Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Epitope-Specific Anti-Respiratory Syncytial Virus (Anti-RSV) Antibody Responses after Natural Infection and after Vaccination with Formalin-Inactivated RSV

ABSTRACT Antibodies against the fusion (F) protein of respiratory syncytial virus (RSV) play an important role in the protective immune response to this important respiratory virus. Little is known, however, about antibody levels against multiple F-specific epitopes induced by infection or after vaccination against RSV, while this is important to guide the evaluation of (novel) vaccines. In this study, we analyzed antibody levels against RSV proteins and F-specific epitopes in human sera and in sera of vaccinated and experimentally infected cotton rats and the correlation thereof with virus neutralization. Analysis of human sera revealed substantial diversity in antibody levels against F-, G (attachment)-, and F-specific epitopes between individuals. The highest correlation with virus neutralization was observed for antibodies recognizing prefusion-specific antigenic site Ø. Nevertheless, our results indicate that high levels of antibodies targeting other parts of the F protein can also mediate a potent antiviral antibody response. In agreement, sera of experimentally infected cotton rats contained high neutralizing activity despite lacking antigenic site Ø-specific antibodies. Strikingly, vaccination with formalin-inactivated RSV (FI-RSV) exclusively resulted in the induction of poorly neutralizing antibodies against postfusion-specific antigenic site I, although antigenic sites I, II, and IV were efficiently displayed in FI-RSV. The apparent immunodominance of antigenic site I in FI-RSV likely explains the low levels of neutralizing antibodies upon vaccination and challenge and may play a role in the vaccination-induced enhancement of disease observed with such preparations. IMPORTANCE RSV is an importance cause of hospitalization of infants. The development of a vaccine against RSV has been hampered by the disastrous results obtained with FI-RSV vaccine preparations in the 1960s that resulted in vaccination-induced enhancement of disease. To get a better understanding of the antibody repertoire induced after infection or after vaccination against RSV, we investigated antibody levels against fusion (F) protein, attachment (G) protein, and F-specific epitopes in human and animal sera. The results indicate the importance of prefusion-specific antigenic site Ø antibodies as well as of antibodies targeting other epitopes in virus neutralization. However, vaccination of cotton rats with FI-RSV specifically resulted in the induction of weakly neutralizing, antigenic site I-specific antibodies, which may play a role in the enhancement of disease observed after vaccination with such preparations.
Influenza Virus Hemagglutinin Glycoproteins with Different N-Glycan Patterns Activate Dendritic Cells In Vitro

ABSTRACT Influenza virus hemagglutinin (HA) N-glycans play important regulatory roles in the control of virus virulence, antigenicity, receptor-binding specificity, and viral escape from the immune response. Considered essential for controlling innate and adaptive immune responses against influenza virus infections, dendritic cells (DCs) trigger proinflammatory and adaptive immune responses in hosts. In this study, we engineered Chinese hamster ovary (CHO) cell lines expressing recombinant HA from pandemic H1, H5, and H7 influenza viruses. rH1HA, rH5HA, and rH7HA were obtained as wild-type proteins or in the presence of kifunensine (KIF) or further with endo-β-N-acetylglucosaminidase-treated KIF (KIF+E) to generate single-N-acetylglucosamine (GlcNAc) N-glycans consisting of (i) terminally sialylated complex-type N-glycans, (ii) high-mannose-type N-glycans, and (iii) single-GlcNAc-type N-glycans. Our results show that high-mannose-type and single-GlcNAc-type N-glycans, but not complex-type N-glycans, are capable of inducing more active hIL12 p40, hIL12 p70, and hIL-10 production in human DCs. Significantly higher HLA-DR, CD40, CD83, and CD86 expression levels, as well reduced endocytotic capacity in human DCs, were noted in the high-mannose-type rH1HA and single-GlcNAc-type rH1HA groups than in the complex-type N-glycan rH1HA group. Our data indicate that native avian rHA proteins (H5N1 and H7N9) are more immunostimulatory than human rHA protein (pH1N1). The high-mannose-type or single-GlcNAc-type N-glycans of both avian and human HA types are more stimulatory than the complex-type N-glycans. HA-stimulated DC activation was accomplished partially through a mannose receptor(s). These results provide more understanding of the contribution of glycosylation of viral proteins to the immune responses and may have implications for vaccine development. IMPORTANCE Influenza viruses trigger seasonal epidemics or pandemics with mild-to-severe consequences for human and poultry populations. DCs are the most potent professional antigen-presenting cells, which play a crucial role in the link between innate and adaptive immunity. In this study, we obtained stable-expression CHO cells to produce rH1HA, rH5HA, and rH7HA proteins containing distinct N-glycan patterns. These rHA proteins, each with a distinct N-glycan pattern, were used to investigate interactions with mouse and human DCs. Our data indicate that native avian rHA proteins (H5N1 and H7N9) are more immunostimulatory than human rHA protein (pH1N1). High-mannose-type and single-GlcNAc-type N-glycans were more effective than complex-type N-glycans in triggering mouse and human DC activation and maturation. We believe these results provide some useful information for influenza vaccine development regarding how influenza virus HA proteins with different types of N-glycans activate DCs.
Technology-Mediated Interventions and Quality of Life for Persons Living with HIV/AIDS

