Hot coffee: associative memory with bump attractor cell assemblies of spiking neurons

Networks of spiking neurons can have persistently firing stable bump attractors to represent continuous spaces (like temperature). This can be done with a topology with local excitatory synapses and local surround inhibitory synapses. Activating large ranges in the attractor can lead to multiple bumps, that show repeller and attractor dynamics; however, these bumps can be merged by overcoming the repeller dynamics. A simple associative memory can include these bump attractors, allowing the use of continuous variables in these memories, and these associations can be learned by Hebbian rules. These simulations are related to biological networks, showing that this is a step toward a more complete neural cognitive associative memory

Mutant cycles at CFTR's non-canonical ATP-binding site support little interface separation during gating

Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel belonging to the adenosine triphosphate (ATP)-binding cassette (ABC) superfamily. ABC proteins share a common molecular mechanism that couples ATP binding and hydrolysis at two nucleotide-binding domains (NBDs) to diverse functions. This involves formation of NBD dimers, with ATP bound at two composite interfacial sites. In CFTR, intramolecular NBD dimerization is coupled to channel opening. Channel closing is triggered by hydrolysis of the ATP molecule bound at composite site 2. Site 1, which is non-canonical, binds nucleotide tightly but is not hydrolytic. Recently, based on kinetic arguments, it was suggested that this site remains closed for several gating cycles. To investigate movements at site 1 by an independent technique, we studied changes in thermodynamic coupling between pairs of residues on opposite sides of this site. The chosen targets are likely to interact based on both phylogenetic analysis and closeness on structural models. First, we mutated T460 in NBD1 and L1353 in NBD2 (the corresponding site-2 residues become energetically coupled as channels open). Mutation T460S accelerated closure in hydrolytic conditions and in the nonhydrolytic K1250R background; mutation L1353M did not affect these rates. Analysis of the double mutant showed additive effects of mutations, suggesting that energetic coupling between the two residues remains unchanged during the gating cycle. We next investigated pairs 460-1348 and 460-1375. Although both mutations H1348A and H1375A produced dramatic changes in hydrolytic and nonhydrolytic channel closing rates, in the corresponding double mutants these changes proved mostly additive with those caused by mutation T460S, suggesting little change in energetic coupling between either positions 460-1348 or positions 460-1375 during gating. These results provide independent support for a gating model in which ATP-bound composite site 1 remains closed throughout the gating cycle

Electrophysiological, biochemical, and bioinformatic methods for studying CFTR channel gating and its regulation.

CFTR is the only member of the ABC (ATP-binding cassette) protein superfamily known to function as an ion channel. Most other ABC proteins are ATP-driven transporters, in which a cycle of ATP binding and hydrolysis, at intracellular nucleotide binding domains (NBDs), powers uphill substrate translocation across the membrane. In CFTR, this same ATP-driven cycle opens and closes a transmembrane pore through which chloride ions flow rapidly down their electrochemical gradient. Detailed analysis of the pattern of gating of CFTR channels thus offers the opportunity to learn about mechanisms of function not only of CFTR channels but also of their ABC transporter ancestors. In addition, CFTR channel gating is subject to complex regulation by kinase-mediated phosphorylation at multiple consensus sites in a cytoplasmic regulatory domain that is unique to CFTR. Here we offer a practical guide to extract useful information about the mechanisms that control opening and closing of CFTR channels: on how to plan (including information obtained from analysis of multiple sequence alignments), carry out, and analyze electrophysiological and biochemical experiments, as well as on how to circumvent potential pitfalls

Spontaneous Participation in Secondary Prevention Programs : The Role of Psychosocial Predictors

Disease prevention is a multifaceted construct that has been widely studied. Nevertheless, in spite of its importance, it is still not sufficiently considered by the general population. Since the reasons for this lack of consideration are not yet fully understood, we created an Online Prevention Survey (OPS) to investigate the role of both sociodemographic and psychological factors in predicting individuals\u2019 spontaneous participation in secondary prevention programs. The results revealed that younger people, men, manual workers, unemployed people, and those who do not regularly practise physical activity were less likely to spontaneously participate in such programs. Furthermore, an analysis of the psychological determinants of the willingness to participate in secondary prevention programs showed that depressive symptoms negatively predict it, while an individual\u2019s perception of receiving high social support acts as a positive predictor. Based on these results, we suggest the need for implementing new tailored approaches to promote prevention initiatives to those segments of the population which are more reluctant to spontaneously undertake prevention paths

