Forces on Bins - The Effect of Random Friction

In this note we re-examine the classic Janssen theory for stresses in bins, including a randomness in the friction coefficient. The Janssen analysis relies on assumptions not met in practice; for this reason, we numerically solve the PDEs expressing balance of momentum in a bin, again including randomness in friction.Comment: 11 pages, LaTeX, with 9 figures encoded, gzippe

Volcanic Hazard Assessment for an Eruption Hiatus, or Post-eruption Unrest Context: Modeling Continued Dome Collapse Hazards for Soufrière Hills Volcano

Effective volcanic hazard management in regions where populations live in close proximity to persistent volcanic activity involves understanding the dynamic nature of hazards, and associated risk. Emphasis until now has been placed on identification and forecasting of the escalation phase of activity, in order to provide adequate warning of what might be to come. However, understanding eruption hiatus and post-eruption unrest hazards, or how to quantify residual hazard after the end of an eruption, is also important and often key to timely post-eruption recovery. Unfortunately, in many cases when the level of activity lessens, the hazards, although reduced, do not necessarily cease altogether. This is due to both the imprecise nature of determination of the “end” of an eruptive phase as well as to the possibility that post-eruption hazardous processes may continue to occur. An example of the latter is continued dome collapse hazard from lava domes which have ceased to grow, or sector collapse of parts of volcanic edifices, including lava dome complexes. We present a new probabilistic model for forecasting pyroclastic density currents (PDCs) from lava dome collapse that takes into account the heavy-tailed distribution of the lengths of eruptive phases, the periods of quiescence, and the forecast window of interest. In the hazard analysis, we also consider probabilistic scenario models describing the flow’s volume and initial direction. Further, with the use of statistical emulators, we combine these models with physics-based simulations of PDCs at Soufrière Hills Volcano to produce a series of probabilistic hazard maps for flow inundation over 5, 10, and 20 year periods. The development and application of this assessment approach is the first of its kind for the quantification of periods of diminished volcanic activity. As such, it offers evidence-based guidance for dome collapse hazards that can be used to inform decision-making around provisions of access and reoccupation in areas around volcanoes that are becoming less active over time

Pooling strength amongst limited datasets using hierarchical Bayesian analysis, with application to pyroclastic density current mobility metrics

In volcanology, the sparsity of datasets for individual volcanoes is an important problem, which, in many cases, compromises our ability to make robust judgments about future volcanic hazards. In this contribution we develop a method for using hierarchical Bayesian analysis of global datasets to combine information across different volcanoes and to thereby improve our knowledge at individual volcanoes. The method is applied to the assessment of mobility metrics for pyroclastic density currents in order to better constrain input parameters and their related uncertainties for forward modeling. Mitigation of risk associated with such flows depends upon accurate forecasting of possible inundation areas, often using empirical models that rely on mobility metrics measured from the deposits of past flows, or on the application of computational models, several of which take mobility metrics, either directly or indirectly, as input parameters. We use hierarchical Bayesian modeling to leverage the global record of mobility metrics from the FlowDat database, leading to considerable improvement in the assessment of flow mobility where the data for a particular volcano is sparse. We estimate the uncertainties involved and demonstrate how they are improved through this approach. The method has broad applicability across other areas of volcanology where relationships established from broader datasets can be used to better constrain more specific, sparser, datasets. Employing such methods allows us to use, rather than shy away from, limited datasets, and allows for transparency with regard to uncertainties, enabling more accountable decision-making

Field-deployable, quantitative, rapid identification of active Ebola virus infection in unprocessed blood

The West African Ebola virus outbreak underlined the importance of delivering mass diagnostic capability outside the clinical or primary care setting in effectively containing public health emergencies caused by infectious disease. Yet, to date, there is no solution for reliably deploying at the point of need the gold standard diagnostic method, real time quantitative reverse transcription polymerase chain reaction (RT- qPCR), in a laboratory infrastructure-free manner. In this proof of principle work, we demonstrate direct performance of RT-qPCR on fresh blood using far-red fluorophores to resolve fluorogenic signal inhibition and controlled, rapid freeze/thawing to achieve viral genome extraction in a single reaction chamber assay. The resulting process is entirely free of manual or automated sample pre-processing, requires no microfluidics or magnetic/mechanical sample handling and thus utilizes low cost consumables. This enables a fast, laboratory infrastructure-free, minimal risk and simple standard operating procedure suited to frontline, field use. Developing this novel approach on recombinant bacteriophage and recombinant human immunodeficiency virus (HIV; Lentivirus), we demonstrate clinical utility in symptomatic EBOV patient screening using live, infectious Filoviruses and surrogate patient samples. Moreover, we evidence assay co-linearity independent of viral particle structure that may enable viral load quantification through pre-calibration, with no loss of specificity across an 8 log- linear maximum dynamic range. The resulting quantitative rapid identification (QuRapID) molecular diagnostic platform, openly accessible for assay development, meets the requirements of resource- limited countries and provides a fast response solution for mass public health screening against emerging biosecurity threats

Specificity of DNA-binding by the FAX-1 and NHR-67 nuclear receptors of Caenorhabditis elegans is partially mediated via a subclass-specific P-box residue

<p>Abstract</p> <p>Background</p> <p>The nuclear receptors of the NR2E class play important roles in pattern formation and nervous system development. Based on a phylogenetic analysis of DNA-binding domains, we define two conserved groups of orthologous NR2E genes: the NR2E1 subclass, which includes <it>C. elegans nhr-67, Drosophila tailless </it>and <it>dissatisfaction</it>, and vertebrate Tlx (NR2E2, NR2E4, NR2E1), and the NR2E3 subclass, which includes <it>C. elegans fax-1 </it>and vertebrate PNR (NR2E5, NR2E3). PNR and Tll nuclear receptors have been shown to bind the hexamer half-site AAGTCA, instead of the hexamer AGGTCA recognized by most other nuclear receptors, suggesting unique DNA-binding properties for NR2E class members.</p> <p>Results</p> <p>We show that NR2E3 subclass member FAX-1, unlike NHR-67 and other NR2E1 subclass members, binds to hexamer half-sites with relaxed specificity: it will bind hexamers with the sequence ANGTCA, although it prefers a purine to a pyrimidine at the second position. We use site-directed mutagenesis to demonstrate that the difference between FAX-1 and NHR-67 binding preference is partially mediated by a conserved subclass-specific asparagine or aspartate residue at position 19 of the DNA-binding domain. This amino acid position is part of the "P box" that plays a critical role in defining binding site specificity and has been shown to make hydrogen-bond contacts to the second position of the hexamer in co-crystal structures for other nuclear receptors. The relaxed specificity allows FAX-1 to bind a much larger repertoire of half-sites than NHR-67. While NR2E1 class proteins bind both monomeric and dimeric sites, the NR2E3 class proteins bind only dimeric sites. The presence of a single strong site adjacent to a very weak site allows dimeric FAX-1 binding, further increasing the number of dimeric binding sites to which FAX-1 may bind <it>in vivo</it>.</p> <p>Conclusion</p> <p>These findings identify subclass-specific DNA-binding specificities and dimerization properties for the NR2E1 and NR2E3 subclasses. For the NR2E1 protein NHR-67, Asp-19 permits binding to AAGTCA half-sites, while Asn-19 permits binding to AGGTCA half-sites. The apparent conservation of DNA-binding properties between vertebrate and nematode NR2E receptors allows for the possibility of evolutionarily-conserved regulatory patterns.</p

Cervical lymph node metastasis in high-grade transformation of head and neck adenoid cystic carcinoma: a collective international review

Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation