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Linear IgE epitopes play essential roles in persistent allergies, including peanut and tree nut allergies. Using chemically synthesized peptides attached to membranes and microarray experiments is one approach for determining predominant epitopes that has seen success. However, the overall expense of this approach and the inherent challenges in scaling up the production and purification of synthetic peptides precludes the general application of this approach. To overcome this problem, we have constructed a plasmid vector for expressing peptides sandwiched between an N-terminal His-tag and a trimeric protein. The vector was used to make overlapping peptides derived from peanut allergens Ara h 2. All the peptides were successfully expressed and purified. The resulting peptides were applied to identify IgE binding epitopes of Ara h 2 using four sera samples from individuals with known peanut allergies. New and previously defined dominant IgE binding epitopes of Ara h 2 were identified. This system may be readily applied to produce agents for component- and epitope-resolved food allergy diagnosis.

Lymphocyte differentiation is regulated by coordinated actions of cytokines and signaling pathways. IL-21 activates STAT1, STAT3, and STAT5 and is fundamental for the differentiation of human B cells into memory cells and antibody-secreting cells. While STAT1 is largely nonessential and STAT3 is critical for this process, the role of STAT5 is unknown.This study sought to delineate unique roles of STAT5 in activation and differentiation of human naive and memory B cells.STAT activation was assessed by phospho-flow cytometry cell sorting. Differential gene expression was determined by RNA-sequencing and quantitative PCR. The requirement for STAT5B in B-cell and CD4IL-21 activated STAT5 and strongly induced SOCS3 in human naive, but not memory, B cells. Deletion of STAT5B in B-cell lines diminished IL-21-mediated SOCS3 induction. PBMCs from STAT5B-null individuals contained expanded populations of immunoglobulin class-switched B cells, CD21These findings reveal novel roles for STAT5B in regulating IL-21-induced human B-cell differentiation. This is achieved by inducing SOCS3 to attenuate IL-21 signaling, and BCL6 to repress class switching and plasma cell generation. Thus, STAT5B is critical for restraining IL-21-mediated B-cell differentiation. These findings provide insights into mechanisms underpinning B-cell responses during primary and subsequent antigen encounter and explain autoimmunity and dysfunctional humoral immunity in STAT5B deficiency.

Keyframe extraction is an effective way to achieve video summarization. More recent studies using deep learning networks are heavily dependent on massive historical datasets for training. For practicality in real applications, we focus more on unsupervised online analysis and present a novel graph-based structural difference analysis method for this purpose. Unlike traditional methods of video representation based on raw features, undirected weighted graphs are constructed from the resulting features to represent video frames. The detailed structural changes between graphs are more consistent with the actual changes between video frames than raw features, thus making the newly proposed method robust for detecting various types of shot transitions, such as hard cuts, dissolves, wipes, and fade-ins/fade-outs. Then, considering the local influence between successive frames, a structural difference analysis of graphs is performed to detect the video shot boundaries. Finally, the median graph of each shot is obtained to extract the corresponding keyframe. Extensive experiments are conducted on three video summarization benchmark datasets. Quantitative and qualitative comparisons are made between the proposed method and other state-of-the-art methods, with the proposed method yielding remarkable improvements from 1.9% to 3.1% in terms of the F-score on the three datasets.

Double short-cut sulfur autotrophic denitrification (DSSADN) coupled with Anammox is of great significance in the low-carbon treatment of nitrogen-containing wastewater. In order to achieve high salinity autotrophic nitrogen removal, the effects of different salinities on the accumulation characteristics of NO