Crumpling-based soft metamaterials: The effects of sheet pore size and porosity

Crumpled-based materials are relatively easy to fabricate and show robust mechanical properties for practical applications, including meta-biomaterials design aimed for improved tissue regeneration. For such requests, however, the structure needs to be porous. We introduce a crumpled holey thin sheet as a robust bio-metamaterial and measure the mechanical response of a crumpled holey thin Mylar sheet as a function of the hole size and hole area fraction. We also study the formation of patterns of crease lines and ridges. The area fraction largely dominated the crumpling mechanism. We also show, the crumpling exponents slightly increases with increasing the hole area fraction and the total perimeter of the holes. Finally, hole edges were found to limit and guide the propagation of crease lines and ridges

Unveiling the population of orphan Gamma Ray Bursts

Gamma Ray Bursts are detectable in the gamma-ray band if their jets are oriented towards the observer. However, for each GRB with a typical theta_jet, there should be ~2/theta_jet^2 bursts whose emission cone is oriented elsewhere in space. These off-axis bursts can be eventually detected when, due to the deceleration of their relativistic jets, the beaming angle becomes comparable to the viewing angle. Orphan Afterglows (OA) should outnumber the current population of bursts detected in the gamma-ray band even if they have not been conclusively observed so far at any frequency. We compute the expected flux of the population of orphan afterglows in the mm, optical and X-ray bands through a population synthesis code of GRBs and the standard afterglow emission model. We estimate the detection rate of OA by on-going and forthcoming surveys. The average duration of OA as transients above a given limiting flux is derived and described with analytical expressions: in general OA should appear as daily transients in optical surveys and as monthly/yearly transients in the mm/radio band. We find that ~ 2 OA yr^-1 could already be detected by Gaia and up to 20 OA yr^-1 could be observed by the ZTF survey. A larger number of 50 OA yr^-1 should be detected by LSST in the optical band. For the X-ray band, ~ 26 OA yr^-1 could be detected by the eROSITA. For the large population of OA detectable by LSST, the X-ray and optical follow up of the light curve (for the brightest cases) and/or the extensive follow up of their emission in the mm and radio band could be the key to disentangle their GRB nature from other extragalactic transients of comparable flux density.Comment: 9 pages, 4 figures, 2 tables. Accepted for publication by Astronomy and Astrophysic

Effective absorbing column density in the gamma-ray burst afterglow X-ray spectra

We investigate the scaling relation between the observed amount of absorption in the X-ray spectra of Gamma Ray Burst (GRB) afterglows and the absorber redshift. Through dedicated numerical simulations of an ideal instrument, we establish that this dependence has a power law shape with index 2.4. However, for real instruments, this value depends on their low energy cut-off, spectral resolution and on the detector spectral response in general. We thus provide appropriate scaling laws for specific instruments. Finally, we discuss the possibility to measure the absorber redshift from X-ray data alone. We find that 10^5-10^6 counts in the 0.3-10 keV band are needed to constrain the redshift with 10% accuracy. As a test case we discuss the XMM-Newton observation of GRB 090618 at z=0.54. We are able to recover the correct redshift of this burst with the expected accuracy.Comment: MNRAS accepted. 6 figures. 3 table

A complete sample of bright Swift short Gamma-Ray Bursts

We present a carefully selected sample of short gamma-ray bursts (SGRBs) observed by the Swift satellite up to June 2013. Inspired by the criteria we used to build a similar sample of bright long GRBs (the BAT6 sample), we selected SGRBs with favorable observing conditions for the redshift determination on ground, ending up with a sample of 36 events, almost half of which with a redshift measure. The redshift completeness increases up to about 70% (with an average redshift value of z = 0.85) by restricting to those events that are bright in the 15-150 keV Swift Burst Alert Telescope energy band. Such flux-limited sample minimizes any redshift-related selection effects, and can provide a robust base for the study of the energetics, redshift distribution and environment of the Swift bright population of SGRBs. For all the events of the sample we derived the prompt and afterglow emission in both the observer and (when possible) rest frame and tested the consistency with the correlations valid for long GRBs. The redshift and intrinsic X-ray absorbing column density distributions we obtain are consistent with the scenario of SGRBs originated by the coalescence of compact objects in primordial binaries, with a possible minor contribution (~10%-25%) of binaries formed by dynamical capture (or experiencing large natal kicks). This sample is expected to significantly increase with further years of Swift activity.Comment: 17 pages, 8 figures, 7 tables. Accepted for publication in MNRA