搜索结果：loop

Comparative protein structure prediction is limited mostly by the errors in alignment and loop modeling. We describe here a new automated modeling technique that significantly improves the accuracy of loop predictions in protein structures. The positions of all nonhydrogen atoms of the loop are optimized in a fixed environment with respect to a pseudo energy function. The energy is a sum of many spatial restraints that include the bond length, bond angle, and improper dihedral angle terms from the CHARMM-22 force field, statistical preferences for the main-chain and side-chain dihedral angles, and statistical preferences for nonbonded atomic contacts that depend on the two atom types, their distance through space, and separation in sequence. The energy function is optimized with the method of conjugate gradients combined with molecular dynamics and simulated annealing. Typically, the predicted loop conformation corresponds to the lowest energy conformation among 500 independent optimizations. Predictions were made for 40 loops of known structure at each length from 1 to 14 residues. The accuracy of loop predictions is evaluated as a function of thoroughness of conformational sampling, loop length, and structural properties of native loops. When accuracy is measured by local superposition of the model on the native loop, 100, 90, and 30% of 4-, 8-, and 12-residue loop predictions, respectively, had <2 A RMSD error for the mainchain N, C(alpha), C, and O atoms; the average accuracies were 0.59 +/- 0.05, 1.16 +/- 0.10, and 2.61 +/- 0.16 A, respectively. To simulate real comparative modeling problems, the method was also evaluated by predicting loops of known structure in only approximately correct environments with errors typical of comparative modeling without misalignment. When the RMSD distortion of the main-chain stem atoms is 2.5 A, the average loop prediction error increased by 180, 25, and 3% for 4-, 8-, and 12-residue loops, respectively. The accuracy of the lowest energy prediction for a given loop can be estimated from the structural variability among a number of low energy predictions. The relative value of the present method is gauged by (1) comparing it with one of the most successful previously described methods, and (2) describing its accuracy in recent blind predictions of protein structure. Finally, it is shown that the average accuracy of prediction is limited primarily by the accuracy of the energy function rather than by the extent of conformational sampling.

Due to the nature of domains, ferroics, including ferromagnetic, ferroelectric, and ferroelastic materials, exhibit hysteresis phenomena with respect to external driving fields (magnetic field, electric field, or stress). In principle, every ferroic material has its own hysteresis loop, like a fingerprint, which contains information related to its properties and structures. For ferroelectrics, many characteristic parameters, such as coercive field, spontaneous, and remnant polarizations can be directly extracted from the hysteresis loops. Furthermore, many impact factors, including the effect of materials (grain size and grain boundary, phase and phase boundary, doping, anisotropy, thickness), aging (with and without poling), and measurement conditions (applied field amplitude, fatigue, frequency, temperature, stress), can affect the hysteretic behaviors of the ferroelectrics. In this feature article, we will first give the background of the ferroic materials and multiferroics, with an emphasis on ferroelectrics. Then it is followed by an introduction of the characterizing techniques for the loops, including the polarization–electric field loops and strain–electric field curves. A caution is made to avoid misinterpretation of the loops due to the existence of conductivity. Based on their morphologic features, the hysteresis loops are categorized to four groups and the corresponding material usages are introduced. The impact factors on the hysteresis loops are discussed based on recent developments in ferroelectric and related materials. It is suggested that decoding the fingerprint of loops in ferroelectrics is feasible and the comprehension of the material properties and structures through the hysteresis loops is established.

Eukaryotic genomes are folded into loops and topologically associating domains, which contribute to chromatin structure, gene regulation, and gene recombination. These structures depend on cohesin, a ring-shaped DNA-entrapping adenosine triphosphatase (ATPase) complex that has been proposed to form loops by extrusion. Such an activity has been observed for condensin, which forms loops in mitosis, but not for cohesin. Using biochemical reconstitution, we found that single human cohesin complexes form DNA loops symmetrically at rates up to 2.1 kilo-base pairs per second. Loop formation and maintenance depend on cohesin's ATPase activity and on NIPBL-MAU2, but not on topological entrapment of DNA by cohesin. During loop formation, cohesin and NIPBL-MAU2 reside at the base of loops, which indicates that they generate loops by extrusion. Our results show that cohesin and NIPBL-MAU2 form an active holoenzyme that interacts with DNA either pseudo-topologically or non-topologically to extrude genomic interphase DNA into loops.

