Limitation of Trypanosoma brucei parasitaemia results from a combination of density-dependent parasite differentiation and parasite killing by the host immune response

In the bloodstream of its mammalian host, the "slender" form of Trypanosoma brucei replicates extracellularly, producing a parasitaemia. At high density, the level of parasitaemia is limited at a sublethal level by differentiation to the non-replicative "stumpy" form and by the host immune response. Here, we derive continuous time equations to model the time-course, cell types and level of trypanosome parasitaemia, and compare the best fits with experimental data. The best fits that were obtained favour a model in which both density-dependent trypanosome differentiation and host immune response have a role in limiting the increase of parasites, much poorer fits being obtained when differentiation and immune response are considered independently of one another. Best fits also favour a model in which the slender-to-stumpy differentiation progresses in a manner that is essentially independent of the cell cycle. Finally, these models also make the prediction that the density-dependent trypanosome differentiation mechanism can give rise to oscillations in parasitaemia level. These oscillations are independent of the immune system and are not due to antigenic variation

Effects of culling white-tailed deer on tree regeneration and Microstegium vimineum, an invasive grass

Reduction of forest regeneration due to overbrowsing by white-tailed deer is a growing concern for land managers. Abundant deer can impede forest regeneration through direct predation on tree seedlings. Additionally high deer density can facilitate the establishment of a dense understory of browse tolerant plant species that shades seedlings and persists even in the absence of deer. In response to these challenges, land managers have sought to reduce deer herds to restore tree regeneration, but few studies have evaluated the effectiveness of this management. Our study took place in Catoctin Mountain Park, a US National Park Service unit with a history of high deer density. The park has been heavily invaded by Microstegium vimineum, an invasive grass that can completely cover the forest floor. Using permanent plots established prior to the start of deer management, we were able to assess the joint effects of deer culling and M. vimineum on tree seedling density. We found that tree seedling density increased in response to deer reductions. M. vimineum cover initially increased, but then decreased. Seedling densities were higher in plots with more M. vimineum cover, indicating that it did not form a recalcitrant understory that would suppress regeneration. However, eight years after deer management began, few tree seedlings were \u3e 30 cm tall, implying that it will be many years before they grow into the sapling stage. Our results indicate that deer culling can be an effective tool in restoring tree regeneration despite the presence of M. vimineum, but that success will require a long-term commitment

The Nikolaevskiy equation with dispersion

The Nikolaevskiy equation was originally proposed as a model for seismic waves and is also a model for a wide variety of systems incorporating a neutral, Goldstone mode, including electroconvection and reaction-diffusion systems. It is known to exhibit chaotic dynamics at the onset of pattern formation, at least when the dispersive terms in the equation are suppressed, as is commonly the practice in previous analyses. In this paper, the effects of reinstating the dispersive terms are examined. It is shown that such terms can stabilise some of the spatially periodic traveling waves; this allows us to study the loss of stability and transition to chaos of the waves. The secondary stability diagram (Busse balloon) for the traveling waves can be remarkably complicated.Comment: 24 pages; accepted for publication in Phys. Rev.

