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Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. An increased risk for HEV infection has been reported in organ-transplant recipients, mainly from Europe. Prospective data on HEV prevalence in the United States (U.S.) organ transplant population are limited. To determine the prevalence and factors associated with HEV infection among solid organ transplant-recipients, we conducted a prospective, cross-sectional, multicentre study among transplant-recipients and age- and organ-matched waitlist patients. Participants answered a risk-exposure questionnaire and were tested for HEV-RNA (in-house PCR), HEV-IgG, and IgM (ELISA, Wantai). Among 456 participants, 224 were transplant-recipients, and 232 were waitlist patients. The mean age was 58 years, 35% female, and 74% White. HEV seroprevalence of the entire cohort was 20.2% and associated with older age (p 0.0001) and organ transplantation (p = 0.02). The HEV seropositivity was significantly higher among transplant-recipients compared with waitlist patients (24% vs. 16.4%, p = 0.042). Among transplant recipients, relative-risk of being HEV seropositive increased with older age (RR = 3.4 [1.07-10.74] in patients70 years compared with ≤50 years, p = 0.037); history of graft hepatitis (2.2 [1.27-3.72], p = 0.005); calcineurin inhibitor use (RR = 1.9 [1.03-3.34], p = 0.02); and kidney transplantation (2.4 [1.15-5.16], p = 0.02). HEV-RNA, genotype 3 was detected in only two patients (0.4%), both transplant-recipients. HEV seroprevalence was higher among transplant-recipients than waitlist patients. HEV should be considered in transplant-recipients presenting with graft hepatitis. Detection of HEV-RNA was rare, suggesting that progression to chronic HEV infection is uncommon in transplant-recipients in the U.S.

Little attention has been given to language support for block-based compression algorithms, despite their high implementation complexity. Current implementations have to deal with both the intricacies of the algorithm itself, as well as the low-level optimizations necessary for generating fast code. However, many block-based compression algorithms share a common structure in terms of their data representations, data partitioning operations, and data traversals. In this work, we propose a set of high-level language abstractions that can succinctly capture this structure. These abstractions provide the building blocks for the development of a domain-specific language and an associated optimizing compiler. With compression-specific language support, researchers can focus on algorithm development rather than the low-level implementation details.

Erythrocytes bind circulating immune complexes (ICs) and facilitate IC clearance from the circulation. Chronic hepatitis C virus (HCV) infection is associated with IC-related disorders. In this study, we investigated the kinetics and mechanism of HCV and HCV-IC binding to and dissociation from erythrocytes. Cell culture-produced HCV was mixed with erythrocytes from healthy blood donors, and erythrocyte-associated virus particles were quantified. Purified complement proteins, complement-depleted serum, and complement receptor antibodies were used to investigate complement-mediated HCV-erythrocyte binding. Purified HCV-specific immunoglobulin G (IgG) from a chronic HCV-infected patient was used to study complement-mediated HCV-IC/erythrocyte binding. Binding of HCV to erythrocytes increased 200- to 1,000-fold after adding complement active human serum in the absence of antibody. Opsonization of free HCV occurred within 10 minutes, and peak binding to erythrocytes was observed at 20-30 minutes. Complement protein C1 was required for binding, whereas C2, C3, and C4 significantly enhanced binding. Complement receptor 1 (CR1, CD35) antibodies blocked the binding of HCV to erythrocytes isolated from chronically infected HCV patients and healthy blood donors. HCV-ICs significantly enhanced complement-mediated binding to erythrocytes compared to unbound HCV. Dissociation of complement-opsonized HCV from erythrocytes depended on the presence of Factor I. HCV released by Factor I bound preferentially to CD19+ B cells compared to other leukocytes. Conclusion: These results demonstrate that complement mediates the binding of free and IC-associated HCV to CR1 on erythrocytes and provide a mechanistic rationale for investigating the differential phenotypic expression of HCV-IC-related disease.

