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We use combined GPS velocities covering Sinai peninsula to estimate the current rates across the Sinai micro-plate boundaries. New GPS velocities were estimated for 67 sites located within and around Sinai (Arabia, Eurasia and Nubia plates) covering the time span 1999-2018 using GAMIT/GLOBK 10.6 (Herring et al., 2015). We have combined our velocity field with two other recent solutions of GPS sites located around Sinai area. We used the VELROT tool from GAMIT/GLOBK package to combine all solutions resulting in a velocity field of 265 GPS sites in ITRF2018. Then, we selected 61 sites that represent the Sinai plate interior to estimate the Euler pole of Sinai micro-plate. Our computed the Euler pole parameters, latitude, longitude, and angular velocity for Sinai are 53.3±1.8°, -7.8±2.2°, and 0.451±0.014°/Ma, respectively, which are comparable to previous estimates, but with better uncertainties. The relative block motions at the Sinai plate boundaries are estimated using the DEFNODE code (McCaffrey, 2002) by minimizing the GPS residual motions within the blocks in a least squares sense. Our block motion model for Sinai sub-plate shows a fault-parallel velocity at the Gulf of Aqaba of 4.7-4.5 mm/yr, associated with negligible fault-normal component, which decreased toward the north direction along the Dead Sea Transform Fault. On the other hand, an opening rate of 3 mm/yr is estimated at the southern part of the Gulf of Suez with negligible fault-parallel component. At central and northern parts of the Gulf of Suez, the opening rate decreases until it vanished at the northern part of the Suez Canal while the fault-parallel component increases.

International audience; New data on some materials at 80ps pulse duration and 1057 nm wavelength give us the option of proportionally combining them to obtain arbitrary values between 35 (aluminum) and 800 N/MW (POM, polyoxymethylene) for momentum coupling coefficient Cm. Laser ablation physics lets us transfer to LEO from Earth, or to interplanetary space using repetitively pulsed lasers and Cm values appropriate for each mission. We discuss practical results for lifting small payloads from Earth to LEO, and space missions such as a cis-Mars orbit with associated laser system parameters.

A possible system suited for Just-In Time Collision Avoidance (JCA) is a cloud injected in a sub-orbital trajectory by a sounding rocket that will drag down the passing object because of the local higher density. The sudden deceleration experienced by the debris will after a few revolutions ensure a consistent deviation from its nominal trajectory and therefore will permit a safe reduction of any collision risk with other objects. This article first introduces a feasibility study of such a system, using as baseline an SRM and then enlarges the study to an enhanced system.

Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that has many essential roles during inflammation, development and cancer. Stat3 is therefore an attractive therapeutic target in many diseases. While current Stat3 knockout mouse models led to a better understanding of the role of Stat3, the irreversible nature of Stat3 ablation does not model the effects of transient Stat3 therapeutic inhibition, and does not inform on potential dosage effects of Stat3. Using RNAi technology, we have generated a new mouse model allowing the inducible and reversible silencing of Stat3 in vivo, which mirrors the effects of specific Stat3 therapeutic interference. We showed that upon Doxycycline-mediated activation of the Stat3 short-hairpin RNA, Stat3 expression was efficiently reduced by about 80% in multiple organs and cell types. Moreover, Stat3 reduction was sufficient to reduce tumor burden in a clinically-validated mouse model of gastric cancer. Finally, we demonstrated that Stat3 silencing during embryonic development led to reduced birth rate without leading to complete embryonic lethality, in contrast to full Stat3 ablation. In conclusion, this new mouse model will be invaluable to understand the effects of Stat3 therapeutic interference and Stat3 dosage effects.

When Ariane 5 ECA development has been decided by Europe to increase Ariane 5 performance, the rule of 25 years in GTO orbit for the upper stage has been anticipated. This was 14 years ago and this rule was known to be satisfied with a perigee lower than 250 km. Even when lowering slightly Ariane 5 ECA performance, this maximum perigee altitude has been held and the whole Launch System has been developed under CNES responsibility with this GTO perigee. In the meantime, more precise calculations demonstrated that such a GTO perigee was giving for the ESCA a mean lifetime higher than 25 years. So studies are in progress inside CNES to decrease the perigee and re-enter inside the 25 years lifetime domain. This paper presents a CNES study to reduce the orbital lifetime of Ariane 5's upper stage that last in GTO after each commercial mission. Usually the aimed orbit has a perigee altitude of 250 km, an apogee altitude near to the geostationary position and an inclination between 2° and 7°. These conditions make stage's mean lifetime superior to 90 years. The CNES study is to expose the possibility to decrease this lifetime by reducing the perigee altitude of the final upper stage orbit through a passivation process optimised to produce orbit modification. It is shown that taking into account material and functional stage constraints the optimised passivation process is able to decrease the perigee by a few tenths of kilometres.