Summary Background Dietary avoidance is recommended for peanut allergies. We evaluated the sustained effects of peanut allergy oral immunotherapy (OIT) in a randomised long-term study in adults and children. Methods In this randomised, double-blind, placebo-controlled, phase 2 study, we enrolled participants at the Sean N Parker Center for Allergy and Asthma Research at Stanford University (Stanford, CA, USA) with peanut allergy aged 7–55 years with a positive result from a double-blind, placebo-controlled, food challenge (DBPCFC; ≤500 mg of peanut protein), a positive skin-prick test (SPT) result (≥5 mm wheal diameter above the negative control), and peanut-specific immunoglobulin (Ig)E concentration of more than 4 kU/L. Participants were randomly assigned (2·4:1·4:1) in a two-by-two block design via a computerised system to be built up and maintained on 4000 mg peanut protein through to week 104 then discontinued on peanut (peanut-0 group), to be built up and maintained on 4000 mg peanut protein through to week 104 then to ingest 300 mg peanut protein daily (peanut-300 group) for 52 weeks, or to receive oat flour (placebo group). DBPCFCs to 4000 mg peanut protein were done at baseline and weeks 104, 117, 130, 143, and 156. The pharmacist assigned treatment on the basis of a randomised computer list. Peanut or placebo (oat) flour was administered orally and participants and the study team were masked throughout by use of oat flour that was similar in look and feel to the peanut flour and nose clips, as tolerated, to mask taste. The statistician was also masked. The primary endpoint was the proportion of participants who passed DBPCFCs to a cumulative dose of 4000 mg at both 104 and 117 weeks. The primary efficacy analysis was done in the intention-to-treat population. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov , NCT02103270 . Findings Between April 15, 2014, and March 2, 2016, of 152 individuals assessed, we enrolled 120 participants, who were randomly assigned to the peanut-0 (n=60), peanut-300 (n=35), and placebo groups (n=25). 21 (35%) of peanut-0 group participants and one (4%) placebo group participant passed the 4000 mg challenge at both 104 and 117 weeks (odds ratio [OR] 12·7, 95% CI 1·8–554·8; p=0·0024). Over the entire study, the most common adverse events were mild gastrointestinal symptoms, which were seen in 90 of 120 patients (50/60 in the peanut-0 group, 29/35 in the peanut-300 group, and 11/25 in the placebo group) and skin disorders, which were seen in 50/120 patients (26/60 in the peanut-0 group, 15/35 in the peanut-300 group, and 9/25 in the placebo group). Adverse events decreased over time in all groups. Two participants in the peanut groups had serious adverse events during the 3-year study. In the peanut-0 group, in which eight (13%) of 60 participants passed DBPCFCs at week 156, higher baseline peanut-specific IgG4 to IgE ratio and lower Ara h 2 IgE and basophil activation responses were associated with sustained unresponsiveness. No treatment-related deaths occurred. Interpretation Our study suggests that peanut OIT could desensitise individuals with peanut allergy to 4000 mg peanut protein but discontinuation, or even reduction to 300 mg daily, could increase the likelihood of regaining clinical reactivity to peanut. Since baseline blood tests correlated with week 117 treatment outcomes, this study might aid in optimal patient selection for this therapy. Funding National Institute of Allergy and Infectious Diseases.

CD8+ T cells are seldom considered in IgE mediated food allergy; we show that peanut specific CD8+ T cells are increased in peanut allergic human subjects.

Glioblastoma multiforme is a malignant neoplasia with a median survival of less than two years and without satisfactory therapeutic options. The so-called glioblastoma stem cells escape the established radio- and chemotherapies and lead to tumor recurrence in most cases. The alkaloid Shikonin with its various anti stem cell properties and the interstitial photodynamic therapy with 5-aminolevulinic acid seem to be promising new options in the therapy of glioblastoma. In this study, in vitro investigations were performed to observe the influence of Shikonin on viability, proliferation, induction of apoptosis and the capability of forming tumor spheres in U-87 MG and the primary glioblastoma cell line GB14. The combined effect with the chemotherapeutic temozolomide and photodynamic treatment on the mRNA expression of glioma specific stem cell markers and further examined intracellular protoporphyrin IX accumulation under Shikonin treatment was analyzed. Shikonin effectively inhibited the capability of forming tumor spheres and enhanced temozolomide effectiveness in the reduction of proliferation and in the induction of apoptosis. Additionally, Shikonin increased the mRNA expression of the tumor suppressing Neurofibromatosis type 1 (NF1) gene and showed modulating effects on intracellular protoporphyrin IX.

