GELATIN-BASED MICROPOROUS INJECTABLE HYDROGELS FOR IN SITU STEM CELL ENCAPSULATION

In this dissertation, I developed and investigated gelatin-based microporous injectable hydrogels for the encapsulation of stem cells for multiple applications in cell delivery. Utilizing microgels composed from a mixture of gelatin and modified gelatin, I demonstrated the utility of a dual crosslinking mechanism, which enabled rapid gelation and tissue adhesion with improved cytocompatibility. Mesenchymal stem cells (MSCs) encapsulated in this hydrogel proliferated at a more rapid rate than in a nonporous counterpart, and showed increased immunomodulatory potential. Then, I investigated gelatin microporous hydrogel for the encapsulation of MSCs for bone tissue regeneration. Encapsulated cells more readily differentiated into osteoblasts (i.e. bone-forming cells) in the microporous environment observed by morphological changes and quantitative assays. This is believed to be due to enhanced cell spreading and cell-cell communication in the unique 3D environment provided to the cells by the microporous hydrogel. Transcriptomic analysis was performed by mRNA sequencing (RNA-seq) of MSCs encapsulated in the differing 3D microenvironments. Results indicated that the 3D environment influenced the expression of genes that are related to cell adhesions, cell-cell interactions, cytoskeletal organization, and matrix remodeling, in addition to MSC differentiation. Because neuronal development is highly dependent on cell-cell communication, I encapsulated an established neural stem cell line (ReNcell) in gelatin microporous hydrogel to investigate neuronal differentiation in comparison to a nonporous analog. Laminin was chemically conjugated to microgel surfaces, which controlled the organization of encapsulated cells in the hydrogel environment. Cell differentiation was examined by immunofluorescence staining, and JC-1 assay was utilized to examine mitochondrial membrane polarization. The microporous hydrogel induced substantially greater cell spreading, morphological changes and cell-cell connections than nonporous hydrogel. The majority of the cells in the microporous hydrogel differentiated into neural lineages, evidenced by immunostaining by MAP2 and GFAP. In summary, this work demonstrates the utility of gelatin microporous injectable hydrogels for applications in in situ cell encapsulation and stem cell delivery for tissue regeneration

Marshall University Music Department Presents a Student Recital, Seth Edwards, euphonium, Joey Graybeal, euphonium, Guy Parker, tuba

https://mds.marshall.edu/music_perf/1364/thumbnail.jp

Environmental memory from a circadian oscillator:the Arabidopsis thaliana clock differentially integrates perception of photic vs. thermal entrainment

The constraint of a rotating earth has led to the evolution of a circadian clock that drives anticipation of future environmental changes. During this daily rotation, the circadian clock of Arabidopsis thaliana (Arabidopsis) intersects with the diurnal environment to orchestrate virtually all transcriptional processes of the plant cell, presumably by detecting, interpreting, and anticipating the environmental alternations of light and temperature. To comparatively assess differential inputs toward phenotypic and physiological responses on a circadian parameter, we surveyed clock periodicity in a recombinant inbred population modified to allow for robust periodicity measurements after entrainment to respective photic vs. thermal cues, termed zeitgebers. Lines previously thermally entrained generally displayed reduced period length compared to those previously photically entrained. This differential zeitgeber response was also detected in a set of diverse Arabidopsis accessions. Thus, the zeitgebers of the preceding environment direct future behavior of the circadian oscillator. Allelic variation at quantitative trait loci generated significant differences in zeitgeber responses in the segregating population. These were important for periodicity variation dependent on the nature of the subsequent entrainment source. Collectively, our results provide a genetic paradigm for the basis of environmental memory of a preceding environment, which leads to the integrated coordination of circadian periodicity

Heavy Quarkonia - A Review of the Experimental Status

A review of the present status of the spectroscopy of heavy quarkonia (b-bbar, c-cbar) is presented.Comment: 6 pages, 4 figures, Presented at the 11th International Conference In Quantum ChromoDynamics (QCD 04), Montpellier, France, 5-9 July 200

Emerging immunotherapies for metastasis

Major advances in cancer immunotherapy have dramatically expanded the potential to manipulate immune cells in cancer patients with metastatic disease to counteract cancer spread and extend patient lifespan. One of the most successful types of immunotherapy is the immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1, that keep anti-tumour T cells active. However, not every patient with metastatic disease benefits from this class of drugs and patients often develop resistance to these therapies over time. Tremendous research effort is now underway to uncover new immunotherapeutic targets that can be used in patients who are refractory to anti-CTLA-4 or anti-PD-1 treatment. Here, we discuss results from experimental model systems demonstrating that modulating the immune response can negatively affect metastasis formation. We focus on molecules that boost anti-tumour immune cells and opportunities to block immunosuppression, as well as cell-based therapies with enhanced tumour recognition properties for solid tumours. We also present a list of challenges in treating metastatic disease with immunotherapy that must be considered in order to move laboratory observations into clinical practice and maximise patient benefit

