Modelling the injured spinal cord using 3-dimensional cell cultures; strategies for improving tissue engineered repair

Abstract not available

Altering the stability of the Cdc8 overlap region modulates the ability of this tropomyosin to bind cooperatively to actin and regulate myosin.

Tropomyosin (Tm) is an evolutionarily conserved ?-helical coiled-coil protein, dimers of which form end-to-end polymers capable of associating with and stabilising actin-filaments and regulate myosin function. The fission yeast, Schizosaccharomyces pombe, possesses a single essential Tm, Cdc8, which can be acetylated on its amino terminal methionine to increase its affinity for actin and enhance its ability to regulate myosin function. We have designed and generated a number of novel Cdc8 mutant proteins with amino terminal substitutions to explore how stability of the Cdc8-polymer overlap region affects the regulatory function of this Tm. By correlating the stability of each protein, its propensity to form stable polymers, its ability to associate with actin and to regulate myosin, we have shown the stability of the amino terminal of the Cdc8 ?-helix is crucial for Tm function. In addition we have identified a novel Cdc8 mutant with increased amino-terminal stability, dimers of which are capable of forming Tm-polymers significantly longer than the wild-type protein. This protein had a reduced affinity for actin with respect to wild type, and was unable to regulate actomyosin interactions. The data presented here are consistent with acetylation providing a mechanism for modulating the formation and stability of Cdc8 polymers within the fission yeast cell. The data also provide evidence for a mechanism in which Tm dimers form end-to-end polymers on the actin-filament, consistent with a cooperative model for Tm binding to actin

A randomised trial evaluating Bevacizumab as adjuvant therapy following resection of AJCC stage IIB, IIC and III cutaneous melanoma : an update

At present, there are no standard therapies for the adjuvant treatment of malignant melanoma. Patients with primary tumours with a high-Breslow thickness (stages IIB and IIC) or with resected loco-regional nodal disease (stage III) are at high risk of developing metastasis and subsequent disease-related death. Given this, it is important that novel therapies are investigated in the adjuvant melanoma setting. Since angiogenesis is essential for primary tumour growth and the development of metastasis, anti-angiogenic agents are attractive potential therapeutic candidates for clinical trials in the adjuvant setting. Therefore, we initiated a phase II trial in resected high-risk cutaneous melanoma, assessing the efficacy of bevacizumab versus observation. In the interim safety data analysis, we demonstrate that bevacizumab is a safe therapy in the adjuvant melanoma setting with no apparent increase in the surgical complication rate after either primary tumour resection and/or loco-regional lymphadenectomy

A groupoid approach to regular ∗*-semigroups

In this paper we develop a new groupoid-based structure theory for the class of regular $*$-semigroups. This class occupies something of a `sweet spot' between the important classes of inverse and regular semigroups, and contains many natural examples. Some of the most significant families include the partition, Brauer and Temperley-Lieb monoids, among other diagram monoids. Our main result is that the category of regular $*$-semigroups is isomorphic to the category of so-called `chained projection groupoids'. Such a groupoid is in fact a triple $(P,\mathcal G,\varepsilon)$, where: $\bullet$ $P$ is a projection algebra (in the sense of Imaoka and Jones), $\bullet$ $\mathcal G$ is an ordered groupoid with object set $P$, and $\bullet$ $\varepsilon:\mathscr C\to\mathcal G$ is a special functor, where $\mathscr C$ is a certain natural `chain groupoid' constructed from $P$. Roughly speaking: the groupoid $\mathcal G=\mathcal G(S)$ remembers only the `easy' products in a regular $*$-semigroup $S$; the projection algebra $P=P(S)$ remembers only the `conjugation action' of the projections of $S$; and the functor $\varepsilon=\varepsilon(S)$ tells us how $\mathcal G$ and $P$ `fit together' in order to recover the entire structure of $S$. In this way, we obtain the first completely general structure theorem for regular $*$-semigroups. As a consequence of our main result, we give a new proof of the celebrated Ehresmann--Schein--Nambooripad Theorem, which establishes an isomorphism between the categories of inverse semigroups and inductive groupoids. Other applications will be given in future works. We consider several examples along the way, and pose a number of problems that we believe are worthy of further attention.Comment: V2 (80 pages, 17 figures) is majorly revised, incorporating referee's suggestions - to appear in Adv Math. Sections on free and fundamental regular *-semigroups have been removed, and will be the subject of future papers. V1 (102 pages; 16 figures

Superlattice barrier varactors

SBV (Single Barrier Varactor) diodes have been proposed as alternatives to Schottky barrier diodes for harmonic multiplier applications. However, these show a higher current than expected. The excess current is due to X valley transport in the barrier. We present experimental results showing that the use of a superlattice barrier and doping spikes in the GaAs depletion regions on either side of the barrier can reduce the excess current and improve the control of the capacitance vs. voltage characteristic. The experimental results consist of data taken from two types of device structures. The first test structure was used to study the performance of AlAs/GaAs superlattice barriers. The wafer was fabricated into 90 micron diameter mesa diodes and the resulting current vs. voltage characteristics were measured. A 10 period superlattice structure with a total thickness of approximately 400 A worked well as an electron barrier. The structure had a current density of about one A/sq cm at one volt at room temperature. The capacitance variation of these structures was small because of the design of the GaAs cladding layers. The second test structure was used to study cladding layer designs. These wafers were InGaAs and InAlAs layers lattice matched to an InP substrate. The layers have n(+) doping spikes near the barrier to increase the zero bias capacitance and control the shape of the capacitance vs. voltage characteristic. These structures have a capacitance ratio of 5:1 and an abrupt change from maximum to minimum capacitance. The measurements were made at 80 K. Based on the information obtained from these two structures, we have designed a structure that combines the low current density barrier with the improved cladding layers. The capacitance and current-voltage characteristics from this structure are presented

