Analysis of the antigen combining site: Correlations between length and sequence composition of the hypervariable loops and the nature of the antigen

It has long been suggested that the overall shape of the antigen combining site (ACS) of antibodies is correlated with the nature of the antigen. For example, deep pockets are characteristic of antibodies that bind haptens, grooves indicate peptide binders, while antibodies that bind to proteins have relatively flat combining sites. In. 1996, MacCallum, Martin and Thornton used a fractal shape descriptor and showed a strong correlation of the shape of the binding region with the general nature of the antigen. However, the shape of the ACS is determined primarily by the lengths of the six complementarity-determining regions (CDRs). Here, we make a direct correlation between the lengths of the CDRs and the nature of the antigen. In addition, we show significant differences in the residue composition of the CDRs of antibodies that bind to different antigen classes. As well as helping us to understand the process of antigen recognition, autoimmune disease and cross-reactivity these results are of direct application in the design of antibody phage libraries and modification of affinity. (C) 2003 Elsevier Science Ltd. All rights reserved.

Differential recognition of Staphylococcus aureus quorum-sensing signals depends on both extracellular loops 1 and 2 of the transmembrane sensor AgrC.

Virulence in Staphylococcus aureus is regulated via agr-dependent quorum sensing in which an autoinducing peptide (AIP) activates AgrC, a histidine protein kinase. AIPs are usually thiolactones containing seven to nine amino acid residues in which the thiol of the central cysteine is linked to the alpha-carboxyl of the C-terminal amino acid residue. The staphylococcal agr locus has diverged such that the AIPs of the four different S. aureus agr groups self-activate but cross-inhibit. Consequently, although the agr system is conserved among the staphylococci, it has undergone significant evolutionary divergence whereby to retain functionality, any changes in the AIP-encoding gene (agrD) that modifies AIP structure must be accompanied by corresponding changes in the AgrC receptor. Since AIP-1 and AIP-4 only differ by a single amino acid, we compared the transmembrane topology of AgrC1 and AgrC4 to identify amino acid residues involved in AIP recognition. As only two of the three predicted extracellular loops exhibited amino acid differences, site-specific mutagenesis was used to exchange the key AgrC1 and AgrC4 amino acid residues in each loop either singly or in combination. A novel lux-based agrP3 reporter gene fusion was constructed to evaluate the response of the mutated AgrC receptors. The data obtained revealed that while differential recognition of AIP-1 and AIP-4 depends primarily on three amino acid residues in loop 2, loop 1 is essential for receptor activation by the cognate AIP. Furthermore, a single mutation in the AgrC1 loop 2 resulted in conversion of (Ala5)AIP-1 from a potent antagonist to an activator, essentially resulting in the forced evolution of a new AIP group. Taken together, our data indicate that loop 2 constitutes the predicted hydrophobic pocket that binds the AIP thiolactone ring while the exocyclic amino acid tail interacts with loop 1 to facilitate receptor activation.

Dynamic simulation for closed loops in heating systems with decision-making support

Nowadays utilising the proper HVAC system is essential both in extreme weather conditions and dense buildings design. Hydraulic loops are the most common parts in all air conditioning systems. This article aims to investigate the performance of different hydraulic loop arrangements in variable flow systems. Technical, economic and environmental assessments have been considered in this process. A dynamic system simulation is generated to evaluate the system performance and an economic evaluation is conducted by whole life cost assessment. Moreover, environmental impacts have been studied by considering the whole life energy consumption, CO2 emission, the embodied energy and embodied CO2 of the system components. Finally, decision-making in choosing the most suitable hydraulic system among five well-known alternatives has been proposed.

Steering without Circe : attending to reinforcing loops in social systems

Relating system dynamics to the broad systems movement, the key notion is that reinforcing loops deserve no less attention than balancing loops. Three specific propositions follow. First, since reinforcing loops arise in surprising places, investigations of complex systems must consider their possible existence and potential impact. Second, because the strength of reinforcing loops can be misinferred - we include an example from the field of servomechanisms - computer simulation can be essential. Be it project management, corporate growth or inventory oscillation, simulation helps to assess consequences of reinforcing loops and options for interventions. Third, in social systems the consequences of reinforcing loops are not inevitable. Examples concerning globalization illustrate how difficult it might be to challenge such assumptions. However, system dynamics and ideas from contemporary social theory help to show that even the most complex social systems are, in principle, subject to human influence. In conclusion, by employing these ideas, by attending to reinforcing as well as balancing loops, system dynamics work can improve the understanding of social systems and illuminate our choices when attempting to steer them.

