A unified approach to linking experimental, statistical and computational analysis of spike train data

A fundamental issue in neuroscience is how to identify the multiple biophysical mechanisms through which neurons generate observed patterns of spiking activity. In previous work, we proposed a method for linking observed patterns of spiking activity to specific biophysical mechanisms based on a state space modeling framework and a sequential Monte Carlo, or particle filter, estimation algorithm. We have shown, in simulation, that this approach is able to identify a space of simple biophysical models that were consistent with observed spiking data (and included the model that generated the data), but have yet to demonstrate the application of the method to identify realistic currents from real spike train data. Here, we apply the particle filter to spiking data recorded from rat layer V cortical neurons, and correctly identify the dynamics of an slow, intrinsic current. The underlying intrinsic current is successfully identified in four distinct neurons, even though the cells exhibit two distinct classes of spiking activity: regular spiking and bursting. This approach – linking statistical, computational, and experimental neuroscience – provides an effective technique to constrain detailed biophysical models to specific mechanisms consistent with observed spike train data.Published versio

Twistors, Harmonics and Holomorphic Chern-Simons

We show that the off-shell N=3 action of N=4 super Yang-Mills can be written as a holomorphic Chern-Simons action whose Dolbeault operator is constructed from a complex-real (CR) structure of harmonic space. We also show that the local space-time operators can be written as a Penrose transform on the coset SU(3)/(U(1) \times U(1)). We observe a strong similarity to ambitwistor space constructions.Comment: 34 pages, 3 figures, v2: replaced with published version, v3: Added referenc

Practical approximation scheme for the pion dynamics in the three-nucleon system

We discuss a working approximation scheme to a recently developed formulation of the coupled piNNN-NNN problem. The approximation scheme is based on the physical assumption that, at low energies, the 2N-subsystem dynamics in the elastic channel is conveniently described by the usual 2N-potential approach, while the explicit pion dynamics describes small, correction-type effects. Using the standard separable-expansion method, we obtain a dynamical equation of the Alt-Grassberger-Sandhas (AGS) type. This is an important result, because the computational techniques used for solving the normal AGS equation can also be used to describe the pion dynamics in the 3N system once the matrix dimension is increased by one component. We have also shown that this approximation scheme treats the conventional 3N problem once the pion degrees of freedom are projected out. Then the 3N system is described with an extended AGS-type equation where the spin-off of the pion dynamics (beyond the 2N potential) is taken into account in additional contributions to the driving term. These new terms are shown to reproduce the diagrams leading to modern 3N-force models. We also recover two sets of irreducible diagrams that are commonly neglected in 3N-force discussions, and conclude that these sets should be further investigated, because a claimed cancellation is questionable.Comment: 18 pages, including 5 figures, RevTeX, Eps

Describing interruptions, multi-tasking and task-switching in the community pharmacy: A qualitative study in England

Background: There is growing evidence base around interruptions and distractions in the community pharmacy setting. There is also evidence to suggest these practices may be associated with dispensing errors. Up to date, qualitative research on this subject is limited. Objective: To explore interruptions and distractions in the community setting; utilising an ethnographic approach to be able to provide a detailed description of the circumstances surrounding such practices. Setting: Community pharmacies in England, July to October 2011. Method: An ethnographic approach was taken. Non participant, unstructured observations were utilised to make records of pharmacists’ every activities. Case studies were formed by combining field notes with detailed information on pharmacists and their respective pharmacy businesses. Content analysis was undertaken both manually and electronically, utilising NVivo 10. Results: Response rate was 12% (n=11). Over fifteen days, a total of 123 hours and 58 minutes of observations were recorded in 11 separate pharmacies of 11 individual pharmacists. The sample was evenly split by gender (female n=6; male n=5) and pharmacy ownership (independent n=5; multiple n=6). Employment statuses included employee pharmacists (n=6), owners (n=4) and a locum (n=1). Average period of registration as a pharmacist was 19 years (range 5-39 years). Average prescriptions busyness of pharmacies ranged from 2,600 – 24,000 items dispensed per month. Two key themes were: “Interruptions and task-switching” and “distractions and multi-tasking.” All observed pharmacists’ work was dominated by interruptions, task-switches, distractions and multi-tasking, often to manage a barrage of conflicting demands. These practices were observed to be part of a deep-rooted culture in the community setting. Directional work maps illustrated the extent and direction of task switching employed by pharmacists. Conclusions: In this study pharmacists’ working practices were permeated by interruptions and multi-tasking. These practices are inefficient and potentially reduce patient safety in terms of dispensing accuracy

Why is the three-nucleon force so odd?

