Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets.

Stimulated CD4(+) T lymphocytes can differentiate into effector T cell (Teff) or inducible regulatory T cell (Treg) subsets with specific immunological roles. We show that Teff and Treg require distinct metabolic programs to support these functions. Th1, Th2, and Th17 cells expressed high surface levels of the glucose transporter Glut1 and were highly glycolytic. Treg, in contrast, expressed low levels of Glut1 and had high lipid oxidation rates. Consistent with glycolysis and lipid oxidation promoting Teff and Treg, respectively, Teff were selectively increased in Glut1 transgenic mice and reliant on glucose metabolism, whereas Treg had activated AMP-activated protein kinase and were dependent on lipid oxidation. Importantly, AMP-activated protein kinase stimulation was sufficient to decrease Glut1 and increase Treg generation in an asthma model. These data demonstrate that CD4(+) T cell subsets require distinct metabolic programs that can be manipulated in vivo to control Treg and Teff development in inflammatory diseases.

Simulation of 2-D metal cutting by means of a distributed algorithm

Temperature distributions involved in some metal-cutting or surface-milling processes may be obtained by solving a non-linear inverse problem. A two-level concept on parallelism is introduced to compute such temperature distribution. The primary level is based on a problem-partitioning concept driven by the nature and properties of the non-linear inverse problem. Such partitioning results to a coarse-grained parallel algorithm. A simplified 2-D metal-cutting process is used as an example to illustrate the concept. A secondary level exploitation of further parallel properties based on the concept of domain-data parallelism is explained and implemented using MPI. Some experiments were performed on a network of loosely coupled machines consist of SUN Sparc Classic workstations and a network of tightly coupled processors, namely the Origin 2000.

Validation of the detection of Alexandrium species using specific RNA probes tested in a microarray format: Calibration of signal using variability of RNA content with environmental conditions.

The dinoflagellate genus Alexandrium contains several toxin producing species and strains, which can cause major economic losses to the shell fish industry. It is therefore important to be able to detect these toxin producers and also distinguish toxic strains from some of the morphologically identical non-toxic strains. To facilitate this DNA probes to be used in a microarray format were designed in silico or developed from existing published probes. These probes targeted either the 18S or 28S ribosomal ribonucleic acid (rRNA) gene in Alexandrium tamarense Group I, Group III and Group IV, Alexandrium ostenfeldii and Alexandrium minutum. Three strains of A. tamarense Group I, A. tamarense Group III, A. minutum and two strains of A. ostenfeldii were grown at optimal conditions and transferred into new environmental conditions changing either the light intensity, salinity, temperature or nutrient concentrations, to check if any of these environmental conditions induced changes in the cellular ribonucleic acid (RNA) concentration or growth rate. The aim of this experiment was the calibration of several species-specific probes for the quantification of the toxic Alexandrium strains. Growth rates were highly variable but only elevated or lowered salinity significantly lowered growth rate for A. tamarense Group I and Group III; differences in RNA content were not significant for the majority of the treatments. Only light intensity seemed to affect significantly the RNA content in A. tamarense Group I and Group III, but this was still within the same range as for the other treatments meaning that a back calibration from RNA to cell numbers was possible. The designed probes allow the production of quantitative information for Alexandrium species for the microarray chip.

Validation of the detection of Pseudo-nitzschia spp. using specific RNA probes tested in a microarray format: Calibration of signal based on variability of RNA content with environmental conditions.

Harmful algal blooms (HAB) occur worldwide and cause health problems and economic damage to fisheries and tourism. Monitoring for toxic algae is therefore essential but is based primarily on light microscopy, which is time consuming and can be limited by insufficient morphological characters such that more time is needed to examine critical features with electron microscopy. Monitoring with molecular tools is done in only a few places world-wide. EU FP7 MIDTAL (Microarray Detection of Toxic Algae) used SSU and LSU rRNA genes as targets on microarrays to identify toxic species. In order to comply with current monitoring requirements to report cell numbers as the relevant threshold measurement to trigger closure of fisheries, it was necessary to calibrate our microarray to convert the hybridisation signal obtained to cell numbers. Calibration curves for two species of Pseudo-nitzschia for use with the MIDTAL microarray are presented to obtain cell numbers following hybridisation. It complements work presented by Barra et al. (2012b. Environ. Sci. Pollut. Res. doi: 10.1007/s11356-012-1330-1v) for two other Pseudo-nitzschia spp., Dittami and Edvardsen (2012a. J. Phycol. 48, 1050) for Pseudochatonella, Blanco et al. (2013. Harmful Algae 24, 80) for Heterosigma, McCoy et al. (2013. FEMS. doi: 10.1111/1574-6941.12277) for Prymnesium spp., Karlodinium veneficum, and cf. Chatonella spp. and Taylor et al. (2014. Harmful Algae, in press) for Alexandrium.

