Anti-programmed cell death protein-1/ligand-1 therapy in different cancers.

Immunologic checkpoint blockade with antibodies against the programmed cell death protein-1 (PD-1) or its ligand (PD-L1) is an effective method for reversing cancer immunosuppression and thereby promoting immune responses against several cancer types. Anti-PD-1 and anti-PD-L1 antibodies have resulted in long-term responses with minimal side effects in significant numbers of patients with melanoma, lung, kidney, bladder and triple-negative breast cancer, as well as in chemotherapy-refractory Hodgkin disease. There is already evidence from at least one randomised trial that anti-PD-1 therapy is superior to chemotherapy in the treatment of patients with metastatic melanoma, and two anti-PD-1 antibodies, pembrolizumab and nivolumab, have been approved by the US Food and Drug Administration for the treatment of patients previously treated for metastatic melanoma. It is anticipated that approvals by drug regulatory bodies will be forthcoming in several cancers in the next months

Characteristics and dynamics of surfzone transverse finger bars

Patches of transverse finger bars have been identified in the surf zone of Noordwijk beach (Netherlands). They consisted of three to nine elongated accumulations of sand attached to the low-tide shoreline. The bars extended up to 50 m into the inner surf zone, had an oblique orientation with respect to the shore-normal, and were quasiregularly spaced in the alongshore direction.Postprint (published version

Photospheric activity, rotation and magnetic interaction in LHS 6343 A

Context. The Kepler mission has recently discovered a brown dwarf companion transiting one member of the M4V+M5V visual binary system LHS 6343 AB with an orbital period of 12.71 days. Aims. The particular interest of this transiting system lies in the synchronicity between the transits of the brown dwarf C component and the main modulation observed in the light curve, which is assumed to be caused by rotating starspots on the A component. We model the activity of this star by deriving maps of the active regions that allow us to study stellar rotation and the possible interaction with the brown dwarf companion. Methods. An average transit profile was derived, and the photometric perturbations due to spots occulted during transits are removed to derive more precise transit parameters. We applied a maximum entropy spot model to fit the out-of-transit optical modulation as observed by Kepler during an uninterrupted interval of 500 days. It assumes that stellar active regions consist of cool spots and bright faculae whose visibility is modulated by stellar rotation. Results. Thanks to the extended photometric time series, we refine the determination of the transit parameters and find evidence of spots that are occulted by the brown dwarf during its transits. The modelling of the out-of-transit light curve of LHS 6343 A reveals several starspots rotating with a slightly longer period than the orbital period of the brown dwarf, i.e., 13.13 +- 0.02 days. No signature attributable to differential rotation is observed. We find evidence of a persistent active longitude on the M dwarf preceding the sub- companion point by 100 deg and lasting for at least 500 days. This can be relevant for understanding how magnetic interaction works in low-mass binary and star-planet systems.Comment: 14 pages, 16 figure

Doppler-beaming in the Kepler light curve of LHS 6343 A

Context. Kepler observations revealed a brown dwarf eclipsing the M-type star LHS 6343 A with a period of 12.71 days. In addition, an out-of-eclipse light modulation with the same period and a relative semi-amplitude of 2 x 10^-4 was observed showing an almost constant phase lag to the eclipses produced by the brown dwarf. In a previous work, we concluded that this was due to the light modulation induced by photospheric active regions in LHS 6343 A. Aims. In the present work, we prove that most of the out-of-eclipse light modulation is caused by the Doppler-beaming induced by the orbital motion of the primary star. Methods. We introduce a model of the Doppler-beaming for an eccentric orbit and also considered the ellipsoidal effect. The data were fitted using a Bayesian approach implemented through a Monte Carlo Markov chain method. Model residuals were analysed by searching for periodicities using a Lomb-Scargle periodogram. Results. For the first seven quarters of Kepler observations and the orbit previously derived from the radial velocity measurements, we show that the light modulation of the system outside eclipses is dominated by the Doppler-beaming effect. A period search performed on the residuals shows a significant periodicity of 42.5 +- 3.2 days with a false-alarm probability of 5 x 10^-4, probably associated with the rotational modulation of the primary component.Comment: 6 pages, 7 figure

