FAIR principles and the IEDB: short-term improvements and a long-term vision of OBO-foundry mediated machine-actionable interoperability.

The Immune Epitope Database (IEDB), at www.iedb.org, has the mission to make published experimental data relating to the recognition of immune epitopes easily available to the scientific public. By presenting curated data in a searchable database, we have liberated it from the tables and figures of journal articles, making it more accessible and usable by immunologists. Recently, the principles of Findability, Accessibility, Interoperability and Reusability have been formulated as goals that data repositories should meet to enhance the usefulness of their data holdings. We here examine how the IEDB complies with these principles and identify broad areas of success, but also areas for improvement. We describe short-term improvements to the IEDB that are being implemented now, as well as a long-term vision of true 'machine-actionable interoperability', which we believe will require community agreement on standardization of knowledge representation that can be built on top of the shared use of ontologies

On the action potential as a propagating density pulse and the role of anesthetics

The Hodgkin-Huxley model of nerve pulse propagation relies on ion currents through specific resistors called ion channels. We discuss a number of classical thermodynamic findings on nerves that are not contained in this classical theory. Particularly striking is the finding of reversible heat changes, thickness and phase changes of the membrane during the action potential. Data on various nerves rather suggest that a reversible density pulse accompanies the action potential of nerves. Here, we attempted to explain these phenomena by propagating solitons that depend on the presence of cooperative phase transitions in the nerve membrane. These transitions are, however, strongly influenced by the presence of anesthetics. Therefore, the thermodynamic theory of nerve pulses suggests a explanation for the famous Meyer-Overton rule that states that the critical anesthetic dose is linearly related to the solubility of the drug in the membranes.Comment: 13 pages, 8 figure

An Improved Private Mechanism for Small Databases

We study the problem of answering a workload of linear queries $\mathcal{Q}$, on a database of size at most $n = o(|\mathcal{Q}|)$ drawn from a universe $\mathcal{U}$ under the constraint of (approximate) differential privacy. Nikolov, Talwar, and Zhang~\cite{NTZ} proposed an efficient mechanism that, for any given $\mathcal{Q}$ and $n$, answers the queries with average error that is at most a factor polynomial in $\log |\mathcal{Q}|$ and $\log |\mathcal{U}|$ worse than the best possible. Here we improve on this guarantee and give a mechanism whose competitiveness ratio is at most polynomial in $\log n$ and $\log |\mathcal{U}|$, and has no dependence on $|\mathcal{Q}|$. Our mechanism is based on the projection mechanism of Nikolov, Talwar, and Zhang, but in place of an ad-hoc noise distribution, we use a distribution which is in a sense optimal for the projection mechanism, and analyze it using convex duality and the restricted invertibility principle.Comment: To appear in ICALP 2015, Track

The small FNR regulon of Neisseria gonorrhoeae: comparison with the larger Escherichia coli FNR regulon and interaction with the NarQ-NarP regulon

BACKGROUND: Neisseria gonorrhoeae can survive during oxygen starvation by reducing nitrite to nitrous oxide catalysed by the nitrite and nitric oxide reductases, AniA and NorB. The oxygen-sensing transcription factor, FNR, is essential for transcription activation at the aniA promoter, and full activation also requires the two-component regulatory system, NarQ-NarP, and the presence of nitrite. The only other gene known to be activated by the gonococcal FNR is ccp encoding a cytochrome c peroxidase, and no FNR-repressed genes have been reported in the gonococcus. In contrast, FNR acts as both an activator and repressor involved in the control of more than 100 operons in E. coli regulating major changes in the adaptation from aerobic to anaerobic conditions. In this study we have performed a microarray-led investigation of the FNR-mediated responses in N. gonorrhoeae to determine the physiological similarities and differences in the role of FNR in cellular regulation in this species. RESULTS: Microarray experiments show that N. gonorrhoeae FNR controls a much smaller regulon than its E. coli counterpart; it activates transcription of aniA and thirteen other genes, and represses transcription of six genes that include dnrN and norB. Having previously shown that a single amino acid substitution is sufficient to enable the gonococcal FNR to complement an E. coli fnr mutation, we investigated whether the gonococcal NarQ-NarP can substitute for E. coli NarX-NarL or NarQ-NarP. A plasmid expressing gonococcal narQ-narP was unable to complement E. coli narQP or narXL mutants, and was insensitive to nitrate or nitrite. Mutations that progressively changed the periplasmic nitrate sensing region, the P box, of E. coli NarQ to the sequence of the corresponding region of gonococcal NarQ resulted in loss of transcription activation in response to the availability of either nitrate or nitrite. However, the previously reported ligand-insensitive ability of gonococcal NarQ, the "locked on" phenotype, to activate either E. coli NarL or NarP was confirmed. CONCLUSION: Despite the sequence similarities between transcription activators of E. coli and N. gonorrhoeae, these results emphasise the fundamental differences in transcription regulation between these two types of pathogenic bacteria

