Late Stage Infection in Sleeping Sickness

At the turn of the 19th century, trypanosomes were identified as the causative agent of sleeping sickness and their presence within the cerebrospinal fluid of late stage sleeping sickness patients was described. However, no definitive proof of how the parasites reach the brain has been presented so far. Analyzing electron micrographs prepared from rodent brains more than 20 days after infection, we present here conclusive evidence that the parasites first enter the brain via the choroid plexus from where they penetrate the epithelial cell layer to reach the ventricular system. Adversely, no trypanosomes were observed within the parenchyma outside blood vessels. We also show that brain infection depends on the formation of long slender trypanosomes and that the cerebrospinal fluid as well as the stroma of the choroid plexus is a hostile environment for the survival of trypanosomes, which enter the pial space including the Virchow-Robin space via the subarachnoid space to escape degradation. Our data suggest that trypanosomes do not intend to colonize the brain but reside near or within the glia limitans, from where they can re-populate blood vessels and disrupt the sleep wake cycles

Balancing, Proportionality, and Constitutional Rights

In the theory and practice of constitutional adjudication, proportionality review plays a crucial role. At a theoretical level, it lies at core of the debate on rights adjudication; in judicial practice, it is a widespread decision-making model characterizing the action of constitutional, supra-national and international courts. Despite its circulation and centrality in contemporary legal discourse, proportionality in rights-adjudication is still extremely controversial. It raises normative questions—concerning its justification and limits—and descriptive questions—regarding its nature and distinctive features. The chapter addresses both orders of questions. Part I centres on the justification of proportionality review, the connection between proportionality, balancing and theories of rights and the critical aspects of this connection. Part II identifies and analyses the different forms of proportionality both in review, as a template for rights-adjudication, and of review, as a way of defining the scope and limits of adjudication

Definitions and pathophysiology of vasoplegic shock.

Vasoplegia is the syndrome of pathological low systemic vascular resistance, the dominant clinical feature of which is reduced blood pressure in the presence of a normal or raised cardiac output. The vasoplegic syndrome is encountered in many clinical scenarios, including septic shock, post-cardiac bypass and after surgery, burns and trauma, but despite this, uniform clinical definitions are lacking, which renders translational research in this area challenging. We discuss the role of vasoplegia in these contexts and the criteria that are used to describe it are discussed. Intrinsic processes which may drive vasoplegia, such as nitric oxide, prostanoids, endothelin-1, hydrogen sulphide and reactive oxygen species production, are reviewed and potential for therapeutic intervention explored. Extrinsic drivers, including those mediated by glucocorticoid, catecholamine and vasopressin responsiveness of the blood vessels, are also discussed. The optimum balance between maintaining adequate systemic vascular resistance against the potentially deleterious effects of treatment with catecholamines is as yet unclear, but development of novel vasoactive agents may facilitate greater understanding of the role of the differing pathways in the development of vasoplegia. In turn, this may provide insights into the best way to care for patients with this common, multifactorial condition

Impact of protozoan cell death on parasite-host interactions and pathogenesis

PCD in protozoan parasites has emerged as a fascinating field of parasite biology. This not only relates to the underlying mechanisms and their evolutionary implications but also to the impact on the parasite-host interactions within mammalian hosts and arthropod vectors. During recent years, common functions of apoptosis and autophagy in protozoa and during parasitic infections have emerged. Here, we review how distinct cell death pathways in Trypanosoma, Leishmania, Plasmodium or Toxoplasma may contribute to regulation of parasite cell densities in vectors and mammalian hosts, to differentiation of parasites, to stress responses, and to modulation of the host immunity. The examples provided indicate crucial roles of PCD in parasite biology. The existence of PCD pathways in these organisms and the identification as being critical for parasite biology and parasite-host interactions could serve as a basis for developing new anti-parasitic drugs that take advantage of these pathways

High-θ polyacetylene: DC conductivity between 14 mK and 300 K

Highly stretch-oriented polyacetylene (6.5:1) yields conductivities σ of typically 20 000–100 000 Ω−1cm−1 at room temperature when highly doped with iodine. Between T = 300 K and T = 14 mK, σ decreases monotonically by about a factor of 5 for fresh samples. Above 400 mK the temperature dependence for fresh samples is fitted by the SHENG formula and can be interpreted within a phenomenological model. On fresh samples, MONTGOMERY measurements of the conductivities parallel (σı) and perpendicular (σσ) to the stretching axis show a temperature independent anisotropy A=σı/σσ of about 25 indicating a common limiting mechanism for both, σı and σσ. Deliberate oxygen ageing drastically changes σ(T) and results in a temperature dependence of A

Assembly Procedures of Trunnion-Hub-Girder for Bascule Bridges

This work is concerned with avoiding failures during the assembly of a trunnion-hub-girder (THG) for bascule bridges. In the current assembly procedure, AP#1, the trunnion is shrunk fit into the hub, followed by the shrink fitting of the trunnion-hub assembly into the girder. Two separate incidents during assembly prompted this study. The first incident involved the development of cracks in the hub during the assembly process using AP#1. The second incident involved the trunnion getting stuck in the hub before the trunnion could be fully inserted. A complete analytical, numerical, and experimental study was conducted to understand these failures, and the results were used to develop specifications and recommendations for assembly. The causes of failures include the development of high stresses at low temperatures during assembly, while noting that fracture toughness of THG materials decreases with temperature. Recommended specifications included following an alternative assembly procedure that nearly doubles allowable crack length, and that lowers cooling temperatures to avoid trunnion sticking in the hub