102 research outputs found

    Vortex merger in surface quasi-geostrophy

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    The merger of two identical surface temperature vortices is studied in the surface quasi- geostrophic model. The motivation for this study is the observation of the merger of sub- mesoscale vortices in the ocean. Firstly, the interaction between two point vortices, in the absence or in the presence of an external deformation field, is investigated. The rotation rate of the vortices, their stationary positions and the stability of these positions are determined. Then, a numerical model provides the steady states of two finite-area, constant-temperature, vortices. Such states are less deformed than their counterparts in two-dimensional incom- pressible flows. Finally, numerical simulations of the nonlinear surface quasi-geostrophic equations are used to investigate the finite-time evolution of initially identical and sym- metric, constant temperature vortices. The critical merger distance is obtained and the deformation of the vortices before or after merger is determined. The addition of external deformation is shown to favor or to oppose merger depending on the orientation of the vor- tex pair with respect to the strain axes. An explanation for this observation is proposed. Conclusions are drawn towards an application of this study to oceanic vortices.PostprintPeer reviewe

    Cyber Security aboard Micro Aerial Vehicles: An OpenTitan-based Visual Communication Use Case

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    Autonomous Micro Aerial Vehicles (MAVs), with a form factor of 10cm in diameter, are an emerging technology thanks to the broad applicability enabled by their onboard intelligence. However, these platforms are strongly limited in the onboard power envelope for processing, i.e., less than a few hundred mW, which confines the onboard processors to the class of simple microcontroller units (MCUs). These MCUs lack advanced security features opening the way to a wide range of cyber security vulnerabilities, from the communication between agents of the same fleet to the onboard execution of malicious code. This work presents an open source System on Chip (SoC) design that integrates a 64 bit Linux capable host processor accelerated by an 8 core 32 bit parallel programmable accelerator. The heterogeneous system architecture is coupled with a security enclave based on an open source OpenTitan root of trust. To demonstrate our design, we propose a use case where OpenTitan detects a security breach on the SoC aboard the MAV and drives its exclusive GPIOs to start a LED blinking routine. This procedure embodies an unconventional visual communication between two palm sized MAVs: the receiver MAV classifies the LED state of the sender (on or off) with an onboard convolutional neural network running on the parallel accelerator. Then, it reconstructs a high-level message in 1.3s, 2.3 times faster than current commercial solutions

    Phase II study of liposomal doxorubicin, docetaxel and trastuzumab in combination with metformin as neoadjuvant therapy for HER2-positive breast cancer

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    Background:The aim of this study was to improve activity over single human epidermal growth factor receptor 2 (HER2)-blockade sequential neaodjuvant regimens for HER2-positive breast cancer, by exploiting the concomitant administration of trastuzumab, taxane and anthracycline, while restraining cardiac toxicity with use of liposomal doxorubicin, and by adding metformin, based on preliminary evidence of antitumor activity.Patients and methods:This multi-center, single-arm, two-stage phase II trial, assessed the safety and the activity of a new treatment regimen for HER2-positive, early or locally advanced breast cancer. Patients received six 21-day cycles of non-pegylated liposomal doxorubicin, 50 mg/m(2) intravenously (i.v.) on day 1, docetaxel, 30 mg/m(2) i.v. on days 2 and 9, trastuzumab, 2 mg/kg/week i.v. on days 2, 9, and 16 (with 4 mg/kg loading dose), in association with metformin 1000 mg orally twice daily. The primary endpoint was the rate of pathological complete response (pCR) in the breast and axilla (ypT0/is ypN0). A subgroup of patients performed a 3-deoxy-3-18F-fluorothymidine positron emission tomography (FLT-PET) at baseline and after one cycle.Results:Among 47 evaluable patients, there were 18 pCR [38.3%, 95% confidence interval (CI) 24.5-53.6%]. A negative estrogen-receptor status, high Ki67, and histological grade 3 were related with pCR, although only grade reached statistical significance. FLT-PET maximum standardized uptake value after one cycle was inversely related to pCR in the breast (odds ratio 0.29, 95% CI 0.06-1.30, p = 0.11). Toxicity included grade 3-4 neutropenia in 70% and febrile neutropenia in 4% of patients, grade 1-2 nausea/vomiting in 60%/38%, and grade 3 in 4%/2%, respectively, grade 1-2 diarrhea in 72%, and grade 3 in 6%. There were two cases of reversible grade 2 left-ventricular ejection-fraction decrease, and one case of sharp troponin-T increase.Conclusions:The concomitant administration of trastuzumab, liposomal doxorubicin, docetaxel, and metformin is safe and shows good activity, but does not appear to improve activity over conventional sequential regimens

    Sub-Femto- g Free Fall for Space-Based Gravitational Wave Observatories: LISA Pathfinder Results

