Hierarchy and assortativity as new tools for affinity investigation: the case of the TBA aptamer-ligand complex

Aptamers are single stranded DNA, RNA or peptide sequences having the ability to bind a variety of specific targets (proteins, molecules as well as ions). Therefore, aptamer production and selection for therapeutic and diagnostic applications is very challenging. Usually they are in vitro generated, but, recently, computational approaches have been developed for the in silico selection, with a higher affinity for the specific target. Anyway, the mechanism of aptamer-ligand formation is not completely clear, and not obvious to predict. This paper aims to develop a computational model able to describe aptamer-ligand affinity performance by using the topological structure of the corresponding graphs, assessed by means of numerical tools such as the conventional degree distribution, but also the rank-degree distribution (hierarchy) and the node assortativity. Calculations are applied to the thrombin binding aptamer (TBA), and the TBA-thrombin complex, produced in the presence of Na+ or K+. The topological analysis reveals different affinity performances between the macromolecules in the presence of the two cations, as expected by previous investigations in literature. These results nominate the graph topological analysis as a novel theoretical tool for testing affinity. Otherwise, starting from the graphs, an electrical network can be obtained by using the specific electrical properties of amino acids and nucleobases. Therefore, a further analysis concerns with the electrical response, which reveals that the resistance sensitively depends on the presence of sodium or potassium thus posing resistance as a crucial physical parameter for testing affinity.Comment: 12 pages, 5 figure

A pH-based bio-rheostat: A proof-of-concept

Biological matter is attracting increasing attention because it shows innovative features that have found several applications in technology, from highly sensitive sensors for medical treatments to devices for energy harvesting. Furthermore, most of its phenomenology remains unclear thus giving hints for speculative investigations. In this letter, we explore the possibility to use a well-known photosensitive protein, the Reaction Center of Rhodobacter Sphaeroides, to build up an electrical pH sensor, i.e., a device able to change its resistance depending on the pH of the solution in which it crystalizes. By using a microscopic model previously tested on analogue proteins, we investigate the electrical response of the Reaction Center single protein under different conditions of applied bias, showing the feasibility of the bio-rheostat hypothesis. As a matter of facts, the calculated resistance of this protein grows of about 100% when going from a pH = 10 to a pH = 6.5. Moreover, calculations of the current voltage characteristics well agree with available experiments performed with a current atomic force microscopy under neutral conditions. All findings are in qualitative agreement with the known role of pH in biochemical activities of Reaction Center and similar proteins, therefore supporting a proof-of-concept for the development of innovative electron devices based on biomaterials

Searching for gas giant planets on Solar System scales - A NACO/APP L'-band survey of A- and F-type Main Sequence stars

We report the results of a direct imaging survey of A- and F-type main sequence stars searching for giant planets. A/F stars are often the targets of surveys, as they are thought to have more massive giant planets relative to solar-type stars. However, most imaging is only sensitive to orbital separations $>$30 AU, where it has been demonstrated that giant planets are rare. In this survey, we take advantage of the high-contrast capabilities of the Apodizing Phase Plate coronagraph on NACO at the Very Large Telescope. Combined with optimized principal component analysis post-processing, we are sensitive to planetary-mass companions (2 to 12 $M_{\rm Jup}$) at Solar System scales ($\leq$30 AU). We obtained data on 13 stars in L'-band and detected one new companion as part of this survey: an M$6.0\pm0.5$ dwarf companion around HD 984. We re-detect low-mass companions around HD 12894 and HD 20385, both reported shortly after the completion of this survey. We use Monte Carlo simulations to determine new constraints on the low-mass ($<$80 $M_{\rm Jup}$) companion frequency, as a function of mass and separation. Assuming solar-type planet mass and separation distributions, normalized to the planet frequency appropriate for A-stars, and the observed companion mass-ratio distribution for stellar companions extrapolated to planetary masses, we derive a truncation radius for the planetary mass companion surface density of $<$135 AU at 95% confidence.Comment: Accepted for publication in MNRAS, 8 pages, 4 figure

Special issue

Mobility as a key feature of a modern society takes place at all geographic scales. The past decades have witnessed an enormous and unprecedented increase in the volume of intercontinental transport (e.g., between Europe and North-America, and between Asia and North-America) (Black and Nijkamp, 2002). Interestingly enough, a similar development is also present at a local level, where not only the activity radius is increasing, but also the frequency of trips. Geographically, our world is becoming less distant (resembling a ‘small world network’; see, e.g., Barabasi, 2002 and Watts, 1999) and more local and close-by, the so-called ‘global village’ (Poot, 2004)