Production of attaching-effacing lesions in ligated large intestine loops of 6-month-old sheep by Escherichia coli O157:H7

Shiga-toxigenic Escherichia coli O157:H7 (STEC O157:H7) is associated with potentially fatal human disease, and a persistent reservoir of the organism is present in some farm animal species, especially cattle and sheep. The mechanisms of persistent colonisation of the ruminant intestine by STEC O157:H7 are poorly understood but may be associated with intimate adherence to eukaryotic cells. Intimate adherence, as evidenced by induction of attaching-effacing (AE) lesions by STEC O157, has been observed in 6-day-old conventional lambs after deliberate oral infection but not in older animals. Thus, the present study used a ligated intestinal loop technique to investigate whether STEC O157:H7 and other attaching-effacing E. coli may adhere intimately to the sheep large intestinal mucosa. To do this, four STEC O157:H7 strains, one STEC 026:K60:H11 and one Shiga toxin-negative E. coli O157:H7 strain, suspended in either phosphate-buffered saline or Dulbecco's modified Eagle's medium, were inoculated into ligated spiral colon loops of each of two lambs. The loops were removed 6 h after inoculation, fixed and examined by light and electron microscopy. AE lesions on the intestinal mucosa were produced by all the inoculated strains. However, the lesions were sparse and small, typically comprising bacterial cells intimately adhered to a single enterocyte, or a few adjacent enterocytes. There was little correlation between the extent of intimate adherence in this model and the bacterial cell density, pre-inoculation growth conditions of the bacteria or the strain tested.

Distributed parallelization of greedy Mobile Network Optimization algorithms

The Mobile Network Optimization (MNO) technologies have advanced at a tremendous pace in recent years. And the Dynamic Network Optimization (DNO) concept emerged years ago, aimed to continuously optimize the network in response to variations in network traffic and conditions. Yet, DNO development is still at its infancy, mainly hindered by a significant bottleneck of the lengthy optimization runtime. This paper identifies parallelism in greedy MNO algorithms and presents an advanced distributed parallel solution. The solution is designed, implemented and applied to real-life projects whose results yield a significant, highly scalable and nearly linear speedup up to 6.9 and 14.5 on distributed 8-core and 16-core systems respectively. Meanwhile, optimization outputs exhibit self-consistency and high precision compared to their sequential counterpart. This is a milestone in realizing the DNO. Further, the techniques may be applied to similar greedy optimization algorithm based applications.

Asynchronous distributed parallelization of mobile network optimization algorithms

It has been years since the introduction of the Dynamic Network Optimization (DNO) concept, yet the DNO development is still at its infant stage, largely due to a lack of breakthrough in minimizing the lengthy optimization runtime. Our previous work, a distributed parallel solution, has achieved a significant speed gain. To cater for the increased optimization complexity pressed by the uptake of smartphones and tablets, however, this paper examines the potential areas for further improvement and presents a novel asynchronous distributed parallel design that minimizes the inter-process communications. The new approach is implemented and applied to real-life projects whose results demonstrate an augmented acceleration of 7.5 times on a 16-core distributed system compared to 6.1 of our previous solution. Moreover, there is no degradation in the optimization outcome. This is a solid sprint towards the realization of DNO.

Investigation of high-efficiency Wireless Power Transfer criteria of resonantly-coupled loops and dipoles through analysis of the figure of merit

The efficiency of a Wireless Power Transfer (WPT) system is greatly dependent on both the geometry and operating frequency of the transmitting and receiving structures. By using Coupled Mode Theory (CMT), the figure of merit is calculated for resonantly-coupled loop and dipole systems. An in-depth analysis of the figure of merit is performed with respect to the key geometric parameters of the loops and dipoles, along with the resonant frequency, in order to identify the key relationships leading to high-efficiency WPT. For systems consisting of two identical single-turn loops, it is shown that the choice of both the loop radius and resonant frequency are essential in achieving high-efficiency WPT. For the dipole geometries studied, it is shown that the choice of length is largely irrelevant and that as a result of their capacitive nature, low-MHz frequency dipoles are able to produce significantly higher figures of merit than those of the loops considered. The results of the figure of merit analysis are used to propose and subsequently compare two mid-range loop and dipole WPT systems of equal size and operating frequency, where it is shown that the dipole system is able to achieve higher efficiencies than the loop system of the distance range examined.

GDASH: a grid-enabled program for structure solution from powder diffraction data

The simulated annealing approach to structure solution from powder diffraction data, as implemented in the DASH program, is easily amenable to parallelization at the individual run level. Very large scale increases in speed of execution can therefore be achieved by distributing individual DASH runs over a network of computers. The GDASH program achieves this by packaging DASH in a form that enables it to run under the Univa UD Grid MP system, which harnesses networks of existing computing resources to perform calculations.

MDASH: a multi-core-enabled program for structure solution from powder diffraction data

The simulated annealing approach to structure solution from powder diffraction data, as implemented in the DASH program, is easily amenable to parallelization at the individual run level. Modest increases in speed of execution can therefore be achieved by executing individual DASH runs on the individual cores of CPUs.

