Interaction between human interleukin-16 and CD4 receptor of HIV-1

AIM: To study the interaction between human interleukin-16 (IL-16) and the receptor CD4 (T-lymphocyte differentiation antigen) of human immunodeficiency virus type 1 (HIV-1). METHODS: Two structurally con served regions (SCRs) of human IL-16 were built by the SYBYL/Biopolymer module using the corresponding transmembrane (TM) domain of human interleukin-1 (HIL-4) and HIL-2 as the templates. The coordinates for amino-terminal residue sequence, carboxyl-terminal residue sequences, and cytoplasm loops were generated using Biopolymer's LOOP SEARCH algorithm. RESULTS: HIL-16 first formed a homodimer, then contacted with CD4 dimer further forming a dimeric complex. Subsequently, the dimeric complex constructed the tetrameric complex by two disulfide bridges between the cysteines of HIL-16 (Cys31-Cys31). CONCLUSION: The interaction model is useful to propose the action mechanism of HIL-16 and is beneficial for rational designing of novel anti-HIV drugs.

Structural and functional characterization of the human CCR5 receptor in complex with HIV gp120 envelope glycoprotein and CD4 receptor by molecular modeling studies

The entry of human immunodeficiency virus (HIV) into cells depends on a sequential interaction of the gp120 envelope glycoprotein with the cellular receptors CD4 and members of the chemokine receptor family. The CC chemokine receptor CCR5 is such a receptor for several chemokines and a major coreceptor for the entry of R5 HIV type-1 (HIV-1) into cells. Although many studies focus on the interaction of CCR5 with HIV-1, the corresponding interaction sites in CCR5 and gp120 have not been matched. Here we used an approach combining protein structure modeling, docking and molecular dynamics simulation to build a series of structural models of the CCR5 in complexes with gp120 and CD4. Interactions such as hydrogen bonds, salt bridges and van der Waals contacts between CCR5 and gp120 were investigated. Three snapshots of CCR5-gp120-CD4 models revealed that the initial interactions of CCR5 with gp120 are involved in the negatively charged N-terminus (Nt) region of CCR5 and positively charged bridging sheet region of gp120. Further interactions occurred between extracellular loop2 (ECL2) of CCR5 and the base of V3 loop regions of gp120. These interactions may induce the conformational changes in gp120 and lead to the final entry of HIV into the cell. These results not only strongly support the two-step gp120-CCR5 binding mechanism, but also rationalize extensive biological data about the role of CCR5 in HIV-1 gp120 binding and entry, and may guide efforts to design novel inhibitors.

Change propagation analysis in complex technical systems

Understanding how and why changes propagate during engineering design is critical because most products and systems emerge from predecessors and not through clean sheet design. This paper applies change propagation analysis methods and extends prior reasoning through examination of a large data set from industry including 41,500 change requests, spanning 8 years during the design of a complex sensor system. Different methods are used to analyze the data and the results are compared to each other and evaluated in the context of previous findings. In particular the networks of connected parent, child and sibling changes are resolved over time and mapped to 46 subsystem areas. A normalized change propagation index (CPI) is then developed, showing the relative strength of each area on the absorber-multiplier spectrum between -1 and +1. Multipliers send out more changes than they receive and are good candidates for more focused change management. Another interesting finding is the quantitative confirmation of the "ripple" change pattern. Unlike the earlier prediction, however, it was found that the peak of cyclical change activity occurred late in the program driven by systems integration and functional testing. Patterns emerged from the data and offer clear implications for technical change management approaches in system design. Copyright © 2007 by ASME.

Large-eddy simulation of complex geometry jets

Computations are made for chevron and coflowing jet nozzles. The latter has a bypass ratio of 6:1. Also, unlike the chevron nozzle, the core flow is heated, making the inlet conditions reminiscent of those for a real engine. A large-eddy resolving approach is used with circa 12 × 10 6 cell meshes. Because the codes being used tend toward being dissipative the subgrid scale model is abandoned, giving what can be termed numerical large-eddy simulation. To overcome near-wall modeling problems a hybrid numerical large-eddy simulation-Reynolds-averaged Navier-Stokes related method is used. For y + ≤ 60 a Reynolds-averaged Navier-Stokes model is used. Blending between the two regions makes use of the differential Hamilton-Jabobi equation, an extension of the eikonal equation. For both nozzles, results show encouraging agreement with measurements of other workers. The eikonal equation is also used for ray tracing to explore the effect of the mean flow on acoustic ray trajectories, thus yielding a coherent solution strategy. © 2011 by Cambridge University.