In Pursuit of Love: First Templated Search for Compact Objects with Large Tidal Deformabilities in the LIGO-Virgo Data

We report results on the first matched-filtering search for binaries with compact objects having large tidal deformabilities in the LIGO-Virgo gravitational wave (GW) data. The tidal deformability of a body is quantified by the ``Love number" $\Lambda \propto \hskip 1pt (r/m)^5$, where $r/m$ is the body's (inverse) compactness. Due to its strong dependence on compactness, the $\Lambda$ of larger-sized compact objects can easily be many orders of magnitude greater than those of black holes and neutron stars, leaving phase shifts which are sufficiently large for these binaries to be missed by binary black hole (BBH) templated searches. In this paper, we conduct a search using inspiral-only waveforms with zero spins but finite tides, with the search space covering chirp masses $3 M_\odot < \mathcal{M} < 15 M_\odot$ and effective tidal deformabilities $10^2 \lesssim \tilde{\Lambda} \lesssim 10^6$. We find no statistically significant GW candidates. This null detection implies an upper limit on the merger rate of such binaries in the range $[1-300] \hskip 2pt \text{Gpc}^{-3} \text{year}^{-1}$, depending on $\mathcal{M}$ and $\tilde{\Lambda}$. While our constraints are model agnostic, we discuss the implications on beyond the Standard Model scenarios that give rise to boson stars and superradiant clouds. Using inspiral-only waveforms we recover many of the BBH signals which were previously identified with full inspiral-merger-ringdown templates. We also constrain the Love number of black holes to $\Lambda \lesssim 10^3$ at the 90\% credible interval. Our work is the first-ever dedicated template-based search for compact objects that are not only black holes and neutron stars. Additionally, our work demonstrates a novel way of finding new physics in GW data, widening the scope of potential discovery to previously unexplored parameter space.Comment: 42+11 pages, 12 figure

The MVGC multivariate Granger causality toolbox: a new approach to Granger-causal inference

Background: Wiener-Granger causality (“G-causality”) is a statistical notion of causality applicable to time series data, whereby cause precedes, and helps predict, effect. It is defined in both time and frequency domains, and allows for the conditioning out of common causal influences. Originally developed in the context of econometric theory, it has since achieved broad application in the neurosciences and beyond. Prediction in the G-causality formalism is based on VAR (Vector AutoRegressive) modelling. New Method: The MVGC Matlab c Toolbox approach to G-causal inference is based on multiple equivalent representations of a VAR model by (i) regression parameters, (ii) the autocovariance sequence and (iii) the cross-power spectral density of the underlying process. It features a variety of algorithms for moving between these representations, enabling selection of the most suitable algorithms with regard to computational efficiency and numerical accuracy. Results: In this paper we explain the theoretical basis, computational strategy and application to empirical G-causal inference of the MVGC Toolbox. We also show via numerical simulations the advantages of our Toolbox over previous methods in terms of computational accuracy and statistical inference. Comparison with Existing Method(s): The standard method of computing G-causality involves estimation of parameters for both a full and a nested (reduced) VAR model. The MVGC approach, by contrast, avoids explicit estimation of the reduced model, thus eliminating a source of estimation error and improving statistical power, and in addition facilitates fast and accurate estimation of the computationally awkward case of conditional G-causality in the frequency domain. Conclusions: The MVGC Toolbox implements a flexible, powerful and efficient approach to G-causal inference. Keywords: Granger causality, vector autoregressive modelling, time series analysi

On the electromagnetic fields produced by marine frequency domain controlled sources

Author Posting. © The Author, 2009. This article is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Geophysical Journal International 179 (2009): 1429-1457, doi:10.1111/j.1365-246X.2009.04367.x.In recent years, marine controlled source electromagnetics (CSEM) has found increasing use in hydrocarbon exploration due to its ability to detect thin resistive zones beneath the seafloor. Although it must be recognized that the quantitative interpretation of marine CSEM data over petroleum-bearing formations will typically require 2-D surveys and 2-D or 3-D modelling, the use of the 1-D approximation is useful under some circumstances and provides considerable insight into the physics of marine CSEM. It is the purpose of this paper to thoroughly explore the 1-D solutions for all four fundamental source types—vertical and horizontal, electric and magnetic dipole (VED, HED, VMD and HMD)—using a set of canonical reservoir models that encompass brine to weak to strong hydrocarbon types. The paper introduces the formalism to solve the Maxwell equations for a 1-D structure in terms of independent and unique toroidal and poloidal magnetic modes that circumscribe the salient diffusion physics. Green's functions for the two modes from which solutions for arbitrary source current distributions can be constructed are derived and used to obtain the electromagnetic (EM) fields produced by finite VED, HED, VMD and HMD sources overlying an arbitrary 1-D electrical structure. Field behaviour is analysed using the Poynting vector that represents the time-averaged flow of energy through the structure and a polarization ellipse decomposition of the triaxial seafloor EM field that is a complete field description. The behaviour of the two EM modes using unimodal VED and VMD sources is presented. The paper closes by extending these results to the bimodal HED and HMD sources