Impact of coronal mass ejections, interchange reconnection, and disconnection on heliospheric magnetic field strength

An update of Owens et al. (2008) shows that the relationship between the coronal mass ejection (CME) rate and the heliospheric magnetic field strength predicts a field floor of less than 4 nT at 1 AU. This implies that the record low values measured during this solar minimum do not necessarily contradict the idea that open flux is conserved. The results are consistent with the hypothesis that CMEs add flux to the heliosphere and interchange reconnection between open flux and closed CME loops subtracts flux. An existing model embracing this hypothesis, however, overestimates flux during the current minimum, even though the CME rate has been low. The discrepancy calls for reasonable changes in model assumptions.

Suprathermal electron evolution in a Parker spiral magnetic field

Suprathermal electrons (>70 eV) form a small fraction of the total solar wind electron density but serve as valuable tracers of heliospheric magnetic field topology. Their usefulness as tracers of magnetic loops with both feet rooted on the Sun, however, most likely fades as the loops expand beyond some distance owing to scattering. As a first step toward quantifying that distance, we construct an observationally constrained model for the evolution of the suprathermal electron pitch-angle distributions on open field lines. We begin with a near-Sun isotropic distribution moving antisunward along a Parker spiral magnetic field while conserving magnetic moment, resulting in a field-aligned strahl within a few solar radii. Past this point, the distribution undergoes little evolution with heliocentric distance. We then add constant (with heliocentric distance, energy, and pitch angle) ad-hoc pitch-angle scattering. Close to the Sun, pitch-angle focusing still dominates, again resulting in a narrow strahl. Farther from the Sun, however, pitch-angle scattering dominates because focusing is effectively weakened by the increasing angle between the magnetic field direction and intensity gradient, a result of the spiral field. We determine the amount of scattering required to match Ulysses observations of strahl width in the fast solar wind, providing an important tool for inferring the large-scale properties and topologies of field lines in the interplanetary medium. Although the pitch-angle scattering term is independent of energy, time-of-flight effects in the spiral geometry result in an energy dependence of the strahl width that is in the observed sense although weaker in magnitude.

Reconciling the electron counterstreaming and dropout occurrence rates with the heliospheric flux budget

Counterstreaming electrons (CSEs) are treated as signatures of closed magnetic flux, i.e., loops connected to the Sun at both ends. However, CSEs at 1 AU likely fade as the apex of a closed loop passes beyond some distance R, owing to scattering of the sunward beam along its continually increasing path length. The remaining antisunward beam at 1 AU would then give a false signature of open flux. Subsequent opening of a loop at the Sun by interchange reconnection with an open field line would produce an electron dropout (ED) at 1 AU, as if two open field lines were reconnecting to completely disconnect from the Sun. Thus EDs can be signatures of interchange reconnection as well as the commonly attributed disconnection. We incorporate CSE fadeout into a model that matches time-varying closed flux from interplanetary coronal mass ejections (ICMEs) to the solar cycle variation in heliospheric flux. Using the observed occurrence rate of CSEs at solar maximum, the model estimates R ∼ 8–10 AU. Hence we demonstrate that EDs should be much rarer than CSEs at 1 AU, as EDs can only be detected when the juncture points of reconnected field lines lie sunward of the detector, whereas CSEs continue to be detected in the legs of all loops that have expanded beyond the detector, out to R. We also demonstrate that if closed flux added to the heliosphere by ICMEs is instead balanced by disconnection elsewhere, then ED occurrence at 1 AU would still be rare, contrary to earlier expectations.

A solar storm observed from the Sun to Venus using the STEREO, Venus Express, and MESSENGER spacecraft

The suite of SECCHI optical imaging instruments on the STEREO-A spacecraft is used to track a solar storm, consisting of several coronal mass ejections (CMEs) and other coronal loops, as it propagates from the Sun into the heliosphere during May 2007. The 3-D propagation path of the largest interplanetary CME (ICME) is determined from the observations made by the SECCHI Heliospheric Imager (HI) on STEREO-A (HI-1/2A). Two parts of the CME are tracked through the SECCHI images, a bright loop and a V-shaped feature located at the rear of the event. We show that these two structures could be the result of line-of-sight integration of the light scattered by electrons located on a single flux rope. In addition to being imaged by HI, the CME is observed simultaneously by the plasma and magnetic field experiments on the Venus Express and MESSENGER spacecraft. The imaged loop and V-shaped structure bound, as expected, the flux rope observed in situ. The SECCHI images reveal that the leading loop-like structure propagated faster than the V-shaped structure, and a decrease in in situ CME speed occurred during the passage of the flux rope.We interpret this as the result of the continuous radial expansion of the flux rope as it progressed outward through the interplanetary medium. An expansion speed in the radial direction of ~30 km s-1 is obtained directly from the SECCHI-HI images and is in agreement with the difference in speed of the two structures observed in situ. This paper shows that the flux rope location can be determined from white light images, which could have important space weather applications.