Mapping of the Epstein-Barr virus and C3dg binding sites to a common domain on complement receptor type 2.

Complement receptor type 2 (CR2;CD21), a member of the superfamily of proteins containing short consensus repeats (SCRs), is the B cell receptor for both the gp350/220 envelope protein of Epstein-Barr virus (EBV), and for the C3dg protein of complement. By analysis of CR2 deletion mutants and chimeras formed with CR1 (CD35) we determined that of the 15 SCRs in CR2, the NH2-terminal two SCRs are necessary and sufficient to bind both gp350/220 and C3dg with affinities equivalent to those of the wild-type receptor. The epitope for OKB-7, a mAb that blocks binding of both EBV and C3dg and shares with these ligands B cell-activating capabilities, also requires both SCR-1 and SCR-2, whereas mAbs lacking these functions bind to other SCRs. Thus, EBV, a polyclonal activator of B cells, has selected a site that is proximate or identical to the natural ligand binding site in CR2, perhaps reflecting the relative immutability of that site as well as its signal transducing function

Synchrotron X-Ray Scattering as a Tool for Characterising Catalysts on Multiple Length Scales

Optimising the properties of catalysts for industrial processes requires a detailed knowledge of their structure and properties on multiple length scales. Synchrotron light sources are ideal tools for characterising catalyts for industrial R&D, providing data with high temporal and spatial resolution, under realistic operating conditions, in a non-destructive way. Here, we describe the different synchrotron techniques that can be employed to gain a wealth of complementary information, and highlight recent developments that have allowed remarkable insight to be gained into working catalytic systems. These techniques have the potential to guide future industrial catalyst design

Pattern scaling using ClimGen: monthly-resolution future climate scenarios including changes in the variability of precipitation

Development, testing and example applications of the pattern-scaling approach for generating future climate change projections are reported here, with a focus on a particular software application called “ClimGen”. A number of innovations have been implemented, including using exponential and logistic functions of global-mean temperature to represent changes in local precipitation and cloud cover, and interpolation from climate model grids to a finer grid while taking into account land-sea contrasts in the climate change patterns. Of particular significance is a new approach for incorporating changes in the inter-annual variability of monthly precipitation simulated by climate models. This is achieved by diagnosing simulated changes in the shape of the gamma distribution of monthly precipitation totals, applying the pattern-scaling approach to estimate changes in the shape parameter under a future scenario, and then perturbing sequences of observed precipitation anomalies so that their distribution changes according to the projected change in the shape parameter. The approach cannot represent changes to the structure of climate timeseries (e.g. changed autocorrelation or teleconnection patterns) were they to occur, but is shown here to be more successful at representing changes in low precipitation extremes than previous pattern-scaling methods

Organic Carbon Emissions from the Co-firing of Coal and Wood in a Fixed Bed Combustor

Co-firing of biomass and coal and biomass reduces the emission of pollutants and the overall effects have been extensively studied, but many aspects of the detailed mechanism remain uncertain. A number of studies have been previously made by us of emissions from the combustion in a fixed-bed furnace of bituminous coal and wood, both individually and together, and it was observed that biomass produced less soot and lower NOX emissions. These data are combined with recent measurements of emissions of black carbon (BC) and organic carbon (OC), which are an important source of climate forcing, from the combustion of a number of solid fuels. Conclusion are drawn about the nature of the OC and how the values are dependent on the measurement technique used. Complementary analytical-scale combustion and pyrolysis experiments were also carried out. The results of the analysis of emissions and reaction products, mainly by gas chromatography–mass spectrometry (GC–MS), were interpreted so as to construct a model for pollutant formation during co-firing

Genome-wide profiling of uncapped mRNA

Gene transcripts are under extensive posttranscriptional regulation, including the regulation of their stability. A major route for mRNA degradation produces uncapped mRNAs, which can be generated by decapping enzymes, endonucleases, and small RNAs. Profiling uncapped mRNA molecules is important for the understanding of the transcriptome, whose composition is determined by a balance between mRNA synthesis and degradation. In this chapter, we describe a method to profile these uncapped mRNAs at the genome scale

An evaluation of enteral nutrition practices and nutritional provision in children during the entire length of stay in critical care

<b>Background</b> Provision of optimal nutrition in children in critical care is often challenging. This study evaluated exclusive enteral nutrition (EN) provision practices and explored predictors of energy intake and delay of EN advancement in critically ill children.<p></p> <b>Methods</b> Data on intake and EN practices were collected on a daily basis and compared against predefined targets and dietary reference values in a paediatric intensive care unit. Factors associated with intake and advancement of EN were explored.<p></p> <b>Results</b> Data were collected from 130 patients and 887 nutritional support days (NSDs). Delay to initiate EN was longer in patients from both the General Surgical and congenital heart defect (CHD) Surgical groups [Median (IQR); CHD Surgical group: 20.3 (16.4) vs General Surgical group: 11.4 (53.5) vs Medical group: 6.5 (10.9) hours; p <= 0.001]. Daily fasting time per patient was significantly longer in patients from the General Surgical and CHD Surgical groups than those from the Medical group [% of 24 h, Median (IQR); CHD Surgical group: 24.0 (29.2) vs General Surgical group: 41.7 (66.7) vs Medical group: 9.4 (21.9); p <= 0.001]. A lower proportion of fluids was delivered as EN per patient (45% vs 73%) or per NSD (56% vs 73%) in those from the CHD Surgical group compared with those with medical conditions. Protein and energy requirements were achieved in 38% and 33% of the NSDs. In a substantial proportion of NSDs, minimum micronutrient recommendations were not met particularly in those patients from the CHD Surgical group. A higher delivery of fluid requirements (p < 0.05) and a greater proportion of these delivered as EN (p < 0.001) were associated with median energy intake during stay and delay of EN advancement. Fasting (31%), fluid restriction (39%) for clinical reasons, procedures requiring feed cessation and establishing EN (22%) were the most common reasons why target energy requirements were not met.<p></p> <b>Conclusions</b> Provision of optimal EN support remains challenging and varies during hospitalisation and among patients. Delivery of EN should be prioritized over other "non-nutritional" fluids whenever this is possible.<p></p&gt