Summary Background: As HIV/AIDS is considered a chronic disease; quality of life (QoL) has become an important focus for researchers and healthcare providers. Technology-mediated interventions have demonstrated improved clinical effectiveness in outcomes, such as viral suppression, for persons living with HIV/AIDS (PLWH). However, the evidence to support the impact of these interventions on QoL is lacking. Objectives: The aim of this paper was to assess the impact of technology-mediated interventions on QoL and to identify the instruments used to measure the QoL of PLWH. Methods: For this review we followed the PRISMA guidelines. A literature search was conducted in PubMed, CINAHL, Cochrane, and EMBASE databases in April 2016. Inclusion criteria limited articles to those with technology-mediated interventions as compared to usual care; articles with the population defined as HIV-infected patients; and articles with QoL measured as a health outcome in randomized controlled trials. The Cochrane Collaboration Risk of Bias Tool was used to assess study quality. Results: Of the 1,554 peer-reviewed articles returned in the searches, 10 met the inclusion criteria. This systematic review identified four types of technology-mediated interventions and two types of QoL instruments used to examine the impact of technology-mediated interventions on PLWH. Four studies of technology-mediated interventions resulted in improvement in QoL. Four studies considered QoL as a secondary outcome and resulted in a negative or neutral impact on QoL. Overall, four studies had a low risk of bias, one study had a moderate risk of bias, and the other five studies had a high risk of bias. Conclusions: The evidence to support the improvement of QoL using technology-mediated interventions is insufficient. This lack of research highlights the need for increased study of QoL as an outcome measure and the need for consistent measures to better understand the role of technology-mediated interventions in improving QoL for PLWH. Citation: Hwayoung Cho, Sarah Iribarren, Rebecca Schnall. Technology-Mediated Interventions and Quality of Life for Persons Living with HIV/AIDS: A Systematic Review. Appl Clin Inform 2017; 8: 348–368 https://doi.org/10.4338/ACI-2016-10-R-0175
Differential Impacts of Land-Based Sources of Pollution on the Microbiota of Southeast Florida Coral Reefs

