Microfluidic systems for neuronal cell culture

At a high level of abstraction, the brain is a system for analysing sensory information, and responding appropriately. That information is encoded and stored in the millions of neural circuits that comprise the brain. Deciphering this code is essential to understanding how memories are implemented in physiologically normal brain tissue, and to inferring the nature of some neurological disorders affecting memory such as Alzheimer’s disease, in which the neural encoding is aberrant or unsuccessful. One approach to this problem is to reduce the complexity of the brain functionality to three elements: stimuli, response, and reinforcement. The electrical activity of individual neurons can be recorded with electrodes, capturing the pathways of signal propagation in a network of cells. Individual neurons can be also induced to reliably respond to electrical or optical stimuli, so that they initiate, relay, or even block a signal. If the stimuli to a finite network of cells can be made heterogeneous so that only a sub-population of cells is targeted, then the network can be trained to react in a repeatable way to a given stimulus, testing the concept that the higher order functions of the brain can emerge from a simple set of underlying computational rules. Training however requires a mechanism for reinforcing only some of the possible pathways, in synchrony with stimuli and in response to the recorded network activity. In the intact brain, this mechanism is pharmacological: a neuromodulator such as dopamine is released throughout the brain, but as it only coincides with some but not all neuronal activity, the reinforcement is temporally selective. The key task of this project is to emulate this selective neuromodulator reinforcement in vitro in a finite neuronal network. The project must also provide capacity for heterogeneous stimulation and individual cell recording, which can be coordinated with the reinforcement under computer control. The strategy used was to develop microscale chambers to house a small network of cultured neurons. The chambers were integrated with existing cell recording and stimulating technologies, so that specific connections between neurons could be both monitored and induced. Neuronal cultures of a few hundred cells were successfully grown in microchannels, on substrates capable of recording their electrical activity. Thus it was possible to create a small cultured network in which complete network activity could be detected, subject to a sufficiently precise recording technique. Additionally, a fluid-handling system was developed in order to emulate the continual replenishment of nutrients and soluble gases that are essential to cell survival. The system is intended to deliver soluble chemicals that modulate neuronal activity, on a timescale that is consistent with neuromodulator delivery in the body. The fluid handling system comprises a set of pressure driven pumps under automated computer control. This system has the capacity to deliver neuromodulator in solution with high spatiotemporal precision. The ability to reliably deliver and wash off precise volumes of drugs in a matter of seconds, with no dilution of the intended concentration, will be of great benefit to researchers investigating the response of various cell types to different agonists

Microfluidic systems for neuronal cell culture

At a high level of abstraction, the brain is a system for analysing sensory information, and responding appropriately. That information is encoded and stored in the millions of neural circuits that comprise the brain. Deciphering this code is essential to understanding how memories are implemented in physiologically normal brain tissue, and to inferring the nature of some neurological disorders affecting memory such as Alzheimer’s disease, in which the neural encoding is aberrant or unsuccessful. One approach to this problem is to reduce the complexity of the brain functionality to three elements: stimuli, response, and reinforcement. The electrical activity of individual neurons can be recorded with electrodes, capturing the pathways of signal propagation in a network of cells. Individual neurons can be also induced to reliably respond to electrical or optical stimuli, so that they initiate, relay, or even block a signal. If the stimuli to a finite network of cells can be made heterogeneous so that only a sub-population of cells is targeted, then the network can be trained to react in a repeatable way to a given stimulus, testing the concept that the higher order functions of the brain can emerge from a simple set of underlying computational rules. Training however requires a mechanism for reinforcing only some of the possible pathways, in synchrony with stimuli and in response to the recorded network activity. In the intact brain, this mechanism is pharmacological: a neuromodulator such as dopamine is released throughout the brain, but as it only coincides with some but not all neuronal activity, the reinforcement is temporally selective. The key task of this project is to emulate this selective neuromodulator reinforcement in vitro in a finite neuronal network. The project must also provide capacity for heterogeneous stimulation and individual cell recording, which can be coordinated with the reinforcement under computer control. The strategy used was to develop microscale chambers to house a small network of cultured neurons. The chambers were integrated with existing cell recording and stimulating technologies, so that specific connections between neurons could be both monitored and induced. Neuronal cultures of a few hundred cells were successfully grown in microchannels, on substrates capable of recording their electrical activity. Thus it was possible to create a small cultured network in which complete network activity could be detected, subject to a sufficiently precise recording technique. Additionally, a fluid-handling system was developed in order to emulate the continual replenishment of nutrients and soluble gases that are essential to cell survival. The system is intended to deliver soluble chemicals that modulate neuronal activity, on a timescale that is consistent with neuromodulator delivery in the body. The fluid handling system comprises a set of pressure driven pumps under automated computer control. This system has the capacity to deliver neuromodulator in solution with high spatiotemporal precision. The ability to reliably deliver and wash off precise volumes of drugs in a matter of seconds, with no dilution of the intended concentration, will be of great benefit to researchers investigating the response of various cell types to different agonists

