Bacterial polymertropism, the response to strain-induced alignment of polymers

In nature, bacteria often live in surface-associated communities known as biofilms. Biofilm-forming bacteria deposit a layer of polysaccharide on the surfaces they inhabit; hence, polysaccharide is their immediate environment on any surface. In this study, we examined how the physical characteristics of polysaccharide substrates influence the behavior of the biofilm-forming bacterium Myxococcus xanthus. M. xanthus colonies, and indeed those of the majority of biofilm-forming species tested, respond to the compression-induced deformation of polysaccharide substrates by preferentially spreading across the surface perpendicular to the axis of compression. This response is conserved across multiple distantly related phyla and is found in species with an array of distinct motility apparatuses.The birefringence and small angle X-ray scattering patterns of compressed polysaccharide substrates indicate that the directed surface movements of these bacteria consistently match the orientation of the long axes of aligned and tightly packed polysaccharide fibers in compressed substrates. Therefore, we refer to this behavior as polymertropism to denote that the directed movements are a response to the physical arrangement of the change in packing and alignment of the polymers in the substrate. In addition to altering the colony morphology we find the behavior of groups of cells, called flares, is also affected in several species resulting in increased flare speed, duration, and displacement on compressed gel substrates.We suggest that polymertropism, which requires a downward-facing motility apparatus in M. xanthus, may be responsible for the observed tendency of bacterial cells to follow trails of extruded and presumably aligned polysaccharides, which their neighbors secrete and deposit on the substrate as they move across it. Polymertropism may also play a role in the organization of bacteria in a biofilm, as the iterative process of polysaccharide trail deposition and following is proposed to yield aggregates of cells

Structural basis of the oligomerization of hepatitis delta antigen

BACKGROUND: The hepatitis D virus (HDV) is a small satellite virus of hepatitis B virus (HBV). Coinfection with HBV and HDV causes severe liver disease in humans. The small 195 amino-acid form of the hepatitis delta antigen (HDAg) functions as a trans activator of HDV replication. A larger form of the protein containing a 19 amino acid C-terminal extension inhibits viral replication. Both of these functions are mediated in part by a stretch of amino acids predicted to form a coiled coil (residues 13-48) that is common to both forms. It is believed that HDAg forms dimers and higher ordered structures through this coiled-coil region. RESULTS: The high-resolution crystal structure of a synthetic peptide corresponding to residues 12 to 60 of HDAg has been solved. The peptide forms an antiparallel coiled coil, with hydrophobic residues near the termini of each peptide forming an extensive hydrophobic core with residues C-terminal to the coiled-coil domain in the dimer protein. The structure shows how HDAg forms dimers, but also shows the dimers forming an octamer that forms a 50 A ring lined with basic sidechains. This is confirmed by cross-linking studies of full-length recombinant small HDAg. CONCLUSIONS: HDAg dimerizes through an antiparallel coiled coil. Dimers then associate further to form octamers through residues in the coiled-coil domain and residues C-terminal to this region. Our findings suggest that the structure of HDAg represents a previously unseen organization of a nucleocapsid protein and raise the possibility that the N terminus may play a role in binding the viral RNA

Automatic annotation of context and speech acts for dialogue corpora

Richly annotated dialogue corpora are essential for new research directions in statistical learning approaches to dialogue management, context-sensitive interpretation, and context-sensitive speech recognition. In particular, large dialogue corpora annotated with contextual information and speech acts are urgently required. We explore how existing dialogue corpora (usually consisting of utterance transcriptions) can be automatically processed to yield new corpora where dialogue context and speech acts are accurately represented. We present a conceptual and computational framework for generating such corpora. As an example, we present and evaluate an automatic annotation system which builds ‘Information State Update' (ISU) representations of dialogue context for the Communicator (2000 and 2001) corpora of human-machine dialogues (2,331 dialogues). The purposes of this annotation are to generate corpora for reinforcement learning of dialogue policies, for building user simulations, for evaluating different dialogue strategies against a baseline, and for training models for context-dependent interpretation and speech recognition. The automatic annotation system parses system and user utterances into speech acts and builds up sequences of dialogue context representations using an ISU dialogue manager. We present the architecture of the automatic annotation system and a detailed example to illustrate how the system components interact to produce the annotations. We also evaluate the annotations, with respect to the task completion metrics of the original corpus and in comparison to hand-annotated data and annotations produced by a baseline automatic system. The automatic annotations perform well and largely outperform the baseline automatic annotations in all measures. The resulting annotated corpus has been used to train high-quality user simulations and to learn successful dialogue strategies. The final corpus will be made publicly availabl

Governing Islam and Security in Tajikistan and Beyond: The Emergence of Transnational Authoritarian Security Governance

