Approximate unitary tt-designs by short random quantum circuits using nearest-neighbor and long-range gates

We prove that $poly(t) \cdot n^{1/D}$-depth local random quantum circuits with two qudit nearest-neighbor gates on a $D$-dimensional lattice with n qudits are approximate $t$-designs in various measures. These include the "monomial" measure, meaning that the monomials of a random circuit from this family have expectation close to the value that would result from the Haar measure. Previously, the best bound was $poly(t)\cdot n$ due to Brandao-Harrow-Horodecki (BHH) for $D=1$. We also improve the "scrambling" and "decoupling" bounds for spatially local random circuits due to Brown and Fawzi. One consequence of our result is that assuming the polynomial hierarchy (PH) is infinite and that certain counting problems are $\#P$-hard on average, sampling within total variation distance from these circuits is hard for classical computers. Previously, exact sampling from the outputs of even constant-depth quantum circuits was known to be hard for classical computers under the assumption that PH is infinite. However, to show the hardness of approximate sampling using this strategy requires that the quantum circuits have a property called "anti-concentration", meaning roughly that the output has near-maximal entropy. Unitary 2-designs have the desired anti-concentration property. Thus our result improves the required depth for this level of anti-concentration from linear depth to a sub-linear value, depending on the geometry of the interactions. This is relevant to a recent proposal by the Google Quantum AI group to perform such a sampling task with 49 qubits on a two-dimensional lattice and confirms their conjecture that $O(\sqrt n)$ depth suffices for anti-concentration. We also prove that anti-concentration is possible in depth O(log(n) loglog(n)) using a different model

Subsurface Facies Analysis of the Late Cambrian Mt. Simon Sandstone in Western Ohio (Midcontinent North America)

The Cambrian Mt. Simon Sandstone (MSS) is a possible unconventional gas reservoir in the Illinois, Michigan, and Appalachian Basins, but comparatively little is known about the unit. This study used core and well logs from two deep exploratory wells to interpret the depositional environment of the MSS under western Ohio, where the MSS is about 120 m thick and found 1060 m below ground surface. In western Ohio, the MSS unconformably overlies the Precambrian Middle Run Formation, is conformably overlain by the Cambrian Eau Claire Formation, and has a distinctive gamma-ray log-signature. In well DGS-2627, the MSS consists of tan, friable, moderately sorted, rounded, coarse- to very coarse-grained siliceous quartz arenite with minor heterolithic sandstone-mudstone couplets (rhythmites) and quartz granule conglomerate. Features indicative of tidally-influenced, shallow marine settings include tidal rhythmites, lenticular-, flaser-, and wavy-bedding, herringbone cross-bedding, mud-drapes, tidal bundles, reactivation surfaces, intraclasts, and bioturbation. The unit generally coarsens- and thickens-upward, and is interpreted as migration of a tidally-influenced transgressive barrier sequence. A subsurface facies model for the MSS is developed by interpreting geophysical logs and cores from DGS-2627l, and this model is semi-quantitatively tested by first interpreting well BP-4 using geophysical logs alone, then confirming the results using core

Toward advanced modular drug and gene delivery system

In chapter two, the development of new a nanoparticulate carrier system for gene delivery was described. The new nanocarrier consists of a blend matrix formed by a poly (lactic-eo-glycolic acid) (PLGA) and Poly(ethylene glycol) bis (3-aminopropyl) terminated (also known as JeffamineTM). Nanopartic1es were formulated based on a 50:50 weight ratio of PLGA:Jeffamine using a modified emulsification-solvent diffusion technique. The potential of these blended matrix nanoparticles for encapsulation efficiency of Calf Thymus DNA and release profile were also studied. The achieved encapsulation efficiency of Calf Thymus DNA was approximately 84% for 0.4% theoretical loading with regard to total amount of PLGA. The PLGA: Jeffamine blended nanoparticles provided continuous and controlled release of Calf Thymus DNA. The PLGA:Jeffamine nanopartic1es were also coated with PLGA-PEGMA&75and PDMAEMA-PEGMA block copolymers using a simple physical adsorption method. After surface coating of the nanoparticles, zeta potential value showed significant reduction of surface charges from -38 mV to near zero value, while TEM micrographs showed a well defined core-shell nanoparticle. In chapter three, A facile route to biocompatible poly (lactic acid-coglycolic acid)-co-poly (ethyleneglycol methacrylate) (PLGA-PEGMA) block co-polymers was described utilising a combination of ring-opening polymerisation (ROP) and Radical Addition Fragmentation Transfer (RAFT) methods. A series of PLGA-PEGMA polymers varying in comonomer content and block length were synthesised with low polydispersities. All the block co-polymers formed micelles in aqueous solution as shown by dynamic light scattering, while critical micelle concentrations were found to be in the micromolar range. The polymer micelles were able to encapsulate model drugs(carboxyfluorescein and fluorescein isothiocyanate) and selected copolymer micelles incubated with 3T3 fibroblasts as a model cell line were rapidly taken up as indicated by fluorescence microscopy assays. The combination of the polymer chemistries opens the way to highly flexible syntheses of micellar drug carrier systems. In chapter four, multifunctional and modular block co-polymers prepared from biocompatible monomers and linked by a bioreducible disulphide linkage have been prepared using a combination of ring-opening and atom-transfer radical polymerizations (ATRP). The presence of terminal functionality via ATRP allowed cell-targeting folic acid groups to be attached in a controllable manner, while the block co-polymer architecture enabled well-defined nanopartic1es to be prepared by a water-oil-water double emulsion procedure to encapsulate DNA with high efficiency. Gene delivery assays in a Calu-3 cell line indicated specific folatereceptor-mediated uptake of the nanoparticles, and triggered release of the DNA payload via cleavage of the disulfide link resulted in enhanced transgene expression compared to non-bioreducible analogues. These materials offer a promising and generic means to deliver a wide variety of therapeutic payloads to cells in a selective and tuneable way