Adaptive multiphoton endomicroscopy through a dynamically deformed multicore optical fiber using proximal detection

This paper demonstrates multiphoton excited fluorescence imaging through a polarisation maintaining multicore fiber (PM-MCF) while the fiber is dynamically deformed using all-proximal detection. Single-shot proximal measurement of the relative optical path lengths of all the cores of the PM-MCF in double pass is achieved using a Mach-Zehnder interferometer read out by a scientific CMOS camera operating at 416 Hz. A non-linear least squares fitting procedure is then employed to determine the deformation-induced lateral shift of the excitation spot at the distal tip of the PM-MCF. An experimental validation of this approach is presented that compares the proximally measured deformation-induced lateral shift in focal spot position to an independent distally measured ground truth. The proximal measurement of deformation-induced shift in focal spot position is applied to correct for deformation-induced shifts in focal spot position during raster-scanning multiphoton excited fluorescence imaging

Factors associated with medication adherence in school-aged children with asthma

Adherence to preventive asthma treatment is poor, particularly in children, yet the factors associated with adherence in this age group are not well understood. Adherence was monitored electronically over 6 months in school-aged children who attended a regional emergency department in New Zealand for an asthma exacerbation and were prescribed twice-daily inhaled corticosteroids. Participants completed questionnaires including assessment of family demographics, asthma responsibility and learning style. Multivariable analysis of factors associated with adherence was conducted. 101 children (mean (range) age 8.9 (6-15) years, 51% male) participated. Median (interquartile range) preventer adherence was 30% (17-48%) of prescribed. Four explanatory factors were identified: female sex (+12% adherence), Asian ethnicity (+19% adherence), living in a smaller household (-3.0% adherence per person in the household), and younger age at diagnosis (+2.7% for every younger year of diagnosis) (all p<0.02). In school-aged children attending the emergency department for asthma, males and non-Asian ethnic groups were at high risk for poor inhaled corticosteroid adherence and may benefit most from intervention. Four factors explained a small proportion of adherence behaviour indicating the difficulty in identifying adherence barriers. Further research is recommended in other similar populations

Signature of effective mass in crackling noise asymmetry

Crackling noise is a common feature in many dynamic systems [1-9], the most familiar instance of which is the sound made by a sheet of paper when crumpled into a ball. Although seemingly random, this noise contains fundamental information about the properties of the system in which it occurs. One potential source of such information lies in the asymmetric shape of noise pulses emitted by a diverse range of noisy systems [8-12], but the cause of this asymmetry has lacked explanation [1]. Here we show that the leftward asymmetry observed in the Barkhausen effect [2] - the noise generated by the jerky motion of domain walls as they interact with impurities in a soft magnet - is a direct consequence of a magnetic domain wall's negative effective mass. As well as providing a means of determining domain wall effective mass from a magnet's Barkhausen noise our work suggests an inertial explanation for the origin of avalanche asymmetries in crackling noise phenomena more generally.Comment: 13 pages, 4 figures, to appear in Nature Physic

Evidence of a metabolic memory to early-life dietary restriction in male C57BL/6 mice

&lt;p&gt;Background: Dietary restriction (DR) extends lifespan and induces beneficial metabolic effects in many animals. What is far less clear is whether animals retain a metabolic memory to previous DR exposure, that is, can early-life DR preserve beneficial metabolic effects later in life even after the resumption of ad libitum (AL) feeding. We examined a range of metabolic parameters (body mass, body composition (lean and fat mass), glucose tolerance, fed blood glucose, fasting plasma insulin and insulin-like growth factor 1 (IGF-1), insulin sensitivity) in male C57BL/6 mice dietary switched from DR to AL (DR-AL) at 11 months of age (mid life). The converse switch (AL-DR) was also undertaken at this time. We then compared metabolic parameters of the switched mice to one another and to age-matched mice maintained exclusively on an AL or DR diet from early life (3 months of age) at 1 month, 6 months or 10 months post switch.&lt;/p&gt; &lt;p&gt;Results: Male mice dietary switched from AL-DR in mid life adopted the metabolic phenotype of mice exposed to DR from early life, so by the 10-month timepoint the AL-DR mice overlapped significantly with the DR mice in terms of their metabolic phenotype. Those animals switched from DR-AL in mid life showed clear evidence of a glycemic memory, with significantly improved glucose tolerance relative to mice maintained exclusively on AL feeding from early life. This difference in glucose tolerance was still apparent 10 months after the dietary switch, despite body mass, fasting insulin levels and insulin sensitivity all being similar to AL mice at this time.&lt;/p&gt; &lt;p&gt;Conclusions: Male C57BL/6 mice retain a long-term glycemic memory of early-life DR, in that glucose tolerance is enhanced in mice switched from DR-AL in mid life, relative to AL mice, even 10 months following the dietary switch. These data therefore indicate that the phenotypic benefits of DR are not completely dissipated following a return to AL feeding. The challenge now is to understand the molecular mechanisms underlying these effects, the time course of these effects and whether similar interventions can confer comparable benefits in humans.&lt;/p&gt