Retrograde transport pathways utilised by viruses and protein toxins

A model has been presented for retrograde transport of certain toxins and viruses from the cell surface to the ER that suggests an obligatory interaction with a glycolipid receptor at the cell surface. Here we review studies on the ER trafficking cholera toxin, Shiga and Shiga-like toxins, Pseudomonas exotoxin A and ricin, and compare the retrograde routes followed by these protein toxins to those of the ER trafficking SV40 and polyoma viruses. We conclude that there is in fact no obligatory requirement for a glycolipid receptor, nor even with a protein receptor in a lipid-rich environment. Emerging data suggests instead that there is no common pathway utilised for retrograde transport by all of these pathogens, the choice of route being determined by the particular receptor utilised

Use of AR to Bring Medical Simulation to Life

Use of simulation facilities and equipment in medical training has become the fabric of curricula across nearly all professions, most notably medical school, nursing, and related medical sciences programs. The gold standard for simulators is SimMan3G, Laerdal Inc., which offers a static electronic mannequin that affords the opportunity to create disease states, signs/symptoms, and real physiological/vital sign data complemented by voice interactions between faculty (within the control room) and student. All sessions are videotaped and, through a 15-30 minute debriefing, students exchange thoughts and impressions with faculty and engage in a deep reflective learning experience. The other option for medical simulation training is the use of “standardized patients”; people who serve as mock patients to mimic signs and symptoms but, clearly, cannot mimic real disease states or physiological changes. To bridge the gap between static mannequin and real human as patient, we have begun work on the utilization of AR to bring our SimMan3G mannequin to life

Structure and Metal Binding Properties of ZnuA, a Periplasmic Zinc Transporter from \u3cem\u3eEscherichia coli\u3c/em\u3e

ZnuA is the periplasmic Zn2+-binding protein associated with the high-affinity ATP-binding cassette ZnuABC transporter from Escherichia coli. Although several structures of ZnuA and its homologs have been determined, details regarding metal ion stoichiometry, affinity, and specificity as well as the mechanism of metal uptake and transfer remain unclear. The crystal structures of E. coli ZnuA (Eco-ZnuA) in the apo, Zn2+-bound, and Co2+-bound forms have been determined. ZnZnuA binds at least two metal ions. The first, observed previously in other structures, is coordinated tetrahedrally by Glu59, His60, His143, and His207. Replacement of Zn2+ with Co2+ results in almost identical coordination geometry at this site. The second metal binding site involves His224 and several yet to be identified residues from the His-rich loop that is unique to Zn2+ periplasmic metal binding receptors. Electron paramagnetic resonance and X-ray absorption spectroscopic data on CoZnuA provide additional insight into possible residues involved in this second site. The second site is also detected by metal analysis and circular dichroism (CD) titrations. Eco-ZnuA binds Zn2+ (estimated K d \u3c 20 nM), Co2+, Ni2+, Cu2+, Cu+, and Cd2+, but not Mn2+. Finally, conformational changes upon metal binding observed in the crystal structures together with fluorescence and CD data indicate that only Zn2+ substantially stabilizes ZnuA and might facilitate recognition of ZnuB and subsequent metal transfer

The Influence of the effect of solute on the thermodynamic driving force on grain refinement of Al alloys

Grain refinement is known to be strongly affected by the solute in cast alloys. Addition of some solute can reduce grain size considerably while others have a limited effect. This is usually attributed to the constitutional supercooling which is quantified by the growth restriction factor, Q. However, one factor that has not been considered is whether different solutes have differing effects on the thermodynamic driving force for solidification. This paper reveals that addition of solute reduces the driving force for solidification for a given undercooling, and that for a particular Q value, it is reduced more substantially when adding eutectic-forming solutes than peritectic-forming elements. Therefore, compared with the eutectic-forming solutes, addition of peritectic-forming solutes into Al alloys not only possesses a higher initial nucleation rate resulted from the larger thermodynamic driving force for solidification, but also promotes nucleation within the constitutionally supercooled zone during growth. As subsequent nucleation can occur at smaller constitutional supercoolings for peritectic-forming elements, a smaller grain size is thus produced. The very small constitutional supercooling required to trigger subsequent nucleation in alloys containing Ti is considered as a major contributor to its extraordinary grain refining efficiency in cast Al alloys even without the deliberate addition of inoculants.The Australian Research Council (ARC DP10955737)

