Genetic Demonstration of a Role for PKA in the Late Phase of LTP and in Hippocampus-Based Long-Term Memory

AbstractTo explore the role of protein kinase A (PKA) in the late phase of long-term potentiation (L-LTP) and memory, we generated transgenic mice that express R(AB), an inhibitory form of the regulatory subunit of PKA, only in the hippocampus and other forebrain regions by using the promoter from the gene encoding Ca2+/calmodulin protein kinase IIα. In these R(AB) transgenic mice, hippocampal PKA activity was reduced, and L-LTP was significantly decreased in area CA1, without affecting basal synaptic transmission or the early phase of LTP. Moreover, the L-LTP deficit was paralleled by behavioral deficits in spatial memory and in long-term but not short-term memory for contextual fear conditioning. These deficits in long-term memory were similar to those produced by protein synthesis inhibition. Thus, PKA plays a critical role in the consolidation of long-term memory

State Sum Models and Simplicial Cohomology

We study a class of subdivision invariant lattice models based on the gauge group $Z_{p}$, with particular emphasis on the four dimensional example. This model is based upon the assignment of field variables to both the $1$- and $2$-dimensional simplices of the simplicial complex. The property of subdivision invariance is achieved when the coupling parameter is quantized and the field configurations are restricted to satisfy a type of mod-$p$ flatness condition. By explicit computation of the partition function for the manifold $RP^{3} \times S^{1}$, we establish that the theory has a quantum Hilbert space which differs from the classical one.Comment: 28 pages, Latex, ITFA-94-13, (Expanded version with two new sections

Calculation of the Spatial Envelope Correlation Between Two Antennas in Terms of the System Scattering Parameters Including Conducting Losses.

yesThe envelope correlation for a two-element antenna array may be calculated using the antenna radiation fields, or more simply from the scattering parameters of the system. The use of scattering parameters provides a major simplification over the direct use of field data. In this paper we propose a modification of the scattering parameter method which also includes the antenna losses. This approach has the advantage of simplifying the antenna design process, especially when low envelope correlations are needed. It also offers a better prediction of the spatial envelope correlation, and a good framework for understanding the effects of the mutual coupling. The accuracy of this proposed method is illustrated by two examples

Organismal Climatology: Analyzing Environmental Variability at Scales Relevant to Physiological Stress

Predicting when, where and with what magnitude climate change is likely to affect the fitness, abundance and distribution of organisms and the functioning of ecosystems has emerged as a high priority for scientists and resource managers. However, even in cases where we have detailed knowledge of current species’ range boundaries, we often do not understand what, if any, aspects of weather and climate act to set these limits. This shortcoming significantly curtails our capacity to predict potential future range shifts in response to climate change, especially since the factors that set range boundaries under those novel conditions may be different from those that set limits today. We quantitatively examine a nine-year time series of temperature records relevant to the body temperatures of intertidal mussels as measured using biomimetic sensors. Specifically, we explore how a ‘climatology’ of body temperatures, as opposed to long-term records of habitat-level parameters such as air and water temperatures, can be used to extrapolate meaningful spatial and temporal patterns of physiological stress. Using different metrics that correspond to various aspects of physiological stress (seasonal means, cumulative temperature and the return time of extremes) we show that these potential environmental stressors do not always occur in synchrony with one another. Our analysis also shows that patterns of animal temperature are not well correlated with simple, commonly used metrics such as air temperature. Detailed physiological studies can provide guidance to predicting the effects of global climate change on natural ecosystems but only if we concomitantly record, archive and model environmental signals at appropriate scales

Mental health in UK Biobank: development, implementation and results from an online questionnaire completed by 157 366 participants

Background UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors. Aims An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders. Method An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders. Results 157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation. Conclusions The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health

