Crystal balls into the future: are global circulation and water balance models ready?

Abstract. Variabilities and changes due to natural and anthropogenic causes in the water cycle always presented a challenge for water management planning. Practitioners traditionally coped with variabilities in the hydrological processes by assuming stationarity in the probability distributions and attempted to address non-stationarity by revising this probabilistic properties via continued hydro-climatological observations. Recently, this practice was questioned and more reliance on Global Circulation Models was put forward as an alternative for water management plannig. This paper takes a brief assessment of the state of Global Circulation Models (GCM) and their applications by presenting case studies over Global, European and African domains accompanied by literature examples. Our paper demonstrates core deficiencies in GCM based water resources assessments and articulates the need for improved Earth system monitoring that is essential not only for water managers, but to aid the improvements of GCMs in the future

In Situ Measurement Activities at the NASA Orbital Debris Program Office

The NASA Orbital Debris Program Office has been involved in the development of several particle impact instruments since 2003. The main objective of this development is to eventually conduct in situ measurements to better characterize the small (millimeter or smaller) orbital debris and micrometeoroid populations in the near-Earth environment. In addition, the Office also supports similar instrument development to define the micrometeoroid and lunar secondary ejecta environment for future lunar exploration activities. The instruments include impact acoustic sensors, resistive grid sensors, fiber optic displacement sensors, and impact ionization sensors. They rely on different mechanisms and detection principles to identify particle impacts. A system consisting of these different sensors will provide data that are complimentary to each other, and will provide a better description of the physical and dynamical properties (e.g., size, mass, and impact speed) of the particles in the environment. Details of several systems being considered by the Office and their intended mission objectives are summarized in this paper

Preclinical immunotherapy with Cytokine-Induced Killer lymphocytes against epithelial ovarian cancer

Despite improvements in surgery and medical treatments, epithelial ovarian cancer (EOC) remains the most lethal gynaecological malignancy. Aim of this study is to investigate the preclinical immunotherapy activity of cytokine-induced killer lymphocytes (CIK) against epithelial ovarian cancers, focusing on platinum-resistant settings. We generated CIK ex vivo starting from human peripheral blood samples (PBMCs) collected from EOC patients. Their antitumor activity was tested in vitro and in vivo against platinum-resistant patient-derived ovarian cancer cells (pdOVCs) and a Patient Derived Xenograft (PDX), respectively. CIK were efficiently generated (48 fold median ex vivo expansion) from EOC patients; pdOVCs lines (n = 9) were successfully generated from metastatic ascites; the expression of CIK target molecules by pdOVC confirmed pre and post treatment in vitro with carboplatin. The results indicate that patient-derived CIK effectively killed autologous pdOVCs in vitro. Such intense activity was maintained against a subset of pdOVC that survived in vitro treatment with carboplatin. Moreover, CIK antitumor activity and tumor homing was confirmed in vivo within an EOC PDX model. Our preliminary data suggest that CIK are active in platinum resistant ovarian cancer models and should be therefore further investigated as a new therapeutic option in this extremely challenging setting

POSEIDON: An integrated system for analysis and forecast of hydrological, meteorological and surface marine fields in the Mediterranean area

The Mediterranean area is characterized by relevant hydrological, meteorological and marine processes developing at horizontal space-scales of the order of 1–100 km. In the recent past, several international programs have been addressed (ALPEX, POEM, MAP, etc.)to “resolving” the dynamics of such motions. Other projects (INTERREG-Flooding, MEDEX, etc.)are at present being developed with special emphasis on catastrophic events with major impact on human society that are, quite often, characterized in their manifestation by processes with the above-mentioned scales of motion. In the dynamical evolution of such events, however, equally important is the dynamics of interaction of the local (and sometimes very damaging)pro cesses with others developing at larger scales of motion. In fact, some of the most catastrophic events in the history of Mediterranean countries are associated with dynamical processes covering all the range of space-time scales from planetary to local. The Prevision Operational System for the mEditerranean basIn and the Defence of the lagOon of veNice (POSEIDON)is an integrated system for the analysis and forecast of hydrological, meteorological, oceanic fields specifically designed and set up in order to bridge the gap between global and local scales of motion, by modeling explicitly the above referred to dynamical processes in the range of scales from Mediterranean to local. The core of POSEIDON consists of a “cascade” of numerical models that, starting from global scale numerical analysisforecast, goes all the way to very local phenomena, like tidal propagation in Venice Lagoon. The large computational load imposed by such operational design requires necessarily parallel computing technology: the first model in the cascade is a parallelised version of BOlogna Limited Area Model (BOLAM)running on a Quadrics 128 processors computer (also known as QBOLAM). POSEIDON, developed in the context of a co-operation between the Italian Agency for New technologies, Energy and Environment (Ente per le Nuove tecnologie, l’Energia e l’Ambiente, ENEA)and the Italian Agency for Environmental Protection and Technical Services (Agenzia per la Protezione dell’Ambiente e per i Servizi Tecnici, APAT), has become operational in 2000 and we are presently in the condition of drawing some preliminary conclusions about its performance. In the paper we describe the scientific concepts that were at the basis of the original planning, the structure of the system, its operational cycle and some preliminary scientific and technical evaluations after two years of experimentation

CD44v6 as innovative sarcoma target for CAR-redirected CIK cells

Purpose of our study was to explore a new immunotherapy for high grade soft tissue sarcomas (STS) based on cytokine-induced killer cells (CIK) redirected with a chimeric antigen receptor (CAR) against the tumor-promoting antigen CD44v6. We aimed at generating bipotential killers, combining the CAR specificity with the intrinsic tumor-killing ability of CIK cells (CAR+.CIK). We set a patient-derived experimental platform. CAR+.CIK were generated by transduction of CIK precursors with a lentiviral vector encoding for anti-CD44v6-CAR. CAR+.CIK were characterized and assessed in vitro against multiple histotypes of patient-derived STS. The anti-sarcoma activity of CAR+.CIK was confirmed in a STS xenograft model. CD44v6 was expressed by 40% (11/27) of patient-derived STS. CAR+.CIK were efficiently expanded from patients (n = 12) and killed multiple histotypes of STS (including autologous targets, n = 4). The killing activity was significantly higher compared with unmodified CIK, especially at low effector/target (E/T) ratios: 98% vs 82% (E/T = 10:1) and 68% vs 26% (1:4), (p<0.0001). Specificity of tumor killing was confirmed by blocking with anti-CD44v6 antibody. CAR+.CIK produced higher amounts of IL6 and IFN-γ compared to control CIK. CAR+.CIK were highly active in mice bearing subcutaneous STS xenografts, with significant delay of tumor growth (p<0.0001) without toxicities. We report first evidence of CAR+.CIK's activity against high grade STS and propose CD44v6 as an innovative target in this setting. CIK are a valuable platform for the translation of CAR-based strategies to challenging field of solid tumors. Our findings support the exploration of CAR+.CIK in clinical trials against high grade STS