Cluster electron observations of the separatrix layer during traveling compression regions

[ 1] We present Cluster 4-point observations of electrons during traveling compression regions ( TCRs) on 19 September 2001. The electron and \B\ signatures vary with distance from the plasma sheet, confirming that transient plasma sheet bulges propagate past Cluster. TCRs with \B\ increases have either no electron signature, or unidirectional similar to1 keV electrons at the plasma sheet edge. However, spacecraft initially near the plasma sheet edge are engulfed within the bulge and observe a diamagnetic reduction in \B\. In cases where the underlying plasma sheet bulge moves earthward, electrons at the plasma sheet edge stream tailward. We suggest this represents either a remote observation of electrons closing the Hall current system in an ion diffusion region located farther tailward, or the outflow jets along the separatrix formed by a second neutral line located farther earthward of the spacecraft. The latter case implies the simultaneous action of multiple X-lines in the near-Earth tail

Current measurement by real-time counting of single electrons

The fact that electrical current is carried by individual charges has been known for over 100 years, yet this discreteness has not been directly observed so far. Almost all current measurements involve measuring the voltage drop across a resistor, using Ohm's law, in which the discrete nature of charge does not come into play. However, by sending a direct current through a microelectronic circuit with a chain of islands connected by small tunnel junctions, the individual electrons can be observed one by one. The quantum mechanical tunnelling of single charges in this one-dimensional array is time correlated, and consequently the detected signal has the average frequency f=I/e, where I is the current and e is the electron charge. Here we report a direct observation of these time-correlated single-electron tunnelling oscillations, and show electron counting in the range 5 fA-1 pA. This represents a fundamentally new way to measure extremely small currents, without offset or drift. Moreover, our current measurement, which is based on electron counting, is self-calibrated, as the measured frequency is related to the current only by a natural constant.Comment: 9 pages, 4 figures; v2: minor revisions, 2 refs added, words added to title, typos correcte

Effectiveness and cost-effectiveness of an educational intervention for practice teams to deliver problem focused therapy for insomnia: rationale and design of a pilot cluster randomised trial

Background: Sleep problems are common, affecting over a third of adults in the United Kingdom and leading to reduced productivity and impaired health-related quality of life. Many of those whose lives are affected seek medical help from primary care. Drug treatment is ineffective long term. Psychological methods for managing sleep problems, including cognitive behavioural therapy for insomnia (CBTi) have been shown to be effective and cost effective but have not been widely implemented or evaluated in a general practice setting where they are most likely to be needed and most appropriately delivered. This paper outlines the protocol for a pilot study designed to evaluate the effectiveness and cost-effectiveness of an educational intervention for general practitioners, primary care nurses and other members of the primary care team to deliver problem focused therapy to adult patients presenting with sleep problems due to lifestyle causes, pain or mild to moderate depression or anxiety. Methods and design: This will be a pilot cluster randomised controlled trial of a complex intervention. General practices will be randomised to an educational intervention for problem focused therapy which includes a consultation approach comprising careful assessment (using assessment of secondary causes, sleep diaries and severity) and use of modified CBTi for insomnia in the consultation compared with usual care (general advice on sleep hygiene and pharmacotherapy with hypnotic drugs). Clinicians randomised to the intervention will receive an educational intervention (2 × 2 hours) to implement a complex intervention of problem focused therapy. Clinicians randomised to the control group will receive reinforcement of usual care with sleep hygiene advice. Outcomes will be assessed via self-completion questionnaires and telephone interviews of patients and staff as well as clinical records for interventions and prescribing. Discussion: Previous studies in adults have shown that psychological treatments for insomnia administered by specialist nurses to groups of patients can be effective within a primary care setting. This will be a pilot study to determine whether an educational intervention aimed at primary care teams to deliver problem focused therapy for insomnia can improve sleep management and outcomes for individual adult patients presenting to general practice. The study will also test procedures and collect information in preparation for a larger definitive cluster-randomised trial. The study is funded by The Health Foundation

Semantic distillation: a method for clustering objects by their contextual specificity

Techniques for data-mining, latent semantic analysis, contextual search of databases, etc. have long ago been developed by computer scientists working on information retrieval (IR). Experimental scientists, from all disciplines, having to analyse large collections of raw experimental data (astronomical, physical, biological, etc.) have developed powerful methods for their statistical analysis and for clustering, categorising, and classifying objects. Finally, physicists have developed a theory of quantum measurement, unifying the logical, algebraic, and probabilistic aspects of queries into a single formalism. The purpose of this paper is twofold: first to show that when formulated at an abstract level, problems from IR, from statistical data analysis, and from physical measurement theories are very similar and hence can profitably be cross-fertilised, and, secondly, to propose a novel method of fuzzy hierarchical clustering, termed \textit{semantic distillation} -- strongly inspired from the theory of quantum measurement --, we developed to analyse raw data coming from various types of experiments on DNA arrays. We illustrate the method by analysing DNA arrays experiments and clustering the genes of the array according to their specificity.Comment: Accepted for publication in Studies in Computational Intelligence, Springer-Verla

Engineering a BCR-ABL-activated caspase for the selective elimination of leukemic cells.

