Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation.

Although very similar in sequence, the four subclasses of human immunoglobulin G (IgG) differ markedly in their ability to activate complement. Glu318-Lys320-Lys322 has been identified as a key binding motif for the first component of complement, C1q, and is present in all isotypes of Ig capable of activating complement. This motif, however, is present in all subclasses of human IgG, including those that show little (IgG2) or even no (IgG4) complement activity. Using point mutants of chimeric antibodies, we have identified specific residues responsible for the differing ability of the IgG subclasses to fix complement. In particular, we show that Ser at position 331 in gamma 4 is critical for determining the inability of that isotype to bind C1q and activate complement. Additionally, we provide further evidence that levels of C1q binding do not necessarily correlate with levels of complement activity, and that C1q binding alone is not sufficient for complement activation

Interpreting interpolation: the pattern of interpolation errors in digital surface models derived from laser scanning data

Errors within height models have, in the past, been communicated in terms of global measures ofaccuracy for the model. Such quantification ignores the spatial structure of errors across thesurface, hindering subsequent analysis. This paper demonstrates the importance ofunderstanding the spatial structure of error using, as an example, the creation of a DigitalSurface Model (DSM) from laser scanner data

An investigation of the effects of the common cold on simulated driving performance and detection of collisions

The aim of the present research was to investigate whether individuals with a common cold showed impaired ability on a simulated driving task and the ability to detect potential collisions between moving objects. The study involved comparison of a healthy group with a group with colds. These scores were adjusted for individual differences by collecting further data when both groups were healthy and using these scores as covariates. On both occasions volunteers rated their symptoms, carried out a laboratory task measuring collision detection and also a simulated driving session. Twenty five students from the University of Leeds. 10 volunteers were healthy on both occasions and 15 had a cold on the first session and were healthy on the second. In the collision detection task the main outcomes were correct detections and response to a secondary identification task. In the simulated driving task the outcomes were: speed; lateral control; gap acceptance; overtaking behaviour; car following; vigilance and traffic light violations. Those with a cold detected fewer collisions and had a higher divided attention error than those who were healthy. Many basic driving skills were unimpaired by the illness. However, those with a cold were slower at responding to unexpected events and drove closer to the car in front. The finding that having a common cold reduces the ability to detect collisions and respond quickly to unexpected events is of practical importance. Further research is now required to examine the efficacy of information campaigns and countermeasures such as caffeine

The consequences of replicating in the wrong orientation: Bacterial chromosome duplication without an active replication origin

Chromosome replication is regulated in all organisms at the assembly stage of the replication machinery at specific origins. In Escherichia coli the DnaA initiator protein regulates the assembly of replication forks at oriC. This regulation can be undermined by defects in nucleic acid meta¬bolism. In cells lacking RNase HI replication initiates indepen¬dently of DnaA and oriC, presumably at persisting R-loops. A similar mechanism was assumed for origin-independent synthesis in cells lacking RecG. However, recently we suggested that this synthesis initiates at intermediates resulting from replication fork fusions. Here we present data suggesting that in cells lacking RecG or RNase HI origin-independent synthesis arises by different mechanisms, indicative of these two proteins having different roles in vivo. Our data support the idea that RNase HI processes R-loops, while RecG is required to process replication fork fusion intermediates. However, regardless of how origin-independent synthesis is initiated, a fraction of forks will proceed in an orientation opposite to normal. We show that the resulting head-on encounters with transcription threaten cell viability, especially if taking place in highly-transcribed areas. Thus, despite their different functions, RecG and RNase HI are both important factors for maintaining replication control and orientation. Their absence causes severe replication problems, highlighting the advantages of the normal chromosome arrangement, which exploits a single origin to control the number of forks and their orientation relative to transcription, and a defined termination area to contain fork fusions. Any changes to this arrangement endanger cell cycle control, chromosome dynamics and, ultimately, cell viability.This work was supported by the Royal Society (RG110414 to C.J.R.) and The Biotechnology and Biological Sciences Research Council (BB/K015729/1 to C.J.R.)

Lipidomic profiling in Crohn's disease: abnormalities in phosphatidylinositols, with preservation of ceramide, phosphatidylcholine and phosphatidylserine composition.

Crohn's disease is a chronic inflammatory condition largely affecting the terminal ileum and large bowel. A contributing cause is the failure of an adequate acute inflammatory response as a result of impaired secretion of pro-inflammatory cytokines by macrophages. This defective secretion arises from aberrant vesicle trafficking, misdirecting the cytokines to lysosomal degradation. Aberrant intestinal permeability is also well-established in Crohn's disease. Both the disordered vesicle trafficking and increased bowel permeability could result from abnormal lipid composition. We thus measured the sphingo- and phospholipid composition of macrophages, using mass spectrometry and stable isotope labelling approaches. Stimulation of macrophages with heat-killed Escherichia coli resulted in three main changes; a significant reduction in the amount of individual ceramide species, an altered composition of phosphatidylcholine, and an increased rate of phosphatidylcholine synthesis in macrophages. These changes were observed in macrophages from both healthy control individuals and patients with Crohn's disease. The only difference detected between control and Crohn's disease macrophages was a reduced proportion of newly-synthesised phosphatidylinositol 16:0/18:1 over a defined time period. Shotgun lipidomics analysis of macroscopically non-inflamed ileal biopsies showed a significant decrease in this same lipid species with overall preservation of sphingolipid, phospholipid and cholesterol composition

Multi-vehicle refill scheduling with queueing

© 2017 We consider the problem of refill scheduling for a team of vehicles or robots that must contend for access to a single physical location for refilling. The objective is to minimise time spent in travelling to/from the refill station, and also time lost to queuing (waiting for access). In this paper, we present principled results for this problem in the context of agricultural operations. We first establish that the problem is NP-hard and prove that the maximum number of vehicles that can usefully work together is bounded. We then focus on the design of practical algorithms and present two solutions. The first is an exact algorithm based on dynamic programming that is suitable for small problem instances. The second is an approximate anytime algorithm based on the branch and bound approach that is suitable for large problem instances with many robots. We present simulated results of our algorithms for three classes of agricultural work that cover a range of operations: spot spraying, broadcast spraying and slurry application. We show that the algorithm is reasonably robust to inaccurate prediction of resource utilisation rate, which is difficult to estimate in cases such as spot application of herbicide for weed control, and validate its performance in simulation using realistic scenarios with up to 30 robots

Strong Lefschetz elements of the coinvariant rings of finite Coxeter groups

For the coinvariant rings of finite Coxeter groups of types other than H$_4$, we show that a homogeneous element of degree one is a strong Lefschetz element if and only if it is not fixed by any reflections. We also give the necessary and sufficient condition for strong Lefschetz elements in the invariant subrings of the coinvariant rings of Weyl groups.Comment: 18 page