Large-scale inflatable structures for tunnel protection: a review of the Resilient Tunnel Plug project

The protection of underground civil infrastructure continues to be a high priority for transportation and transit security agencies. In particular, rail transit tunnels running under bodies of water are susceptible to disruptions due to flooding caused by extraordinary climatic events such as hurricanes or other events resulting from human activities. Several events have taken place in the past decades that have demonstrated the need to mitigate vulnerabilities or, at least, minimize the consequences of catastrophic events. Although it is impossible to prevent all situations that can lead to flooding, damage can be substantially decreased by reducing the area affected by the event. To minimize the effects of an event, a possible approach is to compartmentalize the tunnel system by creating temporary barriers that can contain the propagation of flooding until a more permanent solution can be implemented. One way to create a temporary barrier is by the deployment of a large-scale inflatable structure, also known as an inflatable plug. In such an application, the inflatable structure is prepared for placement, either permanently or temporally, and maintained ready for deployment, inflation, and pressurization when needed. The internal plug pressure imparts a normal force against the tunnel wall surface with the friction between the plug and tunnel surfaces opposing axial movement of the plug. The sealing effectiveness depends on the ability of the inflatable structure to self-deploy and fit, without human intervention, to the intricacies of the perimeter of the conduit being sealed. Primary design constraints include having the plug stowed away from the dynamic envelope of the trains and being able to withhold the pressure of the flooding water. This work presents a compilation of the main aspects of the activities completed for the development of large-scale inflatable structures as part of the Resilient Tunnel Plug (RTP) Project. The main test results and lessons learned are presented to demonstrate the viability of implementing large-scale inflatable plugs for the containment of flooding in rail tunnels systems. Over 400 coupon and specimen tests, 200 reduced scale tests, and 100 full-scale tests were conducted to demonstrate the efficacy of the design of different prototypes over a 10-year research and development project. The culmination of the work was 12 large-scale flooding demonstrations where the inflatable tunnel plug was shown able to be deployed remotely and withstand a simulated flooding event

Absence of Face-specific Cortical Activity in the Complete Absence of Awareness: Converging Evidence from Functional Magnetic Resonance Imaging and Event-related Potentials

In this study, we explored the neural correlates of perceptual awareness during a masked face detection task. To assess awareness more precisely than in previous studies, participants employed a 4-point scale to rate subjective visibility. An event-related fMRI and a high-density ERP study were carried out. Imaging data showed that conscious face detection was linked to activation of fusiform and occipital face areas. Frontal and parietal regions, including the pre-SMA, inferior frontal sulcus, anterior insula/frontal operculum, and intraparietal sulcus, also responded strongly when faces were consciously perceived. In contrast, no brain area showed face-selective activity when participants reported no impression of a face. ERP results showed that conscious face detection was associated with enhanced N170 and also with the presence of a second negativity around 300 msec and a slow positivity around 415 msec. Again, face-related activity was absent when faces were not consciously perceived. We suggest that, under conditions of backward masking, ventral stream and fronto-parietal regions show similar, strong links of face-related activity to conscious perception and stress the importance of a detailed assessment of awareness to examine activity related to unseen stimulus events

What is epistemic blame?

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Taking Digital Microphotography and Videos through a Microscope without any Special Lens

Introduction: Photography through a microscope is virtually identical to that used with an astronomical telescope. For years, the 35mm camera was the choice for microphotography, but we live in a digital camera age now. We describe a custom homemade adapter that can be fit most of the cameras and microscopes. [See PDF for complete abstract

Discovery of a Novel Compound with Anti-Venezuelan Equine Encephalitis Virus Activity That Targets the Nonstructural Protein 2

