Concomitant Radiofrequency ??? Microwave Ablation and Atrial Septal Defect Repair

Atrial fibrillation (AF) is the most frequent form of atrial arrhythmias in adults with congenital heart disease. Some serious complications are related with the presence of AF after surgery. Because of the complexity and the risk of bleeding, the Maze III procedure has been largely replaced by alternative energy sources. A patient with multiple atrial septal defects (ASD) and AF underwent surgical closure with autologous pericardial patch and bipolar radiofrequency and microwave ablation

Reducing risk to security and privacy in the selection of trigger-action rules: Implicit vs. explicit priming for domestic smart devices

Smart home device usage is increasing, as is the diversity of users and range of devices. Additionally, it is becoming increasingly common to interconnect devices (e.g., via trigger-action rules) which, while bringing benefits, can bring unforeseen security and privacy risks. Developing strategies to protect users as well as understanding what biographical or attitudinal characteristics contribute to these risks is a critical step for ensuring empowered, but safe, interconnected smart device usage. Using narrative descriptions of domestic smart devices, two experiments explored how the prevailing security/privacy contexts—priming conditions—in which 20 trigger-action rules (developed via a Delphi Study) were presented influenced the adoption of rules favoring either security or privacy. Both experiments contrasted three priming conditions: no prime, security prime, privacy prime. Experiment 1 (n = 254) used explicit priming, giving direct instruction to maximize a security or privacy outcome while Experiment 2 (n = 325) used implicit priming, with an apparently unrelated security or privacy problem-solving puzzle. Across both experiments, priming promoted safer rule adoption, markedly so when explicit. Explicit priming produced an asymmetry however: privacy priming improved privacy scores with security scores unchanged and security primes improved security scores while worsening privacy scores. Across experiments, two dimensions of user attitudes shaped riskier rule choice: perceived benefits of technology and pre-existing trusting beliefs in online companies. Our novel findings reveal that implicit and explicit priming shape safe use of trigger-action rules in domestic settings and that age, perceived trust and perceived benefits should be considered when designing safety messaging

Mapping B-cell responses to Salmonella enterica serovars Typhimurium and Enteritidis in chickens for the discrimination of infected from vaccinated animals

Serological surveillance and vaccination are important strategies for controlling infectious diseases of food production animals. However, the compatibility of these strategies is limited by a lack of assays capable of di erentiating infected from vaccinated animals (DIVA tests) for established killed or attenuated vaccines. Here, we used next generation phage-display (NGPD) and a 2-proportion Z score analysis to identify peptides that were preferentially bound by IgY from chickens infected with Salmonella Typhimurium or S. Enteritidis compared to IgY from vaccinates, for both an attenuated and an inactivated commercial vaccine. Peptides that were highly enriched against IgY from at least 4 out of 10 infected chickens were selected: 18 and 12 peptides for the killed and attenuated vaccines, respectively. The ten most discriminatory peptides for each vaccine were identi ed in an ELISA using a training set of IgY samples. These peptides were then used in multi-peptide assays that, when analysing a wider set of samples from infected and vaccinated animals, diagnosed infection with 100% sensitivity and speci city. The data describes a method for the development of DIVA assays for conventional attenuated and killed vaccines

Groundwater Remediation at the 100-HR-3 Operable Unit Hanford Site Washington USA - 11507

The 100-HR-3 Groundwater Operable Unit (OU) at the Hanford Site underlies three former plutonium production reactors and the associated infrastructure at the 100-D and 100-H Areas. The primary contaminant of concern at the site is hexavalent chromium; the secondary contaminants are strontium-90, technetium-99, tritium, uranium, and nitrate. The hexavalent chromium plume is the largest plume of its type in the state of Washington, covering an area of approximately 7 km{sup 2} (2.7 mi{sup 2}) with concentrations greater than 20 {micro}g/L. Concentrations range from 60,000 {micro}g/L near the former dichromate transfer station in the 100-D Area to large areas of 20 to 100 {micro}g/L across much of the plume area. Pump-and-treat operations began in 1997 and continued into 2010 at a limited scale of approximately 200 gal/min. Remediation of groundwater has been fairly successful in reaching remedial action objectives (RAOs) of 20 {micro}g/L over a limited region at the 100-H, but less effective at 100-D. In 2000, an in situ, permeable reactive barrier was installed downgradient of the hotspot in 100-D as a second remedy. The RAOs are still being exceeded over a large portion of the area. The CH2M HILL Plateau Remediation Company was awarded the remediation contract for groundwater in 2008 and initiated a remedial process optimization study consisting of modeling and technical studies intended to enhance the remediation. As a result of the study, 1,400 gal/min of expanded treatment capacity are being implemented. These new systems are designed to meet 2012 and 2020 target milestones for protection of the Columbia River and cleanup of the groundwater plumes

Exploratory factor analysis of graphical features for link prediction in social networks

Social Networks attract much attention due to their ability to replicate social interactions at scale. Link prediction, or the assessment of which unconnected nodes are likely to connect in the future, is an interesting but non-trivial research area. Three approaches exist to deal with the link prediction problem: feature-based models, Bayesian probabilistic models, probabilistic relational models. In feature-based methods, graphical features are extracted and used for classification. Usually, these features are subdivided into three feature groups based on their formula. Some formulas are extracted based on neighborhood graph traverse. Accordingly, there exists three groups of features, neighborhood features, path-based features, node-based features. In this paper, we attempt to validate the underlying structure of topological features used in feature-based link prediction. The results of our analysis indicate differing results from the prevailing grouping of these features, which indicates that current literatures\u27 classification of feature groups should be redefined. Thus, the contribution of this work is exploring the factor loading of graphical features in link prediction in social networks. To the best of our knowledge, there is no prior studies had addressed it

