316 research outputs found
Концепції мовної гри як теоретичні засади організації навчально-ігрової діяльності
У статті розглянуто лінгвофілософські й лінгвістичні концепції мовної гри як підґрунтя організації навчально-ігрової діяльності в системі українськомовної освіти. На основі наукового осмислення окреслено зміст понять "гра", "навчально-ігрова діяльність", "мовна гра". Шляхом аналізу наукової літератури й синтезу теоретичних ідей визначено принципи побудови й реалізації навчально-методичної системи, спрямованої на формування мовної особистості школяра в навчально-ігровій діяльності
Systematic coarse-graining of the dynamics of entangled polymer melts: the road from chemistry to rheology
For optimal processing and design of entangled polymeric materials it is
important to establish a rigorous link between the detailed molecular
composition of the polymer and the viscoelastic properties of the macroscopic
melt. We review current and past computer simulation techniques and critically
assess their ability to provide such a link between chemistry and rheology. We
distinguish between two classes of coarse-graining levels, which we term
coarse-grained molecular dynamics (CGMD) and coarse-grained stochastic dynamics
(CGSD). In CGMD the coarse-grained beads are still relatively hard, thus
automatically preventing bond crossing. This also implies an upper limit on the
number of atoms that can be lumped together and therefore on the longest chain
lengths that can be studied. To reach a higher degree of coarse-graining, in
CGSD many more atoms are lumped together, leading to relatively soft beads. In
that case friction and stochastic forces dominate the interactions, and actions
must be undertaken to prevent bond crossing. We also review alternative methods
that make use of the tube model of polymer dynamics, by obtaining the
entanglement characteristics through a primitive path analysis and by
simulation of a primitive chain network. We finally review super-coarse-grained
methods in which an entire polymer is represented by a single particle, and
comment on ways to include memory effects and transient forces.Comment: Topical review, 31 pages, 10 figure
From Network Structure to Dynamics and Back Again: Relating dynamical stability and connection topology in biological complex systems
The recent discovery of universal principles underlying many complex networks
occurring across a wide range of length scales in the biological world has
spurred physicists in trying to understand such features using techniques from
statistical physics and non-linear dynamics. In this paper, we look at a few
examples of biological networks to see how similar questions can come up in
very different contexts. We review some of our recent work that looks at how
network structure (e.g., its connection topology) can dictate the nature of its
dynamics, and conversely, how dynamical considerations constrain the network
structure. We also see how networks occurring in nature can evolve to modular
configurations as a result of simultaneously trying to satisfy multiple
structural and dynamical constraints. The resulting optimal networks possess
hubs and have heterogeneous degree distribution similar to those seen in
biological systems.Comment: 15 pages, 6 figures, to appear in Proceedings of "Dynamics On and Of
Complex Networks", ECSS'07 Satellite Workshop, Dresden, Oct 1-5, 200
Statistical Properties of Contact Maps
A contact map is a simple representation of the structure of proteins and
other chain-like macromolecules. This representation is quite amenable to
numerical studies of folding. We show that the number of contact maps
corresponding to the possible configurations of a polypeptide chain of N amino
acids, represented by (N-1)-step self avoiding walks on a lattice, grows
exponentially with N for all dimensions D>1. We carry out exact enumerations in
D=2 on the square and triangular lattices for walks of up to 20 steps and
investigate various statistical properties of contact maps corresponding to
such walks. We also study the exact statistics of contact maps generated by
walks on a ladder.Comment: Latex file, 15 pages, 12 eps figures. To appear on Phys. Rev.