Measurement of the Interaction Between Recombinant I-domain from Integrin alpha 2 beta 1 and a Triple Helical Collagen Peptide with the GFOGER Binding Motif Using Molecular Force Spectroscopy.

The role of the collagen-platelet interaction is of crucial importance to the haemostatic response during both injury and pathogenesis of the blood vessel wall. Of particular interest is the high affinity interaction of the platelet transmembrane receptor, alpha 2 beta 1, responsible for firm attachment of platelets to collagen at and around injury sites. We employ single molecule force spectroscopy (SMFS) using the atomic force microscope (AFM) to study the interaction of the I-domain from integrin alpha 2 beta 1 with a synthetic collagen related triple-helical peptide containing the high-affinity integrin-binding GFOGER motif, and a control peptide lacking this sequence, referred to as GPP. By utilising synthetic peptides in this manner we are able to study at the molecular level subtleties that would otherwise be lost when considering cell-to-collagen matrix interactions using ensemble techniques. We demonstrate for the first time the complexity of this interaction as illustrated by the complex multi-peaked force spectra and confirm specificity using control blocking experiments. In addition we observe specific interaction of the GPP peptide sequence with the I-domain. We propose a model to explain these observations.

Complex study of transport AC loss in various 2G HTS racetrack coils

HTS racetrack coils are becoming important elements of an emerging number of superconducting devices such as generators or motors. In these devices the issue of AC loss is crucial, as performance and cooling power are derived from this quantity. This paper presents a comparative study of transport AC loss in two different types of 2G HTS racetrack coils. In this study, both experimental measurements and computer simulation approaches were employed. All the experiments were performed using classical AC electrical method. The finite-element computer model was used to estimate electromagnetic properties and calculate transport AC loss. The main difference between the characterized coils is covered inside tape architectures. While one coil uses tape based on RABITS magnetic substrate, the second coil uses a non-magnetic tape. Ferromagnetic loss caused by a magnetic substrate is an important issue involved in the total AC loss. As a result, the coil with the magnetic substrate surprised with high AC loss and rather low performance. © 2013 Elsevier B.V. All rights reserved.

Kelvin-Helmholtz-like instabilities in turbulent flows over complex surfaces

Riblets are small surface protrusions aligned with the flow direction, which confer an anisotropic roughness to the surface [6]. We have recently reported that the transitional-roughness effect in riblets, which limits their performance, is due to a Kelvin–Helmholtz-like instability of the overlying mean flow [7]. According to our DNSs, the instability sets on as the Reynolds number based on the roughness size of the riblets increases, and coherent, elongated spanwise vortices begin to develop immediately above the riblet tips, causing the degradation of the drag-reduction effect. This is a very novel concept, since prior studies had proposed that the degradation was due to the interaction of riblets with the flow as independent units, either to the lodging of quasi-streamwise vortices in the surface grooves [2] or to the shedding of secondary streamwise vorticity at the riblet peaks [9]. We have proposed an approximate inviscid analysis for the instability, in which the presence of riblets is modelled through an average boundary condition for an overlying, spanwise-independent mean flow. This simplification lacks the accuracy of an exact analysis [4], but in turn applies to riblet surfaces in general. Our analysis succeeds in predicting the riblet size for the onset of the instability, while qualitatively reproducing the wavelengths and shapes of the spanwise structures observed in the DNSs. The analysis also connects the observations with the Kelvin–Helmholtz instability of mixing layers. The fundamental riblet length scale for the onset of the instability is a ‘penetration length,’ which reflects how easily the perturbation flow moves through the riblet grooves. This result is in excellent agreement with the available experimental evidence, and has enabled the identification of the key geometric parameters to delay the breakdown. Although the appearance of elongated spanwise vortices was unexpected in the case of riblets, similar phenomena had already been observed over other rough [3], porous [1] and permeable [11] surfaces, as well as over plant [5,14] and urban [12] canopies, both in the transitional and in the fully-rough regimes. However, the theoretical analyses that support the connection of these observations with the Kelvin–Helmholtz instability are somewhat scarce [7, 11, 13]. It has been recently proposed that Kelvin–Helmholtz-like instabilities are a dominant feature common to “obstructed” shear flows [8]. It is interesting that the instability does not require an inflection point to develop, as is often claimed in the literature. The Kelvin-Helmholtz rollers are rather triggered by the apparent wall-normal-transpiration ability of the flow at the plane immediately above the obstructing elements [7,11]. Although both conditions are generally complementary, if wall-normal transpiration is not present the spanwise vortices may not develop, even if an inflection point exists within the roughness [10]. REFERENCES [1] Breugem, W. P., Boersma, B. J. & Uittenbogaard, R. E. 2006 J. Fluid Mech. 562, 35–72. [2] Choi, H., Moin, P. & Kim, J. 1993 J. Fluid Mech. 255, 503–539. [3] Coceal, O., Dobre, A., Thomas, T. G. & Belcher, S. E. 2007 J. Fluid Mech. 589, 375–409. [4] Ehrenstein, U. 2009 Phys. Fluids 8, 3194–3196. [5] Finnigan, J. 2000 Ann. Rev. Fluid Mech. 32, 519–571. [6] Garcia-Mayoral, R. & Jimenez, J. 2011 Phil. Trans. R. Soc. A 369, 1412–1427. [7] Garcia-Mayoral, R. & Jimenez, J. 2011 J. Fluid Mech. doi: 10.1017/jfm.2011.114. [8] Ghisalberti, M. 2009 J. Fluid Mech. 641, 51–61. [9] Goldstein, D. B. & Tuan, T. C. 1998 J. Fluid Mech. 363, 115–151. [10] Hahn, S., Je, J. & Choi, H. 2002 J. Fluid Mech. 450, 259–285. [11] Jimenez, J., Uhlman, M., Pinelli, A. & G., K. 2001 J. Fluid Mech. 442, 89–117. [12] Letzel, M. O., Krane, M. & Raasch, S. 2008 Atmos. Environ. 42, 8770–8784. [13] Py, C., de Langre, E. & Moulia, B. 2006 J. Fluid Mech. 568, 425–449. [14] Raupach, M. R., Finnigan, J. & Brunet, Y. 1996 Boundary-Layer Meteorol. 78, 351–382.