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    We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2±0.1  fm s−2/Hz, or (0.54±0.01)×10−15  g/Hz, with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8±0.3)  fm/Hz, about 2 orders of magnitude better than requirements. At f≀0.5  mHz we observe a low-frequency tail that stays below 12  fm s−2/Hz down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA.CNES 1316634/CNRS 103747UnivEarthS Labex program/ANR-10-LABX-0023UnivEarthS Labex program/ANR-11-IDEX-0005-02DLRFederal Ministry for Economic Affairs and Energy/FKZ 50OQ0501Federal Ministry for Economic Affairs and Energy/FKZ 50OQ1601Agenzia Spaziale ItalianaInstituto Nazionale di Fisica NucleareAYA2010-15709 (MICINN)ESP2013-47637-P (MINECO)ESP2015-67234-P (MINECO)Fundacion General CSICSwiss Space Office (SSO)Swiss National Science FoundationUnited Kingdom Space Agency (UKSA)University of GlasgowUniversity of BirminghamImperial CollegeScottish Universities Physics Alliance (SUPA)U.S. National Aeronautics and Space Administration (NASA

    Bioreducible Liposomes for Gene Delivery: From the Formulation to the Mechanism of Action

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    BACKGROUND: A promising strategy to create stimuli-responsive gene delivery systems is to exploit the redox gradient between the oxidizing extracellular milieu and the reducing cytoplasm in order to disassemble DNA/cationic lipid complexes (lipoplexes). On these premises, we previously described the synthesis of SS14 redox-sensitive gemini surfactant for gene delivery. Although others have attributed the beneficial effects of intracellular reducing environment to reduced glutathione (GSH), these observations cannot rule out the possible implication of the redox milieu in its whole on transfection efficiency of bioreducible transfectants leaving the determinants of DNA release largely undefined. METHODOLOGY/PRINCIPAL FINDINGS: With the aim of addressing this issue, SS14 was here formulated into binary and ternary 100 nm-extruded liposomes and the effects of the helper lipid composition and of the SS14/helper lipids molar ratio on chemical-physical and structural parameters defining transfection effectiveness were investigated. Among all formulations tested, DOPC/DOPE/SS14 at 25:50:25 molar ratio was the most effective in transfection studies owing to the presence of dioleoyl chains and phosphatidylethanolamine head groups in co-lipids. The increase in SS14 content up to 50% along DOPC/DOPE/SS14 liposome series yielded enhanced transfection, up to 2.7-fold higher than that of the benchmark Lipofectamine 2000, without altering cytotoxicity of the corresponding lipoplexes at charge ratio 5. Secondly, we specifically investigated the redox-dependent mechanisms of gene delivery into cells through tailored protocols of transfection in GSH-depleted and repleted vs. increased oxidative stress conditions. Importantly, GSH specifically induced DNA release in batch and in vitro. CONCLUSIONS/SIGNIFICANCE: The presence of helper lipids carrying unsaturated dioleoyl chains and phosphatidylethanolamine head groups significantly improved transfection efficiencies of DOPC/DOPE/SS14 lipoplexes. Most importantly, this study shows that intracellular GSH levels linearly correlated with transfection efficiency while oxidative stress levels did not, highlighting for the first time the pivotal role of GSH rather than oxidative stress in its whole in transfection of bioreducible vectors

    Altimetry for the future: Building on 25 years of progress

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    In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

    Uniparental markers in Italy reveal a sex-biased genetic structure and different historical strata

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    University of Adelaide Genographic Consortium contributers: Christina J. Adler, Alan Cooper, Clio S. I. Der Sarkissian, Wolfgang Haak.Located in the center of the Mediterranean landscape and with an extensive coastal line, the territory of what is today Italy has played an important role in the history of human settlements and movements of Southern Europe and the Mediterranean Basin. Populated since Paleolithic times, the complexity of human movements during the Neolithic, the Metal Ages and the most recent history of the two last millennia (involving the overlapping of different cultural and demic strata) has shaped the pattern of the modern Italian genetic structure. With the aim of disentangling this pattern and understanding which processes more importantly shaped the distribution of diversity, we have analyzed the uniparentally-inherited markers in ~900 individuals from an extensive sampling across the Italian peninsula, Sardinia and Sicily. Spatial PCAs and DAPCs revealed a sex-biased pattern indicating different demographic histories for males and females. Besides the genetic outlier position of Sardinians, a North West–South East Y-chromosome structure is found in continental Italy. Such structure is in agreement with recent archeological syntheses indicating two independent and parallel processes of Neolithisation. In addition, date estimates pinpoint the importance of the cultural and demographic events during the late Neolithic and Metal Ages. On the other hand, mitochondrial diversity is distributed more homogeneously in agreement with older population events that might be related to the presence of an Italian Refugium during the last glacial period in Europe.Alessio Boattini, Begoña Martinez-Cruz, Stefania Sarno, Christine Harmant, Antonella Useli, Paula Sanz, Daniele Yang-Yao, Jeremy Manry, Graziella Ciani, Donata Luiselli, Lluis Quintana- Murci, David Comas, Davide Pettener, the Genographic Consortiu

