maintenance processes are incorporated into the FEA model. The influences of Al alloy (Al3003), stainless steels (STS304 and STS340), and iron-nickel-cobalt superalloy (KOVAR) on the residual stress accumulation are tested and thoroughly discussed. The computation results show that high stress concentration can be developed in the cell joint area. Through the comprehensive computational analysis, it is suggested that applying smaller CTE (less than ∼12 × 10 −6 K −1 ) alloys is necessary to secure the thermo-mechanical stability of NaS cells that can be implemented in a large scale ESS.

Background: Prox1 is a transcription factor necessary for lymphatic function. The main aim of the current study was to investigate the potential role of Prox1 in lymphangiogenesis and lymphatic function, and analyze Prox1-dependent stimulation of lymphatic function on mesenteric lesions and the composition of microbiota in Crohn’s disease. Methods: Prox1flox/+, Tie2-CreERT2 and IL-10 KO mice were included. Disease activity and enterocolitis inflammation were assessed using a grading system. Lymphatic vessel density and lymphatic function were analyzed using immunohistochemistry and lymphangiography. The potential mechanism of Prox1 was analyzed. The effects of lymphatic function on mesenteric adipose tissue (MAT) and the composition of microbiota were evaluated. Results: Systemic delivery of AAV-Prox1 reduced disease activity index and the severity of chronic inflammation in IL-10 KO mice. Without compensatory response of Prox1, IL-10 KO+Prox1 KO mice developed serious inflammation in the colon. For lymphatic vessel, IL-10 KO+Prox1 KO mice showed lower lymphatic vessel density and less functional lymphatic vessels. IL-10 KO+AAV-Prox1 mice showed significantly increased lymphatic vessel density. Delivery of AAV-Prox1 also promoted lymphatic drainage function. The Prox1/VEGFC/VEGFR3 pathway played an important role in lymphangiogenesis and lymphatic function. Additionally, Prox1-dependent stimulation of lymphatic function ameliorated hypertrophy of MAT in IL-10 KO mice. Delivery of AAV-Prox1 also modified the composition of microbiota, the proportion of Firmicutes increased and Bacteroidetes decreased in IL-10 KO+AAV-Prox1 mice compared with IL-10 KO mice. An increase in the diversity of gut microbiota in IL-10 KO+ AAV-Prox1 mice was observed. Conclusions: Our findings demonstrated that Prox1 played the critical role in the lymphangiogenesis and lymphatic function. Additionally, Prox1-dependent stimulation of lymphatic function could ameliorate hypertrophy of MAT and modify the composition of microbiota in experimental Crohn’s disease. Funding Statement: This work was partly supported by National Natural Science Foundation of China (Grant 81670471, 81770556 and 81570500). Declaration of Interests: The authors declare that they have no conflicts of interests. Ethics Approval Statement: All animal protocols were approved by the Institutional Ethics Committee of the Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

We analyzed the concept of patent quality and the status quo of patent quality evaluation, designed the technical classification systems and patent retrieval strategies, set up a database of patent characteristic information on graphene industry. We constructed the patent quality evaluation system on "three dimensions — whole process" from three dimensions that included technical quality, legal quality and economic quality, and from four forming stages that included patent creation, patent application, patent examination and patent authorization. According to totality, compound growth rate, patented authorizer type, technology subfield, quality sub-dimension, etc., we systematically measured patent quality of graphene industry in 31 provinces in China, and compared different characteristics of patent quality. Our conclusions were including characteristics of patent quality in each region, region classifications based on the patent characteristics, distribution of regions with relatively high patent quality, and distribution of regions with high development potentiality for patent quality. We attempted to provide effective reference and accurate direction for further monitoring the patent quality on graphene industry in different regions, formulating policies to improve patent quality and promoting innovative development on related strategic emerging industries.

