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A quantum probability account of individual differences in causal reasoning
We use quantum probability (QP) theory to investigate individual differences in causal reasoning. By analyzing data sets from Rehder (2014) on comparative judgments, and from Rehder & Waldmann (2016) on absolute judgments, we show that a QP model can both account for individual differences in causal judgments, and why these judgments sometimes violate the properties of causal Bayes nets. We implement this and previously proposed models of causal reasoning (including classical probability models) within the same hierarchical Bayesian inferential framework to provide a detailed comparison between these models, including computing Bayes factors. Analysis of the inferred parameters of the QP model illustrates how these can be interpreted in terms of putative cognitive mechanisms of causal reasoning. Additionally, we implement a latent classification mechanism that identifies subcategories of reasoners based on properties of the inferred cognitive process, rather than post hoc clustering. The QP model also provides a parsimonious explanation for aggregate behavior, which alternatively can only be explained by a mixture of multiple existing models. Investigating individual differences through the lens of a QP model reveals simple but strong alternatives to existing explanations for the dichotomies often observed in how people make causal inferences. These alternative explanations arise from the cognitive interpretation of the parameters and structure of the quantum probability model
A trypsin-like serine protease is involved in pseudorabies virus invasion through the basement membrane barrier of porcine nasal respiratory mucosa
Several alphaherpesviruses breach the basement membrane during mucosal invasion. In the present study, the role of proteases in this process was examined. The serine protease-specific inhibitor AEBSF inhibited penetration of the basement membrane by the porcine alphaherpesvirus pseudorabies virus (PRV) by 88.1% without affecting lateral spread. Inhibitors of aspartic-, cysteine-, and metalloproteases did not inhibit viral penetration of the basement membrane. Further analysis using the Soybean Type I-S trypsin inhibitor for the serine protease subcategory of trypsin-like serine proteases resulted in a 96.9% reduction in plaque depth underneath the basement membrane. These data reveal a role of a trypsin-like serine protease in PRV penetration of the basement membrane
Comparative analysis of replication characteristics of BoHV-1 subtypes in bovine respiratory and genital mucosa explants: a phylogenetic enlightenment
In general, members of the Alphaherpesvirinae use the epithelium of the upper respiratory and/or genital tract as a preferential site for primary replication. Bovine herpesvirus type 1 (BoHV-1) may replicate at both sites and cause two major clinical entities designated as infectious bovine rhinotracheitis (IBR) and infectious pustular vulvovaginitis/balanoposthitis (IPV/IPB) in cattle. It has been hypothesized that subtype 1.1 invades preferentially the upper respiratory mucosa whereas subtype 1.2 favors replication at the peripheral genital tract. However, some studies are in contrast with this hypothesis. A thorough study of primary replication at both mucosae could elucidate whether or not different BoHV-1 subtypes show differences in mucosa tropism. We established bovine respiratory and genital organ cultures with emphasis on maintenance of tissue morphology and viability during in vitro culture. In a next step, bovine respiratory and genital mucosa explants of the same animals were inoculated with several BoHV-1 subtypes. A quantitative analysis of viral invasion in the mucosa was performed at 0 h, 24 h, 48 h and 72 h post inoculation (pi) by measuring plaque latitude and penetration depth underneath the basement membrane. All BoHV-1 subtypes exhibited a more profound invasion capacity in respiratory tissue compared to that in genital tissue at 24 h pi. However, at 24 h pi plaque latitude was found to be larger in genital tissue compared to respiratory tissue and this for all subtypes. These similar findings among the different subtypes take the edge off the belief of the existence of specific mucosa tropisms of different BoHV-1 subtypes
Is sexual risk behaviour associated with an increased risk of transfusion-transmissible infections in blood donors from Western and Pacific countries? A systematic review and meta-analysis
Background and Objectives The donor medical questionnaire is designed to aid blood establishments in supporting a safe blood supply. According to blood donor deferral policies, sexual risk behaviour (SRB) leads to a (temporary) deferral from blood donation. This systematic review aimed to scientifically underpin these policies by identifying the best available evidence on the association between SRB and the risk of transfusion transmissible infections (TTIs). Materials & Methods Studies from three databases investigating the link between SRB (excluding men who have sex with men (MSM)) and TTIs (HBV, HCV, HIV, Treponema pallidum) in donors from Western and Pacific countries were obtained and assessed on eligibility by two reviewers independently. The association between SRB and TTIs was expressed by calculating pooled effect measures via meta-analyses. The GRADE methodology (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the quality of evidence. Results We identified 3750 references and finally included 15 observational studies. Meta-analyses showed that there is a significant (P < 0 center dot 05) positive association between the following SRB and HBV and/or HCV infection: having sex with an intravenous drug user (high-certainty evidence), receiving money or goods for sex (moderate-high certainty evidence), having a sex partner with hepatitis/HIV (moderate-certainty evidence) and paid for sex or anal sex (low-certainty evidence). Conclusion Sexual risk behaviour (including having sex with an intravenous drug user, receiving money or goods for sex or having a sex partner with hepatitis/HIV) is probably associated with an increased risk of HBV/HCV infection in blood donors from Western and Pacific countries
Lessons for Employing Participatory Design When Developing Care for Young People with Cancer: A Qualitative Multiple-Case Study
Purpose: Participatory design (PD) is a collective creative design process involving designers and nondesigners. There is limited reporting on the experience of using PD for adolescent and young adult (AYA) care.