Increased understanding of the precise molecular mechanisms involved in cell survival and cell death signaling pathways offers the promise of harnessing these molecules to eliminate cancer cells without damaging normal cells. Tyrosine kinase oncoproteins promote the genesis of leukemias through both increased cell proliferation and inhibition of apoptotic cell death. Although tyrosine kinase inhibitors, such as the BCR-ABL inhibitor imatinib, have demonstrated remarkable efficacy in the clinic, drug-resistant leukemias emerge in some patients because of either the acquisition of point mutations or amplification of the tyrosine kinase, resulting in a poor long-term prognosis. Here, we exploit the molecular mechanisms of caspase activation and tyrosine kinase/adaptor protein signaling to forge a unique approach for selectively killing leukemic cells through the forcible induction of apoptosis. We have engineered caspase variants that can directly be activated in response to BCR-ABL. Because we harness, rather than inhibit, the activity of leukemogenic kinases to kill transformed cells, this approach selectively eliminates leukemic cells regardless of drug-resistant mutations

Representation of Markov chains by random maps: existence and regularity conditions

We systematically investigate the problem of representing Markov chains by families of random maps, and which regularity of these maps can be achieved depending on the properties of the probability measures. Our key idea is to use techniques from optimal transport to select optimal such maps. Optimal transport theory also tells us how convexity properties of the supports of the measures translate into regularity properties of the maps via Legendre transforms. Thus, from this scheme, we cannot only deduce the representation by measurable random maps, but we can also obtain conditions for the representation by continuous random maps. Finally, we present conditions for the representation of Markov chain by random diffeomorphisms.Comment: 22 pages, several changes from the previous version including extended discussion of many detail

Effect of salbutamol on neuromuscular junction function and structure in a mouse model of DOK7 congenital myasthenia.

Congenital myasthenic syndromes (CMS) are characterized by fatigable muscle weakness resulting from impaired neuromuscular transmission. β2-adrenergic agonists are an effective treatment for DOK7-CMS. DOK7 is a component within the AGRN-LRP4-MUSK-DOK7 signalling pathway that is key for the formation and maintenance of the synaptic structure of the neuromuscular junction (NMJ). The precise mechanism of action of β2-adrenergic agonists at the NMJ is not fully understood. In this study, we investigated whether β2-adrenergic agonists improve both neurotransmission and structural integrity of the NMJ in a mouse model of DOK7-CMS. Ex-vivo electrophysiological techniques and microscopy of the NMJ were used to study the effect of salbutamol, a β2-adrenergic agonist, on synaptic structure and function. DOK7-CMS model mice displayed a severe phenotype with reduced weight gain and perinatal lethality. Salbutamol treatment improved weight gain and survival in DOK7 myasthenic mice. Model animals had fewer active NMJs, detectable by endplate recordings, compared with age-matched wild-type littermates. Salbutamol treatment increased the number of detectable NMJs during endplate recording. Correspondingly, model mice had fewer acetylcholine receptor-stained NMJs detected by fluorescent labelling, but following salbutamol treatment an increased number were detectable. The data demonstrate that salbutamol can prolong survival and increase NMJ number in a severe model of DOK7-CMS

Making use of fuzzy cognitive maps in agent-based modeling

One of the main challenges in Agent-Based Modeling (ABM) is to model agents’ preferences and behavioral rules such that the knowledge and decision-making processes of real-life stakeholders will be reflected. To tackle this challenge, we demonstrate the potential use of a participatory method, Fuzzy Cognitive Mapping (FCM), that aggregates agents’ qualitative knowledge (i.e., knowledge co-production). In our proposed approach, the outcome of FCM would be a basis for designing agents’ preferences and behavioral rules in ABM. We apply this method to a social-ecological system of a farming community facing water scarcity

Dual spacecraft determinations of magnetopause motion

We examine the motion of Earth's magnetopause for 16 dawnside traversals of this boundary by the sister spacecraft AMPTE/UKS and IRM in December, 1984, when their separation was 400-900 km. We compare magnetopause normal vectors, n, and speeds of motion, u(n), obtained separately from each spacecraft by use of three different methods, and also compare those u(n) to corresponding speeds, u(n)*, obtained from observed time lags between the two spacecraft. Agreement between u, values and n vectors determined from the three methods ranges from poor to excellent. Comparing u(n)* and u(n) values, we find a clear tendency for \ u(n)*\ to be larger than \ u(n)\: While slightly less than half of the results show reasonable agreement (0.5 < u(n)/u(n)* < 2), there are about as many results in the range 0 < u(n)/u(n)* < 0.5, and a few cases give the wrong sign of u(n)

Towards an ecology of participation: Process philosophy and co-creation of higher education curricula

This article brings together the authors' previous work on co-created curricula (Bovill et al., 2011; Bovill, 2013a; Bovill, 2014) and on partnership and ethics (Taylor and Robinson, 2014; Taylor, 2015), to develop the concept of co-created curricula as an ecology of participation. In doing so, it deploys Alfred North Whitehead’s process philosophy to formulate a new way of considering co-creation in the curriculum and co-creation of the curriculum in higher education. Two empirical examples are used to illuminate what such an approach offers. From this, we outline three dimensions of an ecology of participation: a process of becoming which recasts subjectivity; acting well in relation which enacts concern; and an orientation to harmony in which difference in equality is valued. The contribution of the article is twofold: first, the concept of an ecology of participation takes forward current thinking on higher education curricula and partnership ethics; second, its use of process philosophy provides a new lens to consider co-creation in the curriculum and co-creation of the curriculum