The dynamical environment of asteroid 21 Lutetia according to different internal models

One of the most accurate models currently used to represent the gravity field of irregular bodies is the polyhedral approach. In this model, the mass of the body is assumed to be homogeneous, which may not be true for a real object. The main goal of the present paper is to study the dynamical effects induced by three different internal structures (uniform, three- and four-layers) of asteroid (21) Lutetia, an object that recent results from space probe suggest being at least partially differentiated. The Mascon gravity approach used in the present work, consists of dividing each tetrahedron into eight parts to calculate the gravitational field around the asteroid. The zero-velocity curves show that the greatest displacement of the equilibrium points occurs in the position of the E4 point for the four-layers structure and the smallest one occurs in the position of the E3 point for the three-layers structure. Moreover, stability against impact shows that the planar limit gets slightly closer to the body with the four-layered structure. We then investigated the stability of orbital motion in the equatorial plane of (21) Lutetia and propose numerical stability criteria to map the region of stable motions. Layered structures could stabilize orbits that were unstable in the homogeneous model.Comment: 10 pages, 7 figures, and 4 Tables. Accepted for publication in MNRA

Multiple Integrated Non-clinical Studies Predict the Safety of Lentivirus-Mediated Gene Therapy for \u3b2-Thalassemia

Gene therapy clinical trials require rigorous non-clinical studies in the most relevant models to assess the benefit-to-risk ratio. To support the clinical development of gene therapy for \u3b2-thalassemia, we performed in vitro and in vivo studies for prediction of safety. First we developed newly GLOBE-derived vectors that were tested for their transcriptional activity and potential interference with the expression of surrounding genes. Because these vectors did not show significant advantages, GLOBE lentiviral vector (LV) was elected for further safety characterization. To support the use of hematopoietic stem cells (HSCs) transduced by GLOBE LV for the treatment of \u3b2-thalassemia, we conducted toxicology, tumorigenicity, and biodistribution studies in compliance with the OECD Principles of Good Laboratory Practice. We demonstrated a lack of toxicity and tumorigenic potential associated with GLOBE LV-transduced cells. Vector integration site (IS) studies demonstrated that both murine and human transduced HSCs retain self-renewal capacity and generate new blood cell progeny in the absence of clonal dominance. Moreover, IS analysis showed an absence of enrichment in cancer-related genes, and the genes targeted by GLOBE LV in human HSCs are well known sites of integration, as seen in other lentiviral gene therapy trials, and have not been associated with clonal expansion. Taken together, these integrated studies provide safety data supporting the clinical application of GLOBE-mediated gene therapy for \u3b2-thalassemia

Internal tides off the Amazon shelf – Part 1: The importance of the structuring of ocean temperature during two contrasted seasons

The impact of internal and barotropic tides on the vertical and horizontal temperature structure off the Amazon River was investigated during two highly contrasted seasons (AMJ: April–May–June; ASO: August–September–October) over a 3-year period from 2013 to 2015. Twin regional simulations, with and without tides, were used to highlight the general effect of tides. The findings reveal that tides have a cooling effect on the ocean from the surface (∼ 0.3 ∘C) to above the thermocline (∼ 1.2 ∘C), while warming it up below the thermocline (∼ 1.2 ∘C). The heat budget analysis indicates that the vertical mixing is the dominant process driving temperature variations within the mixed layer, while it is associated with both horizontal and vertical advection to explain temperature variations below. The increased mixing in the simulations including tides is attributed to breaking of internal tides (ITs) on their generation sites over the shelf break and offshore along their propagation pathways. Over the shelf, mixing is driven by the dissipation of the barotropic tides. In addition, the vertical terms of the heat budget equation exhibit wavelength patterns typical of mode-1 IT. The study highlights the key role of tides and particularly how IT-related vertical mixing shapes the ocean temperature off the Amazon. Furthermore, we found that tides impact the interactions between the upper ocean interface and the overlying atmosphere. They contribute significantly to increasing the net heat flux between the atmosphere and the ocean, with a notable seasonal variation from 33.2 % in AMJ to 7.4 % in ASO seasons. This emphasizes the critical role of tidal dynamics in understanding regional-scale climate.</p

Fabrication of complex model oxide catalysts: Mo oxide supported on Fe3O4(111)

Industrial catalysts for the oxidation of methanol to formaldehyde consist of iron molybdate [Fe2(MoO4)3]. Using a variety of techniques we have previously shown that the surface of these catalysts is segregated in MoO3, and in order to understand the relationship between surface structure and reactivity for these systems we have begun a surface science study of this system using model, single crystal oxides. Model catalysts of molybdenum oxide nanoparticles and films on an Fe3O4 (111) single crystal were fabricated by the hot-filament metal oxide deposition technique (HFMOD), where molybdenum oxides were produced using a molybdenum filament heated in an oxygen atmosphere. Low energy electron diffraction (LEED), X-ray photoelectron spectroscopy (XPS), and scanning tunnelling microscopy (STM) have been used to investigate molybdenum oxide nanoparticles and films deposited on Fe3O4 (111). The molybdenum oxide film forms in the highest oxidation state, 6+, and is remarkably stable to thermal treatment, remaining on the surface to at least 973 K. However, above ~ 573 K cation mixing begins to occur, forming an iron molybdate structure, but the process is strongly Mo coverage dependent

