The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page

The response to symmetry in extrastriate areas and its time course are modulated by selective attention

Neurophysiological studies have shown a strong activation in visual areas in response to symmetry. Electrophysiological (EEG) studies, in particular, have confirmed that amplitude at posterior electrodes is more negative for symmetrical compared to asymmetrical patterns. This response is present even when observers perform tasks that do not require processing of symmetry. In this sense the activation is automatic. In this study we test this automaticity more directly by presenting stimuli that contain both symmetry and asymmetry, as overlapping patterns of dots of different colour (black and white). Observers were asked to respond to symmetry in only one of the two colours. If feature-based attention has no role the response should depend on properties of the image. If attention fully filters only the relevant colour the response should depend on properties of the relevant colour only. Neither of these models fully explained the data. We conclude that selective attention does modulate the neural response to symmetry, however we also found a significant contribution from the irrelevant pattern

Ballistic protective properties of material representative of English civil war buff-coats and clothing

One type of clothing system used in the English Civil War, more common amongst cavalrymen than infantrymen, was the linen shirt, wool waistcoat and buff-coat. Ballistic testing was conducted to estimate the velocity at which 50% of 12-bore lead spherical projectiles (V50) would be expected to perforate this clothing system when mounted on gelatine (a tissue simulant used in wound ballistic studies). An estimated six-shot V50 for the clothing system was calculated as 102 m/s. The distance at which the projectile would have decelerated from the muzzle of the weapon to this velocity in free flight was triple the recognised effective range of weapons of the era suggesting that the clothing system would provide limited protection for the wearer. The estimated V50 was also compared with recorded bounce-and-roll data; this suggested that the clothing system could provide some protection to the wearer from ricochets. Finally, potential wounding behind the clothing system was investigated; the results compared favourably with seventeenth century medical writings

Peri- and Postnatal Effects of Prenatal Adenoviral VEGF Gene Therapy in Growth-Restricted Sheep

Uterine artery (UtA) adenovirus vector (Ad)-mediated over-expression of vascular endothelial growth factor (VEGF) enhances uterine blood flow in normal sheep pregnancy and increases fetal growth in the overnourished adolescent sheep model of fetal growth restriction (FGR). Herein we examined its impact on gestation length, neonatal survival, early postnatal growth and metabolism. Singleton-bearing ewes were evenly allocated to receive Ad.VEGF-A165(5 x 10(10)particles/ml, 10 ml, n =17) or Saline (10 ml, n = 16) injected into each UtA at laparotomy (0.6 gestation). Fetal growth was serially monitored (blind) by ultrasound until delivery. Lambs were weighed and blood-sampled weekly and a glucose tolerance test performed (68d postnatal age). Hepatic DNA/RNA was extracted at necropsy (83d postnatal age) to examine methylation status of eight somatotropic axis genes. ITALIC! IGF1mRNA and protein expression were measured by RT-PCR and radioimmunoassay, respectively. All pregnancies remained viable following Ad.VEGF-A165treatment. Fetal abdominal circumference and renal volume were greater in Ad.VEGF-A165versus Saline groups at 21/28 days (p ≤ 0.04) post-injection. At delivery, gestation length (p = 0.07), lamb birthweight (p = 0.08), umbilical girth (p = 0.06) and plasma glucose (p=0.09) tended to be greater in Ad.VEGF-A165treated lambs. Levels of neonatal intervention required to ensure survival was equivalent between groups. Absolute postnatal growth rate (p = 0.02), insulin area-under-the-curve (p = 0.04) and carcass weight at necropsy (p = 0.04) were increased by Ad.VEGF-A165treatment. There was no impact on markers of insulin sensitivity or methylation/expression of key genes involved in somatic growth. Ad.VEGF-A165gene therapy increased fetal growth in a sheep FGR model and lambs continued to thrive during the neonatal and early postnatal period

Geographic access to high capability severe acute respiratory failure centers in the United States

Objective: Optimal care of adults with severe acute respiratory failure requires specific resources and expertise. We sought to measure geographic access to these centers in the United States. Design: Cross-sectional analysis of geographic access to high capability severe acute respiratory failure centers in the United States. We defined high capability centers using two criteria: (1) provision of adult extracorporeal membrane oxygenation (ECMO), based on either 2008-2013 Extracorporeal Life Support Organization reporting or provision of ECMO to 2010 Medicare beneficiaries; or (2) high annual hospital mechanical ventilation volume, based 2010 Medicare claims. Setting: Nonfederal acute care hospitals in the United States. Measurements and Main Results: We defined geographic access as the percentage of the state, region and national population with either direct or hospital-transferred access within one or two hours by air or ground transport. Of 4,822 acute care hospitals, 148 hospitals met our ECMO criteria and 447 hospitals met our mechanical ventilation criteria. Geographic access varied substantially across states and regions in the United States, depending on center criteria. Without interhospital transfer, an estimated 58.5% of the national adult population had geographic access to hospitals performing ECMO and 79.0% had geographic access to hospitals performing a high annual volume of mechanical ventilation. With interhospital transfer and under ideal circumstances, an estimated 96.4% of the national adult population had geographic access to hospitals performing ECMO and 98.6% had geographic access to hospitals performing a high annual volume of mechanical ventilation. However, this degree of geographic access required substantial interhospital transfer of patients, including up to two hours by air. Conclusions: Geographic access to high capability severe acute respiratory failure centers varies widely across states and regions in the United States. Adequate referral center access in the case of disasters and pandemics will depend highly on local and regional care coordination across political boundaries. © 2014 Wallace et al

