Collagen is the primary component of the extracellular matrix in the human body. It has proved challenging to fabricate collagen scaffolds capable of replicating the structure and function of tissues ...and organs. We present a method to 3D-bioprint collagen using freeform reversible embedding of suspended hydrogels (FRESH) to engineer components of the human heart at various scales, from capillaries to the full organ. Control of pH-driven gelation provides 20-micrometer filament resolution, a porous microstructure that enables rapid cellular infiltration and microvascularization, and mechanical strength for fabrication and perfusion of multiscale vasculature and tri-leaflet valves. We found that FRESH 3D-bioprinted hearts accurately reproduce patient-specific anatomical structure as determined by micro-computed tomography. Cardiac ventricles printed with human cardiomyocytes showed synchronized contractions, directional action potential propagation, and wall thickening up to 14% during peak systole.
Dwarf spheroidal (dSph) galaxies are prime targets for present and future γ-ray telescopes hunting for indirect signals of particle dark matter. The interpretation of the data requires careful ...assessment of their dark matter content in order to derive robust constraints on candidate relic particles. Here, we use an optimized spherical Jeans analysis to reconstruct the ‘astrophysical factor’ for both annihilating and decaying dark matter in 21 known dSphs. Improvements with respect to previous works are: (i) the use of more flexible luminosity and anisotropy profiles to minimize biases, (ii) the use of weak priors tailored on extensive sets of contamination-free mock data to improve the confidence intervals, (iii) systematic cross-checks of binned and unbinned analyses on mock and real data, and (iv) the use of mock data including stellar contamination to test the impact on reconstructed signals. Our analysis provides updated values for the dark matter content of 8 ‘classical’ and 13 ‘ultrafaint’ dSphs, with the quoted uncertainties directly linked to the sample size; the more flexible parametrization we use results in changes compared to previous calculations. This translates into our ranking of potentially-brightest and most robust targets – namely Ursa Minor, Draco, Sculptor – and of the more promising, but uncertain targets – namely Ursa Major 2, Coma – for annihilating dark matter. Our analysis of Segue 1 is extremely sensitive to whether we include or exclude a few marginal member stars, making this target one of the most uncertain. Our analysis illustrates challenges that will need to be addressed when inferring the dark matter content of new ‘ultrafaint’ satellites that are beginning to be discovered in southern sky surveys.
The nature of the pseudogap phase of cuprate high-temperature superconductors is a major unsolved problem in condensed matter physics. We studied the commencement of the pseudogap state at ...temperature T* using three different techniques (angle-resolved photoemission spectroscopy, polar Kerr effect, and time-resolved reflectivity) on the same optimally doped Bi2201 crystals. We observed the coincident, abrupt onset at T* of a particle-hole asymmetric antinodal gap in the electronic spectrum, a Kerr rotation in the reflected light polarization, and a change in the ultrafast relaxational dynamics, consistent with a phase transition. Upon further cooling, spectroscopic signatures of superconductivity begin to grow close to the superconducting transition temperature (T c ), entangled in an energy-momentum—dependent manner with the preexisting pseudogap features, ushering in a ground state with coexisting orders.
Context.Ground based Cherenkov telescope systems measure astrophysical γ-ray emission against a background of cosmic-ray induced air showers. The subtraction of this background is a major challenge ...for the extraction of spectra and morphology of γ-ray sources. Aims.The unprecedented sensitivity of the new generation of ground based very-high-energy γ-ray experiments such as HESS has lead to the discovery of many previously unknown extended sources. The analysis of such sources requires a range of different background modelling techniques. Here we describe some of the techniques that have been applied to data from the HESS instrument and compare their performance. Methods.Each background model is introduced and discussed in terms of suitability for image generation or spectral analysis and possible caveats are mentioned. Results.We show that there is not a single multi-purpose model, different models are appropriate for different tasks. To keep systematic uncertainties under control it is important to apply several models to the same data set and compare the results.
The discovery of extended TeV emission around the Geminga and PSR B0656+14 pulsars, with properties consistent with free particle propagation in the interstellar medium (ISM), has led to the ...suggestion of “TeV halos” as a separate source class, which is distinct from pulsar wind nebulae. This has sparked considerable discussion on the possible presence of such halos in other systems. In defining halos as regions where the pulsar no longer dominates the dynamics of the interstellar medium, yet where an over-density of relativistic electrons is present, we make an assessment of the current TeV source population associated with energetic pulsars in terms of size and estimated energy density. Based on two alternative estimators, we conclude that a large majority of the known TeV sources have emission originating in the zone that is energetically and dynamically dominated by the pulsar (i.e. the pulsar wind nebula), rather than from a surrounding halo of escaped particles diffusing into the ISM. Furthermore, whilst the number of established halos will surely increase in the future since there is a known large population of older, less energetic pulsars, we find that it is unlikely that such halos contribute significantly to the total TeV
γ
-ray luminosity from electrons accelerated in pulsar wind nebulae due to their lower intrinsic surface brightness.
