Modeling Accuracy and Variability of Motor Timing in Treated and Untreated Parkinson’s Disease and Healthy Controls

Parkinson’s disease (PD) is characterized by difficulty with the timing of movements. Data collected using the synchronization–continuation paradigm, an established motor timing paradigm, have produced varying results but with most studies finding impairment. Some of this inconsistency comes from variation in the medication state tested, in the inter-stimulus intervals (ISI) selected, and in changeable focus on either the synchronization (tapping in time with a tone) or continuation (maintaining the rhythm in the absence of the tone) phase. We sought to re-visit the paradigm by testing across four groups of participants: healthy controls, medication naïve de novo PD patients, and treated PD patients both “on” and “off” dopaminergic medication. Four finger tapping intervals (ISI) were used: 250, 500, 1000, and 2000 ms. Categorical predictors (group, ISI, and phase) were used to predict accuracy and variability using a linear mixed model. Accuracy was defined as the relative error of a tap, and variability as the deviation of the participant’s tap from group predicted relative error. Our primary finding is that the treated PD group (PD patients “on” and “off” dopaminergic therapy) showed a significantly different pattern of accuracy compared to the de novo group and the healthy controls at the 250-ms interval. At this interval, the treated PD patients performed “ahead” of the beat whilst the other groups performed “behind” the beat. We speculate that this “hastening” relates to the clinical phenomenon of motor festination. Across all groups, variability was smallest for both phases at the 500-ms interval, suggesting an innate preference for finger tapping within this range. Tapping variability for the two phases became increasingly divergent at the longer intervals, with worse performance in the continuation phase. The data suggest that patients with PD can be best discriminated from healthy controls on measures of motor timing accuracy, rather than variability

The great transformation: decarbonising Europeâ??s energy and transport systems

The euro-area crisis dominates the economic news. Yet, the world and Europe may face even more important challenges that will shape our lives and the lives of our children.World population is projected to increase to 9 billion or more by 2050. At the same time, current trends indicate an increase in living standards and a growing middle class around the world. These two mega-trends will have profound implications, and the way they are managed will be one of the key determinants of prosperity and peace in the decades or even centuries to come. A number of factors are important in this respect. More people and more income will increase the global demand for energy. Choosing the right sources of this energy will be one of the determining factors of global temperature. The continued reliance on fossil-fuel energy sources is one of the main factors behind the risk of significant global temperature increases. The internationally agreed goal of limiting the temperature rise to less than two degrees Celsius above pre-industrial levels appears increasingly illusory. Currently, fossil energy sources dominate many economic areas. For instance, our transport infrastructure is largely based on fossil fuels, and is thereby one of the main contributor of the carbon dioxide emissions that are linked to global temperature. Thinking about a decarbonisation strategy is therefore a key challenge with a global dimension. Economic growth in Europe will be affected by the costs of this transition from the current energy and transport system. A smooth transition towards a low-carbon energy and transport system could come at comparatively modest cost. Furthermore, identifying the most economically beneficial solutions early on and becoming a global technology leader and standard setter offers vast opportunities for exports and economic growth. Hence, our decarbonisation strategy may eventually have a greater impact on long-term European growth than the current economic crisis. Bruegel is contributing to this debate with this report, which is based on research that received funding from the Fuel Cell and Hydrogen Joint Undertaking. The authors argue carefully that to make decarbonisation growth friendly, a consistent policy approach is needed. Policy intervention appears indispensable as the energy and transport system is so based around and locked-in into an incumbent technology. Overcoming this lock-in is crucial. The report makes three main proposals. First, the scope, geographical coverage and duration of carbon pricing should be extended. By setting a higher carbon price, incentives for developing and investing in new low-carbon technologies are created. Second, temporary consortia for new infrastructure to solve early-phase market failures could be put in place. This is discussed using the example of hydrogen vehicles. Lastly and importantly, an open and public transition model is needed so that second-best transport solutions do not get a head start that afterwardscannot be reversed. The technological, economic and political challenge ahead is vast. But choosing the right decarbonisaton strategy offers huge economic, environmental and societal benefits. We should not overlook this debate because of the euro crisis.

Glueball masses in the large N limit

The lowest-lying glueball masses are computed in SU($N$) gauge theory on a spacetime lattice for constant value of the lattice spacing $a$ and for $N$ ranging from 3 to 8. The lattice spacing is fixed using the deconfinement temperature at temporal extension of the lattice $N_T = 6$. The calculation is conducted employing in each channel a variational ansatz performed on a large basis of operators that includes also torelon and (for the lightest states) scattering trial functions. This basis is constructed using an automatic algorithm that allows us to build operators of any size and shape in any irreducible representation of the cubic group. A good signal is extracted for the ground state and the first excitation in several symmetry channels. It is shown that all the observed states are well described by their large $N$ values, with modest ${\cal O}(1/N^2)$ corrections. In addition spurious states are identified that couple to torelon and scattering operators. As a byproduct of our calculation, the critical couplings for the deconfinement phase transition for N=5 and N=7 and temporal extension of the lattice $N_T=6$ are determined.Comment: 1+36 pages, 22 tables, 21 figures. Typos corrected, conclusions unchanged, matches the published versio

The Actinomyosin Motor Drives Malaria Parasite Red Blood Cell Invasion but Not Egress.