Current Challenges in Financing Agricultural Cooperatives

Agricultural, Cooperatives, Finance, Agribusiness, L10, L23, L16, Q13,

A possible black hole in the gamma-ray microquasar LS 5039

The population of high energy and very high energy gamma-ray sources, detected with EGRET and the new generation of ground-based Cherenkov telescopes, conforms a reduced but physically important sample. Most of these sources are extragalactic (e.g., blazars), while among the galactic ones there are pulsars and SN remnants. The microquasar LS 5039, previously proposed to be associated with an EGRET source by Paredes et al. (2000), has recently been detected at TeV energies, confirming that microquasars should be regarded as a class of high energy gamma-ray sources. To model and understand how the energetic photons are produced and escape from LS 5039 it is crucial to unveil the nature of the compact object, which remains unknown. Here we present new intermediate-dispersion spectroscopy of this source which, combined with values reported in the literature, provides an orbital period of 3.90603+/-0.00017 d, a mass function f(M)=0.0053+/-0.0009 M_sun, and an eccentricity e=0.35+/-0.04. Atmosphere model fitting to the spectrum of the optical companion, together with our new distance estimate of d=2.5+/-0.1 kpc, yields R_opt=9.3+0.7-0.6 R_sun, log (L_opt/L_sun)=5.26+/-0.06, and M_opt=22.9+3.4-2.9 M_sun. These, combined with our dynamical solution and the assumption of pseudo-synchronization, yield an inclination i=24.9+/-2.8 degree and a compact object mass M_X=3.7+1.3-1.0 M_sun. This is above neutron star masses for most of the standard equations of state and, therefore, we propose that the compact object in LS 5039 is a black hole. We finally discuss about the implications of our orbital solution and new parameters of the binary system on the CNO products, the accretion/ejection energetic balance, the SN explosion scenario, and the behaviour of the TeV emission with the new orbital period.Comment: 10 pages, 8 figures. Accepted for publication in MNRAS. Minor changes according to referee repor

A census of ρ\rho Oph candidate members from Gaia DR2

The Ophiuchus cloud complex is one of the best laboratories to study the earlier stages of the stellar and protoplanetary disc evolution. The wealth of accurate astrometric measurements contained in the Gaia Data Release 2 can be used to update the census of Ophiuchus member candidates. We seek to find potential new members of Ophiuchus and identify those surrounded by a circumstellar disc. We constructed a control sample composed of 188 bona fide Ophiuchus members. Using this sample as a reference we applied three different density-based machine learning clustering algorithms (DBSCAN, OPTICS, and HDBSCAN) to a sample drawn from the Gaia catalogue centred on the Ophiuchus cloud. The clustering analysis was applied in the five astrometric dimensions defined by the three-dimensional Cartesian space and the proper motions in right ascension and declination. The three clustering algorithms systematically identify a similar set of candidate members in a main cluster with astrometric properties consistent with those of the control sample. The increased flexibility of the OPTICS and HDBSCAN algorithms enable these methods to identify a secondary cluster. We constructed a common sample containing 391 member candidates including 166 new objects, which have not yet been discussed in the literature. By combining the Gaia data with 2MASS and WISE photometry, we built the spectral energy distributions from 0.5 to 22\microm for a subset of 48 objects and found a total of 41 discs, including 11 Class II and 1 Class III new discs. Density-based clustering algorithms are a promising tool to identify candidate members of star forming regions in large astrometric databases. If confirmed, the candidate members discussed in this work would represent an increment of roughly 40% of the current census of Ophiuchus.Comment: A&A, Accepted. Abridged abstrac