Patient: Male, 49 Final Diagnosis: T-lymphoid/myeloid bilineal blastic transformation of CML Symptoms: Rapidly enlarging mass in left neck Medication: — Clinical Procedure: Biopsy of the left submandibular lymph nodes Specialty: Hematology Objective: Rare co-existance of disease or pathology Background: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the Philadelphia chromosome generated by the reciprocal translocation t(9: 22)(q34;q11). CML is usually diagnosed in the chronic phase. Blast crisis represents an advanced phase of CML. Extramedullary blast crisis as the initial presentation of CML with bone marrow remaining in chronic phase is an unusual event. Further, extramedullary blast crisis with T lymphoid/myeloid bilineal phenotype as an initial presentation for CML is extremely unusual. Case Report: Here, we report the case of a 49-year-old male with rapidly enlarged submandibular lymph nodes. Biopsy specimen from the nodes revealed a characteristic appearance with morphologically and immunohistochemically distinct myeloblasts and T lymphoblasts co-localized in 2 adjacent regions, accompanied by chronic phase of the disease in bone marrow. The presence of the BCR/ABL1 fusion gene within both cellular populations in this case confirmed the extramedullary disease represented a localized T lymphoid/myeloid bilineal blastic transformation of CML. After 3 courses of combined chemotherapy plus tyrosine kinase inhibitor treatment, the mass was completely regressed with a 3-log decrease in BCR/ABL1 transcript from baseline. Five months after the diagnosis, the patient showed diminished vision, hand tremors, and weakness of lower extremities. Flow cytometric immunophenotyping of cerebrospinal fluid revealed the presence of myeloid blasts. An isolated central nervous system relapse of leukemia was identified. Following high-dose systemic and intrathecal chemotherapy, the patient continued to do well. Conclusions: The possibility of extramedullary blast crisis as an initial presentation in patients with CML should be considered. Further, an isolated central nervous system blast crisis should be considered if neurological symptoms evolve in patients who have shown a good response to therapy.

Poly (lactic-co-glycolic acid) (PLGA) copolymers have been broadly used in controlled drug release applications. Because these polymers are biodegradable, they provide an attractive option for drug delivery vehicles. There are a variety of material, processing, and physiological factors that impact the degradation rates of PLGA polymers and concurrent drug release kinetics. This work is intended to provide a comprehensive and collective review of the physicochemical and physiological factors that dictate the degradation behavior of PLGA polymers and drug release from contemporary PLGA-based drug-polymer products. In conjunction with the existing experimental results, analytical and numerical theories developed to predict drug release from PLGA-based polymers are summarized and correlated with the experimental observations. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1692-1716, 2017.

Full atomistic molecular dynamics simulations are performed on tetra-sulfides and undoped conjugated polymers pernigraniline base polyaniline (PNB), leucoemeraldine base polyaniline (LEB), poly (3,4-ethylenedioxythiophene) (PEDOT) and polypyrrole (PPY) to investigate the binding effectiveness between polysulfides and polymer binders. The weight ratio between sulfur and binder in lithium–sulfur cells is considered in 1:1 v/v mixture of dioxolane/dimethoxyethane. The simulations reveal that the end group 2 of PNB can effectively bind a lithium tetra-sulfide (i.e. Li2S4) cluster or 2 out of 43 Li2S4 molecules with the effect of solvent. However, repeat units of PNB, LEB, PEDOT and PPY seem ineffective in binding solvated Li2S4 through non-bonded interaction, especially when the concentration of tetra-sulfide/binder in a local domain of the cathode is low. Therefore, polymers with this specific functional group (i.e. the end group 2 of PNB) are suggested to be further studied as potential effective binders to inhibit the shuttle effect of solvated lithium polysulfides. Also, since the solvent has considerable impact on the binding effectiveness between tetra-sulfides and binder, it is suggested to take advantage of the explicit solvation models, such as those built in this work, to predict how other influencing factors affect binding between polysulfides and polymers.

Evolution of domestic wastes into competitive battery materials at less expense is a rational strategy of "killing two birds with one stone", and never better for grid-scale energy-storage utilizations wherein achieving great energy density is less crucial than environmental friendliness and cost. To checkout this concept, we herein select Fe2N, a conductive conversion-type anode for Li-/Na-ion batteries (LIBs/SIBs), as a paradigm study. Rusty/plastic wastes-evolved anodes with a proper tap density of 1.74 g cm−3 are composed of numerous nanoparticles where each Fe2N unit is evenly configured in robust carbon sheath. Such electrodes demonstrate impressive specific capacities under varied areal mass loading ratios of 3∼15 mg cm-2, outstanding rate capabilities and cyclic stability. To judge their promise in practical usage, we successively choose economical LiFePO4 and phase-stable Na3V2(PO4)3 as pairing cathodes to build full-cell LIBs/SIBs. This wastes-to-battery protocol may pave a way to advance practical techniques for sustainable usage beyond.