Since 2002, the government of post-Soviet Tajikistan has deployed its security apparatus outside of the state’s territorial borders at least 49 times, intimidating, kidnapping and monitoring its citizens. I use the term transnational authoritarian security governance to refer to these border-spanning security practices. Although both secular and religious opponents to the government have been targeted, in this dissertation, I examine how the government of Tajikistan attempts to manage the threat from Islamic ‘extremism.’ I trace the emergence of the securitisation of Islam back to the Soviet Union, explore its consolidation in the years following independence in 1991, and how it has become operationalised in the form of transnational authoritarian security governance. I argue that the regulation of religious life in Tajikistan is based on an assertive form of secularism, which posits that religion is only safe if it is closely controlled by the state. In theorising transnational authoritarian security governance, I draw on the work of Michel Foucault. I argue that security governance is interwoven with relations of power. Governing Islamic ‘extremism’ in Tajikistan does not merely involve repressive life-taking sovereign power, it involves the moulding of obedient, secular subjects through disciplinary power and biopower. But as Foucault argues, where there is power, there is resistance. Those who are made subjects through security governance do have opportunities to resist it. Rather than being transformative and counterhegemonic, however, this resistance is momentary and anti-hegemonic. My findings are based on critical discourse analysis, a database of extraterritorial security incidents, semi-structured interviews, and extensive ethnographic fieldwork conducted between 2013 and 2015 in Tajikistan and Russia.ESR

Sex-Based Differences in Depth of Soft Tissue and Bone Diameter at the Sternal Intraosseous Catheter Insertion Site

Background Intraosseous (IO) catheters are commonly used to rapidly obtain vascular access for critically-ill patients in the emergency department (ED). While the sternum is a common IO insertion site for adult subjects, little is known about sex-based variation in the proper depth of insertion. Methods A retrospective cohort study was performed, utilizing CT scans obtained from DMC over a ten-year period (2009-2018) to estimate soft tissue depth overlying the recommended sternal IO insertion site. Depths of soft tissue from skin surface to bone surface (Measurement A) and from skin surface to the opposite bony cortex (Measurement B) were measured using standard radiologic software. Results Our data includes 32 male and 21 female subjects with a body mass index (BMI) between 18.5 and 25. Measurement A for males (x̄=17.89 mm, σ=8.91) was significantly larger than for females (x̄=12.98 mm, σ=5.96) (p=0.0308). Sternal diameter (Measurement B-Measurement A) was also significantly larger in males (x̄=17.15 mm, σ=5.06) compared to females (x̄=13.75 mm, σ=4.20) (p=0.0138). Measurement A was ≤25-mm in 78% of males and 90% of females. Conclusions Our results suggest that sex-based differences exist in soft tissue depth and bone diameter at the sternal site, despite similar BMI values. Since common IO needle lengths are 25-mm and 45-mm, these results suggest that 25-mm needles are sufficient for most patients in this BMI category; however, 22% of males and 10% of females studied would have required the longer 45-mm needle. Future studies with larger cohorts are needed to further validate these findings

The Exchange of Carbon Dioxide Between the Atmosphere and the Plant

THE aerodynamic technique has been used to determine the vertical transfer of carbon dioxide between the plant community and the atmosphere. It has also been extended to the aerial environment within the plant canopy to study the vertical distribution of the photosynthetic fixation of CO?. The method permits the study of carbon dioxide exchange under field conditions for agricultural crops. Measurements of windspeed, plant canopy characteristics and carbon dioxide concentration distributions are required. The results give the relative importance of the various zones of the plant community in the net photosynthetic fixation of CO? and the diurnal nature of photosynthesis under field conditions as well as immediate response data to environmental conditions. Such information is valuable for developing models of ideal plant morphology, improved planting patterns for efficient light interception and photosynthesis, and for input into simulation programs

Automatic Annotation of Context and Speech Acts for Dialogue Corpora.

Richly annotated dialogue corpora are essential for new research directions in statistical learning approaches to dialogue management, context-sensitive interpretation, and context-sensitive speech recognition. In particular, large dialogue corpora annotated with contextual information and speech acts are urgently required. We explore how existing dialogue corpora (usually consisting of utterance transcriptions) can be automatically processed to yield new corpora where dialogue context and speech acts are accurately represented. We present a conceptual and computational framework for generating such corpora. As an example, we present and evaluate an automatic annotation system which builds ‘Information State Update’ (ISU) representations of dialogue context for the Communicator (2000 and 2001) corpora of human–machine dialogues (2,331 dialogues). The purposes of this annotation are to generate corpora for reinforcement learning of dialogue policies, for building user simulations, for evaluating different dialogue strategies against a baseline, and for training models for context-dependent interpretation and speech recognition. The automatic annotation system parses system and user utterances into speech acts and builds up sequences of dialogue context representations using an ISU dialogue manager. We present the architecture of the automatic annotation system and a detailed example to illustrate how the system components interact to produce the annotations. We also evaluate the annotations, with respect to the task completion metrics of the original corpus and in comparison to hand-annotated data and annotations produced by a baseline automatic system. The automatic annotations perform well and largely outperform the baseline automatic annotations in all measures. The resulting annotated corpus has been used to train high-quality user simulations and to learn successful dialogue strategies. The final corpus will be made publicly available

