Immunomodulatory Agents with Antivascular Activity in the Treatment of Non-Small Cell Lung Cancer: Focus on TLR9 Agonists, IMiDs and NGR-TNF

Standard treatments for nonsmall cell lung cancer (NSCLC), such as surgery, chemotherapy, and radiotherapy, often lead to disappointing results. Unfortunately, also the various immunotherapeutic approaches so far tested have not produced satisfactory results to be widely applied in the clinical practice. However, the recent development of new immunomodulatory agents may open promising therapeutic options. This paper focuses on PF3512676, lenalidomide, and NGR-TNF, that is, drugs belonging to three different classes of immunomodulatory agents, that are also capable to affect tumor blood vessels with different mechanisms, and discusses the potential role of such agents in NSCLC treatment strategy

High-Sensitivity 86GHz (3.5mm) VLBI Observations of M87: Deep Imaging of the Jet Base at a 10 Schwarzschild-Radius Resolution

We report on results from new high-sensitivity, high-resolution 86GHz (3.5 millimeter) observations of the jet base in the nearby radio galaxy M87, obtained by the Very Long Baseline Array in conjunction with the Green Bank Telescope. The resulting image has a dynamic range exceeding 1500 to 1, the highest ever achieved for this jet at this frequency, resolving and imaging a detailed jet formation/collimation structure down to ~10 Schwarzschild radii (Rs). The obtained 86GHz image clearly confirms some important jet features known at lower frequencies, i.e., a wide-opening angle jet base, a limb-brightened intensity profile, a parabola-shape collimation profile and a counter jet. The limb-brightened structure is already well developed at < 0.2mas (< 28Rs, projected) from the core, where the corresponding apparent opening angle becomes as wide as ~100 degrees. The subsequent jet collimation near the black hole evolves in a complicated manner; there is a "constricted" structure at tens Rs from the core, where the jet cross section is locally shrinking. We suggest that an external pressure support from the inner part of radiatively-inefficient accretion flow may be dynamically important in shaping/confining the footprint of the magnetized jet. We also present the first VLBI 86GHz polarimetric experiment for this source, where a highly polarized (~20%) feature is detected near the jet base, indicating the presence of a well-ordered magnetic field. As a by-product, we additionally report a 43/86 GHz polarimetric result for our calibrator 3C 273 suggesting an extreme rotation measure near the core.Comment: Accepted for publication in ApJ. 39 pages, 11 figures, 3 table

Arbuscular Mycorrhizal Fungi and Associated Microbiota as Plant Biostimulants: Research Strategies for the Selection of the Best Performing Inocula

Arbuscular mycorrhizal fungi (AMF) are beneficial soil microorganisms establishing mutualistic symbioses with the roots of the most important food crops and playing key roles in the maintenance of long-term soil fertility and health. The great inter- and intra-specific AMF diversity can be fully exploited by selecting AMF inocula on the basis of their colonization ability and efficiency, which are aaffected by fungal and plant genotypes and diverse environmental variables. The multiple services provided by AMF are the result of the synergistic activities of the bacterial communities living in the mycorrhizosphere, encompassing nitrogen fixation, P solubilization, and the production of phytohormones, siderophores, and antibiotics. The tripartite association among host plants, mycorrhizal symbionts, and associated bacteria show beneficial emerging properties which could be efficiently exploited in sustainable agriculture. Further in-depth studies, both in microcosms and in the field, performed on different AMF species and isolates, should evaluate their colonization ability, efficiency, and resilience. Transcriptomic studies can reveal the expression levels of nutrient transporter genes in fungal absorbing hyphae in the presence of selected bacterial strains. Eventually, newly designed multifunctional microbial consortia can be utilized as biofertilizers and biostimulants in sustainable and innovative production systems

VERA monitoring of the radio jet 3C 84 during 2007--2013: detection of non-linear motion

We present a kinematic study of the subparsec-scale radio jet of the radio galaxy 3C 84/NGC 1275 with the VLBI Exploration of Radio Astrometry (VERA) array at 22 GHz for 80 epochs from 2007 October to 2013 December. The averaged radial velocity of the bright component "C3" with reference to the radio core is found to be $0.27 pm 0.02c$ between 2007 October and 2013 December. This constant velocity of C3 is naturally explained by the advancing motion of the head of the mini-radio lobe. We also find a non-linear component in the motion of C3 with respect to the radio core. We briefly discuss possible origins of this non-linear motion.Comment: 11 pages, 7 figures, 8 tables (table 1 - 5 are supplementaries), accepted for publication on PAS

Collimation, Acceleration and Recollimation Shock in the Jet of Gamma-Ray-emitting Radio-Loud Narrow-Line Seyfert 1 Galaxy 1H 0323+342

We investigated the detailed radio structure of the jet of 1H 0323+342 using high-resolution multi-frequency Very Long Baseline Array observations. This source is known as the nearest $\gamma$-ray emitting radio-loud narrow-line Seyfert 1 (NLS1) galaxy. We discovered that the morphology of the inner jet is well characterized by a parabolic shape, indicating the jet being continuously collimated near the jet base. On the other hand, we found that the jet expands more rapidly at larger scales, resulting in a conical-like shape. The location of the "collimation break" is coincident with a bright quasi-stationary feature at 7 mas from core (corresponding to a deprojected distance of the order of $\sim$100pc), where the jet width locally contracts together with highly polarized signals, suggesting a recollimation shock. We found that the collimation region is coincident with the region where the jet speed gradually accelerates, suggesting the coexistence of the jet acceleration and collimation zone, ending up with the recollimation shock, which could be a potential site of high-energy $\gamma$-ray flares detected by the Fermi-LAT. Remarkably, these observational features of the 1H 0323+342 jet are overall very similar to those of the nearby radio galaxy M87 and HST-1 as well as some blazars, suggesting that a common jet formation mechanism might be at work. Based on the similarity of the jet profile between the two sources, we also briefly discuss the mass of the central black hole of 1H 0323+342, which is also still highly controversial on this source and NLS1s in general.Comment: Accepted for publication in ApJ. 15pages, 9 figure

Parabolic Jets from the Spinning Black Hole in M87

The M87 jet is extensively examined by utilizing general relativistic magnetohydrodynamic (GRMHD) simulations as well as the steady axisymmetric force-free electrodynamic (FFE) solution. Quasi-steady funnel jets are obtained in GRMHD simulations up to the scale of $\sim 100$ gravitational radius ($r_{\rm g}$) for various black hole (BH) spins. As is known, the funnel edge is approximately determined by the following equipartitions; i) the magnetic and rest-mass energy densities and ii) the gas and magnetic pressures. Our numerical results give an additional factor that they follow the outermost parabolic streamline of the FFE solution, which is anchored to the event horizon on the equatorial plane. We also identify the matter dominated, non-relativistic corona/wind play a dynamical role in shaping the funnel jet into the parabolic geometry. We confirm a quantitative overlap between the outermost parabolic streamline of the FFE jet and the edge of jet sheath in VLBI observations at $\sim 10^{1}$-$10^{5} \, r_{\rm g}$, suggesting that the M87 jet is likely powered by the spinning BH. Our GRMHD simulations also indicate a lateral stratification of the bulk acceleration (i.e., the spine-sheath structure) as well as an emergence of knotty superluminal features. The spin characterizes the location of the jet stagnation surface inside the funnel. We suggest that the limb-brightened feature could be associated with the nature of the BH-driven jet, if the Doppler beaming is a dominant factor. Our findings can be examined with (sub-)mm VLBI observations, giving a clue for the origin of the M87 jet.Comment: 29 pages, 23 figures, accepted for publication in Ap