The oncoprotein RUNX1-ETO is the fusion product of t(8;21)(q22;q22) and constitutes one of the most common genetic alterations in acute myeloid leukemia (AML). Abnormal c-KIT overexpression is considered an independent negative prognostic factor for relapse and survival in t(8;21) AML patients. However, the molecular mechanism of high c-KIT expression in t(8;21) AML remains unknown. In this study, we detected RUNX1-ETO and c-KIT gene expression in AML-M2 patients and verified the overexpression of c-KIT in t(8;21) AML patients. We also found that c-KIT overexpression was a poor prognostic indicator in RUNX1-ETO positive AML patients, but not in RUNX1-ETO negative AML patients. We used the dual-luciferase and ChIP assays to demonstrate that the RUNX1-ETO protein epigenetically trans-activates c-KIT by binding to the c-KIT promoter and recruiting the histone acetyltransferase P300 to the c-KIT promoter, elucidating the mechanism of the abnormally increased c-KIT expression in t(8;21) AML patients. Moreover, pharmacological studies revealed that C646, a P300 inhibitor, could inhibit proliferation, induce apoptosis and arrest the cell cycle more effectively in RUNX1-ETO positive cells than in negative ones. The levels of c-KIT and RUNX1-ETO proteins were also decreased with C646 treatment in RUNX1-ETO positive cells. These findings suggested that P300 could be a therapeutic target and that C646 could be used as a potential treatment for RUNX1-ETO positive AML patients. Interestingly, using the dual-luciferase assay, we also found that the binding capacity of RUNX1-ETO9a, a truncated RUNX1-ETO isoform, to the c-KIT promoter was stronger than that of RUNX1-ETO, suggesting RUNX1-ETO9a as another valuable therapeutic target in t(8;21) AML.

Background Acute high altitude illness is defined as a group of cerebral and pulmonary syndromes that can occur during travel to high altitudes. It is more common above 2500 metres, but can be seen at lower elevations, especially in susceptible people. Acute high altitude illness includes a wide spectrum of syndromes defined under the terms 'acute mountain sickness' (AMS), 'high altitude cerebral oedema' and 'high altitude pulmonary oedema'. There are several interventions available to treat this condition, both pharmacological and non-pharmacological; however, there is a great uncertainty regarding their benefits and harms. Objectives To assess the clinical effectiveness, and safety of interventions (non-pharmacological and pharmacological), as monotherapy or in any combination, for treating acute high altitude illness. Search methods We searched CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science, CINAHL, Wanfang database and the World Health Organization International Clinical Trials Registry Platform for ongoing studies on 10 August 2017. We did not apply any language restriction. Selection criteria We included randomized controlled trials evaluating the effects of pharmacological and non-pharmacological interventions for individuals suffering from acute high altitude illness: acute mountain sickness, high altitude pulmonary oedema or high altitude cerebral oedema. Data collection and analysis Two review authors independently assessed the eligibility of study reports, the risk of bias for each and performed the data extraction. We resolved disagreements through discussion with a third author. We assessed the quality of evidence with GRADE. Main results We included 13 studies enrolling a total of 468 participants. We identified two ongoing studies. All studies included adults, and two studies included both teenagers and adults. The 13 studies took place in high altitude areas, mostly in the European Alps. Twelve studies included participants with acute mountain sickness, and one study included participants with high altitude pulmonary oedema. Follow-up was usually less than one day. We downgraded the quality of the evidence in most cases due to risk of bias and imprecision. We report results for the main comparisons as follows.Non-pharmacological interventions (3 studies, 124 participants)All-cause mortality and complete relief of AMS symptoms were not reported in the three included trials. One study in 64 participants found that a simulated descent of 193 millibars versus 20 millibars may reduce the average of symptoms to 2.5 vs 3.1 units after 12 hours of treatment (clinical score ranged from 0 to 11 ‒ worse; reduction of 0.6 points on average with the intervention; low quality of evidence). In addition, no complications were found with use of hyperbaric chambers versus supplementary oxygen (one study; 29 participants; low-quality evidence).Pharmacological interventions (11 trials, 375 participants)All-cause mortality was not reported in the 11 included trials. One trial found a greater proportion of participants with complete relief of AMS symptoms after 12 and 16 hours when dexamethasone was administered in comparison with placebo (47.1% versus 0%, respectively; one study; 35 participants; low quality of evidence). Likewise, when acetazolamide was compared with placebo, the effects on symptom severity was uncertain (standardized mean difference (SMD) -1.15, 95% CI -2.56 to 0.27; 2 studies, 25 participants; low-quality evidence). One trial of dexamethasone in comparison with placebo in 35 participants found a reduction in symptom severity (difference on change in the AMS score: 3.7 units reported by authors; moderate quality of evidence). The effects from two additional trials comparing gabapentin with placebo and magnesium with placebo on symptom severity at the end of treatment were uncertain. For gabapentin versus placebo: mean visual analogue scale (VAS) score of 2.92 versus 4.75, respectively; 24 participants; low quality of evidence. For magnesium versus placebo: mean scores of 9 and 10.3 units, respectively; 25 participants; low quality of evidence). The trials did not find adverse events from either treatment (low quality of evidence). One trial comparing magnesium sulphate versus placebo found that flushing was a frequent event in the magnesium sulphate arm (percentage of flushing: 75% versus 7.7%, respectively; one study; 25 participants; low quality of evidence). Authors' conclusions There is limited available evidence to determine the effects of non-pharmacological and pharmacological interventions in treating acute high altitude illness. Low-quality evidence suggests that dexamethasone and acetazolamide might reduce AMS score compared to placebo. However, the clinical benefits and harms related to these potential interventions remain unclear. Overall, the evidence is of limited practical significance in the clinical field. High-quality research in this field is needed, since most trials were poorly conducted and reported.

