A water-filled garment to protect astronauts during interplanetary missions tested on board the ISS

Abstract As manned spaceflights beyond low Earth orbit are in the agenda of Space Agencies, the concerns related to space radiation exposure of the crew are still without conclusive solutions. The risk of long-term detrimental health effects needs to be kept below acceptable limits, and emergency countermeasures must be planned to avoid the short-term consequences of exposure to high particle fluxes during hardly predictable solar events. Space habitat shielding cannot be the ultimate solution: the increasing complexity of future missions will require astronauts to protect themselves in low-shielded areas, e.g. during emergency operations. Personal radiation shielding is promising, particularly if using available resources for multi-functional shielding devices. In this work we report on all steps from the conception, design, manufacturing, to the final test on board the International Space Station (ISS) of the first prototype of a water-filled garment for emergency radiation shielding against solar particle events. The garment has a good shielding potential and comfort level. On-board water is used for filling and then recycled without waste. The successful outcome of this experiment represents an important breakthrough in space radiation shielding, opening to the development of similarly conceived devices and their use in interplanetary missions as the one to Mars

Verification of Quantitative Precipitation Forecasts by Stochastic Downscaling

The use of dense networks of rain gauges to verify the skill of quantitative numerical precipitation forecasts requires bridging the scale gap between the finite resolution of the forecast fields and the point measurements provided by each gauge. This is usually achieved either by interpolating the numerical forecasts to the rain gauge positions, or by upscaling the rain gauge measurements by averaging techniques. Both approaches are affected by uncertainties and sampling errors due to the limited density of most rain gauge networks and to the high spatiotemporal variability of precipitation. For this reason, an estimate of the sampling errors is crucial for obtaining a meaningful comparison. This work presents the application of a stochastic rainfall downscaling technique that allows a quantitative comparison between numerical forecasts and rain gauge measurements, in both downscaling and upscaling approaches, and allows a quanti- tative assessment of the significance of the results of the verification procedure

Characterization of “in vivo” sampled VOCs of Bixa orellana and its seeds extracts properties

The purpose of this study was to identify the volatile organic compounds (VOCs) profile of different organs of Bixa orellana plants sampled \u201cin vivo\u201d in the North of Par\ue1 State, Brazil. Sampling was done during an expedition on February 2011 within the Itaputyr project, an Italian-Brazilian experience of bottom-up cooperation for development. (1,2). Moreover, antioxidant capacity, phenolic content and insect repellent activity of powdered seeds extracts (aqueous and ethanolic) were tested. Branches, leaves, fruits and seeds were sampled "in vivo" using Divinylbenzene/Carboxen/Polydimethylsiloxane (DVB/CAR/PDMS) fibers with the HS-SPME technique. Each plant\u2019s part was enclosed in a customised teflon cage (manufactured by SNK, Inc, Fullerton, CA: 11 x 21 cm) into which a manual SPME holder was inserted to extract the headspace. HS-SPME analyses were performed using a Trace GC Ultra Gas Chromatograph coupled to a quadrupole Mass Spectrometer Trace DSQ (Thermo-Fisher Scientific; Waltham, MA, USA). Volatile compounds detected in Bixa orellana seed headspace consisted mainly of sesquiterpenes, monoterpenes, and arenes. Most monoterpenes and sesquiterpenes have been previously detected in other spices and plants (3). \u3b1-humulene is the major volatile present in Bixa orellana seed extracts followed by D-germacrene, \u3b1-and \u3b2-pinene and \u3b3-elemene. Some of the monoterpenes and sesquiterpenes found in plant extracts have been previously described as having antimicrobial and repellent properties (4). Phenolic content and antioxidat capacity, evaluated with Folin-Ciocalteur and DPPH tests respectively, were not so high, while preliminary data on repellency against Aedes aegypti of three different dried seeds extracts (ethanol, hexane, ethanol /water) indicated a significant activit

Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors

The synthesis, structure–activity relationships (SAR) and structural data of a series of indolin-2-one inhibitors of RET tyrosine kinase are described. These compounds were designed to explore the available space around the indolinone scaffold within RET active site. Several substitutions at different positions were tested and biochemical data were used to draw a molecular model of steric and electrostatic interactions, which can be applied to design more potent and selective RET inhibitors. The crystal structures of RET kinase domain in complex with three inhibitors were solved. All three compounds bound in the ATP pocket and formed two hydrogen bonds with the kinase hinge region. Crystallographic analysis confirmed predictions from molecular modelling and helped refine SAR results. These data provide important information for the development of indolinone inhibitors for the treatment of RET-driven cancers