Toward advanced modular drug and gene delivery system

In chapter two, the development of new a nanoparticulate carrier system for gene delivery was described. The new nanocarrier consists of a blend matrix formed by a poly (lactic-eo-glycolic acid) (PLGA) and Poly(ethylene glycol) bis (3-aminopropyl) terminated (also known as JeffamineTM). Nanopartic1es were formulated based on a 50:50 weight ratio of PLGA:Jeffamine using a modified emulsification-solvent diffusion technique. The potential of these blended matrix nanoparticles for encapsulation efficiency of Calf Thymus DNA and release profile were also studied. The achieved encapsulation efficiency of Calf Thymus DNA was approximately 84% for 0.4% theoretical loading with regard to total amount of PLGA. The PLGA: Jeffamine blended nanoparticles provided continuous and controlled release of Calf Thymus DNA. The PLGA:Jeffamine nanopartic1es were also coated with PLGA-PEGMA&75and PDMAEMA-PEGMA block copolymers using a simple physical adsorption method. After surface coating of the nanoparticles, zeta potential value showed significant reduction of surface charges from -38 mV to near zero value, while TEM micrographs showed a well defined core-shell nanoparticle. In chapter three, A facile route to biocompatible poly (lactic acid-coglycolic acid)-co-poly (ethyleneglycol methacrylate) (PLGA-PEGMA) block co-polymers was described utilising a combination of ring-opening polymerisation (ROP) and Radical Addition Fragmentation Transfer (RAFT) methods. A series of PLGA-PEGMA polymers varying in comonomer content and block length were synthesised with low polydispersities. All the block co-polymers formed micelles in aqueous solution as shown by dynamic light scattering, while critical micelle concentrations were found to be in the micromolar range. The polymer micelles were able to encapsulate model drugs(carboxyfluorescein and fluorescein isothiocyanate) and selected copolymer micelles incubated with 3T3 fibroblasts as a model cell line were rapidly taken up as indicated by fluorescence microscopy assays. The combination of the polymer chemistries opens the way to highly flexible syntheses of micellar drug carrier systems. In chapter four, multifunctional and modular block co-polymers prepared from biocompatible monomers and linked by a bioreducible disulphide linkage have been prepared using a combination of ring-opening and atom-transfer radical polymerizations (ATRP). The presence of terminal functionality via ATRP allowed cell-targeting folic acid groups to be attached in a controllable manner, while the block co-polymer architecture enabled well-defined nanopartic1es to be prepared by a water-oil-water double emulsion procedure to encapsulate DNA with high efficiency. Gene delivery assays in a Calu-3 cell line indicated specific folatereceptor-mediated uptake of the nanoparticles, and triggered release of the DNA payload via cleavage of the disulfide link resulted in enhanced transgene expression compared to non-bioreducible analogues. These materials offer a promising and generic means to deliver a wide variety of therapeutic payloads to cells in a selective and tuneable way

Biocompatible 3D printed thermoplastic scaffolds for osteoblast differentiation of equine iPS cells

Horses, like humans, can experience bone fractures and due to their large size and need to bear weight on all limbs during the recovery period, they can be difficult to treat. Surgical techniques to improve fracture repair are improving, but to date, regenerative medicine technologies to aid fracture healing are not commonly applied in horses. We have previously demonstrated that equine induced pluripotent stem cells (iPSCs) can be differentiated into bone forming osteoblasts in 2D culture. Here we report on the use of a thermoplastic, 3D printed polymers to provide a scaffold for successful, in vitro osteoblast differentiation of equine iPSCs. The scaffolds provides a transparent, cost effect solution to allow the analysis of osteoblast differentiation using live cell imaging, immunohistochemistry and quantitative PCR. This in vitro study demonstrates the future feasibility of generating 3D bone constructs through the cell seeding of scaffolds to use in regenerative medicine strategies to work demonstrates the possibility of using cell-based therapies in combination with scaffold technologies for improving improve fracture repair in a relevant, large animal model

Induction of Tendon-Specific Markers in Adipose-Derived Stem Cells in Serum-Free Culture