    Altimetry for the future: building on 25 years of progress

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    In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

    Subsurface-intensified oceanic vortices : impact on the sea-surface and mutual interactions

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    Les tourbillons ocĂ©aniques de subsurface sont des structures dynamiques qui peuplent l'ocĂ©an global. Ils sont souvent gĂ©nĂ©rĂ©s Ă  partir de courants d'Ă©changes entre les bassins d'Ă©vaporation semi-fermĂ©s (comme la Mer MĂ©diterranĂ©e, la Mer Rouge et le Golfe Persique) et l'ocĂ©an ouvert ou pendant des processus de convection profonde. Ces tourbillons peuvent maintenir une gĂ©omĂ©trie cohĂ©rente sur des Ă©chelles de temps pluriannuelles et sont capables, du fait de leur migration, de transporter des quantitĂ©s significatives de chaleur, sel et nutriments. Les tourbillons de subsurface contribuent donc Ă  la redistribution tridimensionnelle des traceurs ocĂ©aniques Ă  Ă©chelle globale, d'oĂč l'intĂ©rĂȘt de connaĂźtre leurs positions et dĂ©placements.En gĂ©nĂ©ral, les tourbillons sont capables de modifier localement la surface de la mer, en gĂ©nĂ©rant des anomalies qui permettent leur suivi Ă  travers des observations satellitaires. Notre Ă©tude se base sur l'utilisation de modĂšles analytiques et numĂ©riques pour caractĂ©riser les signatures induites Ă  la surface par les tourbillons de subsurface; en particulier les anomalies de l'Ă©lĂ©vation (SSH), de tempĂ©rature (SST) et de salinitĂ© (SSS) de la surface ocĂ©anique.D'abord, nous avons Ă©tudiĂ© les signatures de surface (en SSH) dans un cadre idĂ©alisĂ©. Leurs propriĂ©tĂ©s ont Ă©tĂ© mises en relation avec la structure tridimensionnelle des tourbillons, nous permettant de dĂ©terminer que seulement les tourbillons de subsurface de meso-Ă©chelle ocĂ©anique sont dĂ©tectables via les observations altimĂ©triques actuelles. En outre, en utilisant un modĂšle rĂ©aliste, nous avons Ă©tudiĂ© les signatures de surface des tourbillons d'eau mĂ©diterranĂ©enne (MEDDIES) en termes de SSH, SST et SSS. L'Ă©tude a mis en Ă©vidence des diffĂ©rences entre les signatures en SSH et les signatures thermohalines: les premiĂšres montrent des intensitĂ©s et des structures horizontales toujours liĂ©es aux changements structurels des Meddies, alors que les deuxiĂšmes sont plutĂŽt pilotĂ©es par la dynamique locale de surface.Enfin, nos rĂ©sultats montrent que le suivi automatique des tourbillons de subsurface est plutĂŽt envisageable Ă  partir des techniques altimĂ©triques, en valorisant aussi l'apport des futures missions satellitaires Ă  haute rĂ©solution, comme SWOT.Subsurface-intensified vortices are ubiquitous in the world ocean. They are often generated by water mass exchanges between semi-closed evaporation basins (e.g.: Mediterranean Sea, Red Sea, Persian Gulf) and the open ocean or during deep convection processes. These vortices can maintain a coherent geometry during inter-annual timescales and, due to their migration, they are able to carry large amounts of heat, salt and nutrients. Hence, the class of subsurface-intensified vortices participates to the redistribution of oceanic tracers along the three dimensions and at global scale, justifying the interest in determining their positions and mean pathways in the ocean. In general, vortices are able to locally modify the ocean surface generating anomalies that allow one to track them via satellite sensors. Our study, based on the use of analytical and numerical models, deals with the characterization of the sea-surface anomalies generated by subsurface-intensified vortices in terms of Sea-Surface Height (the elevation of the oceanic free-surface, SSH), Sea-Surface Temperature (SST) and Sea-Surface Salinity (SSS).In a first analysis, we have studied the SSH anomalies generated by subsurface vortices in an idealized context. Their properties have been related to the three-dimensional structure of the vortex, allowing us to state that only subsurface mesoscale vortices can be detected by the presentday altimetric observations. Furthermore, using a realistic model, we have studied the sea-surface expression of Mediterranean Water Eddies (MEDDIES) in SSH, SST and SSS. The study has evidenced the main differences between the Meddies-induced SSH anomalies and their thermohaline surface anomalies (i.e., SST and SSS): the first exhibit horizontal structures and intensities that can always be related to the Meddy structural changes at depth, while the second are mostly driven by the local surface dynamics.These studies show that the automatic tracking of subsurface-intensified vortices is mostly possible in an altimetric perspective, further confirming the importance of future high-resolution altimetric satellite missions, like SWOT
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