Active machine learning for transmembrane helix prediction

Abstract Background About 30% of genes code for membrane proteins, which are involved in a wide variety of crucial biological functions. Despite their importance, experimentally determined structures correspond to only about 1.7% of protein structures deposited in the Protein Data Bank due to the difficulty in crystallizing membrane proteins. Algorithms that can identify proteins whose high-resolution structure can aid in predicting the structure of many previously unresolved proteins are therefore of potentially high value. Active machine learning is a supervised machine learning approach which is suitable for this domain where there are a large number of sequences but only very few have known corresponding structures. In essence, active learning seeks to identify proteins whose structure, if revealed experimentally, is maximally predictive of others. Results An active learning approach is presented for selection of a minimal set of proteins whose structures can aid in the determination of transmembrane helices for the remaining proteins. TMpro, an algorithm for high accuracy TM helix prediction we previously developed, is coupled with active learning. We show that with a well-designed selection procedure, high accuracy can be achieved with only few proteins. TMpro, trained with a single protein achieved an F-score of 94% on benchmark evaluation and 91% on MPtopo dataset, which correspond to the state-of-the-art accuracies on TM helix prediction that are achieved usually by training with over 100 training proteins. Conclusion Active learning is suitable for bioinformatics applications, where manually characterized data are not a comprehensive representation of all possible data, and in fact can be a very sparse subset thereof. It aids in selection of data instances which when characterized experimentally can improve the accuracy of computational characterization of remaining raw data. The results presented here also demonstrate that the feature extraction method of TMpro is well designed, achieving a very good separation between TM and non TM segments

Spatio-temporal variability and principal components of the particle number size distribution in an urban atmosphere

A correct description of fine (diameter <1 μm) and ultrafine (<0.1 μm) aerosol particles in urban areas is of interest for particle exposure assessment but also basic atmospheric research. We examined the spatio-temporal variability of atmospheric aerosol particles (size range 3–800 nm) using concurrent number size distribution measurements at a maximum of eight observation sites in and around Leipzig, a city in Central Europe. Two main experiments were conducted with different time span and number of observation sites (2 years at 3 sites; 1 month at 8 sites). A general observation was that the particle number size distribution varied in time and space in a complex fashion as a result of interaction between local and far-range sources, and the meteorological conditions. To identify statistically independent factors in the urban aerosol, different runs of principal component (PC) analysis were conducted encompassing aerosol, gas phase, and meteorological parameters from the multiple sites. Several of the resulting PCs, outstanding with respect to their temporal persistence and spatial coverage, could be associated with aerosol particle modes: a first accumulation mode ("droplet mode", 300–800 nm), considered to be the result of liquid phase processes and far-range transport; a second accumulation mode (centered around diameters 90–250 nm), considered to result from primary emissions as well as aging through condensation and coagulation; an Aitken mode (30–200 nm) linked to urban traffic emissions in addition to an urban and a rural Aitken mode; a nucleation mode (5–20 nm) linked to urban traffic emissions; nucleation modes (3–20 nm) linked to photochemically induced particle formation; an aged nucleation mode (10–50 nm). Additional PCs represented only local sources at a single site, or infrequent phenomena. In summary, the analysis of size distributions of high time and size resolution yielded a surprising wealth of statistical aerosol components occurring in the urban atmosphere over one single city. A paradigm on the behaviour of sub-μm urban aerosol particles is proposed, with recommendations how to efficiently monitor individual sub-fractions across an entire city

No Need for a Cognitive Map: Decentralized Memory for Insect Navigation

In many animals the ability to navigate over long distances is an important prerequisite for foraging. For example, it is widely accepted that desert ants and honey bees, but also mammals, use path integration for finding the way back to their home site. It is however a matter of a long standing debate whether animals in addition are able to acquire and use so called cognitive maps. Such a ‘map’, a global spatial representation of the foraging area, is generally assumed to allow the animal to find shortcuts between two sites although the direct connection has never been travelled before. Using the artificial neural network approach, here we develop an artificial memory system which is based on path integration and various landmark guidance mechanisms (a bank of individual and independent landmark-defined memory elements). Activation of the individual memory elements depends on a separate motivation network and an, in part, asymmetrical lateral inhibition network. The information concerning the absolute position of the agent is present, but resides in a separate memory that can only be used by the path integration subsystem to control the behaviour, but cannot be used for computational purposes with other memory elements of the system. Thus, in this simulation there is no neural basis of a cognitive map. Nevertheless, an agent controlled by this network is able to accomplish various navigational tasks known from ants and bees and often discussed as being dependent on a cognitive map. For example, map-like behaviour as observed in honey bees arises as an emergent property from a decentralized system. This behaviour thus can be explained without referring to the assumption that a cognitive map, a coherent representation of foraging space, must exist. We hypothesize that the proposed network essentially resides in the mushroom bodies of the insect brain

New-particle formation events in a continental boundary layer: first results from the SATURN experiment

International audienceDuring the SATURN experiment, which took place from 27 May to 14 June 2002, new particle formation in the continental boundary layer was investigated. Simultaneous ground-based and tethered-balloon-borne measurements were performed, including meteorological parameters, particle number concentrations and size distributions, gaseous precursor concentrations and SODAR and LIDAR observations. Newly formed particles were observed inside the residual layer, before the break-up process of the nocturnal inversion, and inside the mixing layer throughout the break-up of the nocturnal inversion and during the evolution of the planetary boundary layer.</p