Data curation is the process of acquiring multiple sources of data, assessing and improving data quality, standardizing, and integrating the data into a usable information product, and eventually disposing of the data. The research describes the building of a proof-of-concept for an unsupervised data curation process addressing a basic form of data cleansing in the form of identifying redundant records through entity resolution and spelling corrections. The novelty of the approach is to use ER as the first step using an unsupervised blocking and stop word scheme based on token frequency. A scoring matrix is used for linking unstandardized references, and an unsupervised process for evaluating linking results based on cluster entropy. The ER process is iterative, and in each iteration, the match threshold is increased. The prototype was tested on 18 fully-annotated test samples of primarily synthetic person data varied in two different ways, good data quality versus poor data quality, and a single record layout versus two different record layouts. In samples with good data quality and using both single and mixed layouts, the final clusters had an average F-measure of 0.91, precision of 0.96, and recall of 0.87 outcomes comparable to results from a supervised ER process. In samples with poor data quality whether mixed or single layout, the average F-measure was 0.78, precision 0.74, and recall 0.83 showing that data quality assessment and improvement is still a critical component of successful data curation. The results demonstrate the feasibility of building an unsupervised ER engine to support data integration for good quality references while avoiding the time and effort to standardize reference sources to a common layout, design, and test matching rules, design blocking keys, or test blocking alignment. Also, the paper proposes how unsupervised data quality improvement processes could also be incorporated into the design allowing the model to address an even broader range of data curation applications.

The goal of this study was to determine whether an association exists between circulating microRNA (miRNA) levels and disease progression in chronic hepatitis C (CHC), whether plasma or extracellular vesicles (EVs) were optimal for miRNA measurement and their correlation with hepatic miRNA expression, and the mechanistic plausibility of this association. We studied 130 CHC patients prospectively followed over several decades. A comprehensive miRNA profile in plasma using microarray with 2578 probe sets showed 323 miRNAs differentially expressed between healthy individuals and CHC patients, but only six that distinguished patients with mild versus severe chronic hepatitis. Eventually, let-7a/7c/7d-5p and miR-122-5p were identified as candidate predictors of disease progression. Cross-sectional analyses at the time of initial liver biopsy showed that reduced levels of let-7a/7c/7d-5p (let-7s) in plasma were correlated with advanced histological hepatic fibrosis stage and other fibrotic markers, whereas miR-122-5p levels in plasma were positively correlated with inflammatory activity, but not fibrosis. Measuring let-7s levels in EVs was not superior to intact plasma for discriminating significant hepatic fibrosis. Longitudinal analyses in 60 patients with paired liver biopsies showed that let-7s levels in plasma markedly declined over time in parallel with fibrosis progression. However, circulating let-7s levels did not parallel those in the liver. Conclusion: Of all miRNAs screened, the let-7 family showed the best correlation with hepatic fibrosis in CHC. A single determination of let-7s levels in plasma did not have superior predictive value for significant hepatic fibrosis compared with that of fibrosis-4 index, but the rate of let-7s decline in paired longitudinal samples correlated well with fibrosis progression. Pathway analysis suggested that low levels of let-7 may influence hepatic fibrogenesis through activation of transforming growth factor β signaling in hepatic stellate cells. (Hepatology 2016;64:732-745)

Clinical cases of paralytic shellfish poisoning (PSP) are common in Alaska, and result from human consumption of shellfish contaminated with saxitoxin (STX) and its analogues. Diagnosis of PSP is presumptive and based on recent ingestion of shellfish and presence of manifestations consistent with symptoms of PSP; diagnosis is confirmed by detection of paralytic shellfish toxins in a clinical specimen or food sample. A clinical diagnostic analytical method using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to evaluate the diagnosis of saxitoxin-induced PSP (STX-PSP) in 11 Alaskan patients using urine specimens collected between June 2010 and November 2011. Concentrations of urinary STX were corrected for creatinine concentrations to account for dilution or concentration of urine from water intake or restriction, respectively. Of the 11 patients with suspected PSP, four patients were confirmed to have STX-PSP by urine testing (24-364ng STX/g creatinine). Five patients had clinical manifestations of PSP though no STX was detected in their urine. Two patients were ruled out for STX-PSP based on non-detected urinary STX and the absence of clinical findings. Results revealed that dysphagia and dysarthria may be stronger indicators of PSP than paresthesia and nausea, which are commonly used to clinically diagnose patients with PSP. PSP can also occur from exposure to a number of STX congeners, such as gonyautoxins, however their presence in urine was not assessed in this investigation. In addition, meal remnants obtained from six presumptive PSP cases were analyzed using the Association of Official Analytical Chemists' mouse bioassay. All six samples tested positive for PSP toxins. In the future, the clinical diagnostic method can be used in conjunction with the mouse bioassay or HPLC-MS/MS to assess the extent of STX-PSP in Alaska where it has been suggested that PSP is underreported.

