The tumour microenvironment links complement system dysregulation and hypoxic signalling.

The complement system is an innate immune pathway typically thought of as part of the first line of defence against "non-self" species. In the context of cancer, complement has been described to have an active role in facilitating cancer-associated processes such as increased proliferation, angiogenesis and migration. Several cellular members of the tumour microenvironment express and/or produce complement proteins locally, including tumour cells. Dysregulation of the complement system has been reported in numerous tumours and increased expression of complement activation fragments in cancer patient specimens correlates with poor patient prognosis. Importantly, genetic or pharmacological targeting of complement has been shown to reduce tumour growth in several cancer preclinical models, suggesting that complement could be an attractive therapeutic target. Hypoxia (low oxygen) is frequently found in solid tumours and has a profound biological impact on cellular and non-cellular components of the tumour microenvironment. In this review, we focus on hypoxia since this is a prevailing feature of the tumour microenvironment that, like increased complement, is typically associated with poor prognosis. Furthermore, interesting links between hypoxia and complement have been recently proposed but never collectively reviewed. Here, we explore how hypoxia alters regulation of complement proteins in different cellular components of the tumour microenvironment, as well as the downstream biological consequences of this regulation

De-regulation of JNK and JAK/STAT signaling in ESCRT-II mutant tissues cooperatively contributes to neoplastic tumorigenesis

Multiple genes involved in endocytosis and endosomal protein trafficking in Drosophila have been shown to function as neoplastic tumor suppressor genes (nTSGs), including Endosomal Sorting Complex Required for Transport-II (ESCRT-II) components vacuolar protein sorting 22 (vps22), vps25, and vps36. However, most studies of endocytic nTSGs have been done in mosaic tissues containing both mutant and non-mutant populations of cells, and interactions among mutant and non-mutant cells greatly influence the final phenotype. Thus, the true autonomous phenotype of tissues mutant for endocytic nTSGs remains unclear. Here, we show that tissues predominantly mutant for ESCRT-II components display characteristics of neoplastic transformation and then undergo apoptosis. These neoplastic tissues show upregulation of c-Jun N-terminal Kinase (JNK), Notch, and Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) signaling. Significantly, while inhibition of JNK signaling in mutant tissues partially inhibits proliferation, inhibition of JAK/STAT signaling rescues other aspects of the neoplastic phenotype. This is the first rigorous study of tissues predominantly mutant for endocytic nTSGs and provides clear evidence for cooperation among de-regulated signaling pathways leading to tumorigenesis

Compact x-ray source based on burst-mode inverse Compton scattering at 100 kHz

A design for a compact x-ray light source (CXLS) with flux and brilliance orders of magnitude beyond existing laboratory scale sources is presented. The source is based on inverse Compton scattering of a high brightness electron bunch on a picosecond laser pulse. The accelerator is a novel high-efficiency standing-wave linac and RF photoinjector powered by a single ultrastable RF transmitter at x-band RF frequency. The high efficiency permits operation at repetition rates up to 1 kHz, which is further boosted to 100 kHz by operating with trains of 100 bunches of 100 pC charge, each separated by 5 ns. The entire accelerator is approximately 1 meter long and produces hard x-rays tunable over a wide range of photon energies. The colliding laser is a Yb:YAG solid-state amplifier producing 1030 nm, 100 mJ pulses at the same 1 kHz repetition rate as the accelerator. The laser pulse is frequency-doubled and stored for many passes in a ringdown cavity to match the linac pulse structure. At a photon energy of 12.4 keV, the predicted x-ray flux is $5 \times 10^{11}$ photons/second in a 5% bandwidth and the brilliance is $2 \times 10^{12}\mathrm{photons/(sec\ mm^2\ mrad^2\ 0.1\%)}$ in pulses with RMS pulse length of 490 fs. The nominal electron beam parameters are 18 MeV kinetic energy, 10 microamp average current, 0.5 microsecond macropulse length, resulting in average electron beam power of 180 W. Optimization of the x-ray output is presented along with design of the accelerator, laser, and x-ray optic components that are specific to the particular characteristics of the Compton scattered x-ray pulses.Comment: 25 pages, 24 figures, 54 reference

Periscope pop-in beam monitor

The authors have built monitors for use as beam diagnostics in the narrow gap of an undulator for an FEL experiment. They utilize an intercepting screen of doped YAG scintillating crystal to make light that is imaged through a periscope by conventional video equipment. The absolute position can be ascertained by comparing the electron beam position with the position of a He:Ne laser that is observed by this pop-in monitor. The optical properties of the periscope and the mechanical arrangement of the system mean that beam can be spatially determined to the resolution of the camera, in this case approximately 10 micrometers. The experience with these monitors suggests improvements for successor designs, which they also describe

Andean Land Use And Biodiversity: Humanized Landscapes In A Time Of Change

Some landscapes Cannot be understood without reference., to the kinds. degrees, kinds, degrees, and history of human-caused modifications to the Earth's surface. The tropical latitudes of the Andes represent one such place, with agricultural land-use systems appearing in the Early Holocene. Current land use includes both intensive and extensive grazing and crop- or tree-based agricultural systems found across virtually the, entire range of possible elevations and humidity regimes. Biodiversity found in or adjacent to such humanized landscapes will have been altered in abundance. composition, and distribution in relation to the resiliency of the native Species to harvest, hold cover modifications, and other deliberate or inadvertent human land uses. In addition, the geometries of land cover, resulting flout difference among the shapes, sizes, connectivities, and physical structures of the patches, corridors, and matrices that compose landscape mosaics, will constrain biodiversity, often in predictable ways. This article proposes a conceptual model that alter ins that the Continued persistence of native species may depend as much oil the shifting Of Andean landscape mosaics as on species characteristics, themselves. Furthermore, mountains such as the Andes display long gradients of environmental Conditions that after in relation to latitude, soil moisture, aspect, and elevation. Global environmental change will shift these, especially temperature and humidity regimes along elevational gradients, causing Changes outside the historical range of variation for some species. Both land-use systems and Conservation efforts will need to respond spatially to these shifts in the future, at both landscape and regional scales.Geography and the Environmen