Background Mesenteric fat wrapping and thickening are typical characteristics of Crohn's disease (CD). The purpose of this study was to explore the cause of mesenteric adipose hypertrophy and analyze the role of lymphatic vessels in mesenteric adipose tissue in CD. Methods Twenty-three CD patients who underwent ileocolonic resection were included. In CD patients, specimens were obtained from hypertrophic mesenteric adipose tissue (htMAT) next to the diseased ileum. The mesenteric lymphatic vessels in mesenteric adipose tissue were separated under stereoscope microscope. Transmission electron microscopy and immunofluorescence were used to observe the structure of mesenteric lymphatic vessels. The NF-κB signaling pathway in mesenteric adipose tissue was detected in CD specimens using Western blotting. Results Electron microscopy showed that the structure of mesenteric lymphatic vessel was discontinuous, and the microstructure of lymphatic endothelial cells appeared ruptured and incomplete. Through an immunofluorescence technique, we found that the surface of lymphatic endothelial cells lacked tight junction protein staining in CD. Also, the expression of claudin-1, occludin, and ZO-1 in the mesenteric lymphatic vessel of htMAT was significantly lower than that of control. These results indicated that the structure of the mesenteric lymphatic vessel in htMAT was mispatterned and ruptured, which could lead to lymph leakage. Leaky lymph factors could stimulate adipose tissue to proliferate. Antigens that leaked into the mesenteric adipose tissue could effectively elicit an immune response. The levels of cytokines (TNF-a, IL-1β, IL-6) was increased in the htMAT of CD patients by activated NF-κB signaling pathway. Conclusions Our findings demonstrated that the hypertrophy of mesenteric adipose tissue may result from mispatterned and ruptured lymphatic vessels. Alteration of mesenteric adipose tissue was associated with activated NF-κB signaling pathway. This study enhances support for elucidating the importance of mesenteric lymphatic vessels and adipose tissue in CD.

Intermediate-risk acute myeloid leukemia (IR-AML), which accounts for a substantial number of AML cases, is highly heterogeneous. Although several mutations have been identified, the heterogeneity of AML is uncertain because novel mutations have yet to be discovered. Here we applied next generation sequencing (NGS) platform to screen mutational hotspots in 410 genes relevant to hematological malignancy. IR-AML samples (N=95) were sequenced by Illumina Hiseq and mutations in 101 genes were identified. Only seven genes (CEBPA, NPM1, DNMT3A, FLT3-ITD, NRAS, IDH2 and WT1) were mutated in more than 10% of patients. Genetic interaction analysis identified several cooperative and exclusive patterns of overlapping mutations. Mutational analysis indicated some correlation between genotype and phenotype. FLT3-ITD mutations were identified as independent factors of poor prognosis, while CEBPA mutations were independent favorable factors. Co-occurrence of FLT3-ITD, NPM1 and DNMT3A mutations was identified with associated with specific clinical AML features and poor outcomes. Furthermore, by integrating multiple mutations in the survival analysis, 95 IR-AML patients could be stratified into three distinct risk groups allowing reductions in IR-AML by one-third. Our study offers deep insights into the molecular pathogenesis and biology of AML and indicated that the prognosis of IR-AML could be further stratified by different mutation combinations which may direct future treatment intervention.