Cognitive Tomography Reveals Complex, Task-Independent Mental Representations

Humans develop rich mental representations that guide their behavior in a variety of everyday tasks. However, it is unknown whether these representations, often formalized as priors in Bayesian inference, are specific for each task or subserve multiple tasks. Current approaches cannot distinguish between these two possibilities because they cannot extract comparable representations across different tasks [1-10]. Here, we develop a novel method, termed cognitive tomography, that can extract complex, multidimensional priors across tasks. We apply this method to human judgments in two qualitatively different tasks, "familiarity" and "odd one out," involving an ecologically relevant set of stimuli, human faces. We show that priors over faces are structurally complex and vary dramatically across subjects, but are invariant across the tasks within each subject. The priors we extract from each task allow us to predict with high precision the behavior of subjects for novel stimuli both in the same task as well as in the other task. Our results provide the first evidence for a single high-dimensional structured representation of a naturalistic stimulus set that guides behavior in multiple tasks. Moreover, the representations estimated by cognitive tomography can provide independent, behavior-based regressors for elucidating the neural correlates of complex naturalistic priors. © 2013 The Authors.

Multimode polymer waveguide components for complex on-board optical topologies

Multimode polymer waveguides are an attractive transmission medium for board-level optical links as they provide high bandwidth, relaxed alignment tolerances, and can be directly integrated onto conventional printed circuit boards. However, the performance of multimode waveguide components depends on the launch conditions at the component input, complicating their use in topologies that require the concatenation of multiple multimode components. This paper presents key polymer components for a multichannel optical bus and reports their performance under different launch conditions, enabling useful rules that can be used to design complex interconnection topologies to be derived. The components studied are multimode signal splitters and combiners, 90°-crossings, S-bends, and 90°-bends. By varying the width of the splitter arms, a splitting ratio between 1% and 95% is achieved from the 1 × 2 splitters, while low-loss signal combining is demonstrated with the waveguide combiners. It is shown that a 3 dB improvement in the combiner excess loss can be achieved by increasing the bus width by 50 μm. The worst-case insertion loss of 50 × 100 μm waveguide crossings is measured to be 0.1 dB/crossing. An empirical method is proposed and used to estimate the insertion losses of on-board optical paths of a polymeric four-channel optical bus module. Good agreement is achieved between the predicted and measured values. Although the components and empirical method have been tailored for use in a multichannel optical bus architecture, they can be used for any on-board optical interconnection topology. © 1983-2012 IEEE.