Topologically associating domains (TADs) are fundamental structural and functional building blocks of human interphase chromosomes, yet the mechanisms of TAD formation remain unclear. Here, we propose that loop extrusion underlies TAD formation. In this process, cis-acting loop-extruding factors, likely cohesins, form progressively larger loops but stall at TAD boundaries due to interactions with boundary proteins, including CTCF. Using polymer simulations, we show that this model produces TADs and finer-scale features of Hi-C data. Each TAD emerges from multiple loops dynamically formed through extrusion, contrary to typical illustrations of single static loops. Loop extrusion both explains diverse experimental observations-including the preferential orientation of CTCF motifs, enrichments of architectural proteins at TAD boundaries, and boundary deletion experiments-and makes specific predictions for the depletion of CTCF versus cohesin. Finally, loop extrusion has potentially far-ranging consequences for processes such as enhancer-promoter interactions, orientation-specific chromosomal looping, and compaction of mitotic chromosomes.

We have developed a novel method, termed loop-mediated isothermal amplification (LAMP), that amplifies DNA with high specificity, efficiency and rapidity under isothermal conditions. This method employs a DNA polymerase and a set of four specially designed primers that recognize a total of six distinct sequences on the target DNA. An inner primer containing sequences of the sense and antisense strands of the target DNA initiates LAMP. The following strand displacement DNA synthesis primed by an outer primer releases a single-stranded DNA. This serves as template for DNA synthesis primed by the second inner and outer primers that hybridize to the other end of the target, which produces a stem-loop DNA structure. In subsequent LAMP cycling one inner primer hybridizes to the loop on the product and initiates displacement DNA synthesis, yielding the original stem-loop DNA and a new stem-loop DNA with a stem twice as long. The cycling reaction continues with accumulation of 10(9) copies of target in less than an hour. The final products are stem-loop DNAs with several inverted repeats of the target and cauliflower-like structures with multiple loops formed by annealing between alternately inverted repeats of the target in the same strand. Because LAMP recognizes the target by six distinct sequences initially and by four distinct sequences afterwards, it is expected to amplify the target sequence with high selectivity.

We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes. Here, we combine these maps with new Hi-C, microscopy, and genome-editing experiments to study the physical structure of chromatin fibers, domains, and loops. We find that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer. Combining Hi-C data and novel mathematical theorems, we show that contact domains are also not consistent with a fractal globule. Instead, we use physical simulations to study two models of genome folding. In one, intermonomer attraction during polymer condensation leads to formation of an anisotropic "tension globule." In the other, CCCTC-binding factor (CTCF) and cohesin act together to extrude unknotted loops during interphase. Both models are consistent with the observed contact domains and with the observation that contact domains tend to form inside loops. However, the extrusion model explains a far wider array of observations, such as why loops tend not to overlap and why the CTCF-binding motifs at pairs of loop anchors lie in the convergent orientation. Finally, we perform 13 genome-editing experiments examining the effect of altering CTCF-binding sites on chromatin folding. The convergent rule correctly predicts the affected loops in every case. Moreover, the extrusion model accurately predicts in silico the 3D maps resulting from each experiment using only the location of CTCF-binding sites in the WT. Thus, we show that it is possible to disrupt, restore, and move loops and domains using targeted mutations as small as a single base pair.

We introduce a new technique to generate scattering amplitudes at one loop. Traditional tree algorithms, which handle diagrams with fixed momenta, are promoted to generators of loop-momentum polynomials that we call open loops. Combining open loops with tensor-integral and Ossola-Papadopoulos-Pittau reduction results in a fully flexible, very fast, and numerically stable one-loop generator. As demonstrated with nontrivial applications, the open-loop approach will permit us to obtain precise predictions for a very wide range of collider processes.

A novel microRNA (miRNA) quantification method has been developed using stem-loop RT followed by TaqMan PCR analysis. Stem-loop RT primers are better than conventional ones in terms of RT efficiency and specificity. TaqMan miRNA assays are specific for mature miRNAs and discriminate among related miRNAs that differ by as little as one nucleotide. Furthermore, they are not affected by genomic DNA contamination. Precise quantification is achieved routinely with as little as 25 pg of total RNA for most miRNAs. In fact, the high sensitivity, specificity and precision of this method allows for direct analysis of a single cell without nucleic acid purification. Like standard TaqMan gene expression assays, TaqMan miRNA assays exhibit a dynamic range of seven orders of magnitude. Quantification of five miRNAs in seven mouse tissues showed variation from less than 10 to more than 30,000 copies per cell. This method enables fast, accurate and sensitive miRNA expression profiling and can identify and monitor potential biomarkers specific to tissues or diseases. Stem-loop RT-PCR can be used for the quantification of other small RNA molecules such as short interfering RNAs (siRNAs). Furthermore, the concept of stem-loop RT primer design could be applied in small RNA cloning and multiplex assays for better specificity and efficiency.

