Binding - a proposed experiment and a model

The binding problem is regarded as one of today's key questions about brain function. Several solutions have been proposed, yet the issue is still controversial. The goal of this article is twofold. Firstly, we propose a new experimental paradigm requiring feature binding, the "delayed binding response task". Secondly, we propose a binding mechanism employing fast reversible synaptic plasticity to express the binding between concepts. We discuss the experimental predictions of our model for the delayed binding response task

Parameters of the Effective Singlet-Triplet Model for Band Structure of High-TcT_c Cuprates by Different Approaches

The present paper covers the problem of parameters determination for High-$T_c$ superconductive copper oxides. Different approaches, {\it ab initio} LDA and LDA+U calculations and Generalized Tight-Binding (GTB) method for strongly correlated electron systems, are used to calculate hopping and exchange parameters of the effective singlet-triplet model for $CuO_2$-layer. The resulting parameters are in remarkably good agreement with each other and with parameters extracted from experiment. This set of parameters is proposed for proper quantitative description of physics of hole doped High-$T_c$ cuprates in the framework of effective models.Comment: PACS 74.72.h; 74.20.z; 74.25.Jb; 31.15.A

Application of the extended P+QQ force model to N≈ZN \approx Z fp shell nuclei

To study collective motion, the extended pairing plus $QQ$ force model proposed recently is applied to $A$=46, 48 and 50 nuclei in the $fp$ shell region. Exact shell model calculations in the truncated model space $(f_{7/2},p_{3/2},p_{1/2})$ prove the usefulness of the interaction. The simple model with the pairing plus quadrupole pairing plus $QQ$ force and $J$-independent isoscalar proton-neutron force reproduces unexpectedly well observed binding energies, energy levels of collective (yrast) states and reduced $E2$ transition probabilities in $^{46}$Ti, $^{46}$V, $^{48}$V, $^{48}$Cr, $^{50}$Cr and $^{50}$Mn. The correspondence between theory and experiment is almost comparable to that attained by the full $fp$ shell model calculations with realistic effective interactions. Some predictions are made for energy levels and variations of $B(E2)$ in the yrast bands, in these nuclei. Characteristics of the interaction are investigated by comparing with the realistic effective interactions.Comment: 34 pages including 14 figure

Structural and electronic properties of the metal-metal intramolecular junctions of single-walled carbon nanotubes

Several intramolecular junctions (IMJs) connecting two metallic (11, 8) and (9, 6) carbon nanotubes along their common axis have been realized by using a layer-divided technique to the nanotubes and introducing the topological defects. Atomic structure of each IMJ configuration is optimized with a combination of density-functional theory (DFT) and the universal force field (UFF) method, based upon which a four-orbital tight-binding calculation is made on its electronic properties. Different topological defect structures and their distributions on the IMJ interfaces have been found, showing decisive effects on the localized density of states, while the sigma-pi coupling effect is negligible near Fermi energy (EF). Finally, a new IMJ model has been proposed, which probably reflects a real atomic structure of the M-M IMJ observed in the experiment [Science 291, 97 (2001)].Comment: 11 pages and 3 figure

Ceramic materials lead to underestimated DNA quantifications : a method for reliable measurements

In the context of investigating cell-material interactions or of material-guided generation of tissues, DNA quantification represents an elective method to precisely assess the number of cells attached or embedded within different substrates. Nonetheless, nucleic acids are known to electrostatically bind to ceramics, a class of materials commonly employed in orthopaedic implants and bone tissue engineering scaffolds. This phenomenon is expected to lead to a relevant underestimation of the DNA amount, resulting in erroneous experimental readouts. The present work aims at *lpar;i) investigating the effects of DNA-ceramic bond occurrence on DNA quantification, and (ii) developing a method to reliably extract and accurately quantify DNA in ceramic-containing specimens. A cell-free model was adopted to study DNA-ceramic binding, highlighting an evident DNA loss (up to 90%) over a wide range of DNA/ceramic ratios (w/w). A phosphate buffer-based (800 mM) enzymatic extraction protocol was developed and its efficacy in terms of reliable DNA extraction and measurement was confirmed with commonly used fluorometric assays, for various ceramic substrates. The proposed buffered DNA extraction technique was validated in a cell-based experiment showing 95% DNA retrieval in a cell seeding experiment, demonstrating a 3.5-fold increase in measured DNA amount as compared to a conventional enzymatic extraction protocol. In conclusion, the proposed phosphate buffer method consistently improves the DNA extraction process assuring unbiased analysis of samples and allowing accurate and sensitive cell number quantification on ceramic containing substrates

