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Inverted Berezinskii-Kosterlitz-Thouless singularity and high-temperature algebraic order in an Ising model on a scale-free hierarchical-lattice small-world network
No full textWe have obtained exact results for the Ising model on a hierarchical lattice incorporating three key features characterizing many real-world networks-a scale-free degree distribution, a high clustering coefficient, and the small-world effect. By varying the probability p of long-range bonds, the entire spectrum from an unclustered, non-small-world network to a highly clustered, small-world system is studied. Using the self-similar structure of the network, we obtain analytic expressions for the degree distribution P(k) and clustering coefficient C for all p, as well as the average path length center dot for p=0 and 1. The ferromagnetic Ising model on this network is studied through an exact renormalization-group transformation of the quenched bond probability distribution, using up to 562 500 renormalized probability bins to represent the distribution. For p < 0.494, we find power-law critical behavior of the magnetization and susceptibility, with critical exponents continuously varying with p, and exponential decay of correlations away from T-c. For p >= 0.494, in fact where the network exhibits small-world character, the critical behavior radically changes: We find a highly unusual phase transition, namely an inverted Berezinskii-Kosterlitz-Thouless singularity, between a low-temperature phase with nonzero magnetization and finite correlation length and a high-temperature phase with zero magnetization and infinite correlation length, with power-law decay of correlations throughout the phase. Approaching T-c from below, the magnetization and the susceptibility, respectively, exhibit the singularities of exp(-C/root T-c-T) and exp(D/root T-c-T), with C and D positive constants. With long-range bond strengths decaying with distance, we see a phase transition with power-law critical singularities for all p, and evaluate an unusually narrow critical region and important corrections to power-law behavior that depend on the exponent characterizing the decay of long-range interactions
Predicting important residues and ınteraction pathways in proteins using Gaussian network model: binding and stability of HLA proteins
No full textA statistical thermodynamics approach is proposed to determine structurally and functionally important residues in native proteins that are involved in energy exchange with a ligand and other residues along an interaction pathway. The structure-function relationships, ligand binding and allosteric activities of ten structures of HLA Class I proteins of the immune system are studied by the Gaussian Network Model. Five of these models are associated with inflammatory rheumatic disease and the remaining five are properly functioning. In the Gaussian Network Model, the protein structures are modeled as an elastic network where the inter-residue interactions are harmonic. Important residues and the interaction pathways in the proteins are identified by focusing on the largest eigenvalue of the residue interaction matrix. Predicted important residues match those known from previous experimental and clinical work. Graph perturbation is used to determine the response of the important residues along the interaction pathway. Differences in response patterns of the two sets of proteins are identified and their relations to disease are discussed
A comparative molecular dynamics study of methylation state specificity of JMJD2A
No full textHistone modifications have great importance in epigenetic regulation. JMJD2A is a histone demethylase which is selective for di- and trimethyl forms of residues Lys9 and Lys36 of Histone 3 tail (H3K9 and H3K36). We present a molecular dynamics simulations of mono-, di- and trimethylated histone tails in complex with JMJD2A catalytic domain to gain insight into how JMJD2A discriminates between the methylation states of H3K9. The methyl groups are located at specific distances and orientations with respect to Fe(II) in methylammonium binding pocket. For the trimethyllysine the mechanism which provides the effectual orientation of methyl groups is the symmetry, whereas for the dimethyllysine case the determining factors are the interactions between methyllysine head and its environment and subsequently the restriction on angular motion. The occurrence frequency of methyl groups in a certain proximity of Fe(II) comes out as the explanation of the enzyme activity difference on di-and tri-methylated peptides. Energy analysis suggests that recognition is mostly driven by van der Waals and followed by Coulombic interactions in the enzyme-substrate interface. The number (mono, di or tri) and orientations of methyl groups and water molecules significantly affect the extent of van der Waals interaction strengths. Hydrogen bonding analysis suggests that the interaction between JMJD2A and its substrates mainly comes from main chain-side chain interactions. Binding free energy analysis points out Arg8 as an important residue forming an intra-substrate hydrogen bond with tri and dimethylated Lys9 of the H3 chain. Our study provides new insights into how JMJD2A discriminates between its substrates from both a structural and dynamical point of view