By considering a class of diagrams which has been overlooked also in the most recent literature on three-body forces, we extract a new contribution to the three-nucleon interaction which specifically acts on the triplet odd states of the two nucleon subsystem. In the static approximation, this 3N-force contribution is fixed by the underlying 2N interaction, so in principle there are no free parameters to adjust. The 2N amplitude however enters in the 3NF diagram in a form which cannot be directly accessed or constrained by NN phase-shift analysis. We conclude that this new 3N-force contribution provides a mechanism which implies that the presence of the third nucleon modifies the p-wave (and possibly the f-wave) components of the 2N subsystem in the triplet-isotriplet channels.Comment: 10 Pages, 7 figures, RevTeX, twocolumn, epsf (updated version with minor changes

Dynamic Proteomics of Individual Cancer Cells in Response to a Drug

Why do seemingly identical cells respond differently to a drug? To address this, we studied the dynamics and variability of the protein response of human cancer cells to a chemotherapy drug, camptothecin. We present a dynamic-proteomics approach that measures the levels and locations of nearly 1000 different endogenously tagged proteins in individual living cells at high temporal resolution. All cells show rapid translocation of proteins specific to the drug mechanism, including the drug target (topoisomerase-1), and slower, wide-ranging temporal waves of protein degradation and accumulation. However, the cells differ in the behavior of a subset of proteins. We identify proteins whose dynamics differ widely between cells, in a way that corresponds to the outcomes—cell death or survival. This opens the way to understanding molecular responses to drugs in individual cells

Universality in Bacterial Colonies

The emergent spatial patterns generated by growing bacterial colonies have been the focus of intense study in physics during the last twenty years. Both experimental and theoretical investigations have made possible a clear qualitative picture of the different structures that such colonies can exhibit, depending on the medium on which they are growing. However, there are relatively few quantitative descriptions of these patterns. In this paper, we use a mechanistically detailed simulation framework to measure the scaling exponents associated with the advancing fronts of bacterial colonies on hard agar substrata, aiming to discern the universality class to which the system belongs. We show that the universal behavior exhibited by the colonies can be much richer than previously reported, and we propose the possibility of up to four different sub-phases within the medium-to-high nutrient concentration regime. We hypothesize that the quenched disorder that characterizes one of these sub-phases is an emergent property of the growth and division of bacteria competing for limited space and nutrients.Comment: 12 pages, 5 figure

GRAVITY: getting to the event horizon of Sgr A*

We present the second-generation VLTI instrument GRAVITY, which currently is in the preliminary design phase. GRAVITY is specifically designed to observe highly relativistic motions of matter close to the event horizon of Sgr A*, the massive black hole at center of the Milky Way. We have identified the key design features needed to achieve this goal and present the resulting instrument concept. It includes an integrated optics, 4-telescope, dual feed beam combiner operated in a cryogenic vessel; near infrared wavefront sensing adaptive optics; fringe tracking on secondary sources within the field of view of the VLTI and a novel metrology concept. Simulations show that the planned design matches the scientific needs; in particular that 10 microarcsecond astrometry is feasible for a source with a magnitude of K=15 like Sgr A*, given the availability of suitable phase reference sources.Comment: 13 pages, 11 figures, to appear in the conference proceedings of SPIE Astronomical Instrumentation, 23-28 June 2008, Marseille, Franc

PT-symmetry breaking in complex nonlinear wave equations and their deformations

We investigate complex versions of the Korteweg-deVries equations and an Ito type nonlinear system with two coupled nonlinear fields. We systematically construct rational, trigonometric/hyperbolic, elliptic and soliton solutions for these models and focus in particular on physically feasible systems, that is those with real energies. The reality of the energy is usually attributed to different realisations of an antilinear symmetry, as for instance PT-symmetry. It is shown that the symmetry can be spontaneously broken in two alternative ways either by specific choices of the domain or by manipulating the parameters in the solutions of the model, thus leading to complex energies. Surprisingly the reality of the energies can be regained in some cases by a further breaking of the symmetry on the level of the Hamiltonian. In many examples some of the fixed points in the complex solution for the field undergo a Hopf bifurcation in the PT-symmetry breaking process. By employing several different variants of the symmetries we propose many classes of new invariant extensions of these models and study their properties. The reduction of some of these models yields complex quantum mechanical models previously studied.Comment: 50 pages, 39 figures (compressed in order to comply with arXiv policy; higher resolutions maybe obtained from the authors upon request

The practices of apartheid as a war crime: a critical analysis

The human suffering caused by the political ideology of apartheid in South Africa during the Apartheid era (1948-1994) prompted worldwide condemnation and a variety of diplomatic and legal responses. Amongst these responses was the attempt to have apartheid recognised both as a crime against humanity in the 1973 Apartheid Convention as well as a war crime in Article 85(4)(c) of Additional Protocol I. This article examines the origins, nature and current status of the practices of apartheid as a war crime and its possible application to the Israeli-Palestinian conflict