Quiescence: early evolutionary origins and universality do not imply uniformity

Cell cycle investigations have focused on relentless exponential proliferation of cells, an unsustainable situation in nature. Proliferation of cells, whether microbial or metazoan, is interrupted by periods of quiescence. The vast majority of cells in an adult metazoan lie quiescent. As disruptions in this quiescence are at the foundation of cancer, it will be important for the field to turn its attention to the mechanisms regulating quiescence. While often presented as a single topic, there are multiple forms of quiescence each with complex inputs, some of which are tied to conceptually challenging aspects of metazoan regulation such as size control. In an effort to expose the enormity of the challenge, I describe the differing biological purposes of quiescence, and the coupling of quiescence in metazoans to growth and to the structuring of tissues during development. I emphasize studies in the organism rather than in tissue culture, because these expose the diversity of regulation. While quiescence is likely to be a primitive biological process, it appears that in adapting quiescence to its many distinct biological settings, evolution has diversified it. Consideration of quiescence in different models gives us an overview of this diversity

Col V siRNA Engineered Tenocytes for Tendon Tissue Engineering

The presence of uniformly small collagen fibrils in tendon repair is believed to play a major role in suboptimal tendon healing. Collagen V is significantly elevated in healing tendons and plays an important role in fibrillogenesis. The objective of this study was to investigate the effect of a particular chain of collagen V on the fibrillogenesis of Sprague-Dawley rat tenocytes, as well as the efficacy of Col V siRNA engineered tenocytes for tendon tissue engineering. RNA interference gene therapy and a scaffold free tissue engineered tendon model were employed. The results showed that scaffold free tissue engineered tendon had tissue-specific tendon structure. Down regulation of collagen V α1 or α2 chains by siRNAs (Col5α1 siRNA, Col5α2 siRNA) had different effects on collagen I and decorin gene expressions. Col5α1 siRNA treated tenocytes had smaller collagen fibrils with abnormal morphology; while those Col5α2 siRNA treated tenocytes had the same morphology as normal tenocytes. Furthermore, it was found that tendons formed by coculture of Col5α1 siRNA treated tenocytes with normal tenocytes at a proper ratio had larger collagen fibrils and relative normal contour. Conclusively, it was demonstrated that Col V siRNA engineered tenocytes improved tendon tissue regeneration. And an optimal level of collagen V is vital in regulating collagen fibrillogenesis. This may provide a basis for future development of novel cellular- and molecular biology-based therapeutics for tendon diseases

Yki/YAP, Sd/TEAD and Hth/MEIS Control Tissue Specification in the Drosophila Eye Disc Epithelium

During animal development, accurate control of tissue specification and growth are critical to generate organisms of reproducible shape and size. The eye-antennal disc epithelium of Drosophila is a powerful model system to identify the signaling pathway and transcription factors that mediate and coordinate these processes. We show here that the Yorkie (Yki) pathway plays a major role in tissue specification within the developing fly eye disc epithelium at a time when organ primordia and regional identity domains are specified. RNAi-mediated inactivation of Yki, or its partner Scalloped (Sd), or increased activity of the upstream negative regulators of Yki cause a dramatic reorganization of the eye disc fate map leading to specification of the entire disc epithelium into retina. On the contrary, constitutive expression of Yki suppresses eye formation in a Sd-dependent fashion. We also show that knockdown of the transcription factor Homothorax (Hth), known to partner Yki in some developmental contexts, also induces an ectopic retina domain, that Yki and Scalloped regulate Hth expression, and that the gain-of-function activity of Yki is partially dependent on Hth. Our results support a critical role for Yki- and its partners Sd and Hth - in shaping the fate map of the eye epithelium independently of its universal role as a regulator of proliferation and survival

Yki/YAP, Sd/TEAD and Hth/MEIS Control Tissue Specification in the Drosophila Eye Disc Epithelium

During animal development, accurate control of tissue specification and growth are critical to generate organisms of reproducible shape and size. The eye-antennal disc epithelium of Drosophila is a powerful model system to identify the signaling pathway and transcription factors that mediate and coordinate these processes. We show here that the Yorkie (Yki) pathway plays a major role in tissue specification within the developing fly eye disc epithelium at a time when organ primordia and regional identity domains are specified. RNAi-mediated inactivation of Yki, or its partner Scalloped (Sd), or increased activity of the upstream negative regulators of Yki cause a dramatic reorganization of the eye disc fate map leading to specification of the entire disc epithelium into retina. On the contrary, constitutive expression of Yki suppresses eye formation in a Sd-dependent fashion. We also show that knockdown of the transcription factor Homothorax (Hth), known to partner Yki in some developmental contexts, also induces an ectopic retina domain, that Yki and Scalloped regulate Hth expression, and that the gain-of-function activity of Yki is partially dependent on Hth. Our results support a critical role for Yki- and its partners Sd and Hth - in shaping the fate map of the eye epithelium independently of its universal role as a regulator of proliferation and survival