Apicomplexa are obligate intracellular parasites that actively invade, replicate within, and egress from host cells. The parasite actinomyosin-based molecular motor complex (often referred to as the glideosome) is considered an important mediator of parasite motility and virulence. Mature intracellular parasites often become motile just prior to egress from their host cells, and in some genera, this motility is important for successful egress as well as for subsequent invasion of new host cells. To determine whether actinomyosin-based motility is important in the red blood cell egress and invasion activities of the malaria parasite, we have used a conditional genetic approach to delete GAP45, a primary component of the glideosome, in asexual blood stages of Plasmodium falciparum Our results confirm the essential nature of GAP45 for invasion but show that P. falciparum does not require a functional motor complex to undergo egress from the red blood cell. Malarial egress therefore differs fundamentally from induced egress in the related apicomplexan Toxoplasma gondiiIMPORTANCE Clinical malaria results from cycles of replication of single-celled parasites of the genus Plasmodium in red blood cells. Intracellular parasite replication is followed by a highly regulated, protease-dependent process called egress, in which rupture of the bounding membranes allows explosive release of daughter merozoites which rapidly invade fresh red cells. A parasite actinomyosin-based molecular motor (the glideosome) has been proposed to provide the mechanical force to drive invasion. Studies of the related parasite Toxoplasma gondii have shown that induced egress requires parasite motility, mediated by a functional glideosome. However, whether the glideosome has a similar essential role in egress of malaria merozoites from red blood cells is unknown. Here, we show that although a functional glideosome is required for red blood cell invasion by Plasmodium falciparum merozoites, it is not required for egress. These findings place further emphasis on the key role of the protease cascade in malarial egress

A trapped single ion inside a Bose-Einstein condensate

Improved control of the motional and internal quantum states of ultracold neutral atoms and ions has opened intriguing possibilities for quantum simulation and quantum computation. Many-body effects have been explored with hundreds of thousands of quantum-degenerate neutral atoms and coherent light-matter interfaces have been built. Systems of single or a few trapped ions have been used to demonstrate universal quantum computing algorithms and to detect variations of fundamental constants in precision atomic clocks. Until now, atomic quantum gases and single trapped ions have been treated separately in experiments. Here we investigate whether they can be advantageously combined into one hybrid system, by exploring the immersion of a single trapped ion into a Bose-Einstein condensate of neutral atoms. We demonstrate independent control over the two components within the hybrid system, study the fundamental interaction processes and observe sympathetic cooling of the single ion by the condensate. Our experiment calls for further research into the possibility of using this technique for the continuous cooling of quantum computers. We also anticipate that it will lead to explorations of entanglement in hybrid quantum systems and to fundamental studies of the decoherence of a single, locally controlled impurity particle coupled to a quantum environment

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial : study protocol for a randomized controlled trial

Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI

Index Theorem and Overlap Formalism with Naive and Minimally Doubled Fermions

We present a theoretical foundation for the Index theorem in naive and minimally doubled lattice fermions by studying the spectral flow of a Hermitean version of Dirac operators. We utilize the point splitting method to implement flavored mass terms, which play an important role in constructing proper Hermitean operators. We show the spectral flow correctly detects the index of the would-be zero modes which is determined by gauge field topology. Using the flavored mass terms, we present new types of overlap fermions from the naive fermion kernels, with a number of flavors that depends on the choice of the mass terms. We succeed to obtain a single-flavor naive overlap fermion which maintains hypercubic symmetry.Comment: 27 pages, 17 figures; references added, version accepted in JHE

Holographic GB gravity in arbitrary dimensions

We study the properties of the holographic CFT dual to Gauss-Bonnet gravity in general $D \ge 5$ dimensions. We establish the AdS/CFT dictionary and in particular relate the couplings of the gravitational theory to the universal couplings arising in correlators of the stress tensor of the dual CFT. This allows us to examine constraints on the gravitational couplings by demanding consistency of the CFT. In particular, one can demand positive energy fluxes in scattering processes or the causal propagation of fluctuations. We also examine the holographic hydrodynamics, commenting on the shear viscosity as well as the relaxation time. The latter allows us to consider causality constraints arising from the second-order truncated theory of hydrodynamics.Comment: 48 pages, 9 figures. v2: New discussion on free fields in subsection 3.3 and new appendix B on conformal tensor fields. Added comments on the relation between the central charge appearing in the two-point function and the "central charge" characterizing the entropy density in the discussion. References adde

Entanglement entropy of Wilson surfaces from bubbling geometries in M-theory

We consider solutions of eleven-dimensional supergravity constructed in [1,2] that are half-BPS, locally asymptotic to $AdS_7\times S^4$ and are the holographic dual of heavy Wilson surfaces in the six-dimensional $(2,0)$ theory. Using these bubbling solutions we calculate the holographic entanglement entropy for a spherical entangling surface in the presence of a planar Wilson surface. In addition, we calculate the holographic stress tensor and, by evaluating the on-shell supergravity action, the expectation value of the Wilson surface operator.Comment: 42 pages, 4 figures, v2: minor modification

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391