Tuning hydrogel properties for applications in tissue engineering

Biomaterial design is an important component towards tissue engineering applications. There are many parameters that may be adjusted including physical properties (i.e., degradation and mechanics) and chemical properties (e.g., adhesion and cellular interactions). These design components may dictate the success or failure of a tissue engineering approach. Our group is particularly interested in the use of swollen hydrogels as cell carriers. One material that is used to fabricate hydrogels is hyaluronic acid (HA), which is found in many tissues in the body. Here, we show the control over hydrogel degradation, both in the bulk and locally to cells to control both the distribution of extracellular matrix by cells and whether or not a cell spreads in the hydrogels. These signals are important in the final structure and mechanical properties of engineered tissues, and potentially the differentiation of encapsulated stem cells

Discovery of aza-aromatic anolytes for aqueous redox flow batteries via high-throughput screening

Aza-aromatics have recently emerged as a propitious class of electroactive compounds for energy storage in aqueous redox flow batteries (ARFBs). Here, using high-throughput virtual screening (HTVS), we explored a focused chemical subspace of aza-aromatics to determine the top performing candidates as anolytes in ARFBs. First, we designed a virtual chemical library that contains 13,406 aza-aromatic redox pairs, which was populated through the chemical functionalization of alloxazine, phenazine, and indigo backbones with five different R-groups that are known to affect the key battery properties. Then, we predicted the redox potential, aqueous solubility, and the likelihood of decomposition due to the undesirable hydration and tautomerization reactions of the compounds. An analysis of the decomposition thermodynamics of the aza-aromatic subclasses revealed differing correlations between the redox properties and the chemical stability of the compounds, where the latter is found to strongly depend on the type and quantity of the functional groups. Consequently, a total of 516 anolyte candidates that have lower redox potential and higher solubility than a typical anolyte compound, alloxazine 7-carboxylic acid (ACA), have been identified. Additionally, an automated vendor search for the HTVS-predicted top-performing compounds yielded two molecules that are readily purchasable for experimental validation. Finally, an analysis of the quantitative structure-property relationships showed that the mid-sized aza-aromatics, which are not well-explored in experiments, achieved the largest property tunability windows. Based on the new findings, we also propose a molecular engineering strategy in a way to balance the inherent trade-offs among the redox, solubility and chemical stability features of the aza-aromatic anolytes for ARFBs. &nbsp;</p

New and Old Results in Resultant Theory

Resultants are getting increasingly important in modern theoretical physics: they appear whenever one deals with non-linear (polynomial) equations, with non-quadratic forms or with non-Gaussian integrals. Being a subject of more than three-hundred-year research, resultants are of course rather well studied: a lot of explicit formulas, beautiful properties and intriguing relationships are known in this field. We present a brief overview of these results, including both recent and already classical. Emphasis is made on explicit formulas for resultants, which could be practically useful in a future physics research.Comment: 50 pages, 15 figure

A kinetic model of TBP auto-regulation exhibits bistability

<p>Abstract</p> <p>Background</p> <p>TATA Binding Protein (TBP) is required for transcription initiation by all three eukaryotic RNA polymerases. It participates in transcriptional initiation at the majority of eukaryotic gene promoters, either by direct association to the TATA box upstream of the transcription start site or by indirectly localizing to the promoter through other proteins. TBP exists in solution in a dimeric form but binds to DNA as a monomer. Here, we present the first mathematical model for auto-catalytic TBP expression and use it to study the role of dimerization in maintaining the steady state TBP level.</p> <p>Results</p> <p>We show that the autogenous regulation of TBP results in a system that is capable of exhibiting three steady states: an unstable low TBP state, one stable state corresponding to a physiological TBP concentration, and another stable steady state corresponding to unviable cells where no TBP is expressed. Our model predicts that a basal level of TBP is required to establish the transcription of the TBP gene, and hence for cell viability. It also predicts that, for the condition corresponding to a typical mammalian cell, the high-TBP state and cell viability is sensitive to variation in DNA binding strength. We use the model to explore the effect of the dimer in buffering the response to changes in TBP levels, and show that for some physiological conditions the dimer is not important in buffering against perturbations.</p> <p>Conclusions</p> <p>Results on the necessity of a minimum basal TBP level support the in vivo observations that TBP is maternally inherited, providing the small amount of TBP required to establish its ubiquitous expression. The model shows that the system is sensitive to variations in parameters indicating that it is vulnerable to mutations in TBP. A reduction in TBP-DNA binding constant can lead the system to a regime where the unviable state is the only steady state. Contrary to the current hypotheses, we show that under some physiological conditions the dimer is not very important in restoring the system to steady state. This model demonstrates the use of mathematical modelling to investigate system behaviour and generate hypotheses governing the dynamics of such nonlinear biological systems.</p> <p>Reviewers</p> <p>This article was reviewed by Tomasz Lipniacki, James Faeder and Anna Marciniak-Czochra.</p

