Ratchet universality in the bidirectional escape from a symmetric potential well

The present work discusses symmetry-breaking-induced bidirectional escape from a symmetric metastable potential well by the application of zero-average periodic forces in the presence of dissipation. We characterized the interplay between heteroclinic instabilities leading to chaotic escape and breaking of a generalized parity symmetry leading to directed ratchet escape to an attractor either at infinity or at -infinity. Optimal enhancement of directed ratchet escape is found to occur when the wave form of the zero-average periodic force acting on the damped driven oscillator matches as closely as possible to a universal wave form, as predicted by the theory of ratchet universality. Specifically, the optimal approximation to the universal force triggers the almost complete destruction of the nonescaping basin for driving amplitudes which are systematically lower than those corresponding to a symmetric periodic force having the same period. We expect that this work could be potentially useful in the control of elementary dynamic processes characterized by multidirectional escape from a potential well, such as forced chaotic scattering and laser-induced dissociation of molecular systems, among others

Biomechanical Analysis of Anticipation of Elite and Inexperienced Goalkeepers to Distance Shots in Handball

The objective of this study was to evaluate the anticipation time and kinematic factors in the movement of goalkeepers’ center of mass when making a long-distance throw in handball. The sample group was composed of 14 goalkeepers and field players. A force platform was used to measure the force of the goalkeepers’ reaction movements, while the throwers’ movements were recorded with high-speed cameras. The expert goalkeepers began to move 193 ± 67 ms before the ball was released, with a 67% success rate of interception. The inexperienced goalkeepers began their movement 209 ± 127 ms with a 24% success rate. The time taken by expert goalkeepers to begin a vertical movement of their CM, relative to the moment of the ball’s release, was less than the time taken by inexperienced goalkeepers (77 ± 70 vs. 141 ± 108 ms respectively). The analysis of the velocity and movement indicates that expert goalkeepers wait longer before moving than do inexperienced goalkeepers

Tunneling effects on impurity spectral function in coupled asymmetric quantum wires

The impurity spectral function is studied in coupled double quantum wires at finite temperatures. Simple anisotropy in the confinement direction of the wires leads to finite non-diagonal elements of the impurity spectral function matrix. These non-diagonal elements are responsible for tunneling effects and result in pronounced extra peak in the impurity spectral function up to temperatures as high as 20 K.Comment: Accepted in Phys. Rev.

Evaluation of cholinergic markers in Alzheimer's disease and in a model of cholinergic deficit

Cognitive deficits in neuropsychiatric disorders, such as Alzheimer's disease (AD), have been closely related to cholinergic deficits. We have compared different markers of cholinergic function to assess the best biomarker of cognitive deficits associated to cholinergic hypoactivity. In post-mortem frontal cortex from AD patients, acetylcholine (ACh) levels, cholinacetyltransferase (ChAT) and acetylcholinesterase (AChE) activity were all reduced compared to controls. Both ChAT and AChE activity showed a significant correlation with cognitive deficits. In the frontal cortex of rats with a selective cholinergic lesion, all cholinergic parameters measured (ACh levels, ChAT and AChE activities, "in vitro" and "in vivo" basal ACh release) were significantly reduced. AChE activity was associated to ChAT activity, and even more, to "in vivo" and "in vitro" basal ACh release. Quantification of AChE activity is performed by an easy and cheap method and therefore, these results suggest that determination of AChE activity may be used as an effective first step method to evaluate cholinergic deficits

Two-step ATP-driven opening of cohesin head

The cohesin ring is a protein complex composed of four core subunits: Smc1A, Smc3, Rad21 and Stag1/2. It is involved in chromosome segregation, DNA repair, chromatin organization and transcription regulation. Opening of the ring occurs at the "head" structure, formed of the ATPase domains of Smc1A and Smc3 and Rad21. We investigate the mechanisms of the cohesin ring opening using techniques of free molecular dynamics (MD), steered MD and quantum mechanics/molecular mechanics MD (QM/MM MD). The study allows the thorough analysis of the opening events at the atomic scale: I) ATP hydrolysis at the Smc1A site, evaluating the role of the carboxy-terminal domain of Rad21 in the process; ii) the activation of the Smc3 site potentially mediated by the movement of specific amino acids; and iii) opening of the head domains after the two ATP hydrolysis events. Our study suggests that the cohesin ring opening is triggered by a sequential activation of the ATP sites in which ATP hydrolysis at the Smc1A site induces ATPase activity at the Smc3 site. Our analysis also provides an explanation for the effect of pathogenic variants related to cohesinopathies and cancer

Facilitation of cholinergic transmission by combined treatment of ondansetron with flumazenil after cortical cholinergic deafferentation

