Spaced training enhances memory and prefrontal ensemble stability in mice

It is commonly acknowledged that memory is substantially improved when learning is distributed over time, an effect called the "spacing effect". So far it has not been studied how spaced learning affects the neuronal ensembles presumably underlying memory. In the present study, we investigate whether trial spacing increases the stability or size of neuronal ensembles. Mice were trained in the "everyday memory"task, an appetitive, naturalistic, delayed matching-to-place task. Spacing trials by 60 min produced more robust memories than training with shorter or longer intervals. c-Fos labeling and chemogenetic inactivation established the involvement of the dorsomedial prefrontal cortex (dmPFC) in successful memory storage. In vivo calcium imaging of excitatory dmPFC neurons revealed that longer trial spacing increased the similarity of the population activity pattern on subsequent encoding trials and upon retrieval. Conversely, trial spacing did not affect the size of the total neuronal ensemble or the size of subpopulations dedicated to specific task-related behaviors and events. Thus, spaced learning promotes reactivation of prefrontal neuronal ensembles processing episodic-like memories

Physiological and clinical consequences of relief of right ventricular outflow tract obstruction late after repair of congenital heart defects.

BACKGROUND: Right ventricular outflow tract obstruction (RVOTO) is a common problem after repair of congenital heart disease. Percutaneous pulmonary valve implantation (PPVI) can treat this condition without consequent pulmonary regurgitation or cardiopulmonary bypass. Our aim was to investigate the clinical and physiological response to relieving RVOTO. METHODS AND RESULTS: We studied 18 patients who underwent PPVI for RVOTO (72% male, median age 20 years) from a total of 93 who had this procedure for various indications. All had a right ventricular outflow tract (RVOT) gradient >50 mm Hg on echocardiography without important pulmonary regurgitation (less than mild or regurgitant fraction <10% on magnetic resonance imaging [MRI]). Cardiopulmonary exercise testing, tissue Doppler echocardiography, and MRI were performed before and within 50 days of PPVI. PPVI reduced RVOT gradient (51.4 to 21.7 mm Hg, P<0.001) and right ventricular systolic pressure (72.8 to 47.3 mm Hg, P<0.001) at catheterization. Symptoms and aerobic (25.7 to 28.9 mL.kg(-1).min(-1), P=0.002) and anaerobic (14.4 to 16.2 mL.kg(-1).min(-1), P=0.002) exercise capacity improved. Myocardial systolic velocity improved acutely (tricuspid 4.8 to 5.3 cm/s, P=0.05; mitral 4.7 to 5.5 cm/s, P=0.01), whereas isovolumic acceleration was unchanged. The tricuspid annular velocity was not maintained on intermediate follow-up. Right ventricular end-diastolic volume (99.9 to 89.7 mL/m2, P<0.001) fell, whereas effective stroke volume (43.7 to 48.3 mL/m2, P=0.06) and ejection fraction (48.0% to 56.8%, P=0.01) increased. Left ventricular end-diastolic volume (72.5 to 77.4 mL/m2, P=0.145), stroke volume (45.3 to 50.6 mL/m2, P=0.02), and ejection fraction (62.6% to 65.8%, P=0.03) increased. CONCLUSIONS: PPVI relieves RVOTO, which leads to an early improvement in biventricular performance. Furthermore, it reduces symptoms and improves exercise tolerance. These findings have important implications for the management of this increasingly common condition

Percutaneous pulmonary valve implantation in humans - Results in 59 consecutive patients

Background - Right ventricular outflow tract (RVOT) reconstruction with valved conduits in infancy and childhood leads to reintervention for pulmonary regurgitation and stenosis in later life.Methods and Results - Patients with pulmonary regurgitation with or without stenosis after repair of congenital heart disease had percutaneous pulmonary valve implantation (PPVI). Mortality, hemodynamic improvement, freedom from explantation, and subjective and objective changes in exercise tolerance were end points. PPVI was performed successfully in 58 patients, 32 male, with a median age of 16 years and median weight of 56 kg. The majority had a variant of tetralogy of Fallot (n = 36), or transposition of the great arteries, ventricular septal defect with pulmonary stenosis (n = 8). The right ventricular (RV) pressure (64.4 +/- 17.2 to 50.4 +/- 14 mm Hg, P < 0.001), RVOT gradient (33 +/- 24.6 to 19.5 +/- 15.3, P < 0.001), and pulmonary regurgitation ( PR) (grade 2 of greater before, none greater than grade 2 after, P < 0.001) decreased significantly after PPVI. MRI showed significant reduction in PR fraction (21 +/- 13% versus 3 +/- 4%, P < 0.001) and in RV end-diastolic volume (EDV) (94 +/- 28 versus 82 +/- 24 mL (.) beat(-1) (.) m(-2), P < 0.001) and a significant increase in left ventricular EDV ( 64 +/- 12 versus 71 +/- 13 mL (.) beat(-1.) m(-2), P = 0.005) and effective RV stroke volume ( 37 +/- 7 versus 42 +/- 9 mL (.) beat(-1) (.) m(-2), P = 0.006) in 28 patients (age 19 +/- 8 years). A further 16 subjects, on metabolic exercise testing, showed significant improvement in V(O2)max (26 +/- 7 versus 29 +/- 6 mL (.) kg(-1) (.) min(-1), P < 0.001). There was no mortality.Conclusions - PPVI is feasible at low risk, with quantifiable improvement in MRI-defined ventricular parameters and pulmonary regurgitation, and results in subjective and objective improvement in exercise capacity