Mapping polyclonal antibody responses to bacterial infection using next generation phage display

Mapping polyclonal antibody responses to infectious diseases to identify individual epitopes has the potential to underpin the development of novel serological assays and vaccines. Here, phage-peptide library panning coupled with screening using next generation sequencing was used to map antibody responses to bacterial infections. In the first instance, pigs experimentally infected with Salmonella enterica serovar Typhimurium was investigated. IgG samples from twelve infected pigs were probed in parallel and phage binding compared to that with equivalent IgG from pre-infected animals. Seventy- seven peptide mimotopes were enriched specifically against sera from multiple infected animals. Twenty-seven of these peptides were tested in ELISA and twenty-two were highly discriminatory for sera taken from pigs post-infection (P < 0.05) indicating that these peptides are mimicking epitopes from the bacteria. In order to further test this methodology, it was applied to differentiate antibody responses in poultry to infections with distinct serovars of Salmonella enterica. Twenty-seven peptides were identified as being enriched specifically against IgY from multiple animals infected with S. Enteritidis compared to those infected with S. Hadar. Nine of fifteen peptides tested in ELISA were highly discriminatory for IgY following S. Enteritidis infection (p < 0.05) compared to infections with S. Hadar or S. Typhimurium

Discovery of peptide ligands targeting a specific ubiquitin-like domain– binding site in the deubiquitinase USP11

© 2019 Spiliotopoulos et al. Published by The American Society for Biochemistry and Molecular Biology, Inc. Ubiquitin-specific proteases (USPs) reverse ubiquitination and regulate virtually all cellular processes. Defined noncatalytic domains in USP4 and USP15 are known to interact with E3 ligases and substrate recruitment factors. No such interactions have been reported for these domains in the paralog USP11, a key regulator of DNA double-strand break repair by homologous recombination. We hypothesized that USP11 domains adjacent to its protease domain harbor unique peptide-binding sites. Here, using a next-generation phage display (NGPD) strategy, combining phage display library screening with next-generation sequencing, we discovered unique USP11-interacting peptide motifs. Isothermal titration calorimetry disclosed that the highest affinity peptides (K D of 10 M) exhibit exclusive selectivity for USP11 over USP4 and USP15 in vitro. Furthermore, a crystal structure of a USP11–peptide complex revealed a previously unknown binding site in USP11’s noncatalytic ubiquitin-like (UBL) region. This site interacted with a helical motif and is absent in USP4 and USP15. Reporter assays using USP11-WT versus a binding pocket– deficient double mutant disclosed that this binding site modulates USP11’s function in homologous recombination–mediated DNA repair. The highest affinity USP11 peptide binder fused to a cellular delivery sequence induced significant nuclear localization and cell cycle arrest in S phase, affecting the viability of different mammalian cell lines. The USP11 peptide ligands and the paralog-specific functional site in USP11 identified here provide a framework for the development of new biochemical tools and therapeutic agents. We propose that an NGPD-based strategy for identifying interacting peptides may be applied also to other cellular targets

Monitoring the genomic stability of in vitro cultured rat bone-marrow-derived mesenchymal stem cells

Bone-marrow-derived mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and differentiation into multiple cell types. Accumulating preclinical and clinical evidence indicates that MSCs are good candidates to use as cell therapy in many degenerative diseases. For MSC clinical applications, an adequate number of cells are necessary so an extensive expansion is required. However, spontaneous immortalization and malignant transformation of MSCs after culture expansion have been reported in human and mouse, while very few data are present for rat MSCs (rMSCs). In this study, we monitored the chromosomal status of rMSCs at several passages in vitro, also testing the influence of four different cell culture conditions. We first used the conventional traditional cytogenetic techniques, in order to have the opportunity to observe even minor structural abnormalities and to identify low-degree mosaic conditions. Then, a more detailed genomic analysis was conducted by array comparative genomic hybridization. We demonstrated that, irrespective of culture conditions, rMSCs manifested a markedly aneuploid karyotype and a progressive chromosomal instability in all the passages we analyzed and that they are anything but stable during in vitro culture. Despite the fact that the risk of neoplastic transformation associated with this genomic instability needs to be further addressed and considering the apparent genomic stability reported for in vitro cultured human MSCs (hMSCs), our findings underline the fact that rMSCs may not in fact be a good model for effectively exploring the full clinical therapeutic potential of hMSCs

Distinct Regulatory Functions of Calpain 1 and 2 during Neural Stem Cell Self-Renewal and Differentiation

Calpains are calcium regulated cysteine proteases that have been described in a wide range of cellular processes, including apoptosis, migration and cell cycle regulation. In addition, calpains have been implicated in differentiation, but their impact on neural differentiation requires further investigation. Here, we addressed the role of calpain 1 and calpain 2 in neural stem cell (NSC) self-renewal and differentiation. We found that calpain inhibition using either the chemical inhibitor calpeptin or the endogenous calpain inhibitor calpastatin favored differentiation of NSCs. This effect was associated with significant changes in cell cycle-related proteins and may be regulated by calcium. Interestingly, calpain 1 and calpain 2 were found to play distinct roles in NSC fate decision. Calpain 1 expression levels were higher in self-renewing NSC and decreased with differentiation, while calpain 2 increased throughout differentiation. In addition, calpain 1 silencing resulted in increased levels of both neuronal and glial markers, β-III Tubulin and glial fibrillary acidic protein (GFAP). Calpain 2 silencing elicited decreased levels of GFAP. These results support a role for calpain 1 in repressing differentiation, thus maintaining a proliferative NSC pool, and suggest that calpain 2 is involved in glial differentiation