I study optimal information provision by a search goods seller. While the seller controls a consumer's pre-search information, which decides whether she will search for the product with a cost, he cannot control the consumer's post-search information because the consumer inevitably learns her match upon inspecting the product. Importantly, I allow the consumer to have private information on her best alternative to the seller's product. To accommodate this, a relaxed problem approach is developed, which fully characterizes the seller's optimal design under certain regularity conditions. Based on this characterization, I consider how consumer privacy, revealing of post-search information, reduction in search cost and competition by a large number of sellers would affect the equilibrium information provision. My approach also helps to highlight the key similarity and dissimilarity between information designs for search goods and experience goods.

With the advent of multi-core and even many-core processors, massively parallel computing processing has presented a trend of low cost and popularity. It provides new technical means and feasible solutions for the rapid simulation calculation of large-scale group movements and the simulable problem of super-large group movements. In the process of parallel computing, the design of parallel architecture and parallel algorithm is closely related to the group motion simulation algorithm itself due to the original task needs to be decomposed. A parallel simulation algorithm for the continuum crowds has been proposed in this paper. We use the transition block-based scene segmentation algorithm on the management node to divide the simulated scene after initializing the virtual scene, and assign each block to a different computing node for processing. Then, the compute node gets information about the individual it is responsible for. Based on the method, a parallel simulation prototype system was developed on the Sugon high-performance computing platform. Experimental results show that our parallel simulation algorithm can increase the efficiency of scene-rendering and solve the bottleneck in group scale.

Certain drugs are nitroaromatic compounds, which are potentially toxic. As such, it is of practical importance to assess and predict their mutagenic potency in the process of drug discovery. A classical quantitative structure-activity relationship (QSAR) model was developed using the linear partial least square (PLS) scheme to understand the underline mutagenic mechanism and a non-classical QSAR model was derived using the machine learning-based hierarchical support vector regression (HSVR) to predict the mutagenicity of nitroaromatic compounds based on a series of mutagenicity data (TA98-S9). It was observed that HSVR performed better than PLS as manifested by the predictions of the samples in the training set, test set, and outlier set as well as various statistical validations. A mock test designated to mimic real challenges also confirmed the better performance of HSVR. Furthermore, HSVR exhibited superiority in predictivity, generalization capabilities, consistent performance, and robustness when compared with various published predictive models. PLS, conversely, revealed some mechanistically interpretable relationships between descriptors and mutagenicity. Thus, this two-QSAR approach using the predictive HSVR and interpretable PLS models in a synergistic fashion can be adopted to facilitate drug discovery and development by designing safer drug candidates with nitroaromatic moiety.

OBJECTIVES: Plasma profile of acylcarnitines has been suggested to associate with adverse maternal outcomes such as gestational diabetes. However, data on their associations with neonatal outcomes are sparse. Therefore, this study aimed to examine the prospective profile of acylcarnitines across gestation and its association with neonatal anthropometry, including birthweight (BW), BW z-score, the sum of skinfolds (SSF), length, and circumferences. METHODS: Among 321 pregnant women from the NICHD Fetal Growth Studies-Singletons cohort, we quantified 28 acylcarnitines using electrospray ionization tandem mass spectrometry in the plasma at gestational weeks 10–14, 15–26, 23–31 and 33–39, accordingly. We firstly applied a latent-class trajectory approach to identify trajectories of acylcarnitines across gestation, and secondly examined associations of individual acylcarnitine and distinct trajectory groups with neonatal anthropometry using weighted linear models with robust standard errors, adjusting for maternal age, race/ethnicity, education, parity, gestational week of blood collection, and pre-pregnancy body mass index. RESULTS: We identified three distinct trajectory groups of C2, C3 and C4, and two trajectory groups of C5, C10, C5-DC, C8:1, C10:1 and C12, respectively. Newborns of women with nonlinear decline of C12 levels across gestation (5.7%) had significantly smaller BW (−475 g; 95% CI: −942, −6.79 g), BW z-score (−0.39; −0.71, −0.06), and length (−1.38 cm; −2.49, −0.27 cm) than those with persistently stable C12 levels (94.3%). Newborns of women with consistently higher levels of C10 (6.1%) had greater sum of skinfolds (4.91 mm; 0.85, 8.98 mm) than those with lower levels (93.9%) across pregnancy, whereas newborns of women with declining C10:1 levels (12.6%) had larger sum of skinfolds (3.23 mm; 0.19, 6.27 mm) than those with abruptly increasing levels (87.4%). CONCLUSIONS: In conclusion, gestational trajectories of C10, C10:1, and C12 acylcarnitine levels were significantly associated with neonatal anthropometry. Further studies are needed to verify and further explore the potential clinical utility of these findings. FUNDING SOURCES: Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding; American Recovery and Reinvestment Act funding.

