Retrieval Can Increase or Decrease Suggestibility Depending on How Memory is Tested: The Importance of Source Complexity

Taking an intervening test between learning episodes can enhance later source recollection. Paradoxically, testing can also increase people’s susceptibility to the misinformation effect – a finding termed retrieval-enhanced suggestibility (RES, Chan, Thomas, & Bulevich, 2009). We conducted three experiments to examine this apparent contradiction. Experiment 1 extended the RES effect to a new set of materials. Experiments 2 and 3 showed that testing can produce opposite effects on memory suggestibility depending on the complexity of the source test. Specifically, retrieval facilitated source discriminations when the test contained only items with unique source origins. But when the source test included some items that had appeared in multiple sources, the intervening test actually increased source confusions. These results have implications for a wide variety of learning situations. We focused our discussion on eyewitness memory, source complexity, and reconsolidation

Anti-oxidant inhibition of hyaluronan fragment-induced inflammatory gene expression

<p>Abstract</p> <p>Background</p> <p>The balance between reactive oxygen species (ROS) and endogenous anti-oxidants is important in maintaining healthy tissues. Excessive ROS states occur in diseases such as ARDS and Idiopathic Pulmonary Fibrosis. Redox imbalance breaks down the extracellular matrix component hyaluronan (HA) into fragments that activate innate immune responses and perpetuate tissue injury. HA fragments, via a TLR and NF-κB pathway, induce inflammatory gene expression in macrophages and epithelial cells. NAC and DMSO are potent anti-oxidants which may help balance excess ROS states.</p> <p>Methods</p> <p>We evaluated the effect of H₂O₂, NAC and DMSO on HA fragment induced inflammatory gene expression in alveolar macrophages and epithelial cells.</p> <p>Results</p> <p>NAC and DMSO inhibit HA fragment-induced expression of TNF-α and KC protein in alveolar and peritoneal macrophages. NAC and DMSO also show a dose dependent inhibition of IP-10 protein expression, but not IL-8 protein, in alveolar epithelial cells. In addition, H₂O₂synergizes with HA fragments to induce inflammatory genes, which are inhibited by NAC. Mechanistically, NAC and DMSO inhibit HA induced gene expression by inhibiting NF-κB activation, but NAC had no influence on HA-fragment-AP-1 mediated gene expression.</p> <p>Conclusion</p> <p>ROS play a central role in a pathophysiologic "vicious cycle" of inflammation: tissue injury generates ROS, which fragment the extracellular matrix HA, which in turn synergize with ROS to activate the innate immune system and further promote ROS, HA fragment generation, inflammation, tissue injury and ultimately fibrosis. The anti-oxidants NAC and DMSO, by inhibiting the HA induced inflammatory gene expression, may help re-balance excessive ROS induced inflammation.</p

Lightning talks of EduHPC 2022

The lightning talks at EduHPC provide an opportunity to share early results and insights on parallel and distributed computing (PDC) education and training efforts. The four lightning talks at EduHPC 2022 cover a range of topics in broadening PDC education: (i) curriculum development efforts for the European Masters in HPC program, (ii) bootcamps for CI professionals who support the running of AI workloads on HPC systems, (iii) a GPU programming course following the Carpentries model and (iv) peer-review assignments to help students write efficient parallel algorithms within sustainable software libraries.Peer ReviewedArticle signat per 26 autors/es: Apan Qasem 1, Hartwig Anzt 2,3, Eduard Ayguade 4, Katharine Cahill 5, Ramon Canal 4, Jany Chan 6, Eric Fosler-Lussier 6, Fritz Göbel 2, Arpan Jain 6, Marcel Koch 2, Mateusz Kuzak 7, Josep Llosa 4, Raghu Machiraju 6, Xavier Martorell 4, Pratik Nayak 2, Shameema Oottikkal 5, Marcin Ostasz 8, Dhabaleswar K. Panda 6, Dirk Pleiter 9, Rajiv Ramnath 6, Maria-Ribera Sancho 4, Alessio Sclocco 7, Aamir Shafi 6, Hanno Spreeuw 7, Hari Subramoni 6, Karen Tomko 7 / 1 Department of Computer Science, Texas State University, USA; 2 Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany; 3 University of Tennessee (UTK), Knoxville, USA; 4 Barcelona Supercomputing Center and Universitat Politècnica de Catalunya, Spain; 5 Ohio Supercomputer Center, USA; 6 College of Engineering, The Ohio State University, USA; 7 Netherlands eScience Center, The Netherlands; 8 ETP4HPC, The Netherlands; 9 PDC Center for High Performance Computing, KTH Royal Institute of Technology, SwedenPostprint (author's final draft

A Neutralizing Human Monoclonal Antibody Protects against Lethal Disease in a New Ferret Model of Acute Nipah Virus Infection

Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats. Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. Here, a new ferret model of Nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. Severe disease occurs with viral doses as low as 500 TCID50 within 6 to 10 days following infection. The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues. Using this ferret model a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent. All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died. This study is the first successful post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody

Monitoring Prevalence, Treatment, and Control Of Metabolic Conditions In New York City Adults Using 2013 Primary Care Electronic Health Records: A Surveillance Validation Study

