Expression of LAG-3 by tumor-infiltrating lymphocytes is coincident with the suppression of latent membrane antigen-specific CD8(+) T-cell function in Hodgkin lymphoma patients

In Hodgkin lymphoma (HL), the malignant Hodgkin Reed-Sternberg (HRS) cells constitute only 0.5% of 10% of the diseased tissue. The surrounding cellular infiltrate is enriched with T cells that are hypothesized to modulate antitumor immunity. We show that a marker of regulatory T cells, LAG-3, is strongly expressed on infiltrating lymphocytes present in proximity to HRS cells. Circulating regulatory T cells (CD4(+) CD25(hi) CD45 ROhi, CD4(+) CTLA4(hi), and CD4(+) LAG-3(hi)) were elevated in HL patients with active disease when compared with remission. Longitudinal profiling of EBV-specific CD8(+) T-cell responses in 94 HL patients revealed a selective loss of interferon-gamma expression by CD8(+) T cells specific for latent membrane proteins 1 and 2 (LMP1/2), irrespective of EBV tissue status. Intratumoral LAG-3 expression was associated with EBV tissue positivity, whereas FOXP3 was linked with neither LAG-3 nor EBV tissue status. The level of LAG-3 and FOXP3 expression on the tumor-infiltrating lymphocytes was coincident with impairment of LMP1/2-specific T-cell function. In vitro pre-exposure of peripheral blood mono-nuclear cells to HRS cell line supernatant significantly increased the expansion of regulatory T cells and suppressed LMP-specific T-cell responses. Deletion of CD4(+) LAG-3(+) T cells enhanced LMP-specific reactivity. These findings indicate a pivotal role for regulatory T cells and LAG-3 in the suppression of EBV-specific cell-mediated immunity in HL.

Observation of the suppression of water uptake by marine particles

A 4 week intensive measurement campaign was conducted in March–April 2007 at Agnes Water, a remote coastal site on the east coast of Australia. A Volatility-Hygroscopicity-Tandem Differential Mobility Analyser (VH-TDMA) was used to investigate changes in the hygroscopic properties of ambient particles as volatile components were progressively evaporated. Nine out of 18 VH-TDMA volatility scans detected internally mixed multi-component particles in the nucleation and Aitken modes in clean marine air. Evaporation of a volatile, organic-like component in the VH-TDMA caused significant increases in particle hygroscopicity. In 3 scans the increase in hygroscopicity was so large it was explained by an increase in the absolute volume of water uptake by the particle residuals, and not merely an increase in their relative hygroscopicity. This indicates the presence of organic components that were suppressing the hygroscopic growth of mixed particles on the timescale of humidification in the VH-TDMA (6.5 secs). This observation was supported by ZSR calculations for one scan, which showed that the measured growth factors of mixed particles were up to 18% below those predicted assuming independent water uptake of the individual particle components. The observed suppression of water uptake could be due to a reduced rate of hygroscopic growth caused by the presence of organic films or organic-inorganic interactions in solution droplets that had a negative effect on hygroscopicity.

Promoting the institutional repository at the University of West London

Implementing resource discovery techniques at the University of West London Promoting the institutional repository at the University of West London

Fundamental limits on the suppression of molecular fluctuations.

Negative feedback is common in biological processes and can increase a system's stability to internal and external perturbations. But at the molecular level, control loops always involve signalling steps with finite rates for random births and deaths of individual molecules. Here we show, by developing mathematical tools that merge control and information theory with physical chemistry, that seemingly mild constraints on these rates place severe limits on the ability to suppress molecular fluctuations. Specifically, the minimum standard deviation in abundances decreases with the quartic root of the number of signalling events, making it extremely expensive to increase accuracy. Our results are formulated in terms of experimental observables, and existing data show that cells use brute force when noise suppression is essential; for example, regulatory genes are transcribed tens of thousands of times per cell cycle. The theory challenges conventional beliefs about biochemical accuracy and presents an approach to the rigorous analysis of poorly characterized biological systems.

