Emergence of highly-designable protein-backbone conformations in an off-lattice model

Despite the variety of protein sizes, shapes, and backbone configurations found in nature, the design of novel protein folds remains an open problem. Within simple lattice models it has been shown that all structures are not equally suitable for design. Rather, certain structures are distinguished by unusually high designability: the number of amino-acid sequences for which they represent the unique ground state; sequences associated with such structures possess both robustness to mutation and thermodynamic stability. Here we report that highly designable backbone conformations also emerge in a realistic off-lattice model. The highly designable conformations of a chain of 23 amino acids are identified, and found to be remarkably insensitive to model parameters. While some of these conformations correspond closely to known natural protein folds, such as the zinc finger and the helix-turn-helix motifs, others do not resemble known folds and may be candidates for novel fold design.Comment: 7 figure

Vocal learning promotes patterned inhibitory connectivity.

Skill learning is instantiated by changes to functional connectivity within premotor circuits, but whether the specificity of learning depends on structured changes to inhibitory circuitry remains unclear. We used slice electrophysiology to measure connectivity changes associated with song learning in the avian analog of primary motor cortex (robust nucleus of the arcopallium, RA) in Bengalese Finches. Before song learning, fast-spiking interneurons (FSIs) densely innervated glutamatergic projection neurons (PNs) with apparently random connectivity. After learning, there was a profound reduction in the overall strength and number of inhibitory connections, but this was accompanied by a more than two-fold enrichment in reciprocal FSI-PN connections. Moreover, in singing birds, we found that pharmacological manipulations of RA's inhibitory circuitry drove large shifts in learned vocal features, such as pitch and amplitude, without grossly disrupting the song. Our results indicate that skill learning establishes nonrandom inhibitory connectivity, and implicates this patterning in encoding specific features of learned movements

Magnetocaloric effect in Gd/W thin film heterostructures

In an effort to understand the impact of nanostructuring on the magnetocaloric effect, we have grown and studied gadolinium in MgO/W(50 $\textrm{\AA}$)/[Gd(400 $\textrm{\AA}$)/W(50 $\textrm{\AA}$)]$_8$ heterostructures. The entropy change associated with the second order magnetic phase transition was determined from the isothermal magnetization for numerous temperatures and the appropriate Maxwell relation. The entropy change peaks at a temperature of 284 K with a value of approximately 3.4 J/kg-K for a 0-30 kOe field change; the full width at half max of the entropy change peak is about 70 K, which is significantly wider than that of bulk Gd under similar conditions. The relative cooling power of this nanoscale system is about 240 J/kg, somewhat lower than that of bulk Gd (410 J/kg). An iterative Kovel-Fisher method was used to determine the critical exponents governing the phase transition to be $\beta=0.51$, and $\gamma=1.75$. Along with a suppressed Curie temperature relative to the bulk, the fact that the convergent value of $\gamma$ is that predicted by the 2-D Ising model may suggest that finite size effects play an important role in this system. Together, these observations suggest that nanostructuring may be a promising route to tailoring the magnetocaloric response of materials

The Variable X-ray Spectrum of Markarian 766 - II. Time-Resolved Spectroscopy

CONTEXT: The variable X-ray spectra of AGN systematically show steep power-law high states and hard-spectrum low states. The hard low state has previously been found to be a component with only weak variability. The origin of this component and the relative importance of effects such as absorption and relativistic blurring are currently not clear. AIMS: In a follow-up of previous principal components analysis, we aim to determine the relative importance of scattering and absorption effects on the time-varying X-ray spectrum of the narrow-line Seyfert 1 galaxy Mrk~766. METHODS: Time-resolved spectroscopy, slicing XMM and Suzaku data down to 25 ks elements, is used to investigate whether absorption or scattering components dominate the spectral variations in Mrk 766.Time-resolved spectroscopy confirms that spectral variability in Mrk 766 can be explained by either of two interpretations of principal components analysis. Detailed investigation confirm rapid changes in the relative strengths of scattered and direct emission or rapid changes in absorber covering fraction provide good explanations of most of the spectral variability. However, a strong correlation between the 6.97 keV absorption line and the primary continuum together with rapid opacity changes show that variations in a complex and multi-layered absorber, most likely a disk wind, are the dominant source of spectral variability in Mrk 76

