Designing supramolecular structures from models of cyclic peptide scaffolds with heterocyclic constraints

Cyclic peptides containing oxazole and thiazole heterocycles have been examined for their capacity to be used as scaffolds in larger, more complex, protein-like structures. Both the macrocyclic scaffolds and the supramolecular structures derived therefrom have been visualised by molecular modelling techniques. These molecules are too symmetrical to examine structurally by NMR spectroscopy. The cyclic hexapeptide ([Aaa-Thz](3), [Aaa-Oxz](3)) and cyclic octapeptide ([Aaa-Thz](4), [Aaa-Oxz](4)) analogues are composed of dipeptide surrogates (Aaa: amino acid, Thz: thiazole, Oxz: oxazole) derived from intramolecular condensation of cysteine or serine/threonine side chains in dipeptides like Aaa-Cys, Aaa-Ser and Aaa-Thr. The five-membered heterocyclic rings, like thiazole, oxazole and reduced analogues like thiazoline, thiazolidine and oxazoline have profound influences on the structures and bioactivities of cyclic peptides derived therefrom. This work suggests that such constrained cyclic peptides can be used as scaffolds to create a range of novel protein-like supramolecular structures (e.g. cylinders, troughs, cones, multi-loop structures, helix bundles) that are comparable in size, shape and composition to bioactive surfaces of proteins. They may therefore represent interesting starting points for the design of novel artificial proteins and artificial enzymes. (C) 2002 Elsevier Science Inc. All rights reserved.

Cutaneous stimulation from patella tape causes a differential increase in vasti muscle activity in people with patellofemoral pain

Patella taping reduces pain ill individuals with patellofemoral pain (PFP), although the mechanism remains unclear. One possibility is that patella taping modifies vasti muscle activity via stimulation of cutaneous afferents. The aim of this study was to investigate the effect of stretching the skin over the patella on vasti Muscle activity in people with PFP. Electromyographic activity (EMG) of individual motor units in vastus medialis obliquus (VMO) was recorded via a needle electrode and from Surface electrodes placed over VMO and vastus lateralis (VL). A tape was applied to the skin directly over the patella and stretch was applied via the tape in three directions, while subjects maintained a gentle isometric knee extension effort at constant force. Recordings were made from five separate motor units in each direction. Stretch applied to the skin over the patella increased VMO surface EMG and was greatest with lateral stretch. There was no change in VL surface EMG activity. While there was no net increase in motor unit firing rate, it was increased in the majority of motor units during lateral stretch. Application of stretch to the skin over VMO via the tape can increase VMO activity, suggesting that cutaneous stimulation may be one mechanism by which patella taping produces a clinical effect. (c) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

H-ras, K-ras, and inner plasma membrane raft proteins operate in nanoclusters with differential dependence on the actin cytoskeleton

Plasma membrane compartmentalization imposes lateral segregation on membrane proteins that is important for regulating signal transduction. We use computational modeling of immunogold spatial point patterns on intact plasma membrane sheets to test different models of inner plasma membrane organization. We find compartmentalization at the nanoscale level but show that a classical raft model of preexisting stable domains into which lipid raft proteins partition is incompatible with the spatial point patterns generated by the immunogold labeling of a palmitoylated raft marker protein. Rather, approximate to 30% of the raft protein exists in cholesterol-dependent nanoclusters, with approximate to 70% distributed as monomers. The cluster/monomer ratio (number of proteins in clusters/number of proteins outside clusters) is independent of expression level. H-rasG12V and K-rasG12V proteins also operate in nanoclusters with fixed cluster/monomer ratios that are independent of expression level. Detailed calibration of the immunogold imaging protocol suggests that radii of raft and RasG12V protein nanoclusters may be as small as 11 and 6 nm, respectively, and shows that the nanoclusters contain small numbers (6.0-7.7) of proteins. Raft nanoclusters do not form if the actin cytoskeleton is disassembled. The formation of K-rasG12V but not H-rasG12V nanoclusters also is actin-dependent. K-rasG12V but not H-rasG12V signaling is abrogated by actin cytoskeleton disassembly, which shows that nanoclustering is critical for Ras function. These findings argue against stable preexisting domains on the inner plasma membrane in favor of dynamic actively regulated nanoclusters similar to those proposed for the outer plasma membrane. RasG12V nanoclusters may facilitate the assembly of essential signal transduction complexes.