Interplay of Quantum Criticality and Geometric Frustration in Columbite

Motivated by CoNb2O6 (belonging to the columbite family of minerals), we theoretically study the physics of quantum ferromagnetic Ising chains coupled anti-ferromagnetically on a triangular lattice in the plane perpendicular to the chain direction. We combine exact solutions of the chain physics with perturbative approximations for the transverse couplings. When the triangular lattice has an isosceles distortion (which occurs in the real material), the T=0 phase diagram is rich with five different states of matter: ferrimagnetic, N\'eel, anti-ferromagnetic, paramagnetic and incommensurate phases, separated by quantum phase transitions. Implications of our results to experiments on CoNb2O6 are discussed

Effects of salt water on the ballistic protective performance of bullet-resistant body armour

Bullet-resistant body armour is used by law enforcement agencies and military personnel worldwide, often in inclement weather. Some fibre types used in body armour perform poorly when wet, resulting in a reduced level of protection; this is why most body armour protective elements are water-repellent treated and/or protected by a water-resistant cover. Some of the users operate in the maritime environment. The effect of salt water on body armour performance has not been previously reported. In this work the effect of soaking body armour in salt water and exposing body armour for up to 10 soaking and drying cycles in salt water was investigated. The effectiveness of the water-resistant cover was investigated by considering three cover conditions: (i) intact, (ii) cut and (iii) removed. Wet armour was heavier and provided significantly less protection from 9 mm Luger FMJ ammunition when compared to not-exposed armour irrespective of cover condition. A degradation in performance of armours exposed to soaking and drying cycles was noted, but this was similar across all regimes considered (one, three, five and ten cycles) and not as great as for wet armours

Solar wind interaction with comet 67P: impacts of corotating interaction regions

International audienceWe present observations from the Rosetta Plasma Consortium of the effects of stormy solar wind on comet 67P/Churyumov-Gerasimenko. Four corotating interaction regions (CIRs), where the first event has possibly merged with a coronal mass ejection, are traced from Earth via Mars (using Mars Express and Mars Atmosphere and Volatile EvolutioN mission) to comet 67P from October to December 2014. When the comet is 3.1–2.7 AU from the Sun and the neutral outgassing rate ∼1025–1026 s−1, the CIRs significantly influence the cometary plasma environment at altitudes down to 10–30 km. The ionospheric low-energy (∼5 eV) plasma density increases significantly in all events, by a factor of >2 in events 1 and 2 but less in events 3 and 4. The spacecraft potential drops below −20 V upon impact when the flux of electrons increases. The increased density is likely caused by compression of the plasma environment, increased particle impact ionization, and possibly charge exchange processes and acceleration of mass-loaded plasma back to the comet ionosphere. During all events, the fluxes of suprathermal (∼10–100 eV) electrons increase significantly, suggesting that the heating mechanism of these electrons is coupled to the solar wind energy input. At impact the magnetic field strength in the coma increases by a factor of 2–5 as more interplanetary magnetic field piles up around the comet. During two CIR impact events, we observe possible plasma boundaries forming, or moving past Rosetta, as the strong solar wind compresses the cometary plasma environment. We also discuss the possibility of seeing some signatures of the ionospheric response to tail disconnection events

Theory of Multidimensional Solitons

We review a number of topics germane to higher-dimensional solitons in Bose-Einstein condensates. For dark solitons, we discuss dark band and planar solitons; ring dark solitons and spherical shell solitons; solitary waves in restricted geometries; vortex rings and rarefaction pulses; and multi-component Bose-Einstein condensates. For bright solitons, we discuss instability, stability, and metastability; bright soliton engineering, including pulsed atom lasers; solitons in a thermal bath; soliton-soliton interactions; and bright ring solitons and quantum vortices. A thorough reference list is included.Comment: review paper, to appear as Chapter 5a in "Emergent Nonlinear Phenomena in Bose-Einstein Condensates: Theory and Experiment," edited by P. G. Kevrekidis, D. J. Frantzeskakis, and R. Carretero-Gonzalez (Springer-Verlag

Sub-Planckian black holes and the Generalized Uncertainty Principle

The Black Hole Uncertainty Principle correspondence suggests that there could exist black holes with mass beneath the Planck scale but radius of order the Compton scale rather than Schwarzschild scale. We present a modified, self-dual Schwarzschild-like metric that reproduces desirable aspects of a variety of disparate models in the sub-Planckian limit, while remaining Schwarzschild in the large mass limit. The self-dual nature of this solution under $M \leftrightarrow M^{-1}$ naturally implies a Generalized Uncertainty Principle with the linear form $\Delta x \sim \frac{1}{\Delta p} + \Delta p$. We also demonstrate a natural dimensional reduction feature, in that the gravitational radius and thermodynamics of sub-Planckian objects resemble that of $(1+1)$-D gravity. The temperature of sub-Planckian black holes scales as $M$ rather than $M^{-1}$ but the evaporation of those smaller than $10^{-36}$g is suppressed by the cosmic background radiation. This suggests that relics of this mass could provide the dark matter.Comment: 12 pages, 9 figures, version published in J. High En. Phy