A study of the suppression of the high-temperature helium embrittlement in an oxide-particle dispersion strengthened alloy

In this paper, an investigation on the micro-structure of an Fe-base oxide-dispersion-strengthened (ODS) alloy irradiated with high-energy Ne-20 ions to different doses at a temperature around 0.5T(m) (T-m is the melting point of the alloy) is presented. Investigation with the transmission electron microscopy found that the accelerated growth of voids at grain-boundaries, which is usually a concern in conventional Fe-base alloys under conditions of inert-gas implantation, was not observed in the ODS alloy irradiated even to the highest dose (12000 at.ppm Ne). The reason is ascribed to the enhanced recombination of point defects and strong trapping of Ne atoms at the interfaces of the nano-scale oxide particles in grains. The study showed that ODS alloys have good resistance to the high-temperature inter-granular embrittlement due to inert-gas accumulation, exhibiting prominence of application in harsh situations of considerable helium production at elevated temperatures like in a fusion reactor.

The suppression of Ge-132 on the Maillard reaction of BSA by fluorescence spectrum

The fluorescences of BSA and glycosylated BSA were observed respectively. The lambda(cm) of BSA was 340 nm; while the lambda(cm) of glycosylated BSA was 436 nm. Because the fluorescence spectra of them were different greatly, we can observe the suppression of Ge-132 on the Maillard reaction of BSA without any interference of itself. It was showed that the fluorescence intensity of glycosylated BSA increased continuously with the cultured time, Ge-132 may suppress the Maillard reaction of BSA greatly, and the suppressing efficicency would be 32 %. The key site of the Maillard reaction of BSA is free amino groups of alanine residues on N-terminal amino group, besides the epsilon-amino groups of intrachain Lysine residues.

The Film Society and the Creation of an Alternative Film Culture in Britain in the 1920's

Sexton, J. (2002). The Film Society and the Creation of an Alternative Film Culture in Britain in the 1920's. In A. Higson (Ed.), Young and Innocent?: The Cinema in Britain 1896-1930 (pp.291-305). Exeter: University of Exeter Press. RAE2008

Alternative antecedents, probabilities, and the suppression of fallacies in Wason's selection task

Three experiments examined the influence of a second rule on the pattern of card selections on Wason's selection task. In Experiment 1 participants received a version of the task with a single test rule or one of two versions of the task with the same original test rule together with a second rule. The probability of q was manipulated in the two-rules conditions by varying the size of the antecedent set in the second rule. The results showed a significant suppression of q card and not-p card selections in the alternative-rule conditions, but no difference as a function of antecedent set size. In Experiment 2 the size of the antecendent set in the two-rules conditions was manipulated using the context of a computer printing double-sided cards. The results showed a significant reduction of q card selections in the two-rules conditions, but no effect of p set size. In Experiment 3 the scenario accompanying the rule was manipulated, and it specified a single alternative antecedent or a number of alternative antecedents. The q card selection rates were not affected by the scenario manipulation but again were suppressed by the presence of a second rule. Our results suggest that people make inferences about the unseen side of the cards when engaging with the task and that these inferences are systematically influenced by the presence of a second rule, but are not influenced by the probabilistic characteristics of this rule. These findings are discussed in the context of decision theoretic views of selection task performance (Oaksford Chater, 1994).

The suppression of q card selections: Evidence for deductive inference in Wason's Selection Task

The results of three experiments investigating the role of deductive inference in Wason's selection task are reported. In Experiment 1, participants received either a standard one-rule problem or a task containing a second rule, which specified an alternative antecedent. Both groups of participants were asked to select those cards that they considered were necessary to test whether the rule common to both problems was true or false. The results showed a significant suppression of q card selections in the two-rule condition. In addition there was weak evidence for both decreased p selection and increased not-q selection. In Experiment 2 we again manipulated number of rules and found suppression of q card selections only. Finally, in Experiment 3 we compared one- and two-rule conditions with a two-rule condition where the second rule specified two alternative antecedents in the form of a disjunction. The q card selections were suppressed in both of the two-rule conditions but there was no effect of whether the second rule contained one or two alternative antecedents. We argue that our results support the claim that people make inferences about the unseen side of the cards when engaging with the indicative selection task.