Differentiation of stem cells as a cell-based therapy for repairing, replacing or restoring damaged tissues such as bone, cartilage, and tendon is becoming increasingly attractive within the field of musculoskeletal tissue engineering. Towards this end, there are numerous published and well-defined protocols to differentiate stem cells towards cartilage and bone tissues, but the protocols towards tendon tissue are still emerging and thus less developed. Recent studies focused on the induction of tendon-specific markers in cultured stem cells using different Growth Factors (GFs) including Bone Morphogenetic Proteins (BMPs) and Transforming Growth Factor (TGF) isoforms. However, the inclusion of serum in relatively high concentration across these studies is less favorable, since the components within serum may interfere with the induction of the markers. Alternatively, in vitro studies with low concentration or absence of serum would be ideal. In this study, we assessed the induction effect of BMP-12 and TGF-β1 on tendon-specific markers in Adipose-Derived Stem cells (ADSCs), in serum-free conditions. Specifically, we investigated the temporal and dosing effects of both GFs on several markers. Our results demonstrate that BMP-12 induces late expression of the transcription factors Scleraxis (SCX) and Mohawk (MKX), whereas TGF-β1 induced their earlier expression. Moreover, BMP-12 induced Decorin (DCN) but was inhibited by TGF-β1. Other markers such as Collagen Iα1 (COL1A1) likewise showed this pattern. Importantly, the protein analysis generally supported the gene expression data. Interestingly, differences were observed in the cellular localisation of SCX between BMP-12 and TGF-β1 stimulations. Furthermore, the addition of Ascorbic Acid (AA) with either BMP-12 or TGF-β1 resulted in increased deposition of Collagen I. Our results enhance the existing protocols for the differentiation of ADSCs towards the tenogenic lineage in serum-free conditions and contribute to the understanding and the development of tenogenic induction protocols

Prefunctionalised PLGA microparticles with dimethylaminoethyl moieties promote surface cell adhesion at physiological condition

Synthetic hydrolytically degradable polyesters have seen widespread translation into a variety of clinical and biomedical settings; finding use as cell culture systems, drug delivery systems, tissue repair scaffolds, and medical devices. This success is owed in part due to their biocompatible nature and tuneable degradation profile. However, the lack of adhesion moieties limits the capacity of the polyesters to interact with cellular material and as such hampers their effectiveness within these applications. Several physical and chemical post-modification techniques have been developed to insert adhesion moieties; however, the nature of these methods remains complex and troublesome for translational medicine. To combat this flaw, we present a novel prefunctionalization method for the generation of poly (lactic-co-glycolic acid) PLGA microparticles with integrated adhesion moieties as a proof-of-principle. This strategy promotes surface cell adhesion at physiological conditions without the requirement for further post-modification. The basis of the prefunctionalization method was to utilise the 2-2-dimethylaminoethanol as an initiator in a standard bulk Ring Opening Polymerization process to obtain PLGADMAE polymers. The resultant polymers were subsequently used in the fabrication of the microparticles, via membrane emulsion. This process allowed control over the morphology and size distribution of the microparticles. The surface cell adhesive properties of the new PLGADMAE microparticles were investigated via co-culture with Adipose-Derived Stem Cells. Scanning Electron Microscopy showed that the new PLGADMAE microparticles readily promote adhesion of the ADSCs at physiological conditions. LDH and LIVE/DEAD assays demonstrated that the surface functionalised PLGADMAE microparticles maintained a low toxicity profile compared to the unmodified PLGA microparticles. Both thermogravimetric and differential scanning calorimetric analysis confirmed that the bulk properties of the polymer remained unchanged compared to the control PLGA. Gel Permeation Chromatography and Scanning Electron Microscopy imaging showed that the degradation profile of the new PLGADMAE was enhanced compared to that of standard PLGA polymers. This novel prefunctionalization strategy eliminates the need for post-modification and could evolve rapidly to develop biodegradable biomaterials with enhanced cell adhesion and tuneable surface chemistry to allow greater control and/or maintain interaction with living cells and tissues. The implication of this new approach would be far reaching in the field of cell delivery, cell expansion, tissue engineering and regenerative medicine

A clinical, biological, and biomaterials perspective into tendon injuries and regeneration

Tendon injury is common and debilitating, and it is associated with long-term pain and ineffective healing. It is estimated to afflict 25% of the adult population and is often a career-ending disease in athletes and racehorses. Tendon injury is associated with high morbidity, pain, and long-term suffering for the patient. Due to the low cellularity and vascularity of tendon tissue, once damage has occurred, the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Current treatment options focus on pain management, often being palliative and temporary and ending in reduced function. Most treatments available do not address the underlying cause of the disease and, as such, are often ineffective with variable results. The need for an advanced therapeutic that addresses the underlying pathology is evident. Tissue engineering and regenerative medicine is an emerging field that is aimed at stimulating the body's own repair system to produce de novo tissue through the use of factors such as cells, proteins, and genes that are delivered by a biomaterial scaffold. Successful tissue engineering strategies for tendon regeneration should be built on a foundation of understanding of the molecular and cellular composition of healthy compared with damaged tendon, and the inherent differences seen in the tissue after disease. This article presents a comprehensive clinical, biological, and biomaterials insight into tendon tissue engineering and regeneration toward more advanced therapeutics