A model metal potential exhibiting polytetrahedral clusters

Putative global minima have been located for clusters interacting with an aluminium glue potential for N<190. Virtually all the clusters have polytetrahedral structures, which for larger sizes involve an ordered array of disclinations that are similar to those in the Z, H and sigma Frank-Kasper phases. Comparisons of sequences of larger clusters suggest that the majority of the global minima will adopt the bulk face-centred-cubic structure beyond N=500.Comment: 14 pages, 7 figure

Thermodynamics and the Global Optimization of Lennard-Jones clusters

Theoretical design of global optimization algorithms can profitably utilize recent statistical mechanical treatments of potential energy surfaces (PES's). Here we analyze the basin-hopping algorithm to explain its success in locating the global minima of Lennard-Jones (LJ) clusters, even those such as \LJ{38} for which the PES has a multiple-funnel topography, where trapping in local minima with different morphologies is expected. We find that a key factor in overcoming trapping is the transformation applied to the PES which broadens the thermodynamic transitions. The global minimum then has a significant probability of occupation at temperatures where the free energy barriers between funnels are surmountable.Comment: 13 pages, 13 figures, revte

Mapping the magic numbers in binary Lennard-Jones clusters

Using a global optimization approach that directly searches for the composition of greatest stability, we have been able to find the particularly stable structures for binary Lennard-Jones clusters with up to 100 atoms for a range of Lennard-Jones parameters. In particular, we have shown that just having atoms of different size leads to a remarkable stabilization of polytetrahedral structures, including both polyicosahedral clusters and at larger sizes structures with disclination lines.Comment: 5 pages, 5 figure

The double-funnel energy landscape of the 38-atom Lennard-Jones cluster

The 38-atom Lennard-Jones cluster has a paradigmatic double-funnel energy landscape. One funnel ends in the global minimum, a face-centred-cubic (fcc) truncated octahedron. At the bottom of the other funnel is the second lowest energy minimum which is an incomplete Mackay icosahedron. We characterize the energy landscape in two ways. Firstly, from a large sample of minima and transition states we construct a disconnectivity tree showing which minima are connected below certain energy thresholds. Secondly we compute the free energy as a function of a bond-order parameter. The free energy profile has two minima, one which corresponds to the fcc funnel and the other which at low temperature corresponds to the icosahedral funnel and at higher temperatures to the liquid-like state. These two approaches show that the greater width of the icosahedral funnel, and the greater structural similarity between the icosahedral structures and those associated with the liquid-like state, are the cause of the smaller free energy barrier for entering the icosahedral funnel from the liquid-like state and therefore of the cluster's preferential entry into this funnel on relaxation down the energy landscape. Furthermore, the large free energy barrier between the fcc and icosahedral funnels, which is energetic in origin, causes the cluster to be trapped in one of the funnels at low temperature. These results explain in detail the link between the double-funnel energy landscape and the difficulty of global optimization for this cluster.Comment: 12 pages, 11 figures, revte

A murine model of variant late infantile ceroid lipofuscinosis recapitulates behavioral and pathological phenotypes of human disease.

Neuronal ceroid lipofuscinoses (NCLs; also known collectively as Batten Disease) are a family of autosomal recessive lysosomal storage disorders. Mutations in as many as 13 genes give rise to ∼10 variants of NCL, all with overlapping clinical symptomatology including visual impairment, motor and cognitive dysfunction, seizures, and premature death. Mutations in CLN6 result in both a variant late infantile onset neuronal ceroid lipofuscinosis (vLINCL) as well as an adult-onset form of the disease called Type A Kufs. CLN6 is a non-glycosylated membrane protein of unknown function localized to the endoplasmic reticulum (ER). In this study, we perform a detailed characterization of a naturally occurring Cln6 mutant (Cln6(nclf)) mouse line to validate its utility for translational research. We demonstrate that this Cln6(nclf) mutation leads to deficits in motor coordination, vision, memory, and learning. Pathologically, we demonstrate loss of neurons within specific subregions and lamina of the cortex that correlate to behavioral phenotypes. As in other NCL models, this model displays selective loss of GABAergic interneuron sub-populations in the cortex and the hippocampus with profound, early-onset glial activation. Finally, we demonstrate a novel deficit in memory and learning, including a dramatic reduction in dendritic spine density in the cerebral cortex, which suggests a reduction in synaptic strength following disruption in CLN6. Together, these findings highlight the behavioral and pathological similarities between the Cln6(nclf) mouse model and human NCL patients, validating this model as a reliable format for screening potential therapeutics

Ca2+-activated K+ Channels in Murine Endothelial Cells: Block by Intracellular Calcium and Magnesium

