Cell-to-Cell Communication as a Strategy to Regenerate Three-dimensional Tissue.

Cell-to-cell communication is ubiquitous in the majority of cells and is indispensable for proper development of most tissues. Because cells within tissues constantly interact intercellularly to coordinate normal tissue functions and homeostasis, it was hypothesized that increasing gap junction intercellular communication (GJIC), exogenously and endogenously, could improve cell signaling and differentiation in interior regions of tissue engineering equivalents, thereby regenerating larger and more uniform volumes of tissue. The exogenous approach consists of altering the initial cell seeding strategy and biomimetic environment while in the endogenous approach cells are genetically engineered to over-express gap junction proteins. To test this hypothesis, we used bone as a model tissue, because of the inherent limitation achieving spatially uniform bone regeneration. Bone marrow stromal cells (BMSCs) where seeded using in polymeric and biomimetic (mineralized) scaffolds by two novel seeding techniques, filtration and micromass, and assessed for (a) GJIC, (b) differentiation in three-dimensions and (c) regeneration of bone in-vivo. The results demonstrated significant increases in cell differentiation and regeneration when the alternative seeding techniques and mineralized templates were used over the commonly used static seeding technique and polymer templates, respectively. Both seeding techniques demonstrated increased GJIC over the statically seeded analogue. To assess specifically for the effects of GJIC without the interference of other factors, BMSCs were transduced with a lentivirus containing the Connexin43 gene, the most prominent gap junction protein in bone. The results showed that transduced cells expressed significantly higher levels of Connexin43, had higher GJIC, expressed differentiation markers at higher levels throughout 3D cell cultures and regenerated larger volumes of spatially uniform tissue. GJIC and differentiation were significantly greater at the core regions of the scaffold, suggesting an important role for GJIC in overcoming compromised regeneration in the core of tissue engineered equivalents. This research, therefore, presents a novel platform to obtain full 3D equivalents of engineered tissue that were previously unachievable. These experiments also imply that both targeted delivery and cell-based strategies can be used as treatments to enhance communication in 3D living tissue.Ph.D.Biomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/57617/2/rossello_1.pd

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Thermochronological constraints on the Cambrian to recent geological evolution of the Argentina passive continental margin

Passive continental margins are geo-archives that store information from the interplay of endogenous and exogenous forces related to continental rifting, post-breakup history, and climate changes. The recent South Atlantic passive continental margins (SAPCMs) in Brazil, Namibia, and South Africa are partly high-elevated margins (~ 2000 m a.s.l.), and the recent N-S-trending SAPCM in Argentina and Uruguay is of low elevation. In Argentina, an exception in elevation is arising from the higher topography (> 1000 m a.s.l.) of the two NW-SE-trending mountain ranges Sierras Septentrionales and Sierras Australes. Precambrian metamorphic and intrusive rocks, and siliciclastic rocks of Ordovician to Permian age represent the geological evolution of both areas. The Sierras Australes have been deformed and metamorphosed (incipient - greenschist) during the Gondwanides Orogeny. The low-temperature thermochronological (LTT) data (< 240 °C) indicated that the Upper Jurassic to Lower Cretaceous opening of the South Atlantic has not completely thermally reset the surface rocks. The LTT archives apatite and zircon still revealed information on the pre- to post-orogenic history of the Gondwanides and the Mesozoic and Cenozoic South Atlantic geological evolution. Upper Carboniferous zircon (U-Th/He)-ages (ZHe) indicate the earliest cooling below 180 °C/1 Ma. Most of the ZHe-ages are of Upper Triassic to Jurassic age. The apatite fission-track ages (AFT) of Sierras Septentrionales and the eastern part of Sierras Australes indicate the South Atlantic rifting and, thereafter. AFT-ages of Middle to Upper Triassic on the western side of the Sierras Australes are in contrast, indicating a Triassic exhumation caused by the eastward thrusting along the Sauce Grande wrench. The corresponding t-T models report a complex subsidence and exhumation history with variable rates since the Ordovician. Based on the LTT-data and the numerical modelling we assume that the NW-SE-trending mountain ranges received their geographic NW-SE orientation during the syn- to post-orogenic history of the Gondwanides.Fil: Kollenz, Sebastian. Universität Heidelberg; AlemaniaFil: Glasmacher, Ulrich A.. Universität Heidelberg; AlemaniaFil: Rossello, Eduardo Antonio. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Stockli, Daniel F.. University of Texas at Austin; Estados UnidosFil: Schad, Sabrina. Universität Heidelberg; AlemaniaFil: Pereyra Hafner, Ricardo Eduardo. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The bone diagnostic instrument II: Indentation distance increase

The bone diagnostic instrument (BDI) is being developed with the long-term goal of providing a way for researchers and clinicians to measure bone material properties of human bone in vivo. Such measurements could contribute to the overall assessment of bone fragility in the future. Here, we describe an improved BDI, the Osteoprobe II™. In the Osteoprobe II™, the probe assembly, which is designed to penetrate soft tissue, consists of a reference probe (a 22 gauge hypodermic needle) and a test probe (a small diameter, sharpened rod) which slides through the inside of the reference probe. The probe assembly is inserted through the skin to rest on the bone. The distance that the test probe is indented into the bone can be measured relative to the position of the reference probe. At this stage of development, the indentation distance increase (IDI) with repeated cycling to a fixed force appears to best distinguish bone that is more easily fractured from bone that is less easily fractured. Specifically, in three model systems, in which previous mechanical testing and∕or tests reported here found degraded mechanical properties such as toughness and postyield strain, the BDI found increased IDI. However, it must be emphasized that, at this time, neither the IDI nor any other mechanical measurement by any technique has been shown clinically to correlate with fracture risk. Further, we do not yet understand the mechanism responsible for determining IDI beyond noting that it is a measure of the continuing damage that results from repeated loading. As such, it is more a measure of plasticity than elasticity in the bone