People and Place: the role of public information services in making the global, local

How can libraries, archives and documentation centres help create a shared sense of community in a world where the individual is confronted with an increasingly uniform global culture? How do they enable local communities to benefit from the opportunities to grow and succeed which are offered by the information society? This presentation draws on experience from the UK and from the presenter’s own local authority, Derbyshire, to suggest some lessons for the future

Resonant Orbits and the High Velocity Peaks Towards the Bulge

We extract the resonant orbits from an N-body bar that is a good representation of the Milky Way, using the method recently introduced by Molloy et al. (2015). By decomposing the bar into its constituent orbit families, we show that they are intimately connected to the boxy-peanut shape of the density. We highlight the imprint due solely to resonant orbits on the kinematic landscape towards the Galactic centre. The resonant orbits are shown to have distinct kinematic features and may be used to explain the cold velocity peak seen in the APOGEE commissioning data (Nidever at al., 2012). We show that high velocity peaks are a natural consequence of the motions of stars in the 2:1 orbit family and that stars on other higher order resonances can contribute to the peaks. The locations of the peaks vary with bar angle and, with the tacit assumption that the observed peaks are due to the 2:1 family, we find that the locations of the high velocity peaks correspond to bar angles in the range 10 < theta_bar < 25 (deg). However, some important questions about the nature of the peaks remain, such as their apparent absence in other surveys of the Bulge and the deviations from symmetry between equivalent fields in the north and south. We show that the absence of a peak in surveys at higher latitudes is likely due to the combination of a less prominent peak and a lower number density of bar supporting orbits at these latitudes.Comment: 7 Figures, 1 Table, Now includes figures & discussion of higher order resonances, Minor revisions to text throughout, Conclusions unchange

Resonant Clumping and Substructure in Galactic Discs

We describe a method to extract resonant orbits from N-body simulations exploiting the fact that they close in a frame rotating with a constant pattern speed. Our method is applied to the N-body simulation of the Milky Way by Shen et al. (2010). This simulation hosts a massive bar, which drives strong resonances and persistent angular momentum exchange. Resonant orbits are found throughout the disc, both close to the bar itself and out to the very edges of the disc. Using Fourier spectrograms, we demonstrate that the bar is driving kinematic substructure even in the very outer parts of the disc. We identify two major orbit families in the outskirts of the disc that make significant contributions to the kinematic landscape, namely the m:l = 3:-2 and 1:-1 families resonating with the pattern speed of the bar. A mechanism is described that produces bimodal distributions of Galactocentric radial velocities at selected azimuths in the outer disc. It occurs as a result of the temporal coherence of particles on the 3:-2 resonant orbits, which causes them to arrive simultaneously at pericentre or apocentre. This resonant clumping, due to the in-phase motion of the particles through their epicycle, leads to both inward and outward moving groups which belong to the same orbital family and consequently produce bimodal radial velocity distributions. This is a possible explanation of the bimodal velocity distributions observed towards the Galactic anti-Centre by Liu et al. (2012). Another consequence is that transient overdensities appear and dissipate (in a symmetric fashion) on timescales equal to the their epicyclic period resulting in a periodic pulsing of the disc's surface density.Comment: 11 Figures, 1 Table. Accepted for publication in ApJ. Version 2 reflects minor changes to the text. Animation referenced in Figure 7 is available at http://hubble.shao.ac.cn/~shen/resonantclumping/DensMovie.mp

S-Nitrosoglutathione reduces asymptomatic embolization after carotid angioplasty

Background: The major complication of carotid angioplasty is embolic stroke, which may occur after balloon inflation and deflation or in the early postintervention period. Platelet adhesion and aggregation to the angioplasty site with subsequent embolization seems to plays a major role in early postangioplasty embolization and stroke. During this period, asymptomatic embolic signals can be detected in patients by transcranial Doppler ultrasound despite aspirin and heparin treatment. S-Nitrosoglutathione (GSNO) is a nitric oxide donor that appears to have relative platelet specificity. We evaluated its effectiveness in reducing embolization after carotid angioplasty. Methods and results: Sixteen patients undergoing carotid angioplasty and stenting for symptomatic 70% internal carotid artery stenosis were randomized in a double-blind manner to GSNO or placebo given after surgery for 90 minutes. All patients were pretreated with aspirin and given heparin for 24 hours after the procedure. Transcranial Doppler recordings were made from the ipsilateral middle cerebral artery for 1 hour before treatment and at 0 to 3, 6, and 24 hours after treatment. GSNO resulted in a rapid reduction in the frequency of embolic signals of 95% at 0 to 3 hours and 100% at 6 hours (P=0.007 and P=0.01 versus placebo, respectively). In the placebo group, 2 patients experienced ipsilateral stroke after the angioplasty. No cerebrovascular events occurred in the GSNO group. Conclusions: S-Nitrosoglutathione was highly effective in rapidly reducing the frequency of embolic signals after endovascular treatment for symptomatic high-grade carotid stenosis