Coalgebraic Semantics for Timed Processes

We give a coalgebraic formulation of timed processes and their operational semantics. We model time by a monoid called a “time domain”, and we model processes by “timed transition systems”, which amount to partial monoid actions of the time domain or, equivalently, coalgebras for an “evolution comonad ” generated by the time domain. All our examples of time domains satisfy a partial closure property, yielding a distributive law of a monad for total monoid actions over the evolution comonad, and hence a distributive law of the evolution comonad over a dual comonad for total monoid actions. We show that the induced coalgebras are exactly timed transition systems with delay operators. We then integrate our coalgebraic formulation of time qua timed transition systems into Turi and Plotkin’s formulation of structural operational semantics in terms of distributive laws. We combine timing with action via the more general study of the combination of two arbitrary sorts of behaviour whose operational semantics may interact. We give a modular account of the operational semantics for a combination induced by that of each of its components. Our study necessitates the investigation of products of comonads. In particular, we characterise when a monad lifts to the category of coalgebras for a product comonad, providing constructions with which one can readily calculate. Key words: time domains, timed transition systems, evolution comonads, delay operators, structural operational semantics, modularity, distributive laws

Comparing supermarket loyalty card data with traditional diet survey data for understanding how protein is purchased and consumed in older adults for the UK, 2014-16

The project was funded by the Research Councils UK ‘Priming Food Partnerships’ initiative supported by BBSRC, MRC, EPSRC and ESRC. Project reference number – BB/P023886/1. Thank you to the High Street Retailer for supplying the data.Peer reviewedPublisher PD

A Convenient Category of Domains

We motivate and define a category of "topological domains", whose objects are certain topological spaces, generalising the usual $omega$-continuous dcppos of domain theory. Our category supports all the standard constructions of domain theory, including the solution of recursive domain equations. It also supports the construction of free algebras for (in)equational theories, provides a model of parametric polymorphism, and can be used as the basis for a theory of computability. This answers a question of Gordon Plotkin, who asked whether it was possible to construct a category of domains combining such properties

Oxygen Metallicity Determinations from Optical Emission Lines in Early-type Galaxies

We measured the oxygen abundances of the warm (T$\sim 10^{4}K$) phase of gas in seven early-type galaxies through long-slit observations. A template spectra was constructed from galaxies void of warm gas and subtracted from the emission-line galaxies, allowing for a clean measurement of the nebular lines. The ratios of the emission lines are consistent with photoionization, which likely originates from the UV flux of post-asymototic giant branch (PAGB) stars. We employ H II region photoionization models to determine a mean oxygen metallicity of $1.01\pm0.50$ solar for the warm interstellar medium (ISM) in this sample. This warm ISM 0.5 to 1.5 solar metallicity is consistent with modern determinations of the metallicity in the hot (T$\sim 10^{6}-10^{7}K$) ISM and the upper range of this warm ISM metallicity is consistent with stellar population metallicity determinations. A solar metallicity of the warm ISM favors an internal origin for the warm ISM such as AGB mass loss within the galaxy.Comment: Accepted Astrophysical Journa

Tuberculosis in a South African prison - a transmission modelling analysis

Background. Prisons are recognised internationally as institutions with very high tuberculosis (TB) burdens where transmission is predominantly determined by contact between infectious and susceptible prisoners. A recent South African court case described the conditions under which prisoners awaiting trial were kept. With the use of these data, a mathematical model was developed to explore the interactions between incarceration conditions and TB control measures. Methods. Cell dimensions, cell occupancy, lock-up time, TB incidence and treatment delays were derived from court evidence and judicial reports. Using the Wells-Riley equation and probability analyses of contact between prisoners, we estimated the current TB transmission probability within prison cells, and estimated transmission probabilities of improved levels of case finding in combination with implementation of national and international minimum standards for incarceration. Results. Levels of overcrowding (230%) in communal cells and poor TB case finding result in annual TB transmission risks of 90% per annum. Implementing current national or international cell occupancy recommendations would reduce TB transmission probabilities by 30% and 50%, respectively. Improved passive case finding, modest ventilation increase or decreased lock-up time would minimally impact on transmission if introduced individually. However, active case finding together with implementation of minimum national and international standards of incarceration could reduce transmission by 50% and 94%, respectively. Conclusions. Current conditions of detention for awaiting-trial prisoners are highly conducive for spread of drug-sensitive and drug-resistant TB. Combinations of simple well-established scientific control measures should be implemented urgently

Relating first-order set theories and elementary toposes

We show how to interpret the language of first-order set theory in an elementary topos endowed with, as extra structure, a directed structural system of inclusions (dssi). As our main result, we obtain a complete axiomatization of the intuitionistic set theory validated by all such interpretations. Since every elementary topos is equivalent to one carrying a dssi, we thus obtain a first-order set theory whose associated categories of sets are exactly the elementary toposes. In addition, we show that the full axiom of Separation is validated whenever the dssi is superdirected. This gives a uniform explanation for the known facts that cocomplete and realizability toposes provide models for Intuitionistic Zermelo-Fraenkel set theory (IZF)

Gamow-Teller Strength in the Region of 100^{100}Sn

New calculations are presented for Gamow-Teller beta decay of nuclei near $^{100}$Sn. Essentially all of the $^{100}$Sn Gamow-Teller decay strength is predicted to go to a single state at an excitation energy of 1.8 MeV in $^{100}$In. The first calculations are presented for the decays of neighboring odd-even and odd-odd nuclei which show, in contrast to $^{100}$Sn, surprisingly complex and broad Gamow-Teller strength distributions. The results are compared to existing experimental data and the resulting hindrance factors are discussed.Comment: 12 pages (latex) and 2 figures available on reques