In different parts of the gastrointestinal tract, the rate of drug release from polyelectrolyte hydrogel tablets is highly affected by variance of ionic concentration. This research aims at revealing clearly how the drug release from a hydrogel matrix is affected by ionic concentration of external solution through the finite element simulation and triphasic mechanism model. The coupled relationship of the motions including the polyelectrolyte hydrogel swelling, the water flow and the ion diffusion, is illustrated in the present work. In order to simulate the drug controlled release from a swollen polyelectrolyte hydrogel carrier, the mathematical model was built on the basis of the multiphasic theory of polyelectrolyte hydrogels. Finally, the reliability of the simulation method was verified qualitatively by experimental results. The results reveal that when the initial concentration of fixed anions of polymer network is higher than the concentration of free anions in the external solution, the drug release rate increases with increasing the ionic concentration of the external solution. The research is helpful for the optimal design of oral drug release in gastrointestinal tract.

The resin infiltration stage during the resin transfer molding process is complicated, which involves the edge effect, resin curing reaction and heat transfer phenomenon. In this paper, considering the edge effect, the integrated investigation on curing reaction, physical property, two-dimensional resin flow and three-dimensional temperature distribution is implemented in theory and numerical simulation. And then the evolution of coupling physical fields, such as resin temperature, curing degree and resin viscosity, is analyzed numerically. The present study is helpful for understanding the complex relationships among a variety of parameters during the reactive filling process.

In drug release systems using hydrogels as carriers, the presence of the polymer network will reduce the drug release rate, which can extend the release period. For a controlled-release process of drug, usually the ideal situation is to get a zero-order drug release rate. In this paper, the mathematical model of hydrogel swelling processes is constructed on the basis of a biphasic theory, and then an integrated equation that considers both water convection and drug diffusion phenomena is used to describe the drug release process. The effects of the initial drug concentration with nonuniform distributions along the radial direction of hydrogel carriers on the release of drugs are studied through simulating two-dimensional hydrogel swelling processes by means of the COMSOL Multiphysics software. The simulation results show that along with the hydrogel swelling, the drug release rate is changing, and the major influencing factors of the drug release rate are water convection and drug diffusion coefficient, which are affected by water volume fraction, drug concentration distribution in matrix, and carrier radius. The results also indicate that the initial drug concentration distribution following a sine curve can result in an ideal zero-order release process.

Seasonality is one of the most influential yet subtle factor that affects people's life. At biological level, it affects people's weight, appetite, mood, and susceptibility to certain pathogens and health conditions. At socio-cultural level, it is embedded in the school calendar, holiday plans, and fashion trends. This study investigates the relationship between the seasonality of wedding and the seasonality of people’s health-seeking behaviors. We propose that the seasonality of wedding affects seasonality of health-seeking behaviors (e.g. getting fit, diet, and quitting addictions) among the general public. We develop two hypotheses based on this preposition and test them with Google Trends data. We find the seasonality of wedding is associated with some health-seeking behaviors with certain temporal lags, and discuss the implications for health communication.

We study the impact of investor sentiment on stock returns in China, using as a benchmark the three-factor Fama–French model, and distinguishing between normal and positive sentiment. Sentiment helps explain the mis-pricing component of returns in the Fama–French model and the time variation in the factors themselves. Factor loading patterns noted by Fama-French are evident in China, but they can be equally well modelled by sentimental factors. Fama–French factors are less significant if factors are conditioned by sentiment, suggesting that in China sentiment affects both the way investors judge risks as well as portfolio returns directly.

The infrared normal spectral emissivity of the oxidized molybdenum was measured during thermal oxidation process, and the integral emissivity was calculated from the data of spectral emissivity. It is found that the surface oxidation has a remarkable effect on the spectral emissivity of molybdenum, and the spectral emissivity curves become more fluctuant with the increase in oxidation time. The integral emissivity grows exponentially with the oxidation time at 773 K, remains almost constant at 823 K, and fluctuates at 873 and 923 K. The X-ray fluorescence spectrometer, the X-ray diffraction, and the scanning electron microscopy were employed to analyze the changes in surface composition and surface morphology. The results show that the most probable reason for the variation of integral emissivity is the change in surface roughness caused by the variation in the size and shape of oxide particle on specimen surface.

The purpose of this study is to assess the latest patterns of human papillomavirus (HPV) awareness in the general population and to develop a model that identifies the key determinants of HPV awareness to provide evidence for future HPV health campaigns.

Poly (lactic-co-glycolic acid) (PLGA) copolymers have been broadly used in controlled drug release applications. Because these polymers are biodegradable, they provide an attractive option for drug delivery vehicles. There are a variety of material, processing, and physiological factors that impact the degradation rates of PLGA polymers and concurrent drug release kinetics. This work is intended to provide a comprehensive and collective review of the physicochemical and physiological factors that dictate the degradation behavior of PLGA polymers and drug release from contemporary PLGA-based drug-polymer products. In conjunction with the existing experimental results, analytical and numerical theories developed to predict drug release from PLGA-based polymers are summarized and correlated with the experimental observations. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1692-1716, 2017.