The intermediate (IKCa) and small (SKCa) conductance Ca2+-sensitive K+ channels in endothelial cells (ECs) modulate vascular diameter through regulation of EC membrane potential. However, contribution of IKCa and SKCa channels to membrane current and potential in native endothelial cells remains unclear. In freshly isolated endothelial cells from mouse aorta dialyzed with 3 μM free [Ca2+]i and 1 mM free [Mg2+]i, membrane currents reversed at the potassium equilibrium potential and exhibited an inward rectification at positive membrane potentials. Blockers of large-conductance, Ca2+-sensitive potassium (BKCa) and strong inward rectifier potassium (Kir) channels did not affect the membrane current. However, blockers of IKCa channels, charybdotoxin (ChTX), and of SKCa channels, apamin (Ap), significantly reduced the whole-cell current. Although IKCa and SKCa channels are intrinsically voltage independent, ChTX- and Ap-sensitive currents decreased steeply with membrane potential depolarization. Removal of intracellular Mg2+ significantly increased these currents. Moreover, concomitant reduction of the [Ca2+]i to 1 μM caused an additional increase in ChTX- and Ap-sensitive currents so that the currents exhibited theoretical outward rectification. Block of IKCa and SKCa channels caused a significant endothelial membrane potential depolarization (≈11 mV) and decrease in [Ca2+]i in mesenteric arteries in the absence of an agonist. These results indicate that [Ca2+]i can both activate and block IKCa and SKCa channels in endothelial cells, and that these channels regulate the resting membrane potential and intracellular calcium in native endothelium

Stratigraphy, Radiocarbon Dating and Culture History of Charlie Lake Cave, British Columbia

Three seasons of fieldwork at Charlie Lake Cave, British Columbia, have revealed a sequence of stratified deposits that spans the Late Pleistocene and entire Holocene. Analyses of sediments, radiocarbon dates, faunal remains, and artifacts show that the site was first occupied by people at about 10 500 B.P., when local environments were more open than today. By 9500 B.P., boreal forest had moved into the area, and human use of the site was minimal until about 7000 B.P., when a brief occupation of the site probably included a human burial. Use of the site intensified after about 4500 B.P., possibly because the cave became more accessible. The site was used both as a residential base camp and as a more temporary hunting station or lookout. &nbsp; Article Summary by Jonathan C. Driver, May 2015 &nbsp; After we had completed our excavations in 1991 we decided that we should focus on writing up what we had excavated, and not undertake further excavations at the site. This paper was written to summarize our state of knowledge about the archaeological remains at the site, and focused on describing the stone tools, the overall stratigraphy, and the dating. The stratigraphic summary replaced earlier work based on the 1983 excavations, and we were able to refine our dating of the site as a result of more radiocarbon dates. The different cultural periods were based mainly on the work done by Martin Handly for his M.A. thesis at Trent University. The long list of authors reflects the need for a team approach to archaeological work, and include the project directors (Knut Fladmark and Jon Driver), stone tool analysis and development of the cultural sequence (Martin Handly), animal bone analysis (Randall Preston and Jon Driver), sediment analysis (Greg Sullivan and Knut Fladmark), and radiocarbon dating (Erle Nelson). The most important aspect of the site is that it preserves a very rare record of humanly made artifacts dating from the end of the last ice age (at least 10,500 BC) to very recent times. The many layers at the site allow us to separate the different cultural periods. Good preservation of bone allowed us to submit radiocarbon dates that provide approximate ages for the various cultures that used the site. The artifacts that exhibit the most change through time are projectile points – the sharp stone tips for spears, darts and arrows. In much of western Canada it is difficult to date archaeological sites, because many of them are found in shallow soils where radiocarbon dating is difficult for two reasons. First, animal bone is often not preserved due to the acidic nature of the soils. Second, although charcoal is often found, it cannot be reliably associated with human activity, because natural forest fires also produce charcoal. As a result, archaeologists look at the style of the projectile points to assign approximate ages. Tse’K’wa provides an opportunity to link artifacts of different styles to radiocarbon dates in a site with many distinct layers. So Tse’K’wa is a foundation for understanding the sequence of different cultures in the region. The article also discusses the possible early presence of microblade technology. Microblades are the most efficient way of producing a cutting edge when the base technology is chipped stone. A small piece of high-quality raw material (known as the core) is shaped in such a way that numerous parallel-sided slivers of stone can be removed. These “microblades” can then be hafted in wood or antler to form knives or arrow barbs. The concept is rather like our utility knives that have replaceable blades. This technology allows people to carry small quantities of high quality stone with them, ensuring that they always have a sharp blade available. Not all archaeologists agree that the early microblade core from Tse’K’wa is part of this technology, because it doesn’t conform to the classic methods of core manufacture. However, we argue that evidence for the removal of microblades is very obvious, and the lack of classic core preparation is because of the tabular nature of the raw material. The paper also introduces some information about animal bones, including the raven burials, evidence for environmental change, and the presence of collared lemming. These topics were subsequently explored in more detail in other papers