Transferring small payloads from Earth to low Earth orbit (LEO) and to interplanetary space using laser ablation propulsion is a new application of pulsed laser ablation propulsion, which offers parameters not available with chemical propulsion. In earlier work, we showed how to use a 1 MW average power pulsed laser to launch a 25 kg satellite from LEO to a Mars Hohmann transfer orbit in 18 minutes. Here, we discuss a lower-power application that can achieve the same result, and also cheaply and rapidly launch swarms of microsatellites into geosynchronous orbit (GEO) for communication, Earth observation, and observation of assets in GEO. The result will be a network of satellites with different functions that is robust to failures. Laser propulsion offers orbit/launch mass ratio m/M impossible with chemical rockets as well as low launch cost/kg. The main purpose in this paper is to illustrate satellite launch with repetitive pulse lasers at realistic laser average power levels. The benchmark laser has 80 ps pulsewidth, 5 kJ pulse energy, 355 nm wavelength (third Nd harmonic), and 20 Hz pulse repetition rate, using the “L’ADROIT” laser station design. To minimize laser power, we employ eight loops of steadily increasing apogee, propelled at perigee by a L’ADROIT laser in LEO, followed by a circularization “burn” at apogee using a second L’ADROIT in GEO with similar laser power. We estimate the final mf/M ratio for these maneuvers to be 43%–53%, delivering 10.8 kg into a Mars Hofmann transfer orbit and 13.2 kg to GEO. The ablated mass is contained in a spherical shell surrounding the satellite payload composed of a mixture of metal powder and polyoxymethylene. The mixture is tailored to the mission to give a matched specific impulse Isp and momentum coupling coefficient Cm. For the GEO insertion, the ablation shell splits and is re-entered after one orbit by a final “burn” from the GEO laser.

Seedlings of seven temperate tree species (Acer pseudoplatanus L., Betula pendula Roth, Fagus sylvatica L., Fraxinus excelsior L., Juglans regia L., Quercus petraea Matt. Liebl. and Quercus robur L.) were grown in a nursery under neutral filters transmitting 45% of incident global irradiance. During the second or third year of growth, leaf photosynthetic capacity (i.e., maximal carboxylation rate, Vcmax, maximal photosynthetic electron transport rate, Jmax, and dark respiration, Rd) was estimated for five leaves from each species at five or six leaf temperatures (10, 18, 25, 32, 36 and 40 degrees C). Values of Vcmax and Jmax were obtained by fitting the equations of the Farquhar model on response curves of net CO2 assimilation (A) to sub-stomatal CO2 mole fraction (ci), at high irradiance. Primary parameters describing the kinetic properties of Rubisco (specificity factor, affinity for CO2 and for O2, and their temperature responses) were taken from published data obtained with spinach and tobacco, and were used for all species. The temperature responses of Vcmax and Jmax, which were fitted to a thermodynamic model, differed. Mean values of Vcmax and Jmax at a reference temperature of 25 degrees C were 77.3 and 139 micromol m(-2) s(-1), respectively. The activation energy was higher for Vcmax than for Jmax (mean values of 73.1 versus 57.9 kJ mol(-1)) resulting in a decrease in Jmax/Vcmax ratio with increasing temperature. The mean optimal temperature was higher for Vcmax than for Jmax (38.9 versus 35.9 degrees C). In addition, differences in these temperature responses were observed among species. Temperature optima ranged between 35.9 and above 45 degrees C for Vcmax and between 31.7 and 43.3 degrees C for Jmax, but because of data scatter and the limited range of temperatures tested (10 to 40 degrees C), there were few statistically significant differences among species. The optimal temperature for Jmax was highest in Q. robur, Q. petraea and J. regia, and lowest in A. pseudoplatanus and F. excelsior. Measurements of chlorophyll a fluorescence revealed that the critical temperature at which basal fluorescence begins to increase was close to 47 degrees C, with no difference among species. These results should improve the parameterization of photosynthesis models, and be of particular interest when adapted to heterogeneous forests comprising mixtures of species with diverse ecological requirements.