Standardisation of Practices in Open Source Hardware

Standardisation is an important component in the maturation of any field of technology. It contributes to the formation of a recognisable identity and enables interactions with a wider community. This article reviews past and current standardisation initiatives in the field of Open Source Hardware (OSH). While early initiatives focused on aspects such as licencing, intellectual property and documentation formats, recent efforts extend to ways for users to exercise their rights under open licences and to keep OSH projects discoverable and accessible online. We specifically introduce two standards that are currently being released and call for early users and contributors, the DIN SPEC 3105 and the Open Know How Manifest Specification. Finally, we reflect on challenges around standardisation in the community and relevant areas for future development such as an open tool chain, modularity and hardware specific interface standards.Comment: 9 Pages without abstract and references (else 13), no figure

Crossing Boundaries and Valuing Diversity

Peer reviewedPublisher PD

Pinning It Down: Towards a Practical Definition of ‘Research Data’ for Creative Arts Institutions

There is a widespread understanding among scientific researchers about what is meant by ‘research data’; however this does not readily translate into a creative context. As part of its engagement with the University of the Arts London (UAL) and via its support for the JISC Managing Research Data Programme, the Digital Curation Centre (DCC) and partners have worked towards an acceptable and practical definition of research data for creative arts institutions. This paper describes the activities carried out to help pin down such a definition, including a literature review, short and extended interviews with researchers, interactions with an academic arts research practitioner, and distillation of the results from a one-day workshop which took place in London in September 2012

Evaluating the use of Apo-neocarzinostatin as a cell penetrating protein.

Protein-ligand complex neocarzinostatin (NCS) is a small, thermostable protein-ligand complex that is able to deliver its ligand cargo into live mammalian cells where it induces DNA damage. Apo-NCS is able to functionally display complementarity determining regions loops, and has been hypothesised to act as a cell-penetrating protein, which would make it an ideal scaffold for cell targeting, and subsequent intracellular delivery of small-molecule drugs. In order to evaluate apo-NCS as a cell penetrating protein, we have evaluated the efficiency of its internalisation into live HeLa cells using matrix-assisted laser-desorption ionization-time-of-flight mass spectrometry and fluorescence microscopy. Following incubation of cells with apo-NCS, we observed no evidence of internalisation

Fluconazole Monotherapy Is a Suboptimal Option for Initial Treatment of Cryptococcal Meningitis Because of Emergence of Resistance.

Cryptococcal meningitis is a lethal disease with few therapeutic options. Induction therapy with fluconazole has been consistently demonstrated to be associated with suboptimal microbiological and clinical outcomes. Exposure to fluconazole causes dynamic changes in antifungal susceptibility, which are associated with the development of aneuploidy. The implications of this phenomenon for pharmacodynamics of fluconazole for cryptococcal meningitis are poorly understood. The pharmacodynamics of fluconazole were studied using a hollow-fiber infection model (HFIM) and a well-characterized murine model of cryptococcal meningoencephalitis. The relationship between drug exposure and both antifungal killing and the emergence of resistance was quantified. The same relationships were further evaluated in a recently described group of patients with cryptococcal meningitis undergoing induction therapy with fluconazole at 800 to 1,200 mg/day. The pattern of emergence of fluconazole resistance followed an "inverted U." Resistance amplification was maximal and suppressed at ratios of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (fAUC:MIC) of 34.5 to 138 and 305.6, respectively. Emergence of resistance was observed in vivo with an fAUC:MIC of 231.4. Aneuploidy with duplication of chromosome 1 was demonstrated to be the underlying mechanism in both experimental models. The pharmacokinetic (PK)-pharmacodynamic model accurately described the PK, antifungal killing, and emergence of resistance. Monte Carlo simulations from the clinical pharmacokinetic-pharmacodynamic model showed that only 12.8% of simulated patients receiving fluconazole at 1,200 mg/day achieved sterilization of the cerebrospinal fluid (CSF) after 2 weeks and that 83.4% had a persistent subpopulation that was resistant to fluconazole. Fluconazole is primarily ineffective due to the emergence of resistance. Treatment with 1,200 mg/day leads to the killing of a susceptible subpopulation but is compromised by the emergence of resistance.IMPORTANCE Cryptococcal meningitis is a lethal disease with few treatment options. The incidence remains high and intricately linked with the HIV/AIDS epidemic. In many parts of the world, fluconazole is the only agent that is available for the initial treatment of cryptococcal meningitis despite considerable evidence that it is associated with suboptimal microbiological and clinical outcomes. Fluconazole has a fungistatic mode of action: it predominantly inhibits growth rather than causing fungal killing. Our work shows that the pattern of fluconazole activity is caused by the emergence of resistance in Cryptococcus not detected by standard susceptibility tests, with chromosomal duplication/aneuploidy as the main mechanism. Resistance emergence is related to drug exposure and occurs with the use of clinically relevant regimens. Hence, fluconazole (and potentially other agents that target 14-alpha-demethylase) is compromised by an intrinsic property that limits its effectiveness. However, this resistance may be potentially overcome by dosage escalation or the use of combination therapy