Estimating the feasibility of transition paths in extended finite state machines

There has been significant interest in automating testing on the basis of an extended finite state machine (EFSM) model of the required behaviour of the implementation under test (IUT). Many test criteria require that certain parts of the EFSM are executed. For example, we may want to execute every transition of the EFSM. In order to find a test suite (set of input sequences) that achieves this we might first derive a set of paths through the EFSM that satisfy the criterion using, for example, algorithms from graph theory. We then attempt to produce input sequences that trigger these paths. Unfortunately, however, the EFSM might have infeasible paths and the problem of determining whether a path is feasible is generally undecidable. This paper describes an approach in which a fitness function is used to estimate how easy it is to find an input sequence to trigger a given path through an EFSM. Such a fitness function could be used in a search-based approach in which we search for a path with good fitness that achieves a test objective, such as executing a particular transition, and then search for an input sequence that triggers the path. If this second search fails then we search for another path with good fitness and repeat the process. We give a computationally inexpensive approach (fitness function) that estimates the feasibility of a path. In order to evaluate this fitness function we compared the fitness of a path with the ease with which an input sequence can be produced using search to trigger the path and we used random sampling in order to estimate this. The empirical evidence suggests that a reasonably good correlation (0.72 and 0.62) exists between the fitness of a path, produced using the proposed fitness function, and an estimate of the ease with which we can randomly generate an input sequence to trigger the path

Growth, microstructure, and failure of crazes in glassy polymers

We report on an extensive study of craze formation in glassy polymers. Molecular dynamics simulations of a coarse-grained bead-spring model were employed to investigate the molecular level processes during craze nucleation, widening, and breakdown for a wide range of temperature, polymer chain length $N$, entanglement length $N_e$ and strength of adhesive interactions between polymer chains. Craze widening proceeds via a fibril-drawing process at constant drawing stress. The extension ratio is determined by the entanglement length, and the characteristic length of stretched chain segments in the polymer craze is $N_e/3$. In the craze, tension is mostly carried by the covalent backbone bonds, and the force distribution develops an exponential tail at large tensile forces. The failure mode of crazes changes from disentanglement to scission for $N/N_e\sim 10$, and breakdown through scission is governed by large stress fluctuations. The simulations also reveal inconsistencies with previous theoretical models of craze widening that were based on continuum level hydrodynamics

Industrial applications of ASF+SDF

In recent years, a number of Dutch companies have used the algebraic specification formalism ASF+SDF. Bank MeesPierson has specified a language for describing interest rate products, their translation into COBOL, and their generation from interactive questionnaires. A consultancy company has specified a language to represent the company's object-oriented models, and the compilation of this language into Access. Bank ABN-AMRO has started investigating the use of algebraic specifications for renovating legacy COBOL systems. We discuss the implications of such projects for teaching algebraic specifications and software engineering, and the role students have been playing in these projects

Gaussian quantum computation with oracle-decision problems

We study a simple-harmonic-oscillator quantum computer solving oracle decision problems. We show that such computers can perform better by using nonorthogonal Gaussian wave functions rather than orthogonal top-hat wave functions as input to the information encoding process. Using the Deutsch-Jozsa problem as an example, we demonstrate that Gaussian modulation with optimized width parameter results in a lower error rate than for the top-hat encoding. We conclude that Gaussian modulation can allow for an improved trade-off between encoding, processing and measurement of the information.Comment: RevTeX4, 10 pages with 4 figure

Ruminant Milk-Derived Extracellular Vesicles: A Nutritional and Therapeutic Opportunity?

Milk has been shown to contain a specific fraction of extracellular particles that are reported to resist digestion and are purposefully packaged with lipids, proteins, and nucleic acids to exert specific biological effects. These findings suggest that these particles may have a role in the quality of infant nutrition, particularly in the early phase of life when many of the foundations of an infant’s potential for health and overall wellness are established. However, much of the current research focuses on human or cow milk only, and there is a knowledge gap in how milk from other species, which may be more commonly consumed in different regions, could also have these reported biological effects. Our review provides a summary of the studies into the extracellular particle fraction of milk from a wider range of ruminants and pseudo-ruminants, focusing on how this fraction is isolated and characterised, the stability and uptake of the fraction, and the reported biological effects of these fractions in a range of model systems. As the individual composition of milk from different species is known to differ, we propose that the extracellular particle fraction of milk from non-traditional and minority species may also have important and distinct biological properties that warrant further study