Extending choreography with business contract constraints

Business contracts play a central role in governing commercial interactions between organizations. It is increasingly recognized that business contract conditions need to be closely linked to internal and external business processes, both to reduce the risk of contract violations and to ensure compliance with legislative regimes. Recent research has proposed contract languages allowing the specification of obligations, permissions and prohibitions in business contracts. Business processes that cross-organizational boundaries can be specified in choreography and coordination languages but these do not provide appropriate abstractions for contract constraints. In this paper, we examine the transformation of contract constraints in a business contract language into expressions in a choreography language. An example cross-organizational process is presented, along with a specification of the process in a choreography language and a specification of a set of contract conditions for the process in a business contract language. The contract terms are then translated into choreography expressions that govern the process to ensure compliance. Subsequent discussion explores a number of business and technology issues related to the results. We conclude that cross-organizational business processes can be monitored and enforced according to business contract specifications through the transformation of a contract definition to constraints on process behavior.

Matching poultry production with available feed resources: issues and constraints

Corn and soyabeans may not be available in many countries particularly those which do not have sufficient foreign currency or the capacity to grow them. This paper outlines strategies that may be important under these circumstances. Alternative feedstuffs and various feeding systems may be used to support poultry production. Alternative ingredients such as rice bran, pearl millet, cottonseed meal and grain legumes are discussed. Evidence is presented showing that amino acid requirements of layers and broilers may be too generous particularly in countries where climate, management and disease can impose production constraints. The ability of finishing broilers to perform well on very low-energy diets allows the inclusion of alternative feeds and by-products into formulations. Very low protein diets based on cereals and free amino acids can be used for layers without loss of performance. Self-selection of feedstuffs may be an important strategy in reducing feed costs of broilers and layers. The concept of matching production with available feed resources may compromise broiler growth and egg production, but in many countries this may be the most economical choice. Countries in the humid tropics usually have reduced poultry performance. The effects of high temperature and humidity are difficult to overcome. The vexed questions of the escalation in the price of fossil fuel and the outbreak of avian influenza, both seemingly without a solution, are clouds hanging over an otherwise buoyant industry.

Student Difficulties with units in differential equations in modelling contexts

First-year undergraduate engineering students' understanding of the units of factors and terms in first-order ordinary differential equations used in modelling contexts was investigated using diagnostic quiz questions. Few students appeared to realize that the units of each term in such equations must be the same, or if they did, nevertheless failed to apply that knowledge when needed. In addition, few students were able to determine the units of a proportionality factor in a simple equation. These results indicate that lecturers of modelling courses cannot take this foundational knowledge for granted and should explicitly include it in instruction.

Differential evolution based total transfer capability assessment with optimal dispatch

In this paper, a new differential evolution (DE) based power system optimal available transfer capability (ATC) assessment is presented. Power system total transfer capability (TTC) is traditionally solved by the repeated power flow (RPF) method and the continuation power flow (CPF) method. These methods are based on the assumption that the productions of the source area generators are increased in identical proportion to balance the load increment in the sink area. A new approach based on DE algorithm to generate optimal dispatch both in source area generators and sink area loads is proposed in this paper. This new method can compute ATC between two areas with significant improvement in accuracy compared with the traditional RPF and CPF based methods. A case study using a 30 bus system is given to verify the efficiency and effectiveness of this new DE based ATC optimization approach.

Clustering of neuronal inclusions in "dementia with neurofilament inclusions"

Dementia with neurofilament inclusions (DNI) is a new disorder characterized clinically by early-onset dementia and histologically by the presence of intraneural inclusions immunopositive for neurofilament antigens but lacking tau and α-synuclein reactivity. We studied the clustering patterns of the neurofilament inclusions (NI) in regions of the temporal lobe in three cases of DNI to determine whether they have the same spatial patterns as inclusions in the tauopathies and α-synucleinopathies. The NI exhibited a clustered distribution (mean size of clusters 400 μm, range 50-800 μm, SD 687.8) in 24/28 of the areas studied. In 22 of these areas, the clusters exhibited a regular distribution along the tissue parallel to the pia mater or alveus. In 3 cortical areas, there was evidence of a more complex pattern in which the NI clusters were aggregated into larger superclusters. In 6 cortical areas, the size of the clusters approximated to those of the cells of origin of the cortico-cortical pathways but in the remaining areas cluster size was smaller than 400 μm. Despite the unique molecular profile of the NI, their spatial patterns are similar to those shown by filamentous neuronal inclusions in the tauopathies and α-synucleinopathies.