Agarwood is an important non-timber forest product widely used in religious and cultural activities as perfume and fragrance and as traditional medicine in Asia. The high value of agarwood and the inflated consuming market have led to constant rising of the prices. In general, the price of the agarwood is determined according to its quality, which can be divided into different grades. But up to now, there is not any standard quality grading system which could be used overwhelmingly throughout the agarwood producing, commerce and consumption. Therefore, we reviewed agarwood in diversified grading indexes, systems and methods.

Social applications are becoming one of the most popular applications for users to share data and communicate online. These applications deal with a lot of personal data, e.g., users' locations, interests and documents stored on the remote cloud storage servers. Therefore, we need to pay a deeper attention to data confidentiality and privacy. To address the problem of data confidentiality, existing solutions usually count the security requirement of data owner for data sharing in social applications. However, on the side of the data consumer or member, we want to securely and efficiently get our own interested data. Both the data owner and the member are two roles of users in data sharing applications, and there are little existing research efforts to investigate the implementation of achieving both of their requirements at the same time. In this paper, we propose DASS, a privacy-preserving DAta Sharing Scheme to comprehensively satisfy users' security requirements for social applications. Our solution consists of a fine-grained access control scheme, a dynamic social attribute management model, and a multi-user searchable encryption scheme. We have described our scheme and provided performance evaluation. Validations are done to demonstrate that our scheme is secure, fine-grained and efficient.

Oral immunotherapy (OIT) can successfully desensitize allergic individuals to offending foods such as peanut. Our recent clinical trial ( NCT02103270 ) of peanut OIT allowed us to monitor peanut-specific CD4+ T cells, using MHC-peptide Dextramers, over the course of OIT. We used a single-cell targeted RNAseq assay to analyze these cells at 0, 12, 24, 52, and 104 weeks of OIT. We found a transient increase in TGFβ-producing cells at 52 weeks in those with successful desensitization, which lasted until 117 weeks. We also performed clustering and identified 5 major clusters of Dextramer+ cells, which we tracked over time. One of these clusters appeared to be anergic, while another was consistent with recently described TFH13 cells. The other 3 clusters appeared to be Th2 cells by their coordinated production of IL-4 and IL-13, but they varied in their expression of STAT signaling proteins and other markers. A cluster with high expression of STAT family members also showed a possible transient increase at week 24 in those with successful desensitization. Single cell TCRαβ repertoire sequences were too diverse to track clones over time. Together with increased TGFβ production, these changes may be mechanistic predictors of successful OIT that should be further investigated.

This paper studies optimal disclosure regulation for entrepreneurial public financing with post-financing moral hazard problem. I show that partial disclosure can improve social welfare over full disclosure through reducing efficiency loss caused by the moral hazard problem. As a result, a properly designed partial disclosure rule would be optimal without assuming any disclosure cost. This remains true after allowing for endogenous entrepreneur types with adverse selection concerns. With (constrained) Bayesian persuasion tools, the optimal disclosure rule is fully characterized. Although the paper is developed mainly around entrepreneur equity financing, its intuition can be more generally applicable. For instance, I also adapt the basic model to debt financing and an application to banking system disclosure is provided.