This study summarizes lessons from employing PD to develop care for AYAs with cancer.
Methods: A qualitative multiple-case study method was conducted of three PD processes addressing food
(FfC), intimacy and sexuality (I&S), and integrative medicine (IM) in caring for AYAs with cancer.
Results: Local key stakeholders, who were exposed to a problem and had not been successful at solving it
individually, were recruited to ‘‘dream’’ together. Through this synergy, a shared understanding of the problem
and a joint mission emerged to find a solution. PD tools were used to develop a problem definition. An
open mind and explorative research helped to understand the problems, and stakeholders were managed such
that idea-sharing and learning were enabled. Designers translated ideas into prototypes. The PD process was
prolonged due to the hierarchical hospital environment, business considerations, and additionally required
evidence. The FfC program produced an effective new food service for the whole hospital. The I&S initiative
developed a podcast, two articles, and a prototype website. The IM project developed a pilot study.
Conclusions: For a PD process to successfully develop care for AYAs, one needs to use designers and skilled
people, PD tools, and an open-ended approach to visualize an
CHARACTERIZATION OF F107 FIMBRIAE OF ESCHERICHIA-COLI 107/86, WHICH CAUSES EDEMA DISEASE IN PIGS, AND NUCLEOTIDE-SEQUENCE OF THE F107 MAJOR FIMBRIAL SUBUNIT GENE, FEDA
F107 fimbriae were isolated and purified from edema disease strain 107/86 of Escherichia coli. Plasmid pIH120 was constructed, which contains the gene cluster that codes for adhesive F107 fimbriae. The major fimbrial subunit gene, fedA, was sequenced. An open reading frame that codes for a protein with 170 amino acids, including a 21-amino-acid signal peptide, was found. The protein without the signal sequence has a calculated molecular mass of 15,099 Da. Construction of a nonsense mutation in the open reading frame of fedA abolished both fimbrial expression and the capacity to adhere to isolated porcine intestinal villi. In a screening of 28 reference edema disease strains and isolates from clinically ill piglets, fedA was detected in 24 cases (85.7%). In 20 (83.3%) of these 24 strains, fedA was found in association with Shiga-like toxin II variant genes, coding for the toxin that is characteristic for edema disease strains of E. coli. The fimbrial subunit gene was not detected in enterotoxigenic E. coli strains. Because of the capacity of E. coli HB101(pIH120) transformants to adhere to isolated porcine intestinal villi, the high prevalence of fedA in edema disease strains, and the high correlation with the Shiga-like toxin II variant toxin-encoding genes, we suggest that F107 fimbriae are an important virulence factor in edema disease strains of E. coli
Differential expression of lncRNAs during the HIV replication cycle: an underestimated layer in the HIV-host interplay.
Studying the effects of HIV infection on the host transcriptome has typically focused on protein-coding genes. However, recent advances in the field of RNA sequencing revealed that long non-coding RNAs (lncRNAs) add an extensive additional layer to the cell's molecular network. Here, we performed transcriptome profiling throughout a primary HIV infection in vitro to investigate lncRNA expression at the different HIV replication cycle processes (reverse transcription, integration and particle production). Subsequently, guilt-by-association, transcription factor and co-expression analysis were performed to infer biological roles for the lncRNAs identified in the HIV-host interplay. Many lncRNAs were suggested to play a role in mechanisms relying on proteasomal and ubiquitination pathways, apoptosis, DNA damage responses and cell cycle regulation. Through transcription factor binding analysis, we found that lncRNAs display a distinct transcriptional regulation profile as compared to protein coding mRNAs, suggesting that mRNAs and lncRNAs are independently modulated. In addition, we identified five differentially expressed lncRNA-mRNA pairs with mRNA involvement in HIV pathogenesis with possible cis regulatory lncRNAs that control nearby mRNA expression and function. Altogether, the present study demonstrates that lncRNAs add a new dimension to the HIV-host interplay and should be further investigated as they may represent targets for controlling HIV replication
Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1 : a Phase IIa randomised controlled study
Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin
Background:
Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties.
Methodology/Results:
The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface.
Conclusion:
Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1
Partial molecular characterization of the Nile tilapia (Oreochromis niloticus) alpha-cardiac muscle actin gene and its relationship to actin isoforms of other fish species
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