Abstract Alphaviruses present serious health threats as emerging and re-emerging viruses. Venezuelan equine encephalitis virus (VEEV), a New World alphavirus, can cause encephalitis in humans and horses, but there are no therapeutics for treatment. To date, compounds reported as anti-VEEV or anti-alphavirus inhibitors have shown moderate activity. To discover new classes of anti-VEEV inhibitors with novel viral targets, we used a high-throughput screen based on the measurement of cell protection from live VEEV TC-83-induced cytopathic effect to screen a 340,000 compound library. Of those, we identified five novel anti-VEEV compounds and chose a quinazolinone compound, CID15997213 (IC50 = 0.84 µM), for further characterization. The antiviral effect of CID15997213 was alphavirus-specific, inhibiting VEEV and Western equine encephalitis virus, but not Eastern equine encephalitis virus. In vitro assays confirmed inhibition of viral RNA, protein, and progeny synthesis. No antiviral activity was detected against a select group of RNA viruses. We found mutations conferring the resistance to the compound in the N-terminal domain of nsP2 and confirmed the target residues using a reverse genetic approach. Time of addition studies showed that the compound inhibits the middle stage of replication when viral genome replication is most active. In mice, the compound showed complete protection from lethal VEEV disease at 50 mg/kg/day. Collectively, these results reveal a potent anti-VEEV compound that uniquely targets the viral nsP2 N-terminal domain. While the function of nsP2 has yet to be characterized, our studies suggest that the protein might play a critical role in viral replication, and further, may represent an innovative opportunity to develop therapeutic interventions for alphavirus infection. Author Summary Alphaviruses occur worldwide, causing significant diseases such as encephalitis or arthritis in humans and animals. In addition, some alphaviruses, such as VEEV, pose a biothreat due to their high infectivity and lack of available treatments. To discover small molecule inhibitors with lead development potential, we used a cell-based assay to screen 348,140 compounds for inhibition of a VEEV-induced cytopathic effect. The screen revealed a scaffold with high inhibitory VEEV cellular potency and low cytotoxicity liability. While most previously reported anti-alphavirus compounds inhibit host proteins, evidence supported that this scaffold targeted the VEEV nsP2 protein, and that inhibition was associated with viral replication. Interestingly, compound resistance studies with VEEV mapped activity to the N-terminal domain of nsP2, to which no known function has been attributed. Ultimately, this discovery has delivered a small molecule-derived class of potent VEEV inhibitors whose activity is coupled to the nsP2 viral protein, a novel target with a previously unestablished biological role that is now implicated in viral replication.This research was supported by the following funding sources: NIH R03MH087448-01A1, University of Louisville Internal Research Initiate grant to DHC, USAMRAA W81XWH-10-2-0064 and W81XWH-08-2-0024 to CBJ. Screening was provided by the Southern Research Specialized Screening Center (U54HG005034-0) and chemistry through the University of Kansas Specialized Chemistry Center (U54HG005031). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Granger Causality Analysis of Steady-State Electroencephalographic Signals during Propofol-Induced Anaesthesia

Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed functional (i.e., causal) connectivity as reflected in quantities such as ‘integrated information’ and ‘causal density’. Here we develop and illustrate a rigorous methodology for assessing causal connectivity from electroencephalographic (EEG) signals using Granger causality (GC). Our method addresses the challenges of non-stationarity and bias by dividing data into short segments and applying permutation analysis. We apply the method to EEG data obtained from subjects undergoing propofol-induced anaesthesia, with signals source-localized to the anterior and posterior cingulate cortices. We found significant increases in bidirectional GC in most subjects during loss-of-consciousness, especially in the beta and gamma frequency ranges. Corroborating a previous analysis we also found increases in synchrony in these ranges; importantly, the Granger causality analysis showed higher inter-subject consistency than the synchrony analysis. Finally, we validate our method using simulated data generated from a model for which GC values can be analytically derived. In summary, our findings advance the methodology of Granger causality analysis of EEG data and carry implications for integrated information and causal density theories of consciousness

The 10/66 Dementia Research Group's fully operationalised DSM-IV dementia computerized diagnostic algorithm, compared with the 10/66 dementia algorithm and a clinician diagnosis: a population validation study

