The crucial role of the immune system in the formation and progression of tumors has been widely accepted. On one hand, the surveillance role of the immune system plays an important role in ...endogenous tumor prevention, but on the other hand, in some special circumstances such as in chronic inflammation, the immune system can actually contribute to the formation and progression of tumors. In recent years, there has been an explosion of novel targeted immunotherapies for advanced cancers. In the present manuscript, we explore known and potential various types of cancer prevention strategies and focus on nonvaccine-based cancer preventive strategies targeting the immune system at the early stages of tumorigenesis.
We present the stellar atmospheric parameters (effective temperature, surface gravity, overall metallicity), radial velocities, individual abundances, and distances determined for 425,561 stars, ...which constitute the fourth public data release of the RAdial Velocity Experiment (RAVE). The stellar atmospheric parameters are computed using a new pipeline, based on the algorithms of MATISSE and DEGAS. The spectral degeneracies and the Two Micron All Sky Survey photometric information are now better taken into consideration, improving the parameter determination compared to the previous RAVE data releases. The individual abundances for six elements (magnesium, aluminum, silicon, titanium, iron, and nickel) are also given, based on a special-purpose pipeline that is also improved compared to that available for the RAVE DR3 and Chemical DR1 data releases. Together with photometric information and proper motions, these data can be retrieved from the RAVE collaboration Web site and the Vizier database.
We present the first data release of the Radial Velocity Experiment (RAVE), an ambitious spectroscopic survey to measure radial velocities and stellar atmosphere parameters (temperature, metallicity, ...and surface gravity) of up to one million stars using the Six Degree Field multiobject spectrograph on the 1.2 m UK Schmidt Telescope of the Anglo-Australian Observatory. The RAVE program started in 2003, obtaining medium-resolution spectra (median R = 7500) in the Ca-triplet region (8410-8795 A) for southern hemisphere stars drawn from the Tycho-2 and SuperCOSMOS catalogs, in the magnitude range 9 < I < 12. The first data release is described in this paper and contains radial velocities for 24,748 individual stars (25,274 measurements when including reobservations). Those data were obtained on 67 nights between 2003 April 11 and 2004 April 3. The total sky coverage within this data release is ~4760 deg2. The average signal-to-noise ratio of the observed spectra is 29.5, and 80% of the radial velocities have uncertainties better than 3.4 km s-1. Combining internal errors and zero-point errors, the mode is found to be 2 km s-1. Repeat observations are used to assess the stability of our radial velocity solution, resulting in a variance of 2.8 km s-1. We demonstrate that the radial velocities derived for the first data set do not show any systematic trend with color or signal-to-noise ratio. The RAVE radial velocities are complemented in the data release with proper motions from Starnet 2.0, Tycho-2, and SuperCOSMOS, in addition to photometric data from the major optical and infrared catalogs (Tycho-2, USNO-B, DENIS, and the Two Micron All Sky Survey). The data release can be accessed via the RAVE Web site.
We report the first short-pulse amplification results to several hundred millijoule energies in ceramic Yb:LuAG. We have demonstrated ns-pulse output from a diode-pumped Yb:LuAG amplifier at a ...maximum energy of 580 mJ and a peak optical-to-optical efficiency of 28% at 550 mJ. In cavity dumped operation of a nanosecond oscillator we obtained 1 mJ at up to 100 Hz repetition rate. A gain bandwidth of 5.4 nm was achieved at room temperature by measuring the small-signal single-pass gain. Furthermore, we compared our results with Yb:YAG within the same amplifier system.
Photocatalytic reduction of molecular oxygen is a promising route toward sustainable production of hydrogen peroxide (H2O2). This challenging process requires photoactive semiconductors enabling ...solar energy driven generation and separation of electrons and holes with high charge transfer kinetics. Covalent organic frameworks (COFs) are an emerging class of photoactive semiconductors, tunable at a molecular level for high charge carrier generation and transfer. Herein, we report two newly designed two-dimensional COFs based on a (diarylamino)benzene linker that form a Kagome (kgm) lattice and show strong visible light absorption. Their high crystallinity and large surface areas (up to 1165 m2·g–1) allow efficient charge transfer and diffusion. The diarylamine (donor) unit promotes strong reduction properties, enabling these COFs to efficiently reduce oxygen to form H2O2. Overall, the use of a metal-free, recyclable photocatalytic system allows efficient photocatalytic solar transformations.
Time-resolved measurements of the spectral dielectric function reveal new information about ultrafast phase transitions induced by femtosecond laser pulses in Sb-rich amorphous GeSb films. The ...excitation generates a nonthermal phase within 200 fs. The dielectric function of this phase differs from that of the crystalline phase, contrary to previous suggestions of a disorder-to-order transition. The observed dielectric function is close to that of the liquid phase, indicating an ultrafast transition from the amorphous phase to a different disordered state.