Reanimalizing religion: Hegel, habit, and the nature of spirit

Recently, a number of scholars have sought to reveal the extent to which the concept of religion and the discipline of religious studies depend upon a distinction between humans and other animals for their conceptual and disciplinary integrity. This dissertation is an attempt to deepen this insight by (re)turning to one of the central figures in the history of thinking about religion, G.W.F. Hegel, whose Lectures on the Philosophy of Religion represent one of the first forays into the academic study of religion. By employing the non-human animal as a limit-case, this project attempts to probe Hegel’s concept of religion for a place where it might be possible to think “religion” anew. This “place” can be found in Hegel’s concept of habit or Gewohnheit, since habit unsettles the distinction between nature and spirit, leaving open a way to rethink “religion” as being rooted in the animal or quasi-natural. Chapter 1 considers Alexandre Kojève’s worry that, at the proverbial “end of history,” the human being will become “reanimalized.” We argue that the (im)possibility of such a reanimalization lies in Hegel’s concept of habit or Gewohnheit, that “mechanism,” which aids the natural or feeling-soul in its “transition” to spirit or, more specifically, consciousness. In chapter 2, we consider the relationship between nature and spirit further, exploring the relationship between thought and feeling as thematized in Hegel’s philosophy of religion. Hegel argues (in contrast to the likes of Schleiermacher) that religion cannot have its essence in feeling, because feeling is a form of thought. In chapter 3, we take a closer look at how habit aids in the “transition” or passing-over from nature to spirit, highlighting habit as skill. Habit is a means for the purification of the natural drives and for replacing these drives with those of another, spiritual nature. However, we will find that the transition from nature to spirit cannot be accomplished through habit alone; it depends upon an encounter with the infinite or death, wherein the subject realizes her own in/finitude. In chapter 4, we consider how spirit expresses itself through the human body and, most importantly, through language and (the language of) sacrifice. While the death of the animal is the becoming of spirit, spirit depends upon the death of the animal even after it makes its first appearance in language since speech or language is dependent upon the animal voice. In the final chapter, we discover that religion too is predicated on the death or sacrifice of the animal. Moreover, it is through religion that human beings raise themselves above the animals and learn how to recognize themselves as essentially spiritual beings. Religion brings about this realization, this conversion from nature to spirit, through the cultus – a form of religious practice akin to a habit as skill. In the cultus, the human subject undergoes a conversion and becomes aware of herself as a spiritual rather than a natural being. When performed continuously, this cultus becomes the basis of the ethical as well as the philosophical life

Mononuclear cell transcriptome changes associated with dimethyl fumarate in MS.

ObjectiveTo identify short-term changes in gene expression in peripheral blood mononuclear cells (PBMCs) associated with treatment response to dimethyl fumarate (DMF, Tecfidera) in patients with relapsing-remitting MS (RRMS).MethodsBlood samples were collected from 24 patients with RRMS (median Expanded Disability Status Scale score, 2.0; range 1-7) at baseline, 6 weeks, and 15 months after the initiation of treatment with DMF (BG-12; Tecfidera). Seven healthy controls were also recruited, and blood samples were collected over the same time intervals. PBMCs were extracted from blood samples and sequenced using next-generation RNA sequencing. Treatment responders were defined using the composite outcome measure "no evidence of disease activity" (NEDA-4). Time-course and cross-sectional differential expression analyses were performed to identify transcriptomic markers of treatment response.ResultsTreatment responders (NEDA-4 positive, 8/24) over the 15-month period had 478 differentially expressed genes (DEGs) 6 weeks after the start of treatment. These were enriched for nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and inhibition of nuclear factor κB (NFκB) pathway transcripts. For patients who showed signs of disease activity, there were no DEGs at 6 weeks relative to their (untreated) baseline. Contrasting transcriptomes expressed at 6 weeks with those at 15 months of treatment, 0 and 1,264 DEGs were found in the responder and nonresponder groups, respectively. Transcripts in the nonresponder group (NEDA-4 negative, 18/24) were enriched for T-cell signaling genes.ConclusionShort-term PBMC transcriptome changes reflecting activation of the Nrf2 and inhibition of NFκB pathways distinguish patients who subsequently show a medium-term treatment response with DMF. Relative stabilization of gene expression patterns may accompany treatment-associated suppression of disease activity

Orientation-dependent pinning and homoclinic snaking on a planar lattice

We study homoclinic snaking of one-dimensional, localized states on two-dimensional, bistable lattices via the method of exponential asymptotics. Within a narrow region of parameter space, fronts connecting the two stable states are pinned to the underlying lattice. Localized solutions are formed by matching two such stationary fronts back-to-back; depending on the orientation relative to the lattice, the solution branch may “snake” back and forth within the pinning region via successive saddle-node bifurcations. Standard continuum approximations in the weakly nonlinear limit (equivalently, the limit of small mesh size) do not exhibit this behavior, due to the resultant leading-order reaction-diffusion equation lacking a periodic spatial structure. By including exponentially small effects hidden beyond all algebraic orders in the asymptotic expansion, we find that exponentially small but exponentially growing terms are switched on via error function smoothing near Stokes lines. Eliminating these otherwise unbounded beyond-all-orders terms selects the origin (modulo the mesh size) of the front, and matching two fronts together yields a set of equations describing the snaking bifurcation diagram. This is possible only within an exponentially small region of parameter space—the pinning region. Moreover, by considering fronts orientated at an arbitrary angle ψ to the x-axis, we show that the width of the pinning region is nonzero only if tan ψ is rational or infinite. The asymptotic results are compared with numerical calculations, with good agreement