<p>Abstract</p> <p>Background</p> <p>The criterion for dementia implicit in DSM-IV is widely used in research but not fully operationalised. The 10/66 Dementia Research Group sought to do this using assessments from their one phase dementia diagnostic research interview, and to validate the resulting algorithm in a population-based study in Cuba.</p> <p>Methods</p> <p>The criterion was operationalised as a computerised algorithm, applying clinical principles, based upon the 10/66 cognitive tests, clinical interview and informant reports; the Community Screening Instrument for Dementia, the CERAD 10 word list learning and animal naming tests, the Geriatric Mental State, and the History and Aetiology Schedule – Dementia Diagnosis and Subtype. This was validated in Cuba against a local clinician DSM-IV diagnosis and the 10/66 dementia diagnosis (originally calibrated probabilistically against clinician DSM-IV diagnoses in the 10/66 pilot study).</p> <p>Results</p> <p>The DSM-IV sub-criteria were plausibly distributed among clinically diagnosed dementia cases and controls. The clinician diagnoses agreed better with 10/66 dementia diagnosis than with the more conservative computerized DSM-IV algorithm. The DSM-IV algorithm was particularly likely to miss less severe dementia cases. Those with a 10/66 dementia diagnosis who did not meet the DSM-IV criterion were less cognitively and functionally impaired compared with the DSMIV confirmed cases, but still grossly impaired compared with those free of dementia.</p> <p>Conclusion</p> <p>The DSM-IV criterion, strictly applied, defines a narrow category of unambiguous dementia characterized by marked impairment. It may be specific but incompletely sensitive to clinically relevant cases. The 10/66 dementia diagnosis defines a broader category that may be more sensitive, identifying genuine cases beyond those defined by our DSM-IV algorithm, with relevance to the estimation of the population burden of this disorder.</p

Transcriptional profiling of the effects of 25-hydroxycholesterol on human hepatocyte metabolism and the antiviral state it conveys against the hepatitis C virus

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) infection is a global health problem. A number of studies have implicated a direct role of cellular lipid metabolism in the HCV life cycle and inhibitors of the mevalonate pathway have been demonstrated to result in an antiviral state within the host cell. Transcriptome profiling was conducted on Huh-7 human hepatoma cells bearing subgenomic HCV replicons with and without treatment with 25-hydroxycholesterol (25-HC), an inhibitor of the mevalonate pathway that alters lipid metabolism, to assess metabolic determinants of pro- and antiviral states within the host cell. These data were compared with gene expression profiles from HCV-infected chimpanzees.</p> <p>Results</p> <p>Transcriptome profiling of Huh-7 cells treated with 25-HC gave 47 downregulated genes, 16 of which are clearly related to the mevalonate pathway. Fewer genes were observed to be upregulated (22) in the presence of 25-HC and 5 genes were uniquely upregulated in the HCV replicon bearing cells. Comparison of these gene expression profiles with data collected during the initial rise in viremia in 4 previously characterized HCV-infected chimpanzees yielded 54 overlapping genes, 4 of which showed interesting differential regulation at the mRNA level in both systems. These genes are PROX1, INSIG-1, NK4, and UBD. The expression of these genes was perturbed with siRNAs and with overexpression vectors in HCV replicon cells, and the effect on HCV replication and translation was assessed. Both PROX1 and NK4 regulated HCV replication in conjunction with an antiviral state induced by 25-hydroxycholesterol.</p> <p>Conclusion</p> <p>Treatment of Huh-7 cells bearing HCV replicons with 25-HC leads to the downregulation of many key genes involved in the mevalonate pathway leading to an antiviral state within the host cell. Furthermore, dysregulation of a larger subset of genes not directly related to the mevalonate pathway occurs both in 25-HC-treated HCV replicon harbouring cells as well as during the initial rise in viremia in infected chimpanzees. Functional studies of 3 of these genes demonstrates that they do not directly act as antiviral gene products but that they indirectly contribute to the antiviral state in the host cell. These genes may also represent novel biomarkers for HCV infection, since they demonstrate an outcome-specific expression profile.</p