Many human cancers are dramatically accelerated by chronic inflammation. However, the specific cellular and molecular elements mediating this effect remain largely unknown. Using a murine model of ...pancreatic intraepithelial neoplasia (PanIN), we found that KrasG12D induces expression of functional IL-17 receptors on PanIN epithelial cells and also stimulates infiltration of the pancreatic stroma by IL-17-producing immune cells. Both effects are augmented by associated chronic pancreatitis, resulting in functional in vivo changes in PanIN epithelial gene expression. Forced IL-17 overexpression dramatically accelerates PanIN initiation and progression, while inhibition of IL-17 signaling using genetic or pharmacologic techniques effectively prevents PanIN formation. Together, these studies suggest that a hematopoietic-to-epithelial IL-17 signaling axis is a potent and requisite driver of PanIN formation.
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•IL-17+ T cells are recruited to the pancreas in response to Kras and inflammation•IL-17A overexpression accelerates PanIN initiation and progression•Inhibition of IL-17 signaling effectively prevents PanIN initiation and progression•Kras activates expression of functional IL-17 receptors on PanIN epithelium
McAllister et al. show that KrasG12D induces IL-17 receptors expression on PanIN epithelial cells and stimulates infiltration of IL-17-producing immune cells in a murine PanIN model, the latter of which is confirmed in human PanIN and that inhibition of IL-17 signaling prevents pancreatic neoplasia initiation.
The androgen-receptor isoform encoded by splice variant 7 lacks the ligand-binding domain, which is the target of enzalutamide and abiraterone, but remains constitutively active as a transcription ...factor. We hypothesized that detection of androgen-receptor splice variant 7 messenger RNA (AR-V7) in circulating tumor cells from men with advanced prostate cancer would be associated with resistance to enzalutamide and abiraterone.
We used a quantitative reverse-transcriptase-polymerase-chain-reaction assay to evaluate AR-V7 in circulating tumor cells from prospectively enrolled patients with metastatic castration-resistant prostate cancer who were initiating treatment with either enzalutamide or abiraterone. We examined associations between AR-V7 status (positive vs. negative) and prostate-specific antigen (PSA) response rates (the primary end point), freedom from PSA progression (PSA progression-free survival), clinical or radiographic progression-free survival, and overall survival.
A total of 31 enzalutamide-treated patients and 31 abiraterone-treated patients were enrolled, of whom 39% and 19%, respectively, had detectable AR-V7 in circulating tumor cells. Among men receiving enzalutamide, AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients (0% vs. 53%, P=0.004) and shorter PSA progression-free survival (median, 1.4 months vs. 6.0 months; P<0.001), clinical or radiographic progression-free survival (median, 2.1 months vs. 6.1 months; P<0.001), and overall survival (median, 5.5 months vs. not reached; P=0.002). Similarly, among men receiving abiraterone, AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients (0% vs. 68%, P=0.004) and shorter PSA progression-free survival (median, 1.3 months vs. not reached; P<0.001), clinical or radiographic progression-free survival (median, 2.3 months vs. not reached; P<0.001), and overall survival (median, 10.6 months vs. not reached, P=0.006). The association between AR-V7 detection and therapeutic resistance was maintained after adjustment for expression of full-length androgen receptor messenger RNA.
Detection of AR-V7 in circulating tumor cells from patients with castration-resistant prostate cancer may be associated with resistance to enzalutamide and abiraterone. These findings require large-scale prospective validation. (Funded by the Prostate Cancer Foundation and others.).
Covalent triazine frameworks (CTFs) are a class of porous organic polymers that continuously attract growing interest because of their outstanding chemical and physical properties. However, the ...control of extended porous organic framework structures at the molecular scale for a precise adjustment of their properties has hardly been achieved so far. Here, we present a series of bipyridine-based CTFs synthesized through polycondensation, in which the sequence of specific building blocks is well controlled. The reported synthetic strategy allows us to tailor the physicochemical features of the CTF materials, including the nitrogen content, the apparent specific surface area, and optoelectronic properties. Based on a comprehensive analytical investigation, we demonstrate a direct correlation of the CTF bipyridine content with the material features such as the specific surface area, band gap, charge separation, and surface wettability with water. The entirety of these parameters dictates the catalytic activity as demonstrated for the photocatalytic hydrogen evolution reaction (HER). The material with the optimal balance between optoelectronic properties and highest hydrophilicity enables HER production rates of up to 7.2 mmol/(h·g) under visible light irradiation and in the presence of a platinum cocatalyst.
The "Cosmic Evolution Survey" (COSMOS) enables the study of the spectral energy distributions (SEDs) of active galactic nuclei (AGNs) because of the deep coverage and rich sampling of frequencies ...from X-ray to radio. Here we present an SED catalog of 413 X-ray (XMM-Newton)-selected type 1 (emission line FWHM > 2000 km s super(-1)) AGNs with Magellan, SDSS, or VLT spectrum. The SEDs are corrected for Galactic extinction, broad emission line contributions, constrained variability, and host galaxy contribution. We present the mean SED and the dispersion SEDs after the above corrections in the rest-frame 1.4 GHz to 40 keV, and show examples of the variety of SEDs encountered. In the near-infrared to optical (rest frame ~8 mum-4000 A), the photometry is complete for the whole sample and the mean SED is derived from detections only. Reddening and host galaxy contamination could account for a large fraction of the observed SED variety. The SEDs are all available online.
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