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We consider the dynamics of a gravity current of viscous liquid propagating above a dense granular medium that obeys a $\\mu (I)$-rheology. Initially, the pool of liquid depresses the granular layer to form levees at its edges. Next, these levees are pushed outwards by the gravity-driven slumping of the liquid, but the levees are not surmounted. In the third stage, the top of the levee is pushed out beyond the rest of the levee. This segregates the liquid into a pond trapped by the remnant of the original levees, and a slowly spreading thin film ahead of the levees. The trapped fraction of liquid depends on the extent of the early granular erosion, which in turn is controlled by the initial shape of the deposit and the yield criterion of the granular layer. The key physical ingredients that lead to such dynamics are inertia-less flow and a lower layer with a yield criterion. The latter gives rise to the all-important levees, which lead to the eventual trapping.

The motion of a finite layer of Bingham material on a solid plate that executes in-plane oscillations was reported previously by Balmforth et al. (J. Non-Newtonian Fluid Mech., vol. 158, issue 1–3, 2009, pp. 46–53). There, it was suggested that multiple yielded regions may arise within the material; this contrasts to start-up flow of the same material for which only one yielded region is generated. Here, we explore quantitatively the fluid physics of this oscillatory flow problem through analytical approximations and further numerical computation. Four new key topological properties concerning the generation and termination of the yielded regions are reported. It is shown that the existence of multiple yielded regions is equivalent to the layer never becoming entirely rigid during the periodic motion. For small inertia, the flow is approximately time-reversible with only a single yielded region generated at the plate. For large inertia, shear stress in the material decays rapidly as a function of distance from the plate. A thin zone of yielded material detaches periodically from the plate, and subsequently terminates within the layer. At high oscillation frequency, there can be any number $N$ of distinct rigid regions, satisfying $N= \\lfloor 1- {\\rm \\pi}^{-1} \\log B \\rfloor$ where $B$ is the Bingham number. It is also shown that for $B>0.5370$, there are at most one yielded region and one rigid region throughout the motion. These theoretical results can be used as a basis for oscillatory rheometry, allowing for measurement of the yield stress using existing apparatus.

The effect of microbial activity on buoyancy-driven flow within a porous layer is analysed. The input fluid provides an energy source for the growth of biofilms on the porous rock. At each location within the porous layer, the porosity and permeability begin to decrease once the input fluid has invaded. This leads to an evolving rock heterogeneity that depends on the passing time of the input fluid. Hence, the evolution of the flow is partly controlled by its own history. We present an axisymmetric gravity current model, accounting for this effect. In general, a reduction in permeability leads to the flow having a lesser extent in the radial direction and greater thickness (extent in the cross-flow direction), whilst a reduction in porosity has negligible effect on the thickness but leads to a much greater radial extent. The flow is fastest near the free surface where the permeability is greatest. In the case where the porosity and permeability reduce as power-law functions of fluid residence time, the evolution of the flow and the rock properties are self-similar. Consumption of the input fluid by the microbes is also incorporated in the model and it generally leads to flows with lesser radial extent but little change in the thickness. The three impacts of microbial growth (volume loss owing to consumption and the reduction in permeability and porosity) each influence the flow in substantially different ways and the interplay is analysed. A motivation of the study, the underground storage of hydrogen, is briefly discussed.

Control of transcription is crucial for correct gene expression and orderly development. For many years, bacteriophage T4 has provided a simple model system to investigate mechanisms that regulate this process. Development of T4 requires the transcription of early, middle and late RNAs. Because T4 does not encode its own RNA polymerase, it must redirect the polymerase of its host, E. coli , to the correct class of genes at the correct time. T4 accomplishes this through the action of phage-encoded factors. Here I review recent studies investigating the transcription of T4 prereplicative genes, which are expressed as early and middle transcripts. Early RNAs are generated immediately after infection from T4 promoters that contain excellent recognition sequences for host polymerase. Consequently, the early promoters compete extremely well with host promoters for the available polymerase. T4 early promoter activity is further enhanced by the action of the T4 Alt protein, a component of the phage head that is injected into E. coli along with the phage DNA. Alt modifies Arg265 on one of the two α subunits of RNA polymerase. Although work with host promoters predicts that this modification should decrease promoter activity, transcription from some T4 early promoters increases when RNA polymerase is modified by Alt. Transcription of T4 middle genes begins about 1 minute after infection and proceeds by two pathways: 1) extension of early transcripts into downstream middle genes and 2) activation of T4 middle promoters through a process called sigma appropriation. In this activation, the T4 co-activator AsiA binds to Region 4 of σ 70 , the specificity subunit of RNA polymerase. This binding dramatically remodels this portion of σ 70 , which then allows the T4 activator MotA to also interact with σ 70 . In addition, AsiA restructuring of σ 70 prevents Region 4 from forming its normal contacts with the -35 region of promoter DNA, which in turn allows MotA to interact with its DNA binding site, a MotA box, centered at the -30 region of middle promoter DNA. T4 sigma appropriation reveals how a specific domain within RNA polymerase can be remolded and then exploited to alter promoter specificity.