ABSTRACT Coral reefs are dynamic ecosystems known for decades to be endangered due, in large part, to anthropogenic impacts from land-based sources of pollution (LBSP). In this study, we utilized an Illumina-based next-generation sequencing approach to characterize prokaryotic and fungal communities from samples collected off the southeast coast of Florida. Water samples from coastal inlet discharges, oceanic outfalls of municipal wastewater treatment plants, treated wastewater effluent before discharge, open ocean samples, and coral tissue samples (mucus and polyps) were characterized to determine the relationships between microbial communities in these matrices and those in reef water and coral tissues. Significant differences in microbial communities were noted among all sample types but varied between sampling areas. Contamination from outfalls was found to be the greatest potential source of LBSP influencing native microbial community structure among all reef samples, although pollution from inlets was also noted. Notably, reef water and coral tissue communities were found to be more greatly impacted by LBSP at southern reefs, which also experienced the most degradation during the course of the study. The results of this study provide new insights into how microbial communities from LBSP can impact coral reefs in southeast Florida and suggest that wastewater outfalls may have a greater influence on the microbial diversity and structure of these reef communities than do contaminants carried in runoff, although the influences of runoff and coastal inlet discharge on coral reefs are still substantial. IMPORTANCE Coral reefs are known to be endangered due to sewage discharge and to runoff of nutrients, pesticides, and other substances associated with anthropogenic activity. Here, we used next-generation sequencing to characterize the microbial communities of potential contaminant sources in order to determine how environmental discharges of microbiota and their genetic material may influence the microbiomes of coral reef communities and coastal receiving waters. Runoff delivered through inlet discharges impacted coral microbial communities, but impacts from oceanic outfalls carrying treated wastewater were greater. Geographic differences in the degree of impact suggest that coral microbiomes may be influenced by the microbiological quality of treated wastewater.
Caching for Pattern Matching Queries in Time Evolving Graphs: Challenges and Approaches

Pattern matching is an important class of problemsrelated to graphs. It is a fundamental problem for manyapplications and has been extensively studied in literature. Withthe advent of huge graphs, the challenges in this domain haveincreased manifold. Consequently a lot of recent research has ledto new architectures and approaches for optimized solutions tothe pattern matching problem. A vast majority of these graphshardly remain static and constantly evolve over time (like socialnetworks, web graphs, etc). Recently, caching has been studied inthe context of static graphs to optimize the throughput of queryprocessing systems. In this paper, we list the challenges in cachingin the context of Time Evolving Graphs (TEGs). Amongst others,one major challenge is consistency which entails to making surethe cache is consistent with the streaming changes. We proposean approach to successfully implement caching that addressesthose issues and based on the initial results, we see significantgains in the overall performance of system.
A Cluster Based Approach for Task Scheduling across Multiple Programming Systems

As the data processing demands have been increasing, different types of data processing systems are being developed. The new programming systems have different characteristics like types of data handled, processing technique and performance. However, multiple new systems have introduced difficulties for non-expert users like choosing the right system and usage methodology of the new systems. In order to relieve the burden of common users of conducting data processing tasks and taking relevant advantage of the systems features, we intend to integrate the popular programming systems and provide more efficient data processing services. In this paper, we propose to address the task scheduling problem for integrating multiple programming systems. We have designed a cluster based approach for task scheduling across multiple programming systems. This approach helps in minimizing the makespan of workflows and resource consumption. The simulation results show that the proposed approach can reduce the resource consumption significantly while achieving a low makespan for the workflows.
Patient Health Communication Mediating Effects Between Gastrointestinal Symptoms and Gastrointestinal Worry in Pediatric Inflammatory Bowel Disease

Background: To investigate the effects of patient health communication regarding their inflammatory bowel disease (IBD) to their health care providers and significant others in their daily life as a mediator in the relationship between gastrointestinal symptoms and gastrointestinal worry in pediatric patients. Methods: The Pediatric Quality of Life Inventory Gastrointestinal Symptoms, Gastrointestinal Worry, and Communication Scales, and Pediatric Quality of Life Inventory 4.0 Generic Core Scales were completed in a 9-site study by 252 pediatric patients with IBD. Gastrointestinal Symptoms Scales measuring stomach pain, constipation, or diarrhea and patient communication were tested for bivariate and multivariate linear associations with Gastrointestinal Worry Scales specific to patient worry about stomach pain or bowel movements. Mediational analyses were conducted to test the hypothesized mediating effects of patient health communication as an intervening variable in the relationship between gastrointestinal symptoms and gastrointestinal worry. Results: The predictive effects of gastrointestinal symptoms on gastrointestinal worry were mediated in part by patient health communication with health care providers/significant others in their daily life. In predictive models using multiple regression analyses, the full conceptual model of demographic variables, gastrointestinal symptoms (stomach pain, constipation, or diarrhea), and patient communication significantly accounted for 46, 43, and 54 percent of the variance in gastrointestinal worry (all Ps < 0.001), respectively, reflecting large effect sizes. Conclusions: Patient health communication explains in part the effects of gastrointestinal symptoms on gastrointestinal worry in pediatric patients with IBD. Supporting patient disease-specific communication to their health care providers and significant others may improve health-related quality of life for pediatric patients with IBD.
A REVIEW ON INVESTIGATION OF MIXED MODE FRACTURE IN BRITTLE MATERIALS

A series of mixed mode fracture tests were conducted on specimens made up of brittle materials to find out fracture parameters. Some of the parameters of interest are stress intensity factor (K), fracture toughness (Kc) and crack growth direction. In order to minimize catastrophic effects of mixed mode brittle fracture, investigation of mixed mode fracture is necessary. A number of researches have been carried out utilizing universal testing machine with suitable fixtures. Some of the experiments conducted used techniques like indentation techniques, tension tests, compression tests, bending and so on. Each one has its own advantages and disadvantages. The experimental results obtained were theoretically verified by many mixed mode fracture criteria. Some researchers also came up with empirical relations to approximate results which wouldn’t have been possible by existing famous fracture criteria. Even numerical methods like FEM analysis were carried out using commercially available softwares like ABACUS.
Chondroitin sulfate proteoglycans as novel drivers of leucocyte infiltration in multiple sclerosis

Multiple sclerosis presents with profound changes in the network of molecules involved in maintaining central nervous system architecture, the extracellular matrix. The extracellular matrix components, particularly the chondroitin sulfate proteoglycans, have functions beyond structural support including their potential interaction with, and regulation of, inflammatory molecules. To investigate the roles of chondroitin sulfate proteoglycans in multiple sclerosis, we used the experimental autoimmune encephalomyelitis model in a time course study. We found that the 4-sulfated glycosaminoglycan side chains of chondroitin sulfate proteoglycans, and the core protein of a particular family member, versican V1, were upregulated in the spinal cord of mice at peak clinical severity, correspondent with areas of inflammation. Versican V1 expression in the spinal cord rose progressively over the course of experimental autoimmune encephalomyelitis. A particular structure in the spinal cord and cerebellum that presented with intense upregulation of chondroitin sulfate proteoglycans is the leucocyte-containing perivascular cuff, an important portal of entry of immune cells into the central nervous system parenchyma. In these inflammatory perivascular cuffs, versican V1 and the glycosaminoglycan side chains of chondroitin sulfate proteoglycans were observed by immunohistochemistry within and in proximity to lymphocytes and macrophages as they migrated across the basement membrane into the central nervous system. Expression of versican V1 transcript was also documented in infiltrating CD45+ leucocytes and F4/80+ macrophages by in situ hybridization. To test the hypothesis that the chondroitin sulfate proteoglycans regulate leucocyte mobility, we used macrophages in tissue culture studies. Chondroitin sulfate proteoglycans significantly upregulated pro-inflammatory cytokines and chemokines in macrophages. Strikingly, and more potently than the toll-like receptor-4 ligand lipopolysaccharide, chondroitin sulfate proteoglycans increased the levels of several members of the matrix metalloproteinase family, which are implicated in the capacity of leucocytes to cross barriers. In support, the migratory capacity of macrophages in vitro in a Boyden chamber transwell assay was enhanced by chondroitin sulfate proteoglycans. Finally, using brain specimens from four subjects with multiple sclerosis with active lesions, we found chondroitin sulfate proteoglycans to be associated with leucocytes in inflammatory perivascular cuffs in all four patients. We conclude that the accumulation of chondroitin sulfate proteoglycans in the perivascular cuff in multiple sclerosis and experimental autoimmune encephalomyelitis boosts the activity and migration of leucocytes across the glia limitans into the central nervous system parenchyma. Thus, chondroitin sulfate proteoglycans represent a new class of molecules to overcome in order to reduce the inflammatory cascades and clinical severity of multiple sclerosis.
Selective Neuronal Activation by Cochlear Implant Stimulation in Auditory Cortex of Awake Primate