Nonequilibrium probe of paired electron pockets in the underdoped cuprates

We propose an experimental method that can be used generally to test whether the cuprate pseudogap involves precursor pairing that acts to gap out the Fermi surface. The proposal involves angular-resolved photoemission spectroscopy (ARPES) performed in the presence of a transport current driven through the sample. We illustrate this proposal with a specific model of the pseudogap that contains a phase-incoherent paired electron and unpaired hole Fermi surfaces. We show that even a weak current tilts the paired band and reveals parts of the previously gapped electron Fermi surface in ARPES if the binding energy is smaller but close to the pseudogap. Stronger currents can also reveal the Fermi surface through direct suppression of pairing. The proposed experiment is sufficiently general such that it can be used to reveal putative Fermi surfaces that have been reconstructed from other types of periodic order and are gapped out due to pairing. The observation of the predicted phenomena should help resolve the central question about the existence of pairs in the enigmatic pseudogap regime.Comment: 5 pages, 3 figures (published version

Mechanistic behaviour and molecular interactions of heat shock protein 47 (HSP47)

This project involves the study of heat shock protein 47 (HSP47), which is a molecular chaperone crucial for collagen biosynthesis. It exhibits a high degree of sequence homology with members of the serine protease inhibitor (serpin) superfamily, though HSP47 does not possess the inhibitory activity. It is a single-substrate chaperone, and binds only to collagen. ‘Knock-out’ of the hsp47 gene impairs the secretion of correctly folded collagen triple helix molecules leading to embryonic lethality in mice. Thus the aim of this project was to elucidate the specific mechanism that governs the binding to and release from collagen at the molecular level, known as the ‘pH-switch mechanism’. Emphasis is given on histidine (His) residues as the HSP47-collagen dissociation pH is similar to the pKa of the imidazole side chain of His residues. Site directed mutagenesis was used to mutate surface His residues, based on a mouse HSP47 homology model. The effects of the mutations on the behaviour of HSP47 were then assessed by collagen binding assays and structural analyses with circular dichroism (CD). All mutants were found to have good solubility and retain their binding ability to collagen like wild-type HSP47 in batch assay, but perturbed behaviour was seen in column experiment. Mutation of His residue at position 191 (H191) causes the shift in the collagen dissociation pH, while mutation of H197 and/or 198 disrupt the specific HSP47-collagen interaction. H191, 197 and 198 are predicted to be located in the region near the C-terminus of strand 3 of β-sheet A (s3A) in the homology model, a region specifically known as the ‘breach cluster’ in serpin nomenclature. The extent of conformational rearrangement of this region was further investigated by means of intrinsic tryptophan fluorescence spectroscopy using a series of single tryptophan (Trp) mutants. Results from analyses performed on the mutants did not contradict the observation seen in His mutational work, as Trp residues in the ‘breach’ cluster are likely to be located in the dynamic region of HSP47 pH-triggered conformational change. In conclusion, this study establishes the importance of His residues in the ‘breach cluster’ to HSP47 pH-switch behaviour. Finally, a model for HSP47 pH-switch mechanism was proposed from data obtained via mutagenesis experiments. The model is hoped to assist future research into HSP47 cellular behaviour and will also be of great use in therapeutic applications involving the molecular chaperone

Toward a further understanding of object feature binding: a cognitive neuroscience perspective.

The aim of this thesis is to lead to a further understanding of the neural mechanisms underlying object feature binding in the human brain. The focus is on information processing and integration in the visual system and visual shortterm memory. From a review of the literature it is clear that there are three major competing binding theories, however, none of these individually solves the binding problem satisfactorily. Thus the aim of this research is to conduct behavioural experimentation into object feature binding, paying particular attention to visual short-term memory. The behavioural experiment was designed and conducted using a within-subjects delayed responset ask comprising a battery of sixty-four composite objects each with three features and four dimensions in each of three conditions (spatial, temporal and spatio-temporal).Findings from the experiment,which focus on spatial and temporal aspects of object feature binding and feature proximity on binding errors, support the spatial theories on object feature binding, in addition we propose that temporal theories and convergence, through hierarchical feature analysis, are also involved. Because spatial properties have a dedicated processing neural stream, and temporal properties rely on limited capacity memory systems, memories for sequential information would likely be more difficult to accuratelyr ecall. Our study supports other studies which suggest that both spatial and temporal coherence to differing degrees,may be involved in object feature binding. Traditionally, these theories have purported to provide individual solutions, but this thesis proposes a novel unified theory of object feature binding in which hierarchical feature analysis, spatial attention and temporal synchrony each plays a role. It is further proposed that binding takes place in visual short-term memory through concerted and integrated information processing in distributed cortical areas. A cognitive model detailing this integrated proposal is given. Next, the cognitive model is used to inform the design and suggested implementation of a computational model which would be able to test the theory put forward in this thesis. In order to verify the model, future work is needed to implement the computational model.Thus it is argued that this doctoral thesis provides valuable experimental evidence concerning spatio-temporal aspects of the binding problem and as such is an additional building block in the quest for a solution to the object feature binding problem