Overdiagnosis and overtreatment of breast cancer: Overdiagnosis in randomised controlled trials of breast cancer screening

Data from randomised controlled trials of mammographic screening can be used to determine the extent of any overdiagnosis, as soon as either a time equivalent to the lead-time has elapsed after the final screen, or the control arm has been offered screening. This paper reviews those randomised trials for which breast cancer incidence data are available. In recent trials in which the control group has not been offered screening, an excess incidence of breast cancer remains after many years of follow-up. In those trials in which the control arm has been offered screening, although there is a possible shift from invasive to in situ disease, there is no evidence of overdiagnosis as a result of incident screens

Asynchronous displays for multi-UV search tasks

Synchronous video has long been the preferred mode for controlling remote robots with other modes such as asynchronous control only used when unavoidable as in the case of interplanetary robotics. We identify two basic problems for controlling multiple robots using synchronous displays: operator overload and information fusion. Synchronous displays from multiple robots can easily overwhelm an operator who must search video for targets. If targets are plentiful, the operator will likely miss targets that enter and leave unattended views while dealing with others that were noticed. The related fusion problem arises because robots' multiple fields of view may overlap forcing the operator to reconcile different views from different perspectives and form an awareness of the environment by "piecing them together". We have conducted a series of experiments investigating the suitability of asynchronous displays for multi-UV search. Our first experiments involved static panoramas in which operators selected locations at which robots halted and panned their camera to capture a record of what could be seen from that location. A subsequent experiment investigated the hypothesis that the relative performance of the panoramic display would improve as the number of robots was increased causing greater overload and fusion problems. In a subsequent Image Queue system we used automated path planning and also automated the selection of imagery for presentation by choosing a greedy selection of non-overlapping views. A fourth set of experiments used the SUAVE display, an asynchronous variant of the picture-in-picture technique for video from multiple UAVs. The panoramic displays which addressed only the overload problem led to performance similar to synchronous video while the Image Queue and SUAVE displays which addressed fusion as well led to improved performance on a number of measures. In this paper we will review our experiences in designing and testing asynchronous displays and discuss challenges to their use including tracking dynamic targets. © 2012 by the American Institute of Aeronautics and Astronautics, Inc

Ensuring Trust in One Time Exchanges: Solving the QoS Problem

We describe a pricing structure for the provision of IT services that ensures trust without requiring repeated interactions between service providers and users. It does so by offering a pricing structure that elicits truthful reporting of quality of service (QoS) by providers while making them profitable. This mechanism also induces truth-telling on the part of users reserving the service

The Man Who Mistook His Neuropsychologist For a Popstar: When Configural Processing Fails in Acquired Prosopagnosia

We report the case of an individual with acquired prosopagnosia who experiences extreme difficulties in recognizing familiar faces in everyday life despite excellent object recognition skills. Formal testing indicates that he is also severely impaired at remembering pre-experimentally unfamiliar faces and that he takes an extremely long time to identify famous faces and to match unfamiliar faces. Nevertheless, he performs as accurately and quickly as controls at identifying inverted familiar and unfamiliar faces and can recognize famous faces from their external features. He also performs as accurately as controls at recognizing famous faces when fracturing conceals the configural information in the face. He shows evidence of impaired global processing but normal local processing of Navon figures. This case appears to reflect the clearest example yet of an acquired prosopagnosic patient whose familiar face recognition deficit is caused by a severe configural processing deficit in the absence of any problems in featural processing. These preserved featural skills together with apparently intact visual imagery for faces allow him to identify a surprisingly large number of famous faces when unlimited time is available. The theoretical implications of this pattern of performance for understanding the nature of acquired prosopagnosia are discussed.DY, Avery Braun, Jacob Waite, and Nadine Wanke, Bruno Rossion, Thomas Busigny and the grant awarded by AJ by the Experimental Psychology Society (EPS