We develop direct inversion methods for inferring the rheology of a fluid from observations of its shallow flow. First, the evolution equation for the free-surface flow of an inertia-less current with general constitutive law is derived. The relationship between the volume flux of fluid and the basal stress, $\\tau _b$, is encapsulated by a single function $F(\\tau _b)$, which depends only on the constitutive law. The inversion method consists of (i) determining the flux and basal stress from the free-surface evolution, (ii) comparing the flux with the basal stress to constrain $F$ and (iii) inferring the constitutive law from $F$. Examples are presented for both steady and transient free-surface flows demonstrating that a wide range of constitutive laws can be directly obtained. For flows in which the free-surface velocity is known, we derive a different method, which circumvents the need to calculate the flux.

Nearly all virulence factors in Bordetella pertussis are activated by a master two-component system, BvgAS, composed of the sensor kinase BvgS and the response regulator BvgA. When BvgS is active, BvgA is phosphorylated (BvgA~P), and virulence-activated genes ( vag s) are expressed [Bvg(+) mode]. When BvgS is inactive and BvgA is not phosphorylated, virulence-repressed genes ( vrg s) are induced [Bvg(−) mode]. Here, we have used transcriptome sequencing (RNA-seq) and reverse transcription-quantitative PCR (RT-qPCR) to define the BvgAS-dependent regulon of B. pertussis Tohama I. Our analyses reveal more than 550 BvgA-regulated genes, of which 353 are newly identified. BvgA-activated genes include those encoding two-component systems (such as kdpED ), multiple other transcriptional regulators, and the extracytoplasmic function (ECF) sigma factor brpL , which is needed for type 3 secretion system (T3SS) expression, further establishing the importance of BvgA~P as an apex regulator of transcriptional networks promoting virulence. Using in vitro transcription, we demonstrate that the promoter for brpL is directly activated by BvgA~P. BvgA-FeBABE cleavage reactions identify BvgA~P binding sites centered at positions −41.5 and −63.5 in bprL . Most importantly, we show for the first time that genes for multiple and varied metabolic pathways are significantly upregulated in the B. pertussis Bvg(−) mode. These include genes for fatty acid and lipid metabolism, sugar and amino acid transporters, pyruvate dehydrogenase, phenylacetic acid degradation, and the glycolate/glyoxylate utilization pathway. Our results suggest that metabolic changes in the Bvg(−) mode may be participating in bacterial survival, transmission, and/or persistence and identify over 200 new vrg s that can be tested for function. IMPORTANCE Within the past 20 years, outbreaks of whooping cough, caused by Bordetella pertussis , have led to respiratory disease and infant mortalities, despite good vaccination coverage. This is due, at least in part, to the introduction of a less effective acellular vaccine in the 1990s. It is crucial, then, to understand the molecular basis of B. pertussis growth and infection. The two-component system BvgA (response regulator)/BvgS (histidine kinase) is the master regulator of B. pertussis virulence genes. We report here the first RNA-seq analysis of the BvgAS regulon in B. pertussis , revealing that more than 550 genes are regulated by BvgAS. We show that genes for multiple and varied metabolic pathways are highly regulated in the Bvg(−) mode (absence of BvgA phosphorylation). Our results suggest that metabolic changes in the Bvg(−) mode may be participating in bacterial survival, transmission, and/or persistence. Within the past 20 years, outbreaks of whooping cough, caused by Bordetella pertussis , have led to respiratory disease and infant mortalities, despite good vaccination coverage. This is due, at least in part, to the introduction of a less effective acellular vaccine in the 1990s. It is crucial, then, to understand the molecular basis of B. pertussis growth and infection. The two-component system BvgA (response regulator)/BvgS (histidine kinase) is the master regulator of B. pertussis virulence genes. We report here the first RNA-seq analysis of the BvgAS regulon in B. pertussis , revealing that more than 550 genes are regulated by BvgAS. We show that genes for multiple and varied metabolic pathways are highly regulated in the Bvg(−) mode (absence of BvgA phosphorylation). Our results suggest that metabolic changes in the Bvg(−) mode may be participating in bacterial survival, transmission, and/or persistence.