Statistical modeling of single target cell encapsulation
No full textHigh throughput drop-on-demand systems for separation and encapsulation of individual target cells from heterogeneous mixtures of multiple cell types is an emerging method in biotechnology that has broad applications in tissue engineering and regenerative medicine, genomics, and cryobiology. However, cell encapsulation in droplets is a random process that is hard to control. Statistical models can provide an understanding of the underlying processes and estimation of the relevant parameters, and enable reliable and repeatable control over the encapsulation of cells in droplets during the isolation process with high confidence level. We have modeled and experimentally verified a microdroplet-based cell encapsulation process for various combinations of cell loading and target cell concentrations. Here, we explain theoretically and validate experimentally a model to isolate and pattern single target cells from heterogeneous mixtures without using complex peripheral systems
VitAL: viterbi algorithm for de novo peptide design
No full textBackground: Drug design against proteins to cure various diseases has been studied for several years. Numerous design techniques were discovered for small organic molecules for specific protein targets. The specificity, toxicity and selectivity of small molecules are hard problems to solve. The use of peptide drugs enables a partial solution to the toxicity problem. There has been a wide interest in peptide design, but the design techniques of a specific and selective peptide inhibitor against a protein target have not yet been established. Methodology/Principal Findings: A novel de novo peptide design approach is developed to block activities of disease related protein targets. No prior training, based on known peptides, is necessary. The method sequentially generates the peptide by docking its residues pair by pair along a chosen path on a protein. The binding site on the protein is determined via the coarse grained Gaussian Network Model. A binding path is determined. The best fitting peptide is constructed by generating all possible peptide pairs at each point along the path and determining the binding energies between these pairs and the specific location on the protein using AutoDock. The Markov based partition function for all possible choices of the peptides along the path is generated by a matrix multiplication scheme. The best fitting peptide for the given surface is obtained by a Hidden Markov model using Viterbi decoding. The suitability of the conformations of the peptides that result upon binding on the surface are included in the algorithm by considering the intrinsic Ramachandran potentials. Conclusions/Significance: The model is tested on known protein-peptide inhibitor complexes. The present algorithm predicts peptides that have better binding energies than those of the existing ones. Finally, a heptapeptide is designed for a protein that has excellent binding affinity according to AutoDock results
Impact of reaction variables and PEI/L-cysteine ratio on the optical properties and cytocompatibility of cationic Ag2S quantum dots as NIR bio-imaging probes
No full textNear-infrared emitting semiconductor quantum dots (NIRQDs) are popular fluorescent probes due to better penetration depth and elimination of tissue autofluorescence. Here, we demonstrate one pot aqueous synthesis of cytocompatible, strongly luminescent, cationic Ag2S NIRQDs utilizing a mixed coating composed of branched polyethyleneimine (PEI)-25 kDa and L-cysteine (Cys) as in vitro luminescent tags and in vivo optical imaging agents. Ultrasmall sizes, a clear first excitonic peak in the absorption spectra, relatively narrow emission peaks with maxima between 730 and 775 nm and a Stokes shift less than 100 nm were obtained. Lifetime measurements indicate excitonic and defect-related emissions. Interestingly, not the emission maxima but the intensity was influenced by the Cys amount more dramatically. PEI/Cys 60/40 mol ratio provided the highest quantum yield reported until now for Ag2S NIRQD (157%) emitting at such a short wavelength. Low molecular weight PEI failed to produce luminescent QDs. Cytotoxicity evaluation of the most strongly luminescing NIRQDs, revealed the PEI/Cys (mol mol(-1)) 50/50 composition as the non-toxic composition below 2.4 mu g Ag per mL concentration. Others had low-toxicity. In vitro microscopy experiments showed endosomal distribution of NIRQDs in Hela cells and strong NIR signal. In vivo imaging study demonstrated that Ag2S NIRQDs could effectively be used as strong optical imaging agents