A Study of Work Practices in Tasmanian Government Schools: Final report to the Australian Education Union – Tasmanian Branch

The Australian Council for Educational Research (ACER) conducted an online survey of members on behalf of the Tasmanian Branch of the Australian Education Union (AEU). The survey, which was open to teachers, school leaders (principals and assistant principals) and education support staff working in Tasmanian government schools and offices, was available to the majority of members of the Union in August 2017, and remained open for four weeks during Term 3. The survey was based on one conducted for the Victorian branch of the AEU in 2016. The survey of the work of union members in Tasmanian government schools focussed on the hours of work by school staff, staff perceptions of their work, and the relationship between work practices and the quality of teaching. More than 3000 teachers, school leaders and education support staff completed the survey, a response rate of 60%

The silicon trypanosome

African trypanosomes have emerged as promising unicellular model organisms for the next generation of systems biology. They offer unique advantages, due to their relative simplicity, the availability of all standard genomics techniques and a long history of quantitative research. Reproducible cultivation methods exist for morphologically and physiologically distinct life-cycle stages. The genome has been sequenced, and microarrays, RNA-interference and high-accuracy metabolomics are available. Furthermore, the availability of extensive kinetic data on all glycolytic enzymes has led to the early development of a complete, experiment-based dynamic model of an important biochemical pathway. Here we describe the achievements of trypanosome systems biology so far and outline the necessary steps towards the ambitious aim of creating a , a comprehensive, experiment-based, multi-scale mathematical model of trypanosome physiology. We expect that, in the long run, the quantitative modelling enabled by the Silicon Trypanosome will play a key role in selecting the most suitable targets for developing new anti-parasite drugs

The Signature of Primordial Grain Growth in the Polarized Light of the AU Mic Debris Disk

We have used the Hubble Space Telescope/ACS coronagraph to make polarization maps of the AU Mic debris disk. The fractional linear polarization rises monotonically from about 0.05 to 0.4 between 20 and 80 AU. The polarization is perpendicular to the disk, indicating that the scattered light originates from micron sized grains in an optically thin disk. Disk models, which simultaneously fit the surface brightness and polarization, show that the inner disk (< 40-50 AU) is depleted of micron-sized dust by a factor of more than 300, which means that the disk is collision dominated. The grains have high maximum linear polarization and strong forward scattering. Spherical grains composed of conventional materials cannot reproduce these optical properties. A Mie/Maxwell-Garnett analysis implicates highly porous (91-94%) particles. In the inner Solar System, porous particles form in cometary dust, where the sublimation of ices leaves a "bird's nest" of refractory organic and silicate material. In AU Mic, the grain porosity may be primordial, because the dust "birth ring" lies beyond the ice sublimation point. The observed porosities span the range of values implied by laboratory studies of particle coagulation by ballistic cluster-cluster aggregation. To avoid compactification, the upper size limit for the parent bodies is in the decimeter range, in agreement with theoretical predictions based on collisional lifetime arguments. Consequently, AU Mic may exhibit the signature of the primordial agglomeration process whereby interstellar grains first assembled to form macroscopic objects.Comment: 12 pages, 8 figures, ApJ, in pres

Saturation of intersubband transitions in p-doped GaAs/AlGaAs quantum wells

Optical saturation experiments have been performed on hh1-hh2 intersubband transitions in two samples of p-doped GaAs/AlGaAs quantum wells. The transitions had energies of 183 and 160 meV and the measured population relaxation times were 2±1.5 and 0.3±0.1 ps, respectively. Modeling of the quantum wells with a 6×6 k·p method shows that intersubband scattering by LO phonons can account for these relaxation times. The valence bandstructure is typically more complicated than the conduction bandstructure in a quantum well but these measurements show that LO phonons are the dominant intersubband scattering mechanism in both cases