Invariant higher-order variational problems II

Motivated by applications in computational anatomy, we consider a second-order problem in the calculus of variations on object manifolds that are acted upon by Lie groups of smooth invertible transformations. This problem leads to solution curves known as Riemannian cubics on object manifolds that are endowed with normal metrics. The prime examples of such object manifolds are the symmetric spaces. We characterize the class of cubics on object manifolds that can be lifted horizontally to cubics on the group of transformations. Conversely, we show that certain types of non-horizontal geodesics on the group of transformations project to cubics. Finally, we apply second-order Lagrange--Poincar\'e reduction to the problem of Riemannian cubics on the group of transformations. This leads to a reduced form of the equations that reveals the obstruction for the projection of a cubic on a transformation group to again be a cubic on its object manifold.Comment: 40 pages, 1 figure. First version -- comments welcome

Damage profiles of ultrashallow B implants in Si and the Kinchin-Pease relationship

Damage distributions resulting from 0.1-2 keV B+ implantation at room temperature into Si(100) to doses ranging from 1×1014 to 2×1016 cm-2 have been determined using high-depth-resolution medium-energy-ion scattering in the double alignment mode. For all B+ doses and energies investigated a 3-4 nm deep, near-surface damage peak was observed while for energies at and above 1 keV, a second damage peak developed beyond the mean projected B+ ion range of 5.3 nm. This dual damage peak structure is due to dynamic annealing processes. For the near-surface peak it is observed that, at the lowest implant energies and doses used, for which recombination processes are suppressed due to the proximity of the surface capturing interstitials, the value of the damage production yield for low-mass B+ ions is equal or greater than the modified Kinchin-Pease model predictions [G. H. Kinchin and R. S. Pease, Rep. Prog. Phys. 18, 1 (1955); G. H. Kinchin and R. S. Pease, J. Nucl. Energy 1, 200 (1955); P. Sigmund, Appl. Phys. Lett. 14, 114 (1969)]

Identification of RNA bound to the TDP-43 ribonucleoprotein complex in the adult mouse brain

Cytoplasmic inclusions containing TDP-43 are a pathological hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. TDP-43 is an RNA binding protein involved in gene regulation through control of RNA transcription, splicing and transport. However, the function of TDP-43 in the nervous system is largely unknown and its role in the pathogenesis of ALS is unclear. The aim of this study was to identify genes in the central nervous system that are regulated by TDP-43. RNA-immunoprecipitation with anti-TDP-43 antibody, followed by microarray analysis (RIP-chip), was used to isolate and identify RNA bound to TDP-43 protein from mouse brain. This analysis produced a list of 1839 potential TDP-43 gene targets, many of which overlap with previous studies and whose functions include RNA processing and synaptic function. Immunohistochemistry demonstrated that the TDP-43 protein could be found at the presynaptic membrane of axon terminals in the neuromuscular junction in mice. In conclusion, the finding that TDP-43 binds to RNA that codes for genes related to synaptic function, together with the localization of TDP-43 protein at axon terminals, suggests a role for TDP-43 in the transport of synaptic mRNAs into distal processes

Exploring the cytotoxicity, uptake, cellular response, and proteomics of mono- and dinuclear DNA light-switch complexes

Drug resistance to platinum chemotherapeutics targeting DNA often involves abrogation of apoptosis, and has emerged as a significant challenge in modern, non-targeted chemotherapy. Consequently, there is great interest in the anti-cancer properties of metal complexes - particularly those that interact with DNA - and mechanisms of consequent cell death. Herein we compare a parent cytotoxic complex [Ru(phen)2(tpphz)]2+ [phen = 1,10-phenanthroline, tpphz = tetrapyridyl [3,2-a:2',3'-c:3'',2''-h:2''',3'''-j] phenazine], with a mononuclear analogue with modified intercalating ligand, [Ru(phen)2(taptp)]2+,[taptp = 4,5,9,18-tetraazaphenanthreno[9,10-b] triphenylene], and two structurally related di-nuclear, tpphz-bridged, heterometallic complexes, RuRe and RuPt. These changes result in a switch from intercalation to groove binding DNA interaction, concomitant reduction in cytotoxic potency, but no significant change in relative cytotoxicity toward platinum-resistant A2780CIS cancer cells, indicating that DNA interaction mode is not critical for the mechanism of platinum resistance. All variants exhibited a light-switch effect, which for the first time, was exploited to investigate timing of cell death by live cell microscopy. Surprisingly, cell death occurred rapidly as a consequence of oncosis, characterized by loss of cytoplasmic volume control, absence of significant mitochondrial membrane potential loss, and lack of activation of apoptotic cell death markers. Importantly, a novel, quantitative proteomic analysis of the A2780 cell genome following exposure to either mononuclear complex reveals changes in protein expression associated with global cell responses to oxidative stress, and DNA replication/repair cellular pathways. This combination of a multiple targeting modality and induction of a non-apoptotic death mechanism makes these complexes highly promising chemotherapeutic cytotoxicity leads

RoboCon: A general purpose telerobotic control center

This report describes human factors issues involved in the design of RoboCon, a multi-purpose control center for use in US Department of Energy remote handling applications. RoboCon is intended to be a flexible, modular control center capable of supporting a wide variety of robotic devices

Tick holocyclotoxins trigger host paralysis by presynaptic inhibition

Ticks are important vectors of pathogens and secreted neurotoxins with approximately 69 out of 692 tick species having the ability to induce severe toxicoses in their hosts. The Australian paralysis tick (Ixodes holocyclus) is known to be one of the most virulent tick species producing a flaccid paralysis and fatalities caused by a family of neurotoxins known as holocyclotoxins (HTs). The paralysis mechanism of these toxins is temperature dependent and is thought to involve inhibition of acetylcholine levels at the neuromuscular junction. However, the target and mechanism of this inhibition remain uncharacterised. Here, we report that three members of the holocyclotoxin family; HT-1 (GenBank AY766147), HT-3 (GenBank KP096303) and HT-12 (GenBank KP963967) induce muscle paralysis by inhibiting the dependence of transmitter release on extracellular calcium. Previous study was conducted using extracts from tick salivary glands, while the present study is the first to use pure toxins from I. holocyclus. Our findings provide greater insight into the mechanisms by which these toxins act to induce paralysis