Translating Cultural Safety to the UK

Disproportional morbidity and mortality experienced by ethnic minorities in the UK have been highlighted by the COVID-19 pandemic. The ‘Black Lives Matter’ movement has exposed structural racism’s contribution to these health inequities. ‘Cultural Safety’, an antiracist, decolonising and educational innovation originating in New Zealand, has been adopted in Australia. Cultural Safety aims to dismantle barriers faced by colonised Indigenous peoples in mainstream healthcare by addressing systemic racism. This paper explores what it means to be ‘culturally safe’. The ways in which New Zealand and Australia are incorporating Cultural Safety into educating healthcare professionals and in day-to-day practice in medicine are highlighted. We consider the ‘nuts and bolts’ of translating Cultural Safety into the UK to reduce racism within healthcare. Listening to the voices of black, Asian and minority ethnic National Health Service (NHS) consumers, education in reflexivity, both personal and organisational within the NHS are key. By listening to Indigenous colonised peoples, the ex-Empire may find solutions to health inequity. A decolonising feedback loop is required; however, we should take care not to culturally appropriate this valuable reverse innovation

Surface Fatigue Behaviour of a WC/aC:H Thin-Film and the Tribochemical Impact of Zinc Dialkyldithiophosphate

In wind turbine gearboxes, (near-)surface initiated fatigue is attributed to be the primary failure mechanism. In this work, the surface fatigue of a hydrogenated tungsten carbide/amorphous carbon (WC/aC:H) thin-film was tested under severe cyclic tribo-contact using PolyAlphaOlefin (PAO) and PAO + Zinc DialkylDithioPhosphate (ZDDP) lubricants. The film was characterised in terms of its structure and chemistry using X-ray diffraction, analytical Transmission Electron Microscopy (TEM) including Electron Energy Loss Spectroscopy (EELS), as well as X-ray Photoelectron Spectroscopy (XPS). The multilayer carbon thin-film exhibited promising surface fatigue performance showing a slight change in the hybridization state of the aC:H matrix. Dehydrogenation of the thin-film and subsequent transformation of cleaved C-H bonds to non planar sp2 carbon rings were inferred from EELS and XPS results. Whilst tribo-induced changes to the aC:H matrix were not influenced by a nanometer-thick ZDDP reaction-film, the rate of oxidation of WC and its oxidation state were affected. Whilst accelerating surface fatigue on a steel surface, the ZDDP-tribofilm protected the WC/aC:H film from surface fatigue. In contrast to the formation of polyphosphates from ZDDP molecules on steel surfaces, it appeared that on the WC/aC:H thin film surface ZDDP molecules decompose to ZnO suppressing the oxidative degradation of WC

Standardizing kilonovae and their use as standard candles to measure the Hubble constant

The detection of GW170817 is revolutionizing many areas of astrophysics with the joint observation of gravitational waves and electromagnetic emissions. These multimessenger events provide a new approach to determine the Hubble constant, thus, they are a promising candidate for mitigating the tension between measurements of type-Ia supernovae via the local distance ladder and the cosmic microwave background. In addition to the "standard siren"provided by the gravitational-wave measurement, the kilonova itself has characteristics that allow one to improve existing measurements or to perform yet another, independent measurement of the Hubble constant without gravitational-wave information. Here, we employ standardization techniques borrowed from the type-Ia community and apply them to kilonovae, not using any information from the gravitational-wave signal. We use two versions of this technique, one derived from direct observables measured from the light curve, and the other based on inferred ejecta parameters, e.g., mass, velocity, and composition, for two different models. These lead to Hubble constant measurements of H0=109-35+49 km s-1 Mpc-1 for the measured analysis, and H0=85-17+22 km s-1 Mpc-1 and H0=79-15+23 km s-1 Mpc-1 for the inferred analyses. This measurement has error bars within ∼2 to the gravitational-wave measurements (H0=74-8+16 km s-1 Mpc-1), showing its promise as an independent constraint on H0

Comparing inclination-dependent analyses of kilonova transients

The detection of the optical transient AT2017gfo proved that binary neutron star mergers are progenitors of kilonovae (KNe).Using a combination of numerical-relativity and radiative-transfer simulations, the community has developed sophisticated models for these transients for a wide portion of the expected parameter space. Using these simulations and surrogate models made from them, it has been possible to perform Bayesian inference of the observed signals to infer properties of the ejected matter. It has been pointed out that combining inclination constraints derived from the KN with gravitational-wavemeasurements increases the accuracy with which binary parameters can be estimated, in particular breaking the distance-inclination degeneracy from gravitational wave inference. To avoid bias from the unknown ejecta geometry, constraints on the inclination angle for AT2017gfo should be insensitive to the employed models. In this work, we compare different assumptions about the ejecta and radiative reprocesses used by the community and we investigate their impact on the parameter inference. While most inferred parameters agree, we find disagreement between posteriors for the inclination angle for different geometries that have been used in the current literature. According to our study, the inclusion of reprocessing of the photons between different ejecta types improves the modeling fits to AT2017gfo and, in some cases, affects the inferred constraints. Our study motivates the inclusion of large ~1-mag uncertainties in the KN models employed for Bayesian analysis to capture yet unknown systematics, especially when inferring inclination angles, although smaller uncertainties seem appropriate to capture model systematics for other intrinsic parameters. We can use this method to impose soft constraints on the ejecta geometry of the KN AT2017gfo