The perovskite SrCo0.9Nb0.1O3−δ (SCN) has excellent electrochemical activity toward oxygen reduction, and it is also valuable as a possible model material for other state-of-the-art perovskite catalysts based on strontium and cobalt, such as Ba0.5Sr0.5Co0.8Fe0.2O3−δ (BSCF). Here we report thermogravimetric, conductivity, and diffraction measurements from SCN. We find that the thermodynamic stability limits of SCN are slightly more favorable than those reported for BSCF, although both materials exhibit a slow oxidative partial decomposition under likely operating conditions. In SCN, this decomposition is thermodynamically preferred when the average formal oxidation state of cobalt is greater than ∼3.0+, but due to sluggish kinetics, metastable SCN with higher cobalt valence can be observed. The oxygen stoichiometry 3−δ varies from 2.45 to 2.70 under the conditions studied, 500–1000 °C and 10–4–1 bar O2, which encompass both stable and metastable behavior. The electronic conductivity is p-type and thermally...

Author(s): Mudan, Anita; Copan, Lori; Wang, Richard; Pugh, Amy; Lebin, Jacob; Barreau, Tracy; Jones, Robert L; Ghosal, Sutapa; Lee, Mai; Albertson, Timothy; Jarrett, Jeffery M; Lee, Jean; Betting, David; Ward, Cynthia D; De Leon Salazar, Alfonsina; Smollin, Craig G; Blanc, Paul D

Introduction Polybrominated diphenyl ethers (PBDEs) comprise a class of halogenated compounds used extensively as flame retardant chemicals in consumer products resulting in nearly ubiquitous human exposure. Mounting evidence suggests that PBDEs are developmental neurotoxicants; however, associations between early life exposure and child behavior have been largely limited to a single developmental time point. Methods The study population consists primarily of white, black and Chinese women who were pregnant on 11 September 2001 and delivered at 1 of 3 downtown New York City hospitals. Maternal–child pairs were followed through age 7 years. Cord blood was collected at delivery and PBDE plasma levels for 210 samples were analyzed by the U.S. Centers for Disease Control and Prevention. The Child Behavior Checklist, a validated maternal-report instrument used for assessing child behavior, was administered annually between the ages of 3 and 7 years. We analyzed the association between natural log-transformed and dichotomized (low vs. high) PBDEs and attention problems using multivariable adjusted negative binomial regression. Results We detected 4 PBDE congeners in more than 50% of samples, with concentrations highest for BDE-47 (median ± IQR: 11.2 ± 19.6 ng/g). In adjusted analyses, we detected associations between BDE-47 (1.21, 95% CI: 1.00, 1.47), and BDE-153 (1.18, 95% CI: 1.00, 1.39) in cord plasma and increased attention problems among children at age 4 (n = 109) but not 6 (n = 107) years. Conclusions Our findings demonstrate a positive trend between prenatal PBDE exposure and early childhood attention problems, and are consistent with previous research reporting associations between prenatal PBDE exposure and disrupted child behaviors.

