Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance

Although chemotherapy is designed to eradicate tumor cells, it also has significant effects on normal tissues. The platinum-induced fatty acid 16:4(n-3) (hexadeca-4,7,10,13-tetraenoic acid) induces systemic resistance to a broad range of DNA-damaging chemotherapeutics. We show that 16:4(n-3) exerts its effect by activating splenic F4/80+/CD11blow macrophages, which results in production of chemoprotective lysophosphatidylcholines (LPCs). Pharmacologic studies, together with analysis of expression patterns, identified GPR120 on F4/80+/CD11blow macrophages as the relevant receptor for 16:4(n-3). Studies that used splenocytes from GPR120-deficient mice have confirmed this conclusion. Activation of the 16:4(n-3)-GPR120 axis led to enhanced cPLA2 activity in these splenic macrophages and secretion of the resistance-inducing lipid mediator, lysophosphatidylcholine(24:1). These studies identify a novel and unexpected function for GPR120 and suggest that antagonists of this receptor might be effective agents to limit development of chemotherapy resistance.—Houthuijzen, J. M., Oosterom, I., Hudson, B. D., Hirasawa, A., Daenen, L. G. M., McLean, C. M., Hansen, S. V. F., van Jaarsveld, M. T. M., Peeper, D. S., Jafari Sadatmand, S., Roodhart, J. M. L., van de Lest, C. H. A., Ulven, T., Ishihara, K., Milligan, G., Voest, E. E. Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance

Cavity-enhanced direct frequency comb spectroscopy

Cavity-enhanced direct frequency comb spectroscopy combines broad spectral bandwidth, high spectral resolution, precise frequency calibration, and ultrahigh detection sensitivity, all in one experimental platform based on an optical frequency comb interacting with a high-finesse optical cavity. Precise control of the optical frequency comb allows highly efficient, coherent coupling of individual comb components with corresponding resonant modes of the high-finesse cavity. The long cavity lifetime dramatically enhances the effective interaction between the light field and intracavity matter, increasing the sensitivity for measurement of optical losses by a factor that is on the order of the cavity finesse. The use of low-dispersion mirrors permits almost the entire spectral bandwidth of the frequency comb to be employed for detection, covering a range of ~10% of the actual optical frequency. The light transmitted from the cavity is spectrally resolved to provide a multitude of detection channels with spectral resolutions ranging from a several gigahertz to hundreds of kilohertz. In this review we will discuss the principle of cavity-enhanced direct frequency comb spectroscopy and the various implementations of such systems. In particular, we discuss several types of UV, optical, and IR frequency comb sources and optical cavity designs that can be used for specific spectroscopic applications. We present several cavity-comb coupling methods to take advantage of the broad spectral bandwidth and narrow spectral components of a frequency comb. Finally, we present a series of experimental measurements on trace gas detections, human breath analysis, and characterization of cold molecular beams.Comment: 36 pages, 27 figure

Analysis of fracture induced scattering of microseismic shear-waves

Fractures are pervasive features within the Earth’s crust and have a significant influence on the multi-physical response of the subsurface. The presence of coherent fracture sets often leads to observable seismic scattering enabling seismic techniques to remotely locate and characterise fracture systems. In this study, we confirm the general scale-dependence of seismic scattering and provide new results specific to shear-wave propagation. We do this by generating full waveform synthetics using finite-difference wave simulation within an isotropic background model containing explicit fractures. By considering a suite of fracture models having variable fracture density and fracture size, we examine the widening effect of wavelets due to scattering within a fractured medium by using several different approaches, such as root-mean-square envelope analysis, shear-wave polarisation distortion, differential attenuation analysis and peak frequency shifting. The analysis allows us to assess the scattering behavior of parametrised models in which the propagation direction is either normal or parallel to the fracture surfaces. The quantitative measures show strong observable deviations for fractures size on the order of or greater than the dominant seismic wavelength within the Mie and geometric scattering regime for both propagation normal and parallel to fracture strike. The results suggest that strong scattering is symptomatic of fractures having size on the same order of the probing seismic wave

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

Mineral deficiency and the presence of Pinus sylvestris on mires during the mid- to late Holocene: Palaeoecological data from Cadogan's Bog, Mizen Peninsula, Co. Cork, southwest Ireland

Pollen records across parts of Ireland, England and northern Scotland show a dramatic collapse in Pinus pollen percentages at approximately 4000 radiocarbon years BP. This phenomenon has attracted much palaeoecological interest and several hypotheses have been put forward to account for this often synchronous and rapid reduction in pine from mid-Holocene woodland. Explanations for the 'pine decline' include prehistoric human activity, climatic change, in particular a substantial increase in precipitation resulting in increased mire wetness, and airborne pollution associated with the deposition of tephra. Hitherto, one largely untested hypothesis is that mineral deficiency could adversely affect pine growth and regeneration on mire surfaces. The discovery of pine-tree remains (wood pieces, stumps and trunks) within a peat located at Cadogan's Bog on the Mizen Peninsula, southwest Ireland, provided an opportunity to investigate the history of Pinus sylvestris and also to assess the importance of mineral nutrition in maintaining pine growth on mires. Pollen, plant macrofossils, microscopic charcoal and geochemical data are presented from a radiocarbon dated monolith extracted from this peat together with tree ring-width data and radiocarbon dated age estimates from subfossil wood. Analyses of these data suggest that peat accumulation commenced at the site around 6000 years BP when pine was the dominant local tree. Thereafter Pinus pollen percentages diminish in two stages, with the second decline taking place around 4160 ± 50 years BP. Concomitant with this decline in Pinus pollen, there is a noticeable, short-lived increase in wet-loving mire taxa and a decrease in the concentration of phosphorus, potassium, magnesium, calcium, sodium, iron and zinc. These results suggest that increased mire surface wetness, possibly the result of a change in climate, created conditions unsuitable for pine growth c. 4000 years BP. Mire surface wetness, coupled with a period of associated nutrient deficiency, appears to be a possible explanation for a lack of subsequent pine-seedling establishment for most of the later Holocene