Complications related to corrosion and infection of magnesium (Mg) implants are encountered by physical barrier and local drug delivery system. In this work, the multilayer films composed of ciprofloxacin (CIP) and SiO2 nanoparticles were fabricated on Mg alloys by the spin-spray layer-by-layer assembly method. The resultant films were characterized via FT-IR, XPS, SEM and EDS techniques. The corrosion behaviors of the multilayer films were investigated via electrochemical tests and hydrogen evolution experiment. The obtained films showed corrosion resistance, self-healing ability, antibacterial efficacy and a prolonged release profile. The results also suggested that the loading dosage and the release rate of CIP could be controlled by the assembly parameters. Moreover, the in vitro release kinetics of CIP from the multilayer films could be fitted with the pseudo-second-order model.

As a major mineral of Portland cement, the hydration of tricalcium aluminate (C3A) has a significant impact on various properties of cement-based materials. However, there is little consensus on its mechanism, especially the interaction between C3A and gypsum which usually co-exist in cement systems. Recent researches have shown that sulfate ions play an important role in the kinetics of C3A hydration, which may provide more promising alternatives on controlling cement hydration besides the present solution on adjusting gypsum contents. In this study, effects of different kinds of solid sulfates (gypsum, Na2SO4, MgSO4) on the heat released during the early age of C3A hydration as well as hydration products were investigated first by isothermal calorimetry, SEM, XRD and thermal analysis. Retardation was observed in all the three systems (C3A-gypsum, C3A-Na2SO4 and C3A-MgSO4). But the duration of induction period varied with cations. Then barium nitrate (Ba(NO3)2) aiming to remove the sulfate ions was innovatively employed to highlight the role of sulfate ions. Interestingly, the renewed hydration of C3A occurred immediately after Ba(NO3)2 solution was added into the three systems with different amount of AFt remained. According to the characterization of hydration products, little monosulphoaluminate (s-AFm) was detected in the induction period of C3A-gypsum hydration and a large amount of h-AFm was found to cover the surface of C3A particles after adding Ba(NO3)2 solution. It is concluded that the coexistence of calcium and sulfate ions absorbed at C3A surface is more likely to dominate the retardation of C3A hydration in the presence of gypsum, rather than the alleged physical barrier mechanism caused by the precipitation of hydration products.

Background The frequencies, cellular phenotypes, epitope specificity, and clonal diversity of allergen-specific B cells in patients with food allergy are not fully understood but are of major pathogenic and therapeutic significance. Objective We sought to characterize peanut allergen–specific B-cell populations and the sequences and binding activities of their antibodies before and during immunotherapy. Methods B cells binding fluorescently labeled Ara h 1 or Ara h 2 were phenotyped and isolated by means of flow cytometric sorting from 18 patients at baseline and 13 patients during therapy. Fifty-seven mAbs derived from allergen-binding single B cells were evaluated by using ELISA, Western blotting, and peptide epitope mapping. Deep sequencing of the B-cell repertoires identified additional members of the allergen-specific B-cell clones. Results Median allergen-binding B-cell frequencies were 0.0097% (Ara h 1) or 0.029% (Ara h 2) of B cells in baseline blood from allergic patients and approximately 3-fold higher during immunotherapy. Five of 57 allergen-specific cells belonged to clones containing IgE-expressing members. Almost all allergen-specific antibodies were mutated, and binding to both conformational and linear allergen epitopes was detected. Increasing somatic mutation of IgG 4 members of a clone was seen in immunotherapy, whereas IgE mutation levels in the clone did not increase. Conclusion Most peanut allergen–binding B cells isolated by means of antigen-specific flow sorting express mutated and isotype-switched antibodies. Immunotherapy increases their frequency in the blood, and even narrowly defined allergen epitopes are recognized by numerous distinct B-cell clones in a patient. The results also suggest that oral immunotherapy can stimulate somatic mutation of allergen-specific IgG 4 .