A novel form of recessive limb girdle muscular dystrophy with mental retardation and abnormal expression of alpha-dystroglycan
Cataloged from PDF version of article.The limb girdle muscular dystrophies are a heterogeneous group of conditions characterized by proximal muscle weakness and disease onset ranging from infancy to adulthood. We report here eight patients from seven unrelated families affected by a novel and relatively mild form of autosomal recessive limb girdle muscular dystrophy (LGMD2) with onset in the first decade of life and characterized by severe mental retardation but normal brain imaging. Immunocytochemical studies revealed a significant selective reduction of α-dystroglycan expression in the muscle biopsies. Linkage analysis excluded known loci for both limb girdle muscular dystrophy and congenital muscular dystrophies in the consanguineous families. We consider that this represents a novel form of muscular dystrophy with associated brain involvement. The biochemical studies suggest that it may belong to the growing number of muscular dystrophies with abnormal expression of α-dystroglycan. © 2003 Published by Elsevier B.V
Universal behavior of localization of residue fluctuations in globular proteins
Localization properties of residue fluctuations in globular proteins are
studied theoretically by using the Gaussian network model. Participation ratio
for each residue fluctuation mode is calculated. It is found that the
relationship between participation ratio and frequency is similar for all
globular proteins, indicating a universal behavior in spite of their different
size, shape, and architecture.Comment: 4 pages, 3 figures. To appear in Phys. Rev.
Bi-allelic mutations in MYL1 cause a severe congenital myopathy.
OBJECTIVE: Congenital myopathies are typically characterised by early onset hypotonia, weakness and hallmark features on biopsy. Despite the rapid pace of gene discovery, approximately 50% of patients with a congenital myopathy remain without a genetic diagnosis following screening of known disease genes. METHODS: We performed exome sequencing on two consanguineous probands diagnosed with a congenital myopathy and muscle biopsy showing selective atrophy/hypotrophy or absence of type II myofibres. RESULTS: We identified variants in the gene (MYL1) encoding the skeletal muscle fast-twitch specific myosin essential light chain in both probands. A homozygous essential splice acceptor variant (c.479-2A>G, predicted to result in skipping of exon 5 was identified in Proband 1, and a homozygous missense substitution (c.488T>G, p.(Met163Arg)) was identified in Proband 2. Protein modeling of the p.(Met163Arg) substitution predicted it might impede intermolecular interactions that facilitate binding to the IQ domain of myosin heavy chain, thus likely impacting on the structure and functioning of the myosin motor. MYL1 was markedly reduced in skeletal muscle from both probands, suggesting that the missense substitution likely results in an unstable protein. Knock down of myl1 in zebrafish resulted in abnormal morphology, disrupted muscle structure and impaired touch-evoked escape responses, thus confirming that skeletal muscle fast-twitch specific myosin essential light chain is critical for myofibre development and function. INTERPRETATION: Our data implicate MYL1 as a crucial protein for adequate skeletal muscle function and that MYL1 deficiency is associated with a severe congenital myopathy
Exploring the Conformational Transitions of Biomolecular Systems Using a Simple Two-State Anisotropic Network Model
Biomolecular conformational transitions are essential to biological functions. Most experimental methods report on the long-lived functional states of biomolecules, but information about the transition pathways between these stable states is generally scarce. Such transitions involve short-lived conformational states that are difficult to detect experimentally. For this reason, computational methods are needed to produce plausible hypothetical transition pathways that can then be probed experimentally. Here we propose a simple and computationally efficient method, called ANMPathway, for constructing a physically reasonable pathway between two endpoints of a conformational transition. We adopt a coarse-grained representation of the protein and construct a two-state potential by combining two elastic network models (ENMs) representative of the experimental structures resolved for the endpoints. The two-state potential has a cusp hypersurface in the configuration space where the energies from both the ENMs are equal. We first search for the minimum energy structure on the cusp hypersurface and then treat it as the transition state. The continuous pathway is subsequently constructed by following the steepest descent energy minimization trajectories starting from the transition state on each side of the cusp hypersurface. Application to several systems of broad biological interest such as adenylate kinase, ATP-driven calcium pump SERCA, leucine transporter and glutamate transporter shows that ANMPathway yields results in good agreement with those from other similar methods and with data obtained from all-atom molecular dynamics simulations, in support of the utility of this simple and efficient approach. Notably the method provides experimentally testable predictions, including the formation of non-native contacts during the transition which we were able to detect in two of the systems we studied. An open-access web server has been created to deliver ANMPathway results. © 2014 Das et al
Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine
[This corrects the article DOI: 10.1186/s13054-016-1208-6.]
Predicting Important Residues and Interaction Pathways in Proteins Using Gaussian Network Model: Binding and Stability of HLA Proteins
A 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
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