Sex-Based Differences in Depth of Soft Tissue at the Proximal Tibia Intraosseous Catheter Insertion Site

Background Intraosseous (IO) catheters are commonly used to rapidly obtain vascular access for critically-ill patients in the emergency department (ED). Although the proximal tibia (PT) is a standard IO insertion site for adult subjects, little is known about sex-based variation in the proper depth of insertion. Methods A retrospective cohort study was performed, utilizing CT scans obtained from DMC over a ten-year period (2009-2018) to estimate soft tissue depth overlying the recommended PT-IO insertion site. Depths of soft tissue from skin surface to bone surface (Measurement A) and from skin surface to the opposite bony cortex (Measurement B) were measured using standard radiologic software. Results A total of 217 subjects were enrolled, including 106 (48.9%) males. Body mass index (BMI) was not significantly different between sexes (p=0.188). Measurement A for females (x̄=21.65 mm, σ=8.17) was significantly greater than for males (x̄=13.64 mm, σ=5.52) (p\u3c0.0001). Measurement A was \u3e25-mm in 5.7% of males and 27.0% of females (p\u3c0.001). Measurement B was \u3c45-mm in 24.5% of males and 21.6% of females. Conclusion Our results suggest that sex-based differences exist in soft tissue depth at the PT site, despite similar BMI values. Since common IO needle lengths are 25-mm and 45-mm, these results have profound implications. The 25-mm needle would have been too short for more than one-fourth of female subjects. However, a 45-mm catheter would have been too long for almost one-fourth of all subjects. Further study is needed to determine whether this sex difference exists in a larger cohort of patients

Ultra-deep sequencing reveals dynamics of drug Resistance-Associated variants in Hepatitis C viruses: Relevance to treatment outcome and resistance screening

Hepatitis C is a global health issue with approximately 3% of the worlds’ population estimated to be infected with the hepatitis C virus (HCV) Inefficiencies in treatment has led to development of direct-acting antivirals (DAAs) that specifically target HCV proteins involved in the virus’s lifecycle1. One of the major concerns arising from the use of the DAAs is the emergence of resistance-associated variants (RAVs) that affect the efficacy of the drugs. RAVs are generally associated with a fitness cost and the use of ultra-deep pyrosequencing technology has shown that in most treatment naïve subjects low frequency circulating strains carry RAVs2. The aim of the study was to investigate i) the clinical relevance of low frequency RAVs; ii) the persistence of RAVs and iii) compensatory mutations in a subset of subjects who had failed boceprevir (SCH503034; protease inhibitor)

Analysis of the first gigantic jet recorded over continental North America

[1] Two low-light cameras near Marfa, Texas, recorded a gigantic jet over northern Mexico on 13 May 2005 at approximately 0423:50 UTC. Assuming that the farthest of two candidate storm systems was its source, the bright lower channel ended in a fork at around 50–59 km height with the very dim upper branches extended to 69–80 km altitude. During the time window containing the jet, extremely low frequency magnetic field recordings show that there was no fast charge moment change larger than 50 coulomb times kilometers (C km) but there was a larger and slower charge moment change of 520 C km over 70 ms. The likely parent thunderstorm was a high-precipitation supercell cluster containing a persistent mesocyclone, with radar echo tops of at least 17 km. However, photogrammetric analysis suggests that the gigantic jet occurred over the forward flank downdraft region with echo tops of 14 km. This part of the supercell may have had an inverted-polarity charge configuration as evidenced by positive cloud-to-ground lightning flashes (+CG) dominating over negative flashes (-CG), while -CGs occurred under the downwind anvil. Four minutes before the gigantic jet, -CG activity practically ceased in this area, while +CG rates increased, culminating during the 20 s leading up to the gigantic jet with four National Lightning Detection Network–detected +CGs. A relative lull in lightning activity of both polarities was observed for up to 1.5 min after the gigantic jet. The maturing storm subsequently produced 30 sprites between 0454 and 0820 UTC, some associated with extremely large impulse charge moment change values.Peer ReviewedPostprint (published version