Polydimethylsiloxane (PDMS) elastomer is used in a wide range of biomaterial applications including microfluidics, cell culture substrates, flexible electronics, and medical devices. However, it has ...proved challenging to 3D print PDMS in complex structures due to its low elastic modulus and need for support during the printing process. Here we demonstrate the 3D printing of hydrophobic PDMS prepolymer resins within a hydrophilic Carbopol gel support via freeform reversible embedding (FRE). In the FRE printing process, the Carbopol support acts as a Bingham plastic that yields and fluidizes when the syringe tip of the 3D printer moves through it, but acts as a solid for the PDMS extruded within it. This, in combination with the immiscibility of hydrophobic PDMS in the hydrophilic Carbopol, confines the PDMS prepolymer within the support for curing times up to 72 h while maintaining dimensional stability. After printing and curing, the Carbopol support gel releases the embedded PDMS prints by using phosphate buffered saline solution to reduce the Carbopol yield stress. As proof-of-concept, we used Sylgard 184 PDMS to 3D print linear and helical filaments via continuous extrusion and cylindrical and helical tubes via layer-by-layer fabrication. Importantly, we show that the 3D printed tubes were manifold and perfusable. The results demonstrate that hydrophobic polymers with low viscosity and long cure times can be 3D printed using a hydrophilic support, expanding the range of biomaterials that can be used in additive manufacturing. Further, by implementing the technology using low cost open-source hardware and software tools, the FRE printing technique can be rapidly implemented for research applications.
Cosmic ray electrons and positrons are tracers of particle propagation in the interstellar medium (ISM). A recent measurement performed using the High Energy Stereoscopic System extends the ...all-electron (electron+positron) spectrum up to 20 TeV, probing very local sources and transport due to the ∼10 kyr cooling time of these particles. An additional key local measurement was the recent estimation of the ISM diffusion coefficient around Geminga performed using the High-Altitude Water Cherenkov Observatory. The inferred diffusion coefficient is much lower than typically assumed values. It has been argued that if this diffusion coefficient is representative of the local ISM, pulsars would not be able to account for the all-electron spectrum measured at Earth. Here we show that a low diffusion coefficient in the local ISM is compatible with a pulsar wind nebula origin of the highest energy electrons, if a so-far-undiscovered pulsar with spin-down power ∼10^{33-34} erg/s exists within 30-80 pc of Earth. The existence of such a pulsar is broadly consistent with the known population and may be detected in near future survey observations.
Invasion of intestinal epithelial cells by Salmonella enterica is decreased after exposure to butyric acid. To understand the molecular mechanisms of this phenomenon, a comparative transcriptomic ...analysis of Salmonella enterica serovar Enteritidis and Salmonella enterica serovar Typhimurium grown in medium supplemented with butyrate was performed. We found that butyrate down-regulated the expression of 19 genes common to both serovars by a factor of twofold or more, and 17 of these genes localized to the Salmonella pathogenicity island 1 (SPI1). These included the SPI1 regulatory genes hilD and invF. Of the remaining two genes, ampH has 91% homology to an Escherichia coli penicillin-binding protein and sopE2 encodes a type III-secreted effector protein associated with invasion but located at a separate site on the chromosome from SPI1.
Cell-laden microgels have been used as tissue building blocks to create three-dimensional (3D) tissues and organs. However, traditional assembly methods cannot be used to fabricate functional tissue ...constructs with biomechanical and structural complexity. In this study, we present directed assembly of cell-laden dual-crosslinkable alginate microgels that comprised oxidized and methacrylated alginate (OMA). Cell-laden OMA microgels can be directly assembled into well-defined 3D shapes and structures under low-level ultraviolet light. Stem cell–laden OMA microgels can be successfully cryopreserved for long-term storage and on-demand applications, and the recovered encapsulated cells maintained equivalent viability and functionality to the freshly processed stem cells. Finally, we have successfully demonstrated that cell-laden microgels can be assembled into complicated 3D tissue structures via freeform reversible embedding of suspended hydrogels (FRESH) 3D bioprinting. This highly innovative bottom-up strategy using FRESH 3D bioprinting of cell-laden OMA microgels, which are cryopreservable, provides a powerful and highly scalable tool for fabrication of customized and biomimetic 3D tissue constructs.
Stem cell–laden microgels, which are cryopreservable for long-term storage and future application, can be assembled into complex tissue structures using free-form reversible embedding of suspended hydrogels 3D bioprinting. Display omitted
The presence of muons in air-showers initiated by cosmic ray protons and nuclei is well established as a powerful tool to separate such showers from those initiated by gamma rays. However, so far ...this approach has been fully exploited only for ground level particle detecting arrays. We explore the feasibility of using Cherenkov light from muons as a background rejection tool for imaging atmospheric Cherenkov telescope arrays at the highest energies. We adopt an analytical model of the Cherenkov light from individual muons to allow rapid simulation of a large number of showers in a hybrid mode. This allows us to explore the very high background rejection power regime at acceptable cost in terms of computing time. We show that for very large (
≳
20
m mirror diameter) telescopes, efficient identification of muon light can potentially lead to background rejection levels up to 10
-
5
whilst retaining high efficiency for gamma rays. While many challenges remain in the effective exploitation of the muon Cherenkov light in the data analysis for imaging Cherenkov telescope arrays, our study indicates that for arrays containing at least one large telescope, this is a very worthwhile endeavor.
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