Despite the success of cochlear implants (CIs) in human populations, most users perform poorly in noisy environments and music and tonal language perception. How CI devices engage the brain at the single neuron level has remained largely unknown, in particular in the primate brain. By comparing neuronal responses with acoustic and CI stimulation in marmoset monkeys unilaterally implanted with a CI electrode array, we discovered that CI stimulation was surprisingly ineffective at activating many neurons in auditory cortex, particularly in the hemisphere ipsilateral to the CI. Further analyses revealed that the CI-nonresponsive neurons were narrowly tuned to frequency and sound level when probed with acoustic stimuli; such neurons likely play a role in perceptual behaviors requiring fine frequency and level discrimination, tasks that CI users find especially challenging. These findings suggest potential deficits in central auditory processing of CI stimulation and provide important insights into factors responsible for poor CI user performance in a wide range of perceptual tasks. SIGNIFICANCE STATEMENT The cochlear implant (CI) is the most successful neural prosthetic device to date and has restored hearing in hundreds of thousands of deaf individuals worldwide. However, despite its huge successes, CI users still face many perceptual limitations, and the brain mechanisms involved in hearing through CI devices remain poorly understood. By directly comparing single-neuron responses to acoustic and CI stimulation in auditory cortex of awake marmoset monkeys, we discovered that neurons unresponsive to CI stimulation were sharply tuned to frequency and sound level. Our results point out a major deficit in central auditory processing of CI stimulation and provide important insights into mechanisms underlying the poor CI user performance in a wide range of perceptual tasks.
Engineering properties of geopolymer incorporating slag, fly ash, silica sand and pumice

The aim of this study is concrete production made with blast furnace slag, fly ash, silica sand and pumice were activated with Noah geopolymer. For this purpose, ground granulated blast furnace slag, fly ash, silica sand and pumice using alkali solution is prepared by Noah 4x4x16 cm and 10x10x10 cm in size geopolymer concrete mortars were produced. Water absorption, flexural and compressive strength of unit weight, ultrasonic sound transmission and linear absorption coefficient of samples were determined. Geopolymerin obtained by blast-furnace slag by water absorption ratio is lower than the other samples. Ultrasonic sound transmission rates were found lower than that of the samples with higher water absorption values. Moreover, flexural and compressive strengths of these samples were much higher than the others. Permeability of radioactive material so at least these structures that are exposed to radiation may be used.
Genome-Scale Modeling of NADPH-Driven β-Lapachone Sensitization in Head and Neck Squamous Cell Carcinoma.

AIMS The purpose of this study was to investigate differential nicotinamide adenine dinucleotide phosphate, reduced (NADPH) production between radiation-sensitive and -resistant head and neck squamous cell carcinoma (HNSCC) cell lines and whether these differences are predictive of sensitivity to the chemotherapeutic β-lapachone. RESULTS We have developed a novel human genome-scale metabolic modeling platform that combines transcriptomic, kinetic, thermodynamic, and metabolite concentration data. Upon incorporation of this information into cell line-specific models, we observed that the radiation-resistant HNSCC model redistributed flux through several major NADPH-producing reactions. Upon RNA interference of canonical NADPH-producing genes, the metabolic network can further reroute flux through alternate NADPH biosynthesis pathways in a cell line-specific manner. Model predictions of perturbations in cellular NADPH production after gene knockdown match well with experimentally verified effects of β-lapachone treatment on NADPH/NADP+ ratio and cell viability. This computational approach accurately predicts HNSCC-specific oxidoreductase genes that differentially affect cell viability between radiation-responsive and radiation-resistant cancer cells upon β-lapachone treatment. INNOVATION Quantitative genome-scale metabolic models that incorporate multiple levels of biological data are applied to provide accurate predictions of responses to a NADPH-dependent redox cycling chemotherapeutic drug under a variety of perturbations. CONCLUSION Our modeling approach suggests differences in metabolism and β-lapachone redox cycling that underlie phenotypic differences in radiation-sensitive and -resistant cancer cells. This approach can be extended to investigate the synergistic action of NAD(P)H: quinone oxidoreductase 1 bioactivatable drugs and radiation therapy. Antioxid. Redox Signal. 29, 937-952.