Stabilization of a complex perovskite superstructure under ambient conditions: Influence of cation composition and ordering, and evaluation as an SOFC cathode

Ba1.6Ca2.3Y1.1Fe5O13 is an Fe3+ oxide adopting a complex perovskite superstructure, which is an ordered intergrowth between the Ca2Fe2O5 and YBa2Fe3O8 structures featuring octahedral, square pyramidal, and tetrahedral B sites and three distinct A site environments. The distribution of A site cations was evaluated by combined neutron and X-ray powder diffraction. Consistent with the Fe3+ charge state, the material is an antiferromagnetic insulator with a Néel temperature of 480-485 °C and has a relatively low d.c. conductivity of 2.06 S cm-1 at 700 °C. The observed area specific resistance in symmetrical cell cathodes with the samarium-doped ceria electrolyte is 0.87 Ω cm2 at 700 °C, consistent with the square pyramidal Fe3+ layer favoring oxide ion formation and mobility in the oxygen reduction reaction. Density functional theory calculations reveal factors favoring the observed cation ordering and its influence on the electronic structure, in particular the frontier occupied and unoccupied electronic states. © 2010 American Chemical Society.

Bead-probe complex capture a couple of SINE and LINE family from genomes of two closely related species of East Asian cyprinid directly using magnetic separation

Background: Short and long interspersed elements (SINEs and LINEs, respectively), two types of retroposons, are active in shaping the architecture of genomes and powerful tools for studies of phylogeny and population biology. Here we developed special protocol to apply biotin-streptavidin bead system into isolation of interspersed repeated sequences rapidly and efficiently, in which SINEs and LINEs were captured directly from digested genomic DNA by hybridization to bead-probe complex in solution instead of traditional strategy including genomic library construction and screening. Results: A new couple of SINEs and LINEs that shared an almost identical 3'tail was isolated and characterized in silver carp and bighead carp of two closely related species. These SINEs (34 members), designated HAmo SINE family, were little divergent in sequence and flanked by obvious TSD indicated that HAmo SINE was very young family. The copy numbers of this family was estimated to 2 x 10(5) and 1.7 x 10(5) per haploid genome by Real-Time qPCR, respectively. The LINEs, identified as the homologs of LINE2 in other fishes, had a conserved primary sequence and secondary structures of the 3'tail region that was almost identical to that of HAmo SINE. These evidences suggest that HAmo SINEs are active and amplified recently utilizing the enzymatic machinery for retroposition of HAmoL2 through the recognition of higher-order structures of the conserved 42-tail region. We analyzed the possible structures of HAmo SINE that lead to successful amplification in genome and then deduced that HAmo SINE, SmaI SINE and FokI SINE that were similar in sequence each other, were probably generated independently and created by LINE family within the same lineage of a LINE phylogeny in the genomes of different hosts. Conclusion: The presented results show the advantage of the novel method for retroposons isolation and a pair of young SINE family and its partner LINE family in two carp fishes, which strengthened the hypotheses containing the slippage model for initiation of reverse transcription, retropositional parasitism of SINEs on LINEs, the formation of the stem loop structure in 3'tail region of some SINEs and LINEs and the mechanism of template switching in generating new SINE family.

Developing ISO 14649-based conversational programming system for multi-channel complex machine tools

A multi-channel complex machine tool (MCCM) is a versatile machining system equipped with more than two spindles and turrets for both turning and milling operations. Despite the potential of such a tool, the value of the hardware is largely dependent on how the machine tools are effectively programmed for machining. In this paper we consider a shop-floor programming system based on ISO 14649 (called e-CAM), the international standard for the interface between computer-aided manufacture (CAM) and computer numerical control (CNC). To be deployed in practical industrial usage a great deal of research has to be carried out. In this paper we present: 1) Design consideration for an e-CAM system, 2) The architecture design of e-CAM, 3) Major algorithms to fulfill the modules defined in the architecture, and 4) Implementation details.

Mutations stabilize small subunit ribosomal RNA in desiccation-tolerant cyanobacteria Nostoc

The ribosomal RNA molecule is an ideal model for evaluating the stability of a gene product under desiccation stress. We isolated 8 Nostoc strains that had the capacity to withstand desiccation in habitats and sequenced their 16S rRNA genes. The stabilities of 16S rRNAs secondary structures, indicated by free energy change of folding, were compared among Nostoc and other related species. The results suggested that 163 rRNA secondary structures of the desiccation-tolerant Nostoc strains were more stable than that of planktonic Nostocaceae species. The stabilizing mutations were divided into two categories: (1) those causing GC to replace other types of base pairs in stems and (2) those causing extension of stems. By mapping stabilizing mutations onto the Nostoc phylogenetic tree based on 16S rRNA gene, it was shown that most of stabilizing mutations had evolved during adaptive radiation among Nostoc spp. The evolution of 16S rRNA along the Nostoc lineage is suggested to be selectively advantageous under desiccation stress.