Sodium nickel chloride (Na-NiCl2) batteries are gaining growing attentions as a strong potential contender for advanced electric vehicle (EV) and stationary energy storage system (ESS) applications. The cathode compartment of a Na-NiCl2 battery features by a mixture of solid NaCl and Ni granules impregnated with a liquid NaAlCl4 catholyte. During charge-discharge cycles, complicated electrochemical reactions take place, including transportation of Na+ ions through NaAlCl4 catholyte, the dissolution/coarsening of NaCl particles, formation/decomposition of NiCl2 layers on the active Ni surface, and electron transport through the Ni granules. We are developing advanced Na-NiCl2 batteries that operate at relatively lower temperatures of below 200 °C to minimize its cell degradation typically observed at high operation temperature (over ~270 °C) and to enable application of simple and cheaper polymer seals for cell manufacturing. However, the diffusion and the ionic migration kinetics of active Na+ ions are restricted at the lower temperatures that may limit cell performance. In this presentation, we introduce a multi-physics continuum computational model to capture the electrochemical behaviors of planar lower temperature Na-NiCl2 batteries. The computational results will elucidate impacts of (i) cell operation temperatures, (ii) current densities, and (iii) cathode dimensions on the electrochemical performance of prototype planar Na-NiCl2 cells. The developed prediction model is expected to provide a useful guideline for the experimental fabrication of advanced Na-NiCl2 batteries with maximized cell performance at relatively lower temperatures.

The mechanisms by which AML1/ETO (A/E) fusion protein induces leukemogenesis in acute myeloid leukemia (AML) without mutagenic events remain elusive. Here we show that interactions between A/E and hypoxia-inducible factor 1α (HIF1α) are sufficient to prime leukemia cells for subsequent aggressive growth. In agreement with this, HIF1α is highly expressed in A/E-positive AML patients and strongly predicts inferior outcomes, regardless of gene mutations. Co-expression of A/E and HIF1α in leukemia cells causes a higher cell proliferation rate in vitro and more serious leukemic status in mice. Mechanistically, A/E and HIF1α form a positive regulatory circuit and cooperate to transactivate DNMT3a gene leading to DNA hypermethylation. Pharmacological or genetic interventions in the A/E-HIF1α loop results in DNA hypomethylation, a re-expression of hypermethylated tumor-suppressor p15(INK4b) and the blockage of leukemia growth. Thus high HIF1α expression serves as a reliable marker, which identifies patients with a poor prognosis in an otherwise prognostically favorable AML group and represents an innovative therapeutic target in high-risk A/E-driven leukemia.

To investigate the clinical value of multiplex nested reverse transcription PCR (RT-nPCR) in screening acute myeloid leukemia(AML)fusion genes.A novel multiplex RT-nPCR assay was developed to detect 16 AML-related fusion genes (AML1-EVI1, AML1-ETO, AML1-MDS1, AML1-MTG16, MLL-AF9, MLL-AF6, MLL-AF10, MLL-ENL, MLL-MLL, PML-RARα, PLZFRARα, NPM1-RARα, CBFB-MYH11, DEK-CAN, SET-CAN and TLS-ERG) according to 2008 WHO classification of AML. The chromosome reciprocal translocations of 356 AML cases were detected by multiplex RT-nPCR and karyotyping. The positive samples were further confirmed by split- out PCR and FISH.The fusion genes were detected in 172 patients with the positive detection rate of 48.31%(172/356), which was higher than that of karyotyping (31.46%) (χ²=70.314, P0.01). Multiplex RT-nPCR is superior to karyotyping and FISH in identifying the rare, cryptic chromosome translocation (χ²=96.074, P0.01).The multiplex RT-nPCR used in this study can quickly, effectively and accurately screen the fusion genes in AML patients, which can provide important evidence for assessing diagnosis and treatment, and also provide necessary information for minimal residual disease (MRD) and prognosis.