Delayed failure of a deep cutting in lodgement till

Recent research on the delayed failure of cuttings in clay clearly recognises and predicts progressive delayed failure of deep cuttings. This is due to a combination of strain-softening, weathering, dissipation of negative excess pore water pressure generated at the time of excavation, and frequent occurrence of prolonged periods of wet weather. There have been several slope failures of this kind in Northern Ireland. This paper discusses a case study based on a failure of a deep cutting, excavated at a slope of 1 in 2, on the A1 near Dromore (County Down) in Northern Ireland. The cutting was in lodgement till, a stiff, heavily overconsolidated clay. The failure occurred approximately 30 years after the cutting was excavated, following a prolonged period of heavy rainfall. An analysis of the failure, together with laboratory test data on soil samples taken from the site, confirmed that by using long-term soil strength parameters the factor of safety of this slope was unity. The conclusion of the analysis is that slopes excavated in this soil should be designed (and assessed) on long-term strength parameters.

Packet classification by multi-level cutting of the classification space: An algorithmic-architectural solution for IP packet classification in next generation networks

Traditionally, the Internet provides only a “best-effort” service, treating all packets going to the same destination equally. However, providing differentiated services for different users based on their quality requirements is increasingly becoming a demanding issue. For this, routers need to have the capability to distinguish and isolate traffic belonging to different flows. This ability to determine the flow each packet belongs to is called packet classification. Technology vendors are reluctant to support algorithmic solutions for classification due to their non-deterministic performance. Although CAMs are favoured by technology vendors due to their deterministic high lookup rates, they suffer from the problems of high power dissipation and high silicon cost. This paper provides a new algorithmic-architectural solution for packet classification that mixes CAMs with algorithms based on multi-level cutting the classification space into smaller spaces. The provided solution utilizes the geometrical distribution of rules in the classification space. It provides the deterministic performance of CAMs, support for dynamic updates, and added flexibility for system designers.

Cutting edge: Langerin+ dendritic cells in the mesenteric lymph node set the stage for skin and gut immune system cross-talk.

Topical transcutaneous immunization (TCI) presents many clinical advantages, but its underlying mechanism remains unknown. TCI induced Ag-specific IgA Ab-secreting cells expressing CCR9 and CCR10 in the small intestine in a retinoic acid-dependent manner. These intestinal IgA Abs were maintained in Peyer\'s patch-null mice but abolished in the Peyer\'s patch- and lymph node-null mice. The mesenteric lymph node (MLN) was shown to be the site of IgA isotype class switching after TCI. Unexpectedly, langerin(+)CD8alpha(-) dendritic cells emerged in the MLN after TCI; they did not migrate from the skin but rather differentiated rapidly from bone marrow precursors. Depletion of langerin(+) cells impaired intestinal IgA Ab responses after TCI. Taken together, these findings suggest that MLN is indispensable for the induction of intestinal IgA Abs following skin immunization and that cross-talk between the skin and gut immune systems might be mediated by langerin(+) dendritic cells in the MLN.

Cut down by some cowardly miscreants’: Plant maiming, or the Malicious Cutting of Plants as an Act of Protest in Eighteenth and Nineteenth Century Rural England

Since the publication of Hobsbawm and Rudé's Captain Swing our understanding of the role(s) of covert protests in Hanoverian rural England has advanced considerably. Whilst we now know much about the dramatic practices of incendiarism and animal maiming and the voices of resistance in seemingly straightforward acquisitive acts, one major gap remains. Despite the fact that almost thirty years have passed since E. P. Thompson brought to our attention that under the notorious ‘Black Act’ the malicious cutting of trees was a capital offence, no subsequent research has been published. This paper seeks to address this major lacuna by systematically analysing the practices and patterns of malicious attacks on plants (‘plant maiming’) in the context of late eighteenth- and early nineteenth-century southern England. It is shown that not only did plant maiming take many different forms, attacking every conceivable type of flora, but also that it was universally understood and practised. In some communities plant maiming was the protestors' weapon of choice. As a social practice it therefore embodied wider community beliefs regarding the defence of plebeian livelihoods and identities.

Packet classification by multi-level cutting of the classification space

Traditionally, the Internet provides only a “best-effort” service, treating all packets going to the same destination equally. However, providing differentiated services for different users based on their quality requirements is increasingly becoming a demanding issue. For this, routers need to have the capability to distinguish and isolate traffic belonging to different flows. This ability to determine the flow each packet belongs to is called packet classification. Technology vendors are reluctant to support algorithmic solutions for classification due to their nondeterministic performance. Although content addressable memories (CAMs) are favoured by technology vendors due to their deterministic high-lookup rates, they suffer from the problems of high-power consumption and high-silicon cost. This paper provides a new algorithmic-architectural solution for packet classification that mixes CAMs with algorithms based on multilevel cutting of the classification space into smaller spaces. The provided solution utilizes the geometrical distribution of rules in the classification space. It provides the deterministic performance of CAMs, support for dynamic updates, and added flexibility for system designers.