We have studied the effects of concomitant blockade of 5-HT(3) and GABA(A) receptors on acetylcholine (ACh) release in the frontal cortex of rats with a selective cholinergic lesion. Lesions were performed by microinjection of the cholinergic toxin 192 IgG-saporin into the nucleus basalis magnocellularis. Single treatment with either the 5-HT(3) receptor antagonist ondansetron, 0.1 microg/kg, or the GABA(A) receptor benzodiazepine site antagonist flumazenil, 10 mg/kg, did not affect ACh release. However, the combined ondansetron + flumazenil administration significantly increased ACh release to a similar extent as a depolarising stimulus with K(+), 100 mM, at both 7 and 30 days post-lesion. Cortical perfusion with the combined ondansetron + flumazenil treatment also increased [(3)H]ACh efflux "in vitro" 30 days after lesion, suggesting that local events within the frontal cortex may participate in the interaction of ondansetron with GABAergic neurons, modulating ACh release in situations of cholinergic hypoactivity. No differences in the expression of 5-HT(3) and GABA(A) receptors in the frontal cortex were found after the cholinergic lesion. These results suggest that a combined ondansetron + flumazenil treatment would contribute to restoring a diminished cholinergic function and may provide a basis for using this treatment in the therapy of cognitive disorders associated with degeneration of the cholinergic system

Identification and Functional Characterization of Two Intronic NIPBL Mutations in Two Patients with Cornelia de Lange Syndrome

Cornelia de Lange syndrome (CdLS) is a rare genetically heterogeneous disorder with a high phenotypic variability including mental retardation, developmental delay, and limb malformations. The genetic causes in about 30% of patients with CdLS are still unknown. We report on the functional characterization of two intronic NIPBL mutations in two patients with CdLS that do not affect a conserved splice-donor or acceptor site. Interestingly, mRNA analyses showed aberrantly spliced transcripts missing exon 28 or 37, suggesting the loss of the branch site by the c.5329-15A>G transition and a disruption of the polypyrimidine by the c.6344del(-13)-(-8) deletion. While the loss of exon 28 retains the reading frame of the NIBPL transcript resulting in a shortened protein, the loss of exon 37 shifts the reading frame with the consequence of a premature stop of translation. Subsequent quantitative PCR analysis demonstrated a 30% decrease of the total NIPBL mRNA levels associated with the frameshift transcript. Consistent with our results, this patient shows a more severe phenotype compared to the patient with the aberrant transcript that retains its reading frame. Thus, intronic variants identified by sequencing analysis in CdLS diagnostics should carefully be examined before excluding them as nonrelevant to disease

Spin-Orbit Splitting in Non-Relativistic and Relativistic Self-Consistent Models

The splitting of single-particle energies between spin-orbit partners in nuclei is examined in the framework of different self-consistent approachs, non-relativistic as well as relativistic. Analytical expressions of spin-orbit potentials are given for various cases. Proton spin-orbit splittings are calculated along some isotopic chains (O, Ca, Sn) and they are compared with existing data. It is found that the isotopic dependence of the relativistic mean field predictions is similar to that of some Skyrme forces while the relativistic Hartree-Fock approach leads to a very different dependence due to the strong non-locality.Comment: 12 pages, RevTeX, 4 new figs.in .zip format, unchanged conclusions, Phys. ReV.

Involvement of an altered 5-HT -{6} receptor function in behavioral symptoms of Alzheimer's disease

We studied the hypothesis that disturbances in 5-HT_{6} receptor function in the temporal cortex may contribute to clinical symptoms of Alzheimer's disease (AD). 5-HT_{6} density and 5-HT levels were significantly decreased in a cohort of AD patients prospectively assessed for cognitive/behavioral symptoms. cAMP formation after stimulation with the selective 5-HT_{6} receptor agonist E-6801 was significantly lower (p<0.01) in AD (170.02 +/- 27.53 pmol/mg prot.) compared to controls (823.33 +/-196.67). In addition, the ratio cAMP formation after stimulation with E-6801/5-HT_{6} receptor density was significantly lower (p< 0.01) in AD (6.67 +/- 0.83) compared to controls (16.67 +/- 3.33). Splitting these results by sex, 5-HT_{6} receptor activation was significantly lower (p< 0.01) in AD females compared to males (121.67 +/- 30.02 vs. 231.67 +/- 34.17 pmol/mg prot). 5-HT_{6} density and 5-HT levels were significantly correlated (p < or = 0.01) in both controls and AD patients, although in AD, this correlation was lost in females. Psychosis factor was the best predictor of reduced 5-HT levels or adenylate cyclase activity after E-6801 stimulation, the former result being due to females. It may be suggested that psychotic symptoms may be related to a dysregulation of 5-HT_{6} activation by 5-HT in the temporal cortex. These results are discussed in terms of purported influence of sex and therapeutical approaches to psychosis in AD

Persistence in a Stationary Time-series

We study the persistence in a class of continuous stochastic processes that are stationary only under integer shifts of time. We show that under certain conditions, the persistence of such a continuous process reduces to the persistence of a corresponding discrete sequence obtained from the measurement of the process only at integer times. We then construct a specific sequence for which the persistence can be computed even though the sequence is non-Markovian. We show that this may be considered as a limiting case of persistence in the diffusion process on a hierarchical lattice.Comment: 8 pages revte