High temperature dielectric properties of Apical, Kapton, Peek, Teflon AF, and Upilex polymers

Reliable lightweight systems capable of providing electrical power at the magawatt level are a requirement for future manned space exploration missions. This can be achieved by the development of high temperature insulating materials which are not only capable of surviving the hostile space environment but can contribute to reducing the mass and weight of the heat rejection system. In this work, Apical, Upilex, Kapton, Teflon AF, and Peek polymers are characterized for AC and DC dielectric breakdown in air and in silicone oil at temperatures up to 250 C. The materials are also tested in terms of their dielectric constant and dissipation factor at high temperatures with an electrical stress of 60 Hz, 200 V/mil present. The effects of thermal aging on the properties of the films are determined after 15 hours of exposure to 200 and 250 C, each. The results obtained are discussed and conclusions are made concerning the suitability of these dielectrics for use in capacitors and cable insulations in high temperature environments

Drug therapies for attentional disorders alter the signal-to-noise ratio in the superior colliculus

Despite high levels of use, the mechanism of action of effective pharmacotherapies in attention deficit hyperactivity disorder (ADHD) is unknown. It has recently been hypothesized that one site of therapeutic action is the midbrain superior colliculus, a structure traditionally associated with visual processing, but also strongly implicated in distractibility, a core symptom of ADHD. We used male juvenile Wistar rats to examine the effects of therapeutically relevant doses of methylphenidate and d-amphetamine on collicular activity in vitro. Here we report a novel shared mechanism of the two drugs whereby they enhance the signal-to-noise ratio in the superior colliculus. The effects on the signal-to-noise ratio were mediated by serotonin (5-HT) via a pre-synaptic mechanism. This modulatory action would bias the system towards salient events and lead to an overall decrease in distractibility

The Evolution of X-ray Bursts in the "Bursting Pulsar" GRO J1744-28

GRO J1744-28, commonly known as the `Bursting Pulsar', is a low mass X-ray binary containing a neutron star and an evolved giant star. This system, together with the Rapid Burster (MXB 1730-33), are the only two systems that display the so-called Type II X-ray bursts. These type of bursts, which last for 10s of seconds, are thought to be caused by viscous instabilities in the disk; however the Type II bursts seen in GRO J1744-28 are qualitatively very different from those seen in the archetypal Type II bursting source the Rapid Burster. To understand these differences and to create a framework for future study, we perform a study of all X-ray observations of all 3 known outbursts of the Bursting Pulsar which contained Type II bursts, including a population study of all Type II X-ray bursts seen by RXTE. We find that the bursts from this source are best described in four distinct phenomena or `classes' and that the characteristics of the bursts evolve in a predictable way. We compare our results with what is known for the Rapid Burster and put out results in the context of models that try to explain this phenomena.Comment: Accepted to MNRAS Aug 17 201

Coupling between gamma-band power and cerebral blood volume during recurrent acute neocortical seizures

Characterization of neural and hemodynamic biomarkers of epileptic activity that can be measured using non-invasive techniques is fundamental to the accurate identification of the epileptogenic zone (EZ) in the clinical setting. Recently, oscillations at gamma-band frequencies and above (>30 Hz) have been suggested to provide valuable localizing information of the EZ and track cortical activation associated with epileptogenic processes. Although a tight coupling between gamma-band activity and hemodynamic-based signals has been consistently demonstrated in non-pathological conditions, very little is known about whether such a relationship is maintained in epilepsy and the laminar etiology of these signals. Confirmation of this relationship may elucidate the underpinnings of perfusion-based signals in epilepsy and the potential value of localizing the EZ using hemodynamic correlates of pathological rhythms. Here, we use concurrent multi-depth electrophysiology and 2-dimensional optical imaging spectroscopy to examine the coupling between multi-band neural activity and cerebral blood volume (CBV) during recurrent acute focal neocortical seizures in the urethane-anesthetized rat. We show a powerful correlation between gamma-band power (25-90 Hz) and CBV across cortical laminae, in particular layer 5, and a close association between gamma measures and multi-unit activity (MUA). Our findings provide insights into the laminar electrophysiological basis of perfusion-based imaging signals in the epileptic state and may have implications for further research using non-invasive multi-modal techniques to localize epileptogenic tissue