Ultrafast Spin Dynamics in Nickel

The spin dynamics in Ni is studied by an exact diagonalization method on the ultrafast time scale. It is shown that the femtosecond relaxation of the magneto-optical response results from exchange interaction and spin-orbit coupling. Each of the two mechanisms affects the relaxation process differently. We find that the intrinsic spin dynamics occurs during about 10 fs while extrinsic effects such as laser-pulse duration and spectral width can slow down the observed dynamics considerably. Thus, our theory indicates that there is still room to accelerate the spin dynamics in experiments.Comment: 4 pages, Latex, 4 postscript figure

Specialized ommatidia of the polarization-sensitive dorsal rim area in the eye of monarch butterflies have non-functional reflecting tapeta

Many insects exploit sky light polarization for navigation or cruising-course control. The detection of polarized sky light is mediated by the ommatidia of a small specialized part of the compound eye: the dorsal rim area (DRA). We describe the morphology and fine structure of the DRA in monarch butterflies (Danaus plexippus). The DRA consists of approximately 100 ommatidia forming a narrow ribbon along the dorsal eye margin. Each ommatidium contains two types of photoreceptor with mutually orthogonal microvilli orientations occurring in a 2:6 ratio. Within each rhabdomere, the microvilli are well aligned. Rhabdom structure and orientation remain constant at all retinal levels, but the rhabdom profiles, as seen in tangential sections through the DRA, change their orientations in a fan-like fashion from the frontal to the caudal end of the DRA. Whereas these properties (two microvillar orientations per rhabdom, microvillar alignment along rhabdomeres, ommatidial fan array) are typical for insect DRAs in general, we also report and discuss here a novel feature. The ommatidia of monarch butterflies are equipped with reflecting tapeta, which are directly connected to the proximal ends of the rhabdoms. Although tapeta are also present in the DRA, they are separated from the rhabdoms by a space of approximately 55 μm effectively inactivating them. This reduces self-screening effects, keeping polarization sensitivity of all photoreceptors of the DRA ommatidia both high and approximately equal

A Distinct Layer of the Medulla Integrates Sky Compass Signals in the Brain of an Insect

Mass migration of desert locusts is a common phenomenon in North Africa and the Middle East but how these insects navigate is still poorly understood. Laboratory studies suggest that locusts are able to exploit the sky polarization pattern as a navigational cue. Like other insects locusts detect polarized light through a specialized dorsal rim area (DRA) of the eye. Polarization signals are transmitted through the optic lobe to the anterior optic tubercle (AOTu) and, finally, to the central complex in the brain. Whereas neurons of the AOTu integrate sky polarization and chromatic cues in a daytime dependent manner, the central complex holds a topographic representation of azimuthal directions suggesting a role as an internal sky compass. To understand further the integration of sky compass cues we studied polarization-sensitive (POL) neurons in the medulla that may be intercalated between DRA photoreceptors and AOTu neurons. Five types of POL-neuron were characterized and four of these in multiple recordings. All neurons had wide arborizations in medulla layer 4 and most, additionally, in the dorsal rim area of the medulla and in the accessory medulla, the presumed circadian clock. The neurons showed type-specific orientational tuning to zenithal polarized light and azimuth tuning to unpolarized green and UV light spots. In contrast to neurons of the AOTu, we found no evidence for color opponency and daytime dependent adjustment of sky compass signals. Therefore, medulla layer 4 is a distinct stage in the integration of sky compass signals that precedes the time-compensated integration of celestial cues in the AOTu

Plasma functionalization of polycarbonaturethane to improve endothelialization—Effect of shear stress as a critical factor for biocompatibility control

Medical devices made of polycarbonaturethane (PCU) combine excellent mechanical properties and little biological degradation, but restricted hemocompatibility. Modifications of PCU might reduce platelet adhesion and promote stable endothelialization. PCU was modified using gas plasma treatment, binding of hydrogels, and coupling of cell-active molecules (modified heparin, anti-thrombin III (ATIII), argatroban, fibronectin, laminin-nonapeptide, peptides with integrin-binding arginine-glycine-aspartic acid (RGD) motif). Biocompatibility was verified with static and dynamic cell culture techniques. Blinded analysis focused on improvement in endothelial cell (EC) adhesion/proliferation, anti-thrombogenicity, reproducible manufacturing process, and shear stress tolerance of ECs. EC adhesion and antithrombogenicity were achieved with 9/35 modifications. Additionally, 6/9 stimulated EC proliferation and 3/6 modification processes were highly reproducible for endothelialization. The latter modifications comprised immobilization of ATIII (A), polyethyleneglycole-diamine-hydrogel (E) and polyethylenimine-hydrogel connected with modified heparin (IH). Under sheer stress, only the IH modification improved EC adhesion within the graft. However, ECs did not arrange in flow direction and cell anchorage was restricted. Despite large variation in surface modification chemistry and improved EC adhesion under static culture conditions, additional introduction of shear stress foiled promising preliminary data. Therefore, biocompatibility testing required not only static tests but also usage of physiological conditions such as shear stress in the case of vascular grafts

Steps in the Negative-Differential-Conductivity Regime of a Superconductor

Current-voltage characteristics were measured in the mixed state of Y1Ba2Cu3O(7-delta) superconducting films in the regime where flux flow becomes unstable and the differential conductivity dj/dE becomes negative. Under conditions where its negative slope is steep, the j(E) curve develops a pronounced staircase like pattern. We attribute the steps in j(E) to the formation of a dynamical phase consisting of the succesive nucleation of quantized distortions in the local vortex velocity and flux distribution within the moving flux matter.Comment: 5 pages, 3 figure