Introduction: Electronic health records (EHRs) can potentially extend chronic disease surveillance, but few EHR-based initiatives tracking population-based metrics have been validated for accuracy. We designed a new EHR-based population health surveillance system for New York City (NYC) known as NYC Macroscope. This report is the third in a 3-part series describing the development and validation of that system. The first report describes governance and technical infrastructure underlying the NYC Macroscope. The second report describes validation methods and presents validation results for estimates of obesity, smoking, depression and influenza vaccination. In this third paper we present validation findings for metabolic indicators (hypertension, hyperlipidemia, diabetes). Methods:We compared EHR-based estimates to those from a gold standard surveillance source – the 2013-2014 NYC Health and Nutrition Examination Survey (NYC HANES) – overall and stratified by sex and age group, using the two one-sided test of equivalence and other validation criteria. Results: EHR-based hypertension prevalence estimates were highly concordant with NYC HANES estimates. Diabetes prevalence estimates were highly concordant when measuring diagnosed diabetes but less so when incorporating laboratory results. Hypercholesterolemia prevalence estimates were less concordant overall. Measures to assess treatment and control of the 3 metabolic conditions performed poorly. Discussion:While indicator performance was variable, findings here confirm that a carefully constructed EHR-based surveillance system can generate prevalence estimates comparable to those from gold-standard examination surveys for certain metabolic conditions such as hypertension and diabetes. Conclusions: Standardized EHR metrics have potential utility for surveillance at lower annual costs than surveys, especially as representativeness of contributing clinical practices to EHR-based surveillance systems increases

Infectivity of Plasmodium falciparum in malaria-naive individuals is related to knob expression and cytoadherence of the parasite

Plasmodium falciparum is the most virulent human malaria parasite because of its ability to cytoadhere in the microvasculature. Nonhuman primate studies demonstrated relationships among knob expression, cytoadherence, and infectivity. This has not been examined in humans. Cultured clinical-grade P. falciparum parasites (NF54, 7G8, and 3D7B) and ex vivo-derived cell banks were characterized. Knob and knob-associated histidine-rich protein expression, CD36 adhesion, and antibody recognition of parasitized erythrocytes (PEs) were evaluated. Parasites from the cell banks were administered to malaria-naive human volunteers to explore infectivity. For the NF54 and 3D7B cell banks, blood was collected from the study participants for in vitro characterization. All parasites were infective in vivo. However, infectivity of NF54 was dramatically reduced. In vitro characterization revealed that unlike other cell bank parasites, NF54 PEs lacked knobs and did not cytoadhere. Recognition of NF54 PEs by immune sera was observed, suggesting P. falciparum erythrocyte membrane protein 1 expression. Subsequent recovery of knob expression and CD36-mediated adhesion were observed in PEs derived from participants infected with NF54. Knobless cell bank parasites have a dramatic reduction in infectivity and the ability to adhere to CD36. Subsequent infection of malaria-naive volunteers restored knob expression and CD36-mediated cytoadherence, thereby showing that the human environment can modulate virulence

CD or not CD, that is the question - a digital interobserver agreement study in coeliac disease

OBJECTIVE: Coeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of IgA tTG and haemoglobin (Hb) data improves the inter-observer agreement of diagnosis.DESIGN: We undertook a large study of the concordance in histological examination of duodenal biopsies using digitised WSIs in an entirely virtual reporting setting. Our study was organised in two phases: in phase one, 13 pathologists independently classified 100 duodenal biopsies (40 normal; 40 CD; 20 indeterminate enteropathy) in the absence of any clinical or laboratory data. In phase two, the same pathologists examined the (re-anonymised) WSIs with the inclusion of IgA tTG and Hb data.RESULTS: We found the mean probability of two observers agreeing in the absence of additional data to be 0.73 (±0.08) with a corresponding Cohen's kappa of 0.59 (±0.11). We further showed that the inclusion of additional data increased the concordance to 0.80 (±0.06) with a Cohen's kappa coefficient of 0.67 (±0.09).CONCLUSION: We showed that the addition of serological data significantly improves the quality of CD diagnosis. However, the limited inter-observer agreement in CD diagnosis using digitised WSIs, even after the inclusion of IgA tTG and Hb data, indicates the important of interpreting duodenal biopsy in the appropriate clinical context. It further highlights the unmet need for an objective means of reproducible duodenal biopsy diagnosis, such as the automated analysis of WSIs using AI.<br/

Imaging Trans-Cellular Neurexin-Neuroligin Interactions by Enzymatic Probe Ligation

Neurexin and neuroligin are transmembrane adhesion proteins that play an important role in organizing the neuronal synaptic cleft. Our lab previously reported a method for imaging the trans-synaptic binding of neurexin and neuroligin called BLINC (Biotin Labeling of INtercellular Contacts). In BLINC, biotin ligase (BirA) is fused to one protein while its 15-amino acid acceptor peptide substrate (AP) is fused to the binding partner. When the two fusion proteins interact across cellular junctions, BirA catalyzes the site-specific biotinylation of AP, which can be read out by staining with streptavidin-fluorophore conjugates. Here, we report that BLINC in neurons cannot be reproduced using the reporter constructs and labeling protocol previously described. We uncover the technical reasons for the lack of reproducibilty and then re-design the BLINC reporters and labeling protocol to achieve neurexin-neuroligin BLINC imaging in neuron cultures. In addition, we introduce a new method, based on lipoic acid ligase instead of biotin ligase, to image trans-cellular neurexin-neuroligin interactions in human embryonic kidney cells and in neuron cultures. This method, called ID-PRIME for Interaction-Dependent PRobe Incorporation Mediated by Enzymes, is more robust than BLINC due to higher surface expression of lipoic acid ligase fusion constructs, gives stronger and more localized labeling, and is more versatile than BLINC in terms of signal readout. ID-PRIME expands the toolkit of methods available to study trans-cellular protein-protein interactions in living systems.National Institutes of Health (U.S.) (DP1 OD003961