Enhancing student academic performance and transdisciplinary ability is challenging, but the time and effort put into accomplishing this ambitious feat is priceless. We develop secure privacy preserving across Personal Health Data (PHD) repository and single-cell genomics research for building an Innovative Systematic Pedagogy for Integrated Research - Education (INSPIRE) (http://americancse.org/events/csce2017/csce17_awards). In this paper we further build a novel, eclectic, and insightful framework based on classical and popular machine learning approaches to help us meet the educational challenge. Our framework focuses on using integrative research technologies to help solve “Education’s Performance Prediction Data Mining Crisis” (EPPDMC), by putting to rest issues associated with mining and making best use of big data for educational enhancement, such as multi-source education acquisition, data fusion, and unstructured data analysis. We exploit the uses of deep learning, text classification, and semi-supervised learning approaches to solve challenging problems that educators face when analyzing multiplatform big data involved in education, research and training students. Based on new machine learning approached we developed for genomic big-data research and in combination with machine learning methods (http://americancse.org/events/csce2017/keynotes_lectures/yang_talk) and the vast availability of education data available to us, not only can we utilize structured, unstructured, and even multi-media data, but while engaging in leaning intelligent thinking along the way, we can also maximize the utilization of big data by studying the motion and performance of these data. Hence we build the INSPIRE model that can further incorporate Student Face Expression in Class (SFEiC) to help educators and managers make further improvements as they become involved in the teaching-learning process. This research further facilitates the effectiveness of the INSPIRE model.

Renewable energy systems need to be able to make frequent and rapid adjustments to address shifting solar and wind production. This requires increasingly sophisticated industrial control systems (ICS). But, that also increases the potential risks from cyber-attacks. Despite increasing attention to technical aspects (i.e., software and hardware) of cybersecurity, many professionals and scholars pay little or no attention to its organizational aspects, particularly to stakeholders’ perceptions of the status of cybersecurity within organizations. Given that cybersecurity decisions and policies are mainly made based on stakeholders’ perceived needs and security views, it is critical to measure such perceptions. In this paper, we introduce a methodology for analyzing differences in perceptions of cybersecurity among organizational stakeholders. To measure these perceptions, we first designed House of Security (HoS) as a framework that includes eight constructs of security: confidentiality, integrity, availability, technology resources, financial resources, business strategy, policy and procedures, and culture. We then developed a survey instrument to analyze stakeholders’ perceptions based on these eight constructs. In a pilot study, we used the survey with people in various functional areas and levels of management in two energy and ICS organizations, and conducted a gap analysis to uncover differences in cybersecurity perceptions. This paper introduces the HoS and describes the survey instrument, as well as some of the preliminary findings.

Extrahepatic disease manifestations are common in chronic hepatitis C virus (HCV) infection. The mechanism of HCV-related lymphoproliferative disorders is not fully understood. Recent studies have found that HCV in peripheral blood mononuclear cells (PBMCs) from chronically infected patients is mainly associated with CD19+ B cells. To further elucidate this preferential association of HCV with B cells, we used in vitro cultured virus and uninfected PBMCs from healthy blood donors to investigate the necessary serum components that activate the binding of HCV to B cells. First, we found that the active serum components were present not only in HCV carriers, but also in HCV recovered patients and HCV negative healthy blood donors and that the serum components were heat labile. Second, the preferential binding activity of HCV to B cells could be blocked by anti-complement C3 antibodies. In experiments with complement-depleted serum and purified complement proteins, we demonstrated that complement proteins C1, C2, and C3 were required to activate such binding activity. Complement protein C4 was partially involved in this process. Third, using antibodies against cell surface markers, we showed that the binding complex mainly involved CD21 (complement receptor 2), CD19, CD20, and CD81; CD35 (complement receptor 1) was involved but had lower binding activity. Fourth, both anti-CD21 and anti-CD35 antibodies could block the binding of patient-derived HCV to B cells. Fifth, complement also mediated HCV binding to Raji cells, a cultured B cell line derived from Burkitt´s lymphoma.CONCLUSION:In chronic HCV infection, the preferential association of HCV with B cells is mediated by the complement system, mainly through complement receptor 2 (CD21), in conjunction with the CD19 and CD81 complex. This article is protected by copyright. All rights reserved. Fil: Wang, Richard. National Institutes of Health; Estados Unidos Fil: Baré, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. National Institutes of Health; Estados Unidos Fil: De Giorgi, Valeria. National Institutes of Health; Estados Unidos Fil: Matsuura, Kentaro. Nagoya City University Graduate School of Medicine; Japón. National Institutes of Health; Estados Unidos Fil: Salam, Kazi Abdus. National Institutes of Health; Estados Unidos. University of Rajshahi; India Fil: Grandinetti, Teresa. National Institutes of Health; Estados Unidos Fil: Schechterly, Cathy. National Institutes of Health; Estados Unidos Fil: Alter, Harvey J.. National Institutes of Health; Estados Unidos