Background Mortality increases during heat waves have been reported worldwide. The magnitude of these increases can vary within regions according to sociodemographic and urban landscape characteristics. The objectives of this study were to explore this variation and its determinants, and to identify the most heat-vulnerable areas by mapping heat vulnerability. Methods We conducted a time-stratified case-crossover analysis using daily mortality in the Barcelona metropolitan area during the warm seasons of 1999-2006. Temperature data on the date of death were assigned to each individual, which were assigned to their census tract of residence. Eight census tract-level variables on socioeconomic or built environment characteristics were obtained from the census. Residence surrounding greenness was obtained from satellite data. The relative risk (RR) of mortality after three consecutive hot days (defined as those exceeding the 95th percentile of maximum temperature) was calculated via conditional logistic regression. Effect modification was examined by including interaction terms. Results Analyses were based on 52 806 deaths. The effect of three consecutive hot days was a 30% increase in all-cause mortality (RR=1.30, 95% CI 1.24 to 1.38). Heterogeneity of this effect was observed across census tracts. The effect of heat on mortality was higher in the census tracts with a large percentage of old buildings (RR = 1.21, 95% CI 1.00 to 1.46), manual workers (RR = 1.25, 95% CI 0.96 to 1.64) and residents perceiving little surrounding greenness (RR = 1.29, 95% CI 1.01 to 1.65). After three consecutive hot days, mortality doubled in the most heat-vulnerable census tracts. Conclusions Sociodemographic and urban landscape characteristics are associated to mortality risk during heat waves and are useful to build heat vulnerability maps.

Na/metal chloride batteries (i.e., Na-NiCl2 or Na-FeCl2 batteries) possess a number of excellent properties including high safety and stability, high energy density, high voltage, no self-discharge, and good cycle life. Relying on these advantageous features, these Na/metal chloride secondary cells have a high potential for applications of transportation and vehicles as well as the advanced stationary energy storage systems (ESS). In these Na/metal chloride batteries, the electrochemical performance is largely determined by the thermodynamics and kinetic reactions in the cathode area comprised of NaCl particles, Ni/NiCl2 and/or Fe/FeCl2 powders, NaAlCl4 secondary electrolyte (i.e., catholyte), and various additives. During the charge-discharge process, complicated electrochemical reactions will occur in this cathode of the cell, including ionic diffusion of Na+ through NaAlCl4 catholyte driven by the chemical potential and the electric potential gradients, dissolution/coarsening of NaCl particles, and precipitation/decomposition of NiCl2 or FeCl2. The presentation introduces a continuum computational model to capture the quantitative effects of reaction thermodynamics and transport kinetics on the electrochemical performance of Na/metal chloride batteries with a Na-NiCl2 cell chemistry. The computational model was developed using a commercial COMSOL multi-physics software package. The model was applied to characterize a novel planar cell, which was designed adopting a disc shaped beta-alumina solid electrolyte (BASE) instead of a conventional cloverleaf shaped BASE. The planar cell geometry was intended to lower the cell operation temperature by optimizing the cell performance. In this multi-physics computational model, relevant physicochemical materials properties of active materials have been incorporated. The cell voltage was calculated using the Butler-Volmer kinetic equation and the temporal volume change of the active materials was computed based on the local current densities. The computation results were used to quantitatively investigate the effects of (1) cell operation temperature, (2) cathode active materials to catholyte ratio, and (3) cell dimension on the charge-discharge characteristics of the planar Na-NiCl2 cell. Especially, the combined effect of operation temperature and cell size on the cell performance was of special interest. It turns out that the electrochemical performance of the Na-NiCl2 cells is highly dependent on the cell operation temperature to show reduced cell voltages with decreased operation temperatures.