Error Thresholds on Dynamic Fittness-Landscapes

In this paper we investigate error-thresholds on dynamics fitness-landscapes. We show that there exists both lower and an upper threshold, representing limits to the copying fidelity of simple replicators. The lower bound can be expressed as a correction term to the error-threshold present on a static landscape. The upper error-threshold is a new limit that only exists on dynamic fitness-landscapes. We also show that for long genomes on highly dynamic fitness-landscapes there exists a lower bound on the selection pressure needed to enable effective selection of genomes with superior fitness independent of mutation rates, i.e., there are distinct limits to the evolutionary parameters in dynamic environments.Comment: 5 page

Hyperbolic planforms in relation to visual edges and textures perception

We propose to use bifurcation theory and pattern formation as theoretical probes for various hypotheses about the neural organization of the brain. This allows us to make predictions about the kinds of patterns that should be observed in the activity of real brains through, e.g. optical imaging, and opens the door to the design of experiments to test these hypotheses. We study the specific problem of visual edges and textures perception and suggest that these features may be represented at the population level in the visual cortex as a specific second-order tensor, the structure tensor, perhaps within a hypercolumn. We then extend the classical ring model to this case and show that its natural framework is the non-Euclidean hyperbolic geometry. This brings in the beautiful structure of its group of isometries and certain of its subgroups which have a direct interpretation in terms of the organization of the neural populations that are assumed to encode the structure tensor. By studying the bifurcations of the solutions of the structure tensor equations, the analog of the classical Wilson and Cowan equations, under the assumption of invariance with respect to the action of these subgroups, we predict the appearance of characteristic patterns. These patterns can be described by what we call hyperbolic or H-planforms that are reminiscent of Euclidean planar waves and of the planforms that were used in [1, 2] to account for some visual hallucinations. If these patterns could be observed through brain imaging techniques they would reveal the built-in or acquired invariance of the neural organization to the action of the corresponding subgroups.Comment: 34 pages, 11 figures, 2 table

Antibiotic cycling versus mixing: the difficulty of using mathematical models to definitively quantify their relative merits.

Published PDF version deposited in accordance with SHERPA RoMEO guidelines.We ask the question Which antibiotic deployment protocols select best against drug-resistant microbes: mixing or periodic cycling? and demonstrate that the statistical distribution of the performances of both sets of protocols, mixing and periodic cycling, must have overlapping supports. In other words, it is a general, mathematical result that there must be mixing policies that outperform cycling policies and vice versa. As a result, we agree with the tenet of Bonhoefer et al. [1] that one should not apply the results of [2] to conclude that an antibiotic cycling policy that implements cycles of drug restriction and prioritisation on an ad-hoc basis can select against drug-resistant microbial pathogens in a clinical setting any better than random drug use. However, nor should we conclude that a random, per-patient drug-assignment protocol is the de facto optimal method for allocating antibiotics to patients in any general sense

Theory of nuclear spin conversion in ethylene

First theoretical analysis of the nuclear spin conversion in ethylene molecules (13^CCH4) has been performed. The conversion rate was found equal approx. 3x10^{-4} 1/s*Torr, which is in qualitative agreement with the recently obtained experimental value. It was shown that the ortho-para mixing in 13^CCH4 is dominated by the spin-rotation coupling. Mixing of only two pairs of ortho-para levels were found to contribute significantly to the spin conversion.Comment: 20 pages, 5 eps figure

Co-Evolution of quasispecies: B-cell mutation rates maximize viral error catastrophes

Co-evolution of two coupled quasispecies is studied, motivated by the competition between viral evolution and adapting immune response. In this co-adaptive model, besides the classical error catastrophe for high virus mutation rates, a second ``adaptation-'' catastrophe occurs, when virus mutation rates are too small to escape immune attack. Maximizing both regimes of viral error catastrophes is a possible strategy for an optimal immune response, reducing the range of allowed viral mutation rates to a minimum. From this requirement one obtains constraints on B-cell mutation rates and receptor lengths, yielding an estimate of somatic hypermutation rates in the germinal center in accordance with observation.Comment: 4 pages RevTeX including 2 figure

Defining forgiveness: Christian clergy and general population perspectives.

The lack of any consensual definition of forgiveness is a serious weakness in the research literature (McCullough, Pargament &amp; Thoresen, 2000). As forgiveness is at the core of Christianity, this study returns to the Christian source of the concept to explore the meaning of forgiveness for practicing Christian clergy. Comparisons are made with a general population sample and social science definitions of forgiveness to ensure that a shared meaning of forgiveness is articulated. Anglican and Roman Catholic clergy (N = 209) and a general population sample (N = 159) completed a postal questionnaire about forgiveness. There is agreement on the existence of individual differences in forgiveness. Clergy and the general population perceive reconciliation as necessary for forgiveness while there is no consensus within psychology. The clergy suggests that forgiveness is limitless and that repentance is unnecessary while the general population suggests that there are limits and that repentance is necessary. Psychological definitions do not conceptualize repentance as necessary for forgiveness and the question of limits has not been addressed although within therapy the implicit assumption is that forgiveness is limitless.</p