Intrinsic K-Ras dynamics: a novel molecular dynamics data analysis method shows causality between residue pair motions
No full textK-Ras is the most frequently mutated oncogene in human cancers, but there are still no drugs that directly target it in the clinic. Recent studies utilizing dynamics information show promising results for selectively targeting mutant K-Ras. However, despite extensive characterization, the mechanisms by which K-Ras residue fluctuations transfer allosteric regulatory information remain unknown. Understanding the direction of information flow can provide new mechanistic insights for K-Ras targeting. Here, we present a novel approach - conditional time-delayed correlations (CTC) - using the motions of all residue pairs of a protein to predict directionality in the allosteric regulation of the protein fluctuations. Analyzing nucleotide-dependent intrinsic K-Ras motions with the new approach yields predictions that agree with the literature, showing that GTP-binding stabilizes K-Ras motions and leads to residue correlations with relatively long characteristic decay times. Furthermore, our study is the first to identify driver-follower relationships in correlated motions of K-Ras residue pairs, revealing the direction of information flow during allosteric modulation of its nucleotide-dependent intrinsic activity: active K-Ras Switch-II region motions drive Switch-I region motions, while alpha-helix-3L7 motions control both. Our results provide novel insights for strategies that directly target mutant K-Ras
Resonant cavity enhanced silicon photodetector integrated to a fiber optic coupler
No full textMorphology dependent resonances of dielectric microspheres are used for polarization insensitive optical channel dropping from an optical fiber half coupler to a silicon photodetector in the M-band. The dropped channels are observed in the elastic scattering and the transmission spectra. The highest quality factor morphology dependent resonances have a repetitive channel separation of 0.14 nm and a linewidth of 0.06 nm. The filter drops approximately 10% (0.5 dB) of the power at the resonance wavelength. The power detected by the photodiode is estimated to be approximately 3.5% of the power in the fiber
Gender, competitiveness, and socialization at a young age: evidence from a matrilineal and a patriarchal society
No full textRecent literature presents evidence that men are more competitively inclined than women. Since top-level careers usually require competitiveness, competitiveness differences provide an explanation for gender gaps in wages and differences in occupational choice. A natural question is whether women are born less competitive or whether they become so through the process of socialization. To pinpoint when in the socialization process the difference arises, we compare the competitiveness of children in matrilineal and patriarchal societies. We find that while there is no difference at any age in the matrilineal society, girls become less competitive around puberty in the patriarchal society
Failures of the discourse of ethnicity: Turkey, Kurds, and the emerging Iraq
No full textThis article analyzes the discursive-ideational barriers restricting regional cooperation by examining Turkey's relations with Iraqi Kurds from a critical, theoretical perspective in the context of Turkey's domestic reforms and its relations with the USA and the EU. It is argued that the ethnicity discourse undermines cooperation, insofar as it feeds the perception of rival groups with zero-sum interests. Presenting a simple model, the article argues that replacing the ethnicity discourse with alternative, post-ethnic discourses requires combining alternative discourses with policies that produce positive-sum interests, coordination between groups, and opportunities for joint collective actions. Hence, state capacity to formulate and implement such policies is crucial. Predictions and policy implications are generated accordingly. First, further reconciliation of Turkey's domestic Kurdish conflict through democratic and administrative reforms, EU integration, and the promotion of national-identity models that are more flexible and more reflective of diversity will facilitate cooperation with Iraqi Kurds. Second, prosperity and democratic stability in Iraq will help achieve a lasting resolution in Turkey. Third, regional cooperation requires that domestic and external actors promote the positive-sum perception of Turkish and Kurdish interests. Fourth, research can help by developing linguistic-analytical categories that transcend the narrow discourse of ethnicity in favor of discourses that reflect multiple and compatible group belongings