This study aims to understand through statistical learning the basic biophysical mechanisms behind three-dimensional folding of epigenomes. The 3DEpiLoop algorithm predicts three-dimensional chromatin looping interactions within topologically associating domains (TADs) from one-dimensional epigenomics and transcription factor profiles using the statistical learning. The predictions obtained by 3DEpiLoop are highly consistent with the reported experimental interactions. The complex signatures of epigenomic and transcription factors within the physically interacting chromatin regions (anchors) are similar across all genomic scales: genomic domains, chromosomal territories, cell types, and different individuals. We report the most important epigenetic and transcription factor features used for interaction identification either shared, or unique for each of sixteen (16) cell lines. The analysis shows that CTCF interaction anchors are enriched by transcription factors yet deficient in histone modifications, while the opposite is true in the case of RNAP II mediated interactions. The code is available at the repository https://bitbucket.org/4dnucleome/3depiloop .

A relatively simple model of the phonological loop (A. D. Baddeley, 1986), a component of working memory, has proved capable of accommodating a great deal of experimental evidence from normal adult participants, children, and neuropsychological patients. Until recently, however, the role of this subsystem in everyday cognitive activities was unclear. In this article the authors review studies of word learning by normal adults and children, neuropsychological patients, and special developmental populations, which provide evidence that the phonological loop plays a crucial role in learning the novel phonological forms of new words. The authors propose that the primary purpose for which the phonological loop evolved is to store unfamiliar sound patterns while more permanent memory records are being constructed. Its use in retaining sequences of familiar words is, it is argued, secondary.

We show that, in the mouse, the core mechanism for the master circadian clock consists of interacting positive and negative transcription and translation feedback loops. Analysis of Clock/Clock mutant mice, homozygous Period2(Brdm1) mutants, and Cryptochrome-deficient mice reveals substantially altered Bmal1 rhythms, consistent with a dominant role of PERIOD2 in the positive regulation of the Bmal1 loop. In vitro analysis of CRYPTOCHROME inhibition of CLOCK: BMAL1-mediated transcription shows that the inhibition is through direct protein:protein interactions, independent of the PERIOD and TIMELESS proteins. PERIOD2 is a positive regulator of the Bmal1 loop, and CRYPTOCHROMES are the negative regulators of the Period and Cryptochrome cycles.

Portable laser range-finders, further referred to as LIDAR, and simultaneous localization and mapping (SLAM) are an efficient method of acquiring as-built floor plans. Generating and visualizing floor plans in real-time helps the operator assess the quality and coverage of capture data. Building a portable capture platform necessitates operating under limited computational resources. We present the approach used in our backpack mapping platform which achieves real-time mapping and loop closure at a 5 cm resolution. To achieve realtime loop closure, we use a branch-and-bound approach for computing scan-to-submap matches as constraints. We provide experimental results and comparisons to other well known approaches which show that, in terms of quality, our approach is competitive with established techniques.

Based on environmental, legal, social, and economic factors, reverse logistics and closed-loop supply chain issues have attracted attention among both academia and practitioners. This attention is evident by the vast number of publications in scientific journals which have been published in recent years. Hence, a comprehensive literature review of recent and state-of-the-art papers is vital to draw a framework of the past, and to shed light on future directions. The aim of this paper is to review recently published papers in reverse logistic and closed-loop supply chain in scientific journals. A total of 382 papers published between January 2007 and March 2013 are selected and reviewed. The papers are then analyzed and categorized to construct a useful foundation of past research. Finally, gaps in the literature are identified to clarify and to suggest future research opportunities.

Magnetic field and plasma data from five spacecraft (Voyager 1 and 2, Helios 1 and 2, and IMP 8) were used to analyze the flow behind an interplanetary shock. The shock was followed by a turbulent sheath in which there were large fluctuations in both the strength and the direction of the magnetic field. This in turn was followed by a region (magnetic cloud) in which the magnetic field vectors were observed to change by rotating nearly parallel to a plane, consistent with the passage of a magnetic loop. This loop extended at least 30° in longitude between 1 and 2 AU, and its radial dimension was approximately 0.5 AU. In the cloud the field strength was high, and the density and temperature were relatively low. Thus the dominant pressure in the cloud was that of the magnetic field. The total pressure inside the cloud was higher than outside, implying that the cloud was expanding as it moved outward, even at the distance of 2 AU. The momentum flux of the cloud at 2 AU was not higher than that of the preshock plasma, indicating that the cloud was not driving the shock at this distance. It is possible, however, that the shock was driven by the cloud closer to the sun where the cloud may have moved faster. An extraordinary filament was observed at the rear of the cloud. It was bounded by current sheets whose orientations were preserved over at least 0.12 AU and which were related to the plane of maximum variance of the magnetic field in the cloud.

