Dendritic cells activated with products released by schistosome larvae drive Th2-type immune responses, which can be inhibited by manipulation of CD40 costimulation

The early immune events in response to infective larvae of the parasitic helminth Schistosoma mansoni are poorly understood, but here for the first time we report on the potential of products released by schistosome larvae (material released in the first 3 It after transformation [0-3hRP]) to stimulate the maturation of dendritic cells (DC) and alter their T-cell-polarizing function. This was performed in comparison with lipopolysaccharide (LPS) and zymosan A, which classically activate DC to prime for Th1- and Th2-type responses, respectively. In our study, immature bone marrow-derived DC stimulated in vitro with 0-3hRP exhibited up-regulated expression of major histocompatibility complex class II, CD40, and CD86 and increased production of interleukin 12p40 (IL-12p40) and IL-6, albeit at lower levels than in response to LPS or zymosan A. Using an in vitro ovalbumin peptide-restricted priming assay, DC matured with 0-3hRP exhibited a potent capacity to drive Th2 polarization of CD4(+) cells from DO11.10 transgenic mice. This was characterized by increased IL-4 production (but not gamma interferon) of a magnitude similar to that primed by DC matured with zymosan A. Inoculation of DO11.10 mice with 0-3hRP-activated DC pulsed with ovalbumin peptide also led to the development of a Th2-type polarized response in the skin-draining lymph nodes and spleen. However, ligation of CD40 on DC by anti-CD40 antibody treatment reversed the ability of 0-3hRP-activated DC to prime for Th2-type responses and instead caused the induction of a more Th1-type response

Recent Load Calibrations Experience with the YF-12 Airplane

The use of calibrated strain gages to measure wing loads on the YF-12A airplane is discussed as well as structural configurations relative to the thermal environment and resulting thermal stresses. A thermal calibration of the YF-12A is described to illustrate how contaminating thermal effects can be removed from loads equations. The relationship between ground load calibrations and flight measurements is examined for possible errors, and an analytical approach to accommodate such errors is presented

A study of the effect of radical load distributions on calibrated strain gage load equations

For several decades, calibrated strain gages have been used to measure loads on airplanes. The accuracy of the equations used to relate the strain gage measurements to the applied loads has been based primarily on the results of the load calibration. An approach is presented for studying the effect of widely varying load distributions on strain gage load equations. The computational procedure provides a link between the load calibration and the load to be measured in flight. A matrix approach to equation selection is presented, which is based on equation standard error, load distribution, and influence coefficient plots of the strain gage equations, and is applied to a complex, delta-wing structure

Experimental creep data for a built-up aluminum/titanium structure subjected to heating and loading

Experimental creep, temperature, and strain data resulting from a laboratory experiment on a built-up aluminum/titanium structure are presented. The structure and the experiment are described in detail. A heating and loading experiment lasting approximately six hours is conducted on a test structure. Considerable creep strain resulted from compressive stresses in the heated skin. Large residual stresses were found after the experiment was completed. The residual stresses in the substructure frames were large enough to preclude further cycles of creep experiments with this built-up structure because of concern that the frame webs would buckle

Understanding the role of P2X7 in affective disorders—are glial cells the major players?

Pathophysiology associated with several psychiatric disorders has been linked to inflammatory biomarkers. This has generated a theory of major depressive disorders as an inflammatory disease. The idea of pro-inflammatory cytokines altering behavior is now well accepted however many questions remain. Microglia can produce a plethora of inflammatory cytokines and these cells appear to be critical in the link between inflammatory changes and depressive disorders. Microglia play a known role in sickness behavior which has many components of depressive-like behavior such as social withdrawal, sleep alterations, and anorexia. Numerous candidate genes have been identified for psychiatric disorders in the last decade. Single nucleotide polymorphisms (SNPs) in the human P2X7 gene have been linked to bipolar disorder, depression, and to the severity of depressive symptoms. P2X7 is a ligand-gated cation channel expressed on microglia with lower levels found on astrocytes and on some neuronal populations. In microglia P2X7 is a major regulator of pro-inflammatory cytokines of the interleukin-1 family. Genetic deletion of P2X7 in mice is protective for depressive behavior in addition to inflammatory responses. P2X7−/− mice have been shown to demonstrate anti-depressive-like behavior in forced swim and tail suspension behavioral tests and stressor-induced behavioral responses were blunted. Both neurochemical (norepinephrine, serotonin, and dopamine) and inflammatory changes have been observed in the brains of P2X7−/− mice. This review will discuss the recent evidence for involvement of P2X7 in the pathophysiology of depressive disorders and propose mechanisms by which altered signaling through this ion channel may affect the inflammatory state of the brain

A temporal switch model for estimating transcriptional activity in gene expression

Motivation: The analysis and mechanistic modelling of time series gene expression data provided by techniques such as microarrays, NanoString, reverse transcription–polymerase chain reaction and advanced sequencing are invaluable for developing an understanding of the variation in key biological processes. We address this by proposing the estimation of a flexible dynamic model, which decouples temporal synthesis and degradation of mRNA and, hence, allows for transcriptional activity to switch between different states. Results: The model is flexible enough to capture a variety of observed transcriptional dynamics, including oscillatory behaviour, in a way that is compatible with the demands imposed by the quality, time-resolution and quantity of the data. We show that the timing and number of switch events in transcriptional activity can be estimated alongside individual gene mRNA stability with the help of a Bayesian reversible jump Markov chain Monte Carlo algorithm. To demonstrate the methodology, we focus on modelling the wild-type behaviour of a selection of 200 circadian genes of the model plant Arabidopsis thaliana. The results support the idea that using a mechanistic model to identify transcriptional switch points is likely to strongly contribute to efforts in elucidating and understanding key biological processes, such as transcription and degradation

Hilbert Series for Flavor Invariants of the Standard Model

The Hilbert series is computed for the lepton flavor invariants of the Standard Model with three generations including the right-handed neutrino sector needed to generate light neutrino masses via the see-saw mechanism. We also compute the Hilbert series of the quark flavor invariants for the case of four generations.Comment: 6 page

The use of a simplified structural model as an aid in the strain gage calibration of a complex wing

The use of a relatively simple structural model to characterize the load responses of strain gages located on various spars of a delta wing is examined. Strains measured during a laboratory load calibration of a wing structure are compared with calculations obtained from a simplified structural analysis model. Calculated and measured influence coefficient plots that show the shear, bending, and torsion characteristics of typical strain gage bridges are presented. Typical influence coefficient plots are shown for several load equations to illustrate the derivation of the equations from the component strain gage bridges. A relatively simple structural model was found to be effective in predicting the general nature of strain distributions and influence coefficient plots. The analytical processes are shown to be an aid in obtaining a good load calibration. The analytical processes cannot, however, be used in lieu of an actual load calibration of an aircraft wing

The 5g yields 4f pionic transition in Th 232 and U 238

X ray energy measurements in 5g yields 4f pionic transitions of Th-232 and U-23