Excessive activation of the myeloid-specific Src-family kinase Hematopoietic Cell Kinase (HCK) acts as a tumor intrinsic oncogene by promoting proliferation and survival of immune cells, and confers a poor prognosis for leukemia. However, the role of HCK in the tumor stroma of solid malignancies remains unexplored. We analyzed the expression level of HCK in matched biopsies from sporadic colorectal cancer patients and observed elevated HCK phosphorylation in tumors compared to unaffected colons. Analysis of corresponding RNAseq data revealed a striking correlation between tumors with high HCK gene expression and a gene signature indicative of a tumor-promoting alternatively-activated macrophage (AAM) endotype. To functionally assess this observation, we exploited HckCA mice [Ernst et al., J Exp Med 2002] that express a constitutively active form of Hck as a knockin mutation, and subjected these mice to a chemically-induced model of sporadic colorectal cancer. HckCA mice developed more and larger tumors compared to wild-type (WT) animals, and this was associated with a significant bias towards CD206+ AAMs in tumors of HckCA mice without affecting the total number of tumor-associated leukocyte and lymphocytes. Likewise, adoptive bone-marrow transfer experiments revealed enhanced tumor formation and AAM differentiation in WT mice reconstituted with HckCA bone marrow, with a reciprocal decrease of these parameters in HckCA mice reconstituted with WT marrow. Finally, pharmacologic targeting of the catalytic activity of Hck with a small molecule inhibitor significantly reduced tumor progression and impaired AAM polarisation. Collectively, our findings suggest that excessive Hck activity in the tumor stroma promotes the progression of solid cancers by modulating the endotype of tumor-associated myeloid cells. Therefore, Hck represents a rational therapeutic target for macrophage re-education in solid cancers by limiting polarization of tumor-promoting AAM. Citation Format: Matthias Ernst, Ashleigh Poh, Frederic Masson, Tracy Putoczki, Robert O’Donoghue. Excessive HCK kinase activity in the tumor stroma promotes colorectal cancer progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 536.

Gloury et al. reveal an essential role for the Id3–E-protein axis in the transcriptional regulation of humoral immunity., The generation of high-affinity antibodies requires germinal center (GC) development and differentiation of long-lived plasma cells in a multilayered process that is tightly controlled by the activity of multiple transcription factors. Here, we reveal a new layer of complexity by demonstrating that dynamic changes in Id3 and E-protein activity govern both GC and plasma cell differentiation. We show that down-regulation of Id3 in B cells is essential for releasing E2A and E2-2, which in a redundant manner are required for antigen-induced B cell differentiation. We demonstrate that this pathway controls the expression of multiple key factors, including Blimp1, Xbp1, and CXCR4, and is therefore critical for establishing the transcriptional network that controls GC B cell and plasma cell differentiation.

The European Commission Horizon 2020 funded DEMOCRITOS project (2015-2017) will be primary focused to prepare preliminary design of the ground, core and space demonstrators and their test benches for the mega-watt class nuclear electric space propulsion INPPS flagship (International Nuclear Power and Propulsion System). In addition programmatic, organizational and funding aspects for international cooperation related to INPPS realization are sketched. The new project includes partners from Europe, Russia and the Brazilian guest observer IEAv and is the follow-up of the mega-watt class nuclear electric propulsion European-Russian MEGAHIT project (www.megahit-eu.org). In Europe was already established the high power nuclear MEGAHIT and the low power nuclear (20 to 200 kW NEP) DiPoP (www.DiPoP.eu) roadmaps. Because Europe has started the implementations for INPPS flagship in the 2030-2040 timeframe, both roadmaps will be also described – from MEGAHIT the INPPS technology options, the launcher, assembly and system architecture, space mission requirements, communications and public support. In case of DiPoP it will be explained the survey of European capabilities, technical options, potential space missions and the public acceptance as well.

Colorectal cancer is the second most commonly diagnosed cancer worldwide, and may develop sporadically or due to chronic colitis. Macrophages are a major component of the colorectal tumour microenvironment and may be broadly classified as classically-activated (CAM) ‘inflammatory’ or alternatively-activated (AAM) ‘pro-angiogenic’ macrophages. Hematopoietic Cell Kinase (Hck) is a myeloid-specific Src family kinase involved in alternative macrophage polarisation, which correlates with a poor prognosis in human colorectal cancer. To investigate the role of Hck in colorectal tumourigenesis, Hck mutant mice that express a constitutively active form of Hck (HckCA) were subjected to models of sporadic and colitis-associated colorectal cancer. In both models, HckCA mice demonstrated increased tumour size and multiplicity compared to wild-type animals. FACS analysis of tumour immune-cell infiltrates did not reveal a difference in the number of tumour-associated macrophages (TAMs) between genotypes; however, CD206+ alternatively-activated TAMs were significantly greater in HckCA mice compared to wild-type. Furthermore, qPCR analysis highlighted a significant increase in genes associated with alternative-macrophage activation in HckCA TAMs. To confirm the role of macrophages in HckCA-driven tumourigenesis, wild-type mice were reconstituted with HckCA bone-marrow, and subjected to sporadic or colitis-associated colon cancer induction, after which we observed an increased tumour burden and an AAM phenotype compared to wild-type bone-marrow recipients. Finally, we have shown that the inhibition of Hck using a small molecule inhibitor reduces alternative macrophage polarisation. Collectively, our results suggest that excessive Hck activation enhances colorectal tumourigenesis by facilitating alternative macrophage polarisation, which may be alleviated through the therapeutic targeting of this kinase.