Special issue

Mobility as a key feature of a modern society takes place at all geographic scales. The past decades have witnessed an enormous and unprecedented increase in the volume of intercontinental transport (e.g., between Europe and North-America, and between Asia and North-America) (Black and Nijkamp, 2002). Interestingly enough, a similar development is also present at a local level, where not only the activity radius is increasing, but also the frequency of trips. Geographically, our world is becoming less distant (resembling a 'small world network'; see, e.g., Barabasi, 2002 and Watts, 1999) and more local and close-by, the so-called 'global village' (Poot, 2004)

Neural networks for cross-sectional employment forecasts: A comparison of model specifications for Germany

In this paper, we present a review of various computational experiments – and consequent results – concerning Neural Network (NN) models developed for regional employment forecasting. NNs are widely used in several fields because of their flexible specification structure. Their utilization in studying/predicting economic variables, such as employment or migration, is justified by the ability of NNs of learning from data, in other words, of finding functional relationships – by means of data – among the economic variables under analysis. A series of NN experiments is presented in the paper. Using two data sets on German NUTS 3 districts (326 and 113 labour market districts in the former West and East Germany, respectively), the results emerging from the implementation of various NN models – in order to forecast variations in full-time employment – are provided and discussed In our approach, single forecasts are computed by the models for each district. Different specifications of the NN models are first tested in terms of: (a) explanatory variables; and (b) NN structures. The average statistical results of simulated out-of-sample forecasts on different periods are summarized and commented on. In addition to variable and structure specification, the choice of NN learning parameters and internal functions is also critical to the success of NNs. Comprehensive testing of these parameters is, however, limited in the literature. A sensitivity analysis is therefore carried out and discussed, in order to evaluate different combinations of NN parameters. The paper concludes with methodological and empirical remarks, as well as with suggestions for future research

Iron-rich Metal-poor Stars and the Astrophysics of Thermonuclear Events Observationally Classified as Type Ia Supernovae. I. Establishing the Connection

The progenitor systems and explosion mechanisms responsible for the thermonuclear events observationally classified as Type Ia supernovae are uncertain and difficult to uniquely constrain using traditional observations of Type Ia supernova host galaxies, progenitors, light curves, and remnants. For the subset of thermonuclear events that are prolific producers of iron, we use published theoretical nucleosynthetic yields to identify a set of elemental abundance ratios infrequently observed in metal-poor stars but shared across a range of progenitor systems and explosion mechanisms: [Na,Mg,Co/Fe]<0. We label stars with this abundance signature ``iron-rich metal-poor'' or IRMP stars. We suggest that IRMP stars formed in environments dominated by thermonuclear nucleosynthesis and consequently that their elemental abundances can be used to constrain both the progenitor systems and explosion mechanisms responsible for thermonuclear explosions. We identify three IRMP in the literature and homogeneously infer their elemental abundances. We find that the elemental abundances of BD+80 245, HE 0533--5340, and SMSS J034249.53--284216.0 are best explained by the (double) detonations of sub-Chandrasekhar mass CO white dwarfs. If our interpretation of IRMP stars is accurate, then they should be very rare in globular clusters and more common in the Magellanic Clouds and dwarf spheroidal galaxies than in the Milky Way's halo. We propose that future studies of IRMP stars will quantify the relative occurrences of different thermonuclear event progenitor systems and explosion mechanisms.Comment: Accepted for publication at A

Tbr1 instructs laminar patterning of retinal ganglion cell dendrites.

Visual information is delivered to the brain by &gt;40 types of retinal ganglion cells (RGCs). Diversity in this representation arises within the inner plexiform layer (IPL), where dendrites of each RGC type are restricted to specific sublaminae, limiting the interneuronal types that can innervate them. How such dendritic restriction arises is unclear. We show that the transcription factor Tbr1 is expressed by four mouse RGC types with dendrites in the outer IPL and is required for their laminar specification. Loss of Tbr1 results in elaboration of dendrites within the inner IPL, while misexpression in other cells retargets their neurites to the outer IPL. Two transmembrane molecules, Sorcs3 and Cdh8, act as effectors of the Tbr1-controlled lamination program. However, they are expressed in just one Tbr1+ RGC type, supporting a model in which a single transcription factor implements similar laminar choices in distinct cell types by recruiting partially non-overlapping effectors