Prussian Blue analogues (PBAs) have shown promise as electrode materials for grid-scale batteries because of their high cycle life and rapid kinetics in aqueous-based electrolytes. However, these materials suffer from relatively low specific capacity, which may limit their practical applications. Here, we investigate strategies to improve the specific capacity of these materials while maintaining their cycling stability and elucidate mechanisms that enhance their electrochemical properties. In particular, we have studied the electrochemical and structural properties of manganese hexacyanoferrate (MnHCFe) and cobalt hexacyanoferrate (CoHCFe) in an aqueous, sodium-ion electrolyte. We also studied manganese–cobalt hexacyanoferrate (Mn–CoHCFe) solid solutions with different Mn/Co ratios that combine properties of both MnHCFe and CoHCFe. The materials have the characteristic open-framework crystal structure of PBAs, and their specific capacities can be significantly improved by electrochemically cycling (oxidizing and reducing) both the carbon-coordinated Fe and the nitrogen-coordinated Co or Mn ions. In situ synchrotron X-ray diffraction studies and ex situ soft X-ray absorption spectroscopy combined with an in-depth electrochemical characterization provide insight into the different electrochemical properties associated with the Fe, Co, and Mn redox couples. We show that cycling the C-coordinated Fe preserves the crystal structure and enables the outstanding kinetics and cycle life previously displayed by PBAs in aqueous electrolytes. On the other hand, the N-coordinated Co and Mn ions exhibit a slower kinetic regime due to structural distortions resulting from the weak N-coordinated crystal field, but they still contribute significantly towards increasing the specific capacity of the materials. These results provide the understanding needed to drive future development of PBAs for grid-scale applications that require extremely high cycle life and kinetics.

The importance of neutralizing antibodies (NAbs) in protection against hepatitis C virus (HCV) remains controversial. We infused a chimpanzee with H06 immunoglobulin from a genotype 1a HCV-infected patient and challenged with genotype strains efficiently neutralized by H06 in vitro . Genotype 1a NAbs afforded no protection against genotype 4a or 5a. Protection against homologous 1a lasted 18 weeks, but infection emerged when NAb titers waned. However, 6a infection was prevented. The differential in vivo neutralization patterns have implications for HCV vaccine development.

The reversible electrochemical insertion of multivalent ions into materials has promising applications in many fields, including batteries, seawater desalination, element purification, and wastewater treatment. However, finding materials that allow for the insertion of multivalent ions with fast kinetics and stable cycling has proven difficult because of strong electrostatic interactions between the highly charged insertion ions and atoms in the host framework. Here, an open framework nanomaterial, copper hexacyanoferrate, in the Prussian Blue family is presented that allows for the reversible insertion of a wide variety of monovalent, divalent, and trivalent ions (such as Rb+, Pb2+, Al3+, and Y3+) in aqueous solution beyond that achieved in previous studies. Electrochemical measurements demonstrate the unprecedented kinetics of multivalent ion insertion associated with this material. Synchrotron X-ray diffraction experiments point toward a novel vacancy-mediated ion insertion mechanism that reduces electrostatic repulsion and helps to facilitate the observed rapid ion insertion. The results suggest a new approach to multi­valent ion insertion that may help to advance the understanding of this complex phenomenon.