To better understand host–phage interactions and the genetic bases of phage resistance in a model system relevant to potential phage therapy, we isolated several spontaneous mutants of the USA300 S. aureus clinical isolate NRS384 that were resistant to phage K. Six of these had a single missense mutation in the host rpoC gene, which encodes the RNA polymerase β’ subunit. To examine the hypothesis that mutations in the host RNA polymerase affect the transcription of phage genes, we performed RNA-seq analysis on total RNA samples collected from NRS384 wild-type (WT) and rpoCG17D mutant cultures infected with phage K, at different timepoints after infection. Infection of the WT host led to a steady increase of phage transcription relative to the host. Our analysis allowed us to define 53 transcriptional units and to categorize genes based on their temporal expression patterns. Predicted promoter sequences defined by conserved −35, −10, and, in some cases, extended −10 elements, were found upstream of early and middle genes. However, in many cases, sequences upstream of late genes did not contain clear, complete, canonical promoter sequences, suggesting that factors in addition to host RNA polymerase are required for their expression. Infection of the rpoCG17D mutant host led to a transcriptional pattern that was similar to that of the WT at early timepoints. However, beginning at 20 min after infection, transcription of late genes (such as phage structural genes and host lysis genes) was severely reduced. Our data indicate that the rpoCG17D mutation prevents the expression of phage late genes, resulting in a failed infection cycle for phage K. In addition to illuminating the global transcriptional landscape of phage K throughout the infection cycle, this study will inform our investigations into the basis of phage K’s control of its transcriptional program as well as mechanisms of phage resistance.

Bacterial small non-coding RNA (sRNAs), together with the RNA chaperone Hfq, post-transcriptionally regulate gene expression by affecting ribosome binding or mRNA stability. In the human pathogen Bordetella pertussis, the causative agent of whooping cough, hundreds of sRNAs have been identified, but their roles in B. pertussis biology are mostly unknown. Here we characterize the Hfq-dependent sRNABpsA, whose level is dramatically higher in the virulence (Bvg+) mode. We show that transcription from a σA-dependent promoter yields a long form of 190 nucleotides (nt) that is processed by RNase E to generate a shorter, more stable form (BpsA-S) of 67 nt. The transcript also encodes a small protein of 32 amino acids. Using RNA-seq and real time PCR, we identify 91 genes whose expression significantly increases in the absence of BpsA. Seventy contain sequences at/near their ribosome binding sites that are complementary to single-stranded regions (site 1 or 2) of BpsA-S. Identified genes include those encoding multiple transporters and three transcriptional regulators. Using a lacZ translational reporter system, we demonstrate that BpsA-S directly represses one of these genes, BP2158, a σ54-dependent transcriptional regulator, suggesting Bvg+ mode repression of a σ54 regulon. We find that the BpsA-S region containing sites 1 and 2 is 100% conserved throughout various Betaproteobacteria species, and BpsA-S target sites are often conserved among the homologs of the predicted B. pertussis target genes. We speculate that BpsA-S regulation represents a conserved process that fine-tunes gene expression in the Bvg+ mode of B. pertussis and perhaps under other conditions in related bacteria.IMPORTANCERegulation of gene expression involves controlling transcription, translation, and transcript degradation. sRNAs with short sequences complementary to an mRNA sequence are involved in post-transcriptional regulation by aiding or interfering with either ribosome binding or nuclease attack. In the human pathogen Bordetella pertussis, the causative agent of whooping cough, hundreds of sRNA have been identified, but their functions remain largely unknown. We have characterized an sRNA that is abundant in the virulence mode of B. pertussis and serves to downregulate multiple genes, including transcriptional regulators and various transporters. We demonstrate that this sRNA directly represses a transcriptional factor, suggesting that it influences the regulation of specific B. pertussis regulons. The high conservation of this sRNA and its targets within Betaproteobacteria suggests a conserved pathway for gene regulation.

Argumentation as the public exchange of reasons is widely thought to enhance deliberative interactions that generate and justify reasonable public policies. Adopting an argumentation-theoretic perspective, we survey the norms that should govern public argumentation and address some of the complexities that scholarly treatments have identified. Our focus is on norms associated with the ideals of correctness and participation as sources of a politically legitimate deliberative outcome. In principle, both ideals are mutually coherent. If the information needed for a correct deliberative outcome is distributed among agents, then maximising participation increases information diversity. But both ideals can also be in tension. If participants lack competence or are prone to biases, a correct deliberative outcome requires limiting participation. The central question for public argumentation, therefore, is how to strike a balance between both ideals. Rather than advocating a preferred normative framework, our main purpose is to illustrate the complexity of this theme.