The out-of-the-loop performance problem, a major potential consequence of automation, leaves operators of automated systems handicapped in their ability to take over manual operations in the event of automation failure. This is attributed to a possible loss of skills and of situation awareness (SA) arising from vigilance and complacency problems, a shift from active to passive information processing, and change in feedback provided to the operator. We studied the automation of a navigation task using an expert system and demonstrated that low SA corresponded with out-of-the-loop performance decrements in decision time following a failure of the expert system. Level of operator control in interacting with automation is a major factor in moderating this loss of SA. Results indicated that the shift from active to passive processing was most likely responsible for decreased SA under automated conditions.

The classification of adsorption hysteresis loops recommended by the IUPAC in 1984 was based on experimental observations and the application of classical principles of pore filling (notably the use of the Kelvin equation for mesopore analysis). Recent molecular simulation and density functional (DFT) studies of the physisorption of gases by model pore structures have greatly improved our understanding of the mechanisms of hysteresis and it is therefore timely to revisit the IUPAC recommendations. In this review, we conclude that there is no immediate need to change the IUPAC classification of physisorption isotherms and hysteresis loops. However, in the light of recent advances, we are able to offer a revised checklist for the analysis of nitrogen isotherms on nanoporous solids: this includes a carefully regulated application of DFT in place of a classical procedure such as the well-known Barrett-Joyner-Halenda (BJH) method.

Loop quantum cosmology (LQC) is the result of applying principles of loop quantum gravity (LQG) to cosmological settings. The distinguishing feature of LQC is the prominent role played by the quantum geometry effects of LQG. In particular, quantum geometry creates a brand new repulsive force which is totally negligible at low spacetime curvature but rises very rapidly in the Planck regime, overwhelming the classical gravitational attraction. In cosmological models, while Einstein's equations hold to an excellent degree of approximation at low curvature, they undergo major modifications in the Planck regime: for matter satisfying the usual energy conditions, any time a curvature invariant grows to the Planck scale, quantum geometry effects dilute it, thereby resolving singularities of general relativity. Quantum geometry corrections become more sophisticated as the models become richer. In particular, in anisotropic models, there are significant changes in the dynamics of shear potentials which tame their singular behavior in striking contrast to older results on anisotropies in bouncing models. Once singularities are resolved, the conceptual paradigm of cosmology changes and one has to revisit many of the standard issues - e.g. the 'horizon problem' - from a new perspective. Such conceptual issues as well as potential observational consequences of the new Planck scale physics are being explored, especially within the inflationary paradigm. These considerations have given rise to a burst of activity in LQC in recent years, with contributions from quantum gravity experts, mathematical physicists and cosmologists. The goal of this review is to provide an overview of the current state of the art in LQC for three sets of audiences: young researchers interested in entering this area; the quantum gravity community in general and cosmologists who wish to apply LQC to probe modifications in the standard paradigm of the early universe. In this review, effort has been made to streamline the material so that each of these communities can read only the sections they are most interested in, without loss of continuity. © 2011 IOP Publishing Ltd.

Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells. We show that both HIF-1 subunits are basic-helix-loop-helix proteins containing a PAS domain, defined by its presence in the Drosophila Per and Sim proteins and in the mammalian ARNT and AHR proteins. HIF-1 alpha is most closely related to Sim. HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. HIF-1 alpha and HIF-1 beta (ARNT) RNA and protein levels were induced in cells exposed to 1% O2 and decayed rapidly upon return of the cells to 20% O2, consistent with the role of HIF-1 as a mediator of transcriptional responses to hypoxia.

A series of five experiments explore the influence of articulatory suppression on immediate memory for auditorily presented items with a view to testing the revised concept of an articulatory loop. Experiments 1, 2 and 3 demonstrate that the phonological similarity effect is not abolished by articulatory suppression, whether this occurs only at input or at both input and recall. Experiments 4 and 5 show that the tendency for long words to be less well remembered than short is abolished by articulatory suppression, even when presentation is auditory, provided suppression occurs during both input and recall. These results are consistent with the concept of a loop comprising a phonological store, which is responsible for the phonological similarity effect, coupled with an articulatory rehearsal process that gives rise to the word length effect.