Formins Determine the Functional Properties of Actin Filaments in Yeast

The actin cytoskeleton executes a broad range of essential functions within a living cell. The dynamic nature of the actin polymer is modulated to facilitate specific cellular processes at discrete locations by actin-binding proteins (ABPs), including the formins and tropomyosins (Tms). Formins nucleate actin polymers, while Tms are conserved dimeric proteins that form polymers along the length of actin filaments. Cells possess different Tm isoforms, each capable of differentially regulating the dynamic and func- tional properties of the actin polymer. However, the mecha- nism by which a particular Tm localizes to a specific actin polymer is unknown. Here we show that specific formin family members dictate which Tm isoform will associate with a particular actin filament to modulate its dynamic and functional properties at specific cellular locations. Exchanging the localization of the fission yeast formins For3 and Cdc12 results in an exchange in localizations of Tm forms on actin polymers. This nucleator-driven switch in filament composition is reflected in a switch in actin dynamics, together with a corresponding change in the filament’s ability to regulate ABPs and myosin motor activity. These data establish a role for formins in dictating which specific Tm variant will associate with a growing actin filament and therefore specify the functional capacity of the actin filaments that they create

A 3D <i>in vitro</i> model reveals differences in the astrocyte response elicited by potential stem cell therapies for CNS injury.

Aim: This study aimed to develop a 3D culture model to test the extent to which transplanted stem cells modulate astrocyte reactivity, where exacerbated glial cell activation could be detrimental to CNS repair success. Materials & methods: The reactivity of rat astrocytes to bone marrow mesenchymal stem cells, neural crest stem cells (NCSCs) and differentiated adipose-derived stem cells was assessed after 5 days. Schwann cells were used as a positive control. Results: NCSCs and differentiated Schwann cell-like adipose-derived stem cells did not increase astrocyte reactivity. Highly reactive responses to bone marrow mesenchymal stem cells and Schwann cells were equivalent. Conclusion: This approach can screen therapeutic cells prior to in vivo testing, allowing cells likely to trigger a substantial astrocyte response to be identified at an early stage. NCSCs and differentiated Schwann cell-like adipose-derived stem cells may be useful in treating CNS damage without increasing astrogliosis

Infinite partition monoids

Let $\mathcal P_X$ and $\mathcal S_X$ be the partition monoid and symmetric group on an infinite set $X$. We show that $\mathcal P_X$ may be generated by $\mathcal S_X$ together with two (but no fewer) additional partitions, and we classify the pairs $\alpha,\beta\in\mathcal P_X$ for which $\mathcal P_X$ is generated by $\mathcal S_X\cup\{\alpha,\beta\}$. We also show that $\mathcal P_X$ may be generated by the set $\mathcal E_X$ of all idempotent partitions together with two (but no fewer) additional partitions. In fact, $\mathcal P_X$ is generated by $\mathcal E_X\cup\{\alpha,\beta\}$ if and only if it is generated by $\mathcal E_X\cup\mathcal S_X\cup\{\alpha,\beta\}$. We also classify the pairs $\alpha,\beta\in\mathcal P_X$ for which $\mathcal P_X$ is generated by $\mathcal E_X\cup\{\alpha,\beta\}$. Among other results, we show that any countable subset of $\mathcal P_X$ is contained in a $4$-generated subsemigroup of $\mathcal P_X$, and that the length function on $\mathcal P_X$ is bounded with respect to any generating set

All you need is spin: SU(2) equivariant variational quantum circuits based on spin networks

Variational algorithms require architectures that naturally constrain the optimisation space to run efficiently. In geometric quantum machine learning, one achieves this by encoding group structure into parameterised quantum circuits to include the symmetries of a problem as an inductive bias. However, constructing such circuits is challenging as a concrete guiding principle has yet to emerge. In this paper, we propose the use of spin networks, a form of directed tensor network invariant under a group transformation, to devise SU(2) equivariant quantum circuit ans\"atze -- circuits possessing spin rotation symmetry. By changing to the basis that block diagonalises SU(2) group action, these networks provide a natural building block for constructing parameterised equivariant quantum circuits. We prove that our construction is mathematically equivalent to other known constructions, such as those based on twirling and generalised permutations, but more direct to implement on quantum hardware. The efficacy of our constructed circuits is tested by solving the ground state problem of SU(2) symmetric Heisenberg models on the one-dimensional triangular lattice and on the Kagome lattice. Our results highlight that our equivariant circuits boost the performance of quantum variational algorithms, indicating broader applicability to other real-world problems.Comment: 36+14 page

Nonlinear effects in the black hole ringdown: absorption-induced mode excitation

Gravitational-wave observations of black hole ringdowns are commonly used to characterize binary merger remnants and to test general relativity. These analyses assume linear black hole perturbation theory, in particular that the ringdown can be described in terms of quasinormal modes even for times approaching the merger. Here we investigate a nonlinear effect during the ringdown, namely how a mode excited at early times can excite additional modes as it is absorbed by the black hole. This is a third-order secular effect: the change in the black-hole mass causes a shift in the mode spectrum, so that the original mode is projected onto the new ones. Using nonlinear simulations, we study the ringdown of a spherically-symmetric scalar field around an asymptotically anti-de Sitter black hole, and we find that this "absorption-induced mode excitation" (AIME) is the dominant nonlinear effect. We show that this effect takes place well within the nonadiabatic regime, so we can analytically estimate it using a sudden mass-change approximation. Adapting our estimation technique to asymptotically-flat Schwarzschild black holes, we expect AIME to play a role in the analysis and interpretation of current and future gravitational wave observations