The t(8;21)(q22;q22) translocation, resulting in a chimeric protein AML1/ETO (A/E), is one of the most common chromosomal abnormalities in acute myeloid leukemia (AML). It has been reported that additional mutagenic “hits” are required for A/E to be a leukemic driver, but it is unclear why most A/E-positive patients don’t carry such gene mutations. We hypothesized that unconventional and more universal events might cooperate with A/E to drive leukemogenesis. Hypoxia inducible factor 1a (HIF1a) is a transcription factor mediating the cellular response to hypoxia in malignant cells. To identify the key molecule responsible for A/E-driven leukemia, we focused on HIF1a signaling, as it is selectively activated in AML stem cells in a hypoxia-independent fashion. Using qPCR analysis, we measured HIF1a mRNA levels in bone marrow mononuclear cells from 73 A/E-positive and 59 A/E-negative patients with newly diagnosed AML and 15 healthy donors. HIF1a was highly expressed in A/E-positive patients, as compared to A/E-negative patients and healthy controls. The expression of HIF1a was positively correlated with the expression of A/E, independent of KIT mutation. Patients were grouped into quartiles according to HIF1a expression levels (Q1-Q4, each quartile containing 25% of patients) and divided into high HIF1a (HIF1a high, Q4; n = 33) and low HIF1a (HIF1a low, Q1-Q3; n = 99). AE-positive patients with high HIF1a expression had a significantly shorter OS (median = 19.0 months vs. not reached, P = 0.015) and EFS (median = 9.0 months vs. 24.0 months, P = 0.001) compared to those with low HIF1a expression. Notably, HIF1a-associated inferior prognosis in A/E-positive patients was KIT mutation-independent. In patients carrying wild-type KIT [n = 53, about 73% (53/73) of the entire A/E-patients], those with high HIF1a levels had a shorter OS (median = 23.1 months vs. not reached, P = 0.008) and EFS (median = 9.4 months vs. not reached, P = 0.001) than those with low HIF1a levels. Multivariate analysis revealed that high HIF1a levels were independent prognostic indicators for both OS and EFS (P = 0.014, HR = 3.574 and P = 0.004, HR = 4.304, respectively) in AE-positive patients. Mechanistic studies revealed that A/E and HIF1a formed a positive regulatory circuit, in which A/E bound to HIF1a gene promoter and transactivated HIF1a or vice versa. Co-expression of AE and HIF1a in leukemia cells caused a higher cell proliferation rate in vitro and more serious leukemic status in mice. To gain insight into the molecular basis of A/E-HIF1a functional cooperation in leukemogenesis, we examined the mRNA levels of DNMT1, DNMT3a and DNMT3b expression in bone marrow samples from above-mentioned AML patients and healthy donors using qPCR. The result showed that DNMT3a, but not DNMT1 and DNMT3b, was significantly overexpressed in A/E-positive patients, as compared to A/E-negative patients and healthy donors. DNMT3a levels were positively correlated with both A/E and HIF1a levels. We therefore focused on evaluating the role of DNMT3a in A/E-positive AML. We found that DNMT3a expression was positively correlated with both A/E and HIF1a levels. As an individual event, A/E or HIF1a was enriched on DNMT3a gene promoter and synergistically increased DNMT3a transcription and enhanced global DNA methylation. Pharmacological or genetic interventions in the AE-HIF1a loop resulted in DNA hypomethylation, a reexpression of hypermethylated tumor suppressor p15INK4band the blockage of leukemia growth. In summary, we showed that A/E and HIF1a form a regulatory circuit and cooperatively control aggressive leukemia growth through DNMT3a transactivation and subsequent DNA hypermethylation. Thus, the HIF1a-DNMT3a nexus serves as a reliable marker, which identifies patients with a poor prognosis in an otherwise prognostically favorable AML group, and represents an innovative therapeutic target in high-risk AE-positive leukemia. Disclosures No relevant conflicts of interest to declare.

Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC), a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL) response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight) once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8(+), but not CD4(+) T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy.

The application of nanofiltration in industrial fields is increasing rapidly in recent years, especially in drinking water treatment. Nevertheless, the mechanism of mass transport through these membranes has not yet been fully understood. And the optimal design of nanofiltration processes still faces challenges. At first, the Donnan Steric Pore Model (DSPM) is described in this paper, which is constructed on the basis of the extended Nernst-Planck equation for the prediction of the nanofiltration process of polymeric membrane. Then the DSPM model is used to characterize three kinds of membranes (AFC40, CA30 and NTR7450) for the nanofiltration of 50 mol/m(3) NaCl solution and NTR7450 membrane for the nanofiltration of NaCl and MgSO4 solution with different concentrations. The simulated results and their comparison with experimental results show that the DSPM model can effectively predict the membrane performance. And then a description of the Pores and Polarization Transport Model (PPTM) is presented, which is developed on the basis of the DSPM model, in order for characterizing cross-flow nanofiltration. The PPTM model combines the convection-diffusion-migration transport in the nanopores with the transport through the concentration polarization layer. To improve the PPTM model in the aspect of using an empirical model to describe the velocity field of solution above the membrane, the velocity profile in solution is solved by Navier-Stokes equation and continuity equation in this paper. The cross-flow nanofiltration of polymeric membrane is simulated using the finite element method, by coupling mass transfer in the membrane with ion concentration and velocity profile in solution above the membrane. By the comparison with experimental results and traditional PPTM results, it can be found that the modified method can reflect the change tendencies of ion concentration and velocity profile in solution, and their values are more in line with the values of experiments. The improved model can provide more reliable theoretical basis for the optimal design of cross-flow nanofiltration processes of polymeric membrane.