Wireless sensor networks (WSNs) are inherently susceptible to attacks as malicious nodes can disrupt the communication from any other node to the sink. To address a wide range of attacks, we propose a novel and comprehensive approach called Secure and Scalable Geographic Opportunistic Routing with received signal strength (SGOR), satisfying the requirements of both security and scalability in WSNs. Unlike most of previous secure protocols relying on infrastructure like anchor nodes, a distributed location verification algorithm is presented to utilize the received signal strength to address the location spoofing attack. As one of opportunistic geographic routings, SGOR provides the property of robustness by taking full advantage of the broadcast nature of wireless channels, and scalability for being inherited from geographic routing. Moreover, an ambient-sensitive trust model is proposed to defend against more kinds of attackers in SGOR. The theoretical results are given to demonstrate the effectiveness and robustness of SGOR to survive more severe attacks. In extensive simulations, we compare SGOR with four other representative protocols. The results show that SGOR achieves about two times higher packet delivery rate with acceptable overhead, particularly in large and highly hostile networks.

Objective Using athletes that children value to model eating fruit and vegetables (FV) could be an effective tool to increase FV consumption. The objective was to evaluate a nutrition intervention with athlete mentors aimed at increasing student preferences, knowledge of FV and decreasing FV neophobias. Description Eleven rural Indiana elementary schools were recruited into five strata and randomly assigned to control (n = 6) or intervention (n = 5) in a cluster RCT. Intervention students received an assembly featuring college athlete mentors, a tasting session, followed by six different videos ( Students completed Qualtrics surveys to assess FV familiarity, preferences, knowledge, and habits in September 2017 (pre), May 2018 (post-one), and September 2018 (post-two). Interactions between groups over time were compared using linear mixed models with random effects for school, class; α = 0.050. Evaluation FV preferences for control students (CON) decreased more than intervention students (INT) from pre- to post-one (P = .016), with no difference between groups from post-one to post-two (P = .118) and pre- to post-two (P = .482). Vegetable neophobias decreased from pre to post-two in INT vs. CON (P = .019), although overall treatment x time interaction was only marginally significant (P = .064). Food group knowledge increased from pre to post-one in INT vs. CON (P = .001) and maintained at post-two (P = .050). FV plate fraction knowledge marginally improved for INT from pre- to post-one (P = .066) and increased from pre- to post-two (P = .005). There were no differences in FV familiarity, frequency, variety, fruit neophobias, trying new FV, and being able to select high nutrient dense FV-containing foods. Conclusions and Implications The intervention to improve FV nutrition produced benefits in some, but not all, outcomes. Some improvements in nutritional attitudes and knowledge creates optimism that this program may enhance student nutrition. Program benefits may be enhanced with additional attention to components that support variety, frequency, familiarity, and comfort in trying FV. Grant Year 2016

Under the framework of media system dependency theory, this study investigates and compares traditional media dependency and Internet dependency in public health crisis situations in the context of Mainland China. 373 college students participated in the survey. Empirical data demonstrated that, during public health crises: (1) traditional media and the Internet play different roles for individuals; (2) higher level of threat perception leads to more intense Internet dependency, but does not do the same to traditional media dependency; (3) individuals’ Internet dependency intensity is higher than their traditional media dependency intensity; and (4) the Internet may influence the behavior of young Chinese more directly.

The purpose of this paper is twofold: (1) to identify and compare the crisis communication strategies (CCSs) that organizations used to respond to a congenetic melamine-tainted milk crisis in two Chinese societies (i.e., Mainland China and Taiwan), and (2) to explore the underlying political and media system reasons that led to the differences. Content analysis and discourse analysis of media coverage were used. The most significant finding is that Sanlu (a Mainland China-based organization) and KingCar (a Taiwan-based organization) demonstrated inverse pattern of the CCS adoption. Specifically, according to Coombs’ (1998) defense-accommodation continuum, Sanlu's CCSs moved from defensive to accommodative pole as time went by whereas, in contrast, KingCar started with accommodative strategies and moved towards the defensive pole gradually. Besides, the results showed that both organizations adopted denial, corrective action and apology strategies. However, on the Sanlu part, the most frequently used strategy was denial, while KingCar used justification most often. Moreover, this paper suggests that besides cultural dynamics, political and media systems also play a part in corporate selection of CCSs, and they are among the most important factors that should be taken into account to explain the differences in societies even with an identical traditional culture.