Characterization of compound 584, an Abl kinase inhibitor with lasting effects

BACKGROUND: Resistance to imatinib is an important clinical issue in the treatment of Philadelphia chromosome-positive leukemias which is being tackled by the development of new, more potent drugs, such as the dual Src/Abl tyrosine kinase inhibitors dasatinib and bosutinib and the imatinib analog nilotinib. In the current study we describe the design, synthesis and biological properties of an imatinib analog with a chlorine-substituted benzamide, namely compound 584 (cmp-584). DESIGN AND METHODS: To increase the potency, we rationally designed cmp-584, a compound with enhanced shape complementarity with the kinase domain of Abl. cmp-584 was synthesized and characterized in vitro against a panel of 67 serine/threonine and tyrosine kinases using radioactive and enzyme-linked immunosorbent kinase assays. We studied inhibitory cellular activity using Bcr/Abl-positive human cell lines, murine transfectants in proliferation experiments, and a murine xenotrans-planted model. Kinase assays on isolated Bcr/Abl protein were also performed. Finally, we used a wash-out approach on whole cells to study the binding kinetics of the inhibitor. RESULTS: cmp-584 showed potent anti-Abl activity both on recombinant protein (IC(50): 8 nM) and in cell-based assays (IC(50): 0.1-10 nM). The drug maintained inhibitory activity against platelet-derived growth factor receptors and c-KIT and was also active against Lyn (IC(50): 301 nM). No other kinase of the panel was inhibited at nanomolar doses. cmp-584 was 20- to 300-fold more active than imatinib in cells. This superior activity was evident in intact cells, in which full-length Bcr-Abl is present. In vivo experiments confirmed the activity of cmp-584. Wash-out experiments showed that short exposure to the drug impaired cell proliferation and Bcr-Abl phosphorylation for a substantially longer period of time than imatinib. CONCLUSIONS: The present results suggest a slower off-rate (dissociation rate) of cmp-584 compared to imatinib as an explanation for the increased cellular activity of the former

Characterization of coumpound 584, an Abl kinase inhibitor with lasting effects

Background: Resistance to imatinib is an important clinical issue in the treatment of Philadelphia chromosomepositive leukemias which is being tackled by the development of new, more potent drugs, such as the dual Src/Abl tyrosine kinase inhibitors dasatinib and bosutinib and the imatinib analog nilotinib. In the current study we describe the design, synthesis and biological properties of an imatinib analog with a chlorine-substituted benzamide, namely compound 584 (cmp-584). Design and Methods: To increase the potency, we rationally designed cmp-584, a compound with enhanced shape complementarity with the kinase domain of Abl. cmp-584 was synthesized and characterized in vitro against a panel of 67 serine/threonine and tyrosine kinases using radioactive and enzyme-linked immunosorbent kinase assays. We studied inhibitory cellular activity using Bcr/Abl-positive human cell lines, murine transfectants in proliferation experiments, and a murine xenotransplanted model. Kinase assays on isolated Bcr/Abl protein were also performed. Finally, we used a wash-out approach on whole cells to study the binding kinetics of the inhibitor. Results: cmp-584 showed potent anti-Abl activity both on recombinant protein (IC50: 8 nM) and in cell-based assays (IC50: 0.1-10 nM). The drug maintained inhibitory activity against platelet-derived growth factor receptors and c-KIT and was also active against Lyn (IC50: 301 nM). No other kinase of the panel was inhibited at nanomolar doses. cmp-584 was 20- to 300-fold more active than imatinib in cells. This superior activity was evident in intact cells, in which full-length Bcr-Abl is present. In vivo experiments confirmed the activity of cmp-584. Wash-out experiments showed that short exposure to the drug impaired cell proliferation and Bcr-Abl phosphorylation for a substantially longer period of time than imatinib. Conclusions: The present results suggest a slower off-rate (dissociation rate) of cmp-584 compared to imatinib as an explanation for the increased cellular activity of the former. ©2008 Ferrata Storti Foundation

The PERSEO experience: a water-filled garment prototype for personal radiation protection of astronauts successfully tested on board the International Space Station

The PERSEO project (PErsonal Radiation Shielding for intErplanetary missiOns), funded by the Italian Space Agency, has led to the development of a first technological demonstrator of a radiation shielding garment, to be used in a pressurized space habitat, that can be filled at need with on-board water and used for personal protection in case of solar particle events. The collaboration, including academic partners and companies active in space research and technology development, designed and manufactured the prototype that has been successfully tested on board the International Space Station by the European Space Agency astronaut Paolo Nespoli in November 2017, during the VITA mission. The effectiveness of the garment in terms of reduction of the radiation dose to sensitive organs (subject to the occurrence of short-term non-cancer effects following acute exposure) has been evaluated with Monte Carlo simulations with an anthropomorphic phantom. The successful outcome of the experimental session on board has demonstrated the practicality of use and wearability of the prototype, and, in perspective, the feasibility of a personal radiation shielding strategy, complementary to habitat shielding and based on the use of available resources, of fundamental importance also in view of future manned interplanetary missions

High Rate of Non-Human Feeding by Aedes aegypti Reduces Zika Virus Transmission in South Texas

Mosquito-borne viruses are emerging or re-emerging globally, afflicting millions of people around the world. Aedes aegypti, the yellow fever mosquito, is the principal vector of dengue, Zika, and chikungunya viruses, and has well-established populations across tropical and subtropical urban areas of the Americas, including the southern United States. While intense arboviral epidemics have occurred in Mexico and further south in the Americas, local transmission in the United States has been minimal. Here, we study Ae. aegypti and Culex quinquefasciatus host feeding patterns and vertebrate host communities in residential environments of South Texas to identify host-utilization relative to availability. Only 31% of Ae. aegypti blood meals were derived from humans, while 50% were from dogs and 19% from other wild and domestic animals. In Cx. quinquefasciatus, 67% of blood meals were derived from chicken, 22% came from dogs, 9% from various wild avian species, and 2% from other mammals including one human, one cat, and one pig. We developed a model for the reproductive number, R0, for Zika virus (ZIKV) in South Texas relative to northern Mexico using human disease data from Tamaulipas, Mexico. We show that ZIKV R0 in South Texas communities could be greater than one if the risk of human exposure to Ae. aegypti bites in these communities is at least 60% that of Northern Mexico communities. The high utilization of non-human vertebrates and low risk of human exposure in South Texas diminishes the outbreak potential for human-amplified urban arboviruses transmitted by Ae. aegypti