Determination of Survivable Fires

At NASA, there exists no standardized design or testing protocol for spacecraft fire suppression systems (either handheld or total flooding designs). An extinguisher's efficacy in safely suppressing any reasonable or conceivable fire is the primary benchmark. That concept, however, leads to the question of what a reasonable or conceivable fire is. While there exists the temptation to over-size' the fire extinguisher, weight and volume considerations on spacecraft will always (justifiably) push for the minimum size extinguisher required. This paper attempts to address the question of extinguisher size by examining how large a fire a crew member could successfully survive and extinguish in the confines of a spacecraft. The hazards to the crew and equipment during an accidental fire include excessive pressure rise resulting in a catastrophic rupture of the vehicle skin, excessive temperatures that burn or incapacitate the crew (due to hyperthermia), carbon dioxide build-up or other accumulation of other combustion products (e.g. carbon monoxide). Estimates of these quantities are determined as a function of fire size and mass of material burned. This then becomes the basis for determining the maximum size of a target fire for future fire extinguisher testing

Conceptual design of a nonscaling fixed field alternating gradient accelerator for protons and carbon ions for charged particle therapy

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.The conceptual design for a nonscaling fixed field alternating gradient accelerator suitable for charged particle therapy (the use of protons and other light ions to treat some forms of cancer) is described.EPSR

Design of a hydrophobic tripeptide that self-assembles into amphiphilic superstructures forming a hydrogel biomaterial

We report the rational design of a heterochiral hydrophobic tripeptide self-assembling into amphiphilic D-superstructures that yield a self-supportive hydrogel at physiological pH. The material endures cell culture conditions and sustains fibroblast proliferation. Tripeptide superstructures are thoroughly analysed by several techniques

Early conscious prone positioning in patients with COVID-19 receiving continuous positive airway pressure: A retrospective analysis

The global pandemic of COVID-19 has challenged the management of hypoxaemic respiratory failure and strained intensive care unit resources. While prone positioning (PP) is an established therapy in mechanically ventilated patients with acute respiratory distress syndrome (ARDS), its role in conscious patients is less well defined. We retrospectively reviewed our experience of implementing early PP in a cohort of 24 patients with acute hypoxaemic respiratory failure due to COVID-19 who required support with continuous positive airway pressure (CPAP). The use of PP alongside CPAP significantly increased both the ROX index and arterial oxygen pressure:fractional inspired oxygen (PaO 2:FiO 2) ratio from baseline values (ROX index: 7.0±2.5 baseline vs 11.4±3.7 CPAP+PP,

Terminal valuations, growth rates and the implied cost of capital

This article is published with open access at Springerlink.comWe develop a model based on the notion that prices lead earnings, allowing for a simultaneous estimation of the implied growth rate and the cost of equity capital for US industrial sectors. The major difference between our approach and that in prior literature is that ours avoids the necessity to make assumptions about terminal values and consequently about future growth rates. In fact, growth rates are an endogenous variable, which is estimated simultaneously with the implied cost of equity capital. Since we require only 1-year-ahead forecasts of earnings and no assumptions about dividend payouts, our methodology allows us to estimate ex ante aggregate growth and risk premia over a larger sample of firms than has previously been possible. Our estimate of the risk premium being between 3.1 and 3.9 % is at the lower end of recent estimates, reflecting the inclusion of these short-lived companies. Our estimate of the long run growth is from 4.2 to 4.7 %

The prophylactic role of intravenous and long-term oral acyclovir after allogeneic bone marrow transplantation.

Eighty-two patients were randomly allocated to receive intravenous acyclovir 5 mg kg-1 t.d.s. for 23 days followed by oral acyclovir 800 mg 6-hourly for 6 months or matching placebos after allogeneic bone marrow transplantation. Herpes simplex and varicella zoster virus infections were significantly reduced during the period of administration of acyclovir. No reduction in cytomegalovirus infection was demonstrated. The drug was not toxic