John Spottiswoode, Jacobean archbishop and statesman

This main aim of this thesis is to conclusively demonstrate that John Spottiswoode was one of the most important churchman in early modern Scotland. He was, it will be shown, the most authoritative and impressive of Scotland's post-Refonriation bishops. Spottiswoode was the principal ecclesiastic in James VI's reconstruction of an episcopal church in Scotland after 1603 when he was appointed Archbisiop of Glasgow. This was followed by his prestigious translation to the metropolitan see of St Andrews in 1615 from where he presided over those controversial liturgical reforms of the succeeding years of the Jacobean era. Moreover, as a prominent member of the Scottish government he was heavily involved in secular politics and administration throughout the absentee kingship of James VI and that of his son, Charles I. This study, however, will confine itself to charting the archbishop's ecclesiastical and political ascendancy and involvement within the Scottish Jacobean church and state. Although Spottiswoode was without question a loyal supporter of the crown, it will be shown that he was no sycophant. Therefore, it is necessary to provide an analysis of the qualities and characteristics that made Spottiswoode such an influential figure and beneficiary of royal largesse between 1603 and 1625. Through focusing on the activities and objectives of Archbishop Spottiswoode throughout the reign of James VI, this thesis also aims to challenge the popular notion that the Church of Scotland functioned efficiently and harmoniously throughout the reign of"rex pacificus". Furthermore, the idea that an absolutist state existed in Scotland after the regal union will be exposed as fanciful

Plan for Financial Efficiency in Private Higher Education: Curricula Reorganization in Selected Four-Year Institutions

Educaional Administratio

The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy

Immune checkpoint blockade has recently proven effective in subsets of patients with esophageal adenocarcinoma (EAC) but little is known regarding the EAC immune microenvironment. We determined the single cell transcriptional profile of EAC in 8 patients who were treatment-naive (n = 4) or had received neoadjuvant chemotherapy (n = 4). Analysis of 52,387 cells revealed 10 major cell subsets of tumor, immune and stromal cells. Prior to chemotherapy tumors were heavy infiltrated by T regulatory cells and exhausted effector T cells whilst plasmacytoid dendritic cells were markedly expanded. Two dominant cancer-associated fibroblast populations were also observed whilst endothelial populations were suppressed. Pathological remission following chemotherapy associated with broad reversal of immune abnormalities together with fibroblast transition and an increase in endothelial cells whilst a chemoresistant epithelial stem cell population correlated with poor response. These findings reveal features that underlie and limit the response to current immunotherapy and identify a range of novel opportunities for targeted therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-022-01666-x

Spectroscopic Characterization of Aqua [ fac-Tc(CO)3]+ Complexes at High Ionic Strength.

Understanding fundamental Tc chemistry is important to both the remediation of nuclear waste and the reprocessing of nuclear fuel; however, current knowledge of the electronic structure and spectral signatures of low-valent Tc compounds significantly lags behind the remainder of the d-block elements. In particular, identification and treatment of Tc speciation in legacy nuclear waste is challenging due to the lack of reference data especially for Tc compounds in the less common oxidation states (I-VI). In an effort to establish a spectroscopic library corresponding to the relevant conditions of extremely high ionic strength typical for the legacy nuclear waste, compounds with the general formula of [ fac-Tc(CO)3(OH2)3- n(OH) n]1- n (where n = 0-3) were examined by a range of spectroscopic techniques including 99Tc/13C NMR, IR, XPS, and XAS. In the series of monomeric aqua species, stepwise hydrolysis results in the increase of the Tc metal center electron density and corresponding progressive decrease of the Tc-C bond distances, Tc electron binding energies, and carbonyl stretching frequencies in the order [ fac-Tc(CO)3(OH2)3]+ > [ fac-Tc(CO)3(OH2)2(OH)] > [ fac-Tc(CO)3(OH2)(OH)2]-. These results correlate with established trends of the 99Tc upfield chemical shift and carbonyl 13C downfield chemical shift. The lone exception is [ fac-Tc(CO)3(OH)]4 which exhibits a comparatively low electron density at the metal center attributed to the μ3-bridging nature of the -OH ligands causing less σ-donation and no π-donation. This work also reports the first observations of these compounds by XPS and [ fac-Tc(CO)3Cl3]2- by XAS. The unique and distinguishable spectral features of the aqua [ fac-Tc(CO)3]+ complexes lay the foundation for their identification in the complex aqueous matrixes

Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'

We combined large-scale mRNA expression analysis and gene mapping to identify genes and loci that control hematopoietic stem cell (HSC) function. We measured mRNA expression levels in purified HSCs isolated from a panel of densely genotyped recombinant inbred mouse strains. We mapped quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts. By comparing the physical transcript position with the location of the controlling QTL, we identified polymorphic cis-acting stem cell genes. We also identified multiple trans-acting control loci that modify expression of large numbers of genes. These groups of coregulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of candidate genes involved with HSC turnover. We compared expression QTLs in HSCs and brain from the same mice and identified both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of coregulated transcripts.

Cr(VI) Effect on Tc-99 Removal from Hanford Low-Activity Waste Simulant by Ferrous Hydroxide.

Here, Cr(VI) effects on Tc-immobilization by Fe(OH)2(s) are investigated while assessing Fe(OH)2(s) as a potential treatment method for Hanford low-activity waste destined for vitrification. Batch studies using simulated low-activity waste indicate that Tc(VII) and Cr(VI) removal is contingent on reduction to Tc(IV) and Cr(III). Furthermore, complete removal of both Cr and Tc depends on the amount of Fe(OH)2(s) present, where complete Cr and Tc removal requires more Fe(OH)2(s) (∼200 g/L of simulant), than removing Cr alone (∼50 g/L of simulant). XRD analysis suggests that Fe(OH)2(s) reaction and transformation in the simulant produces mostly goethite (α-FeOOH), where Fe(OH)2(s) transformation to goethite rather than magnetite is likely due to the simulant chemistry, which includes high levels of nitrite and other constituents. Once reduced, a fraction of Cr(III) and Tc(IV) substitute for octahedral Fe(III) within the goethite crystal lattice as supported by XPS, XANES, and/or EXAFS results. The remaining Cr(III) forms oxide and/or hydroxide phases, whereas Tc(IV) not fully incorporated into goethite persists as either adsorbed or partially incorporated Tc(IV)-oxide species. As such, to fully incorporate Tc(IV) into the goethite crystal structure, additional Fe(OH)2(s) (>200 g/L of simulant) may be required

CD70 identifies alloreactive T cells and represents a potential target for prevention and treatment of acute GvHD

Graft-versus-host disease (GvHD) remains a major challenge following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and further understanding of its immunopathology is crucial for developing new treatments. CD70 interacts with CD27 and is upregulated transiently on T cells following recent TCR engagement. Here we investigated the functional and clinical significance of CD70 expression on T cells during the early post-transplantation period. CD70 was expressed on a subset of highly activated memory T cells within the first 2 weeks post-transplant which then gradually declined in most patients. CD70+ T cells exhibited an open chromatin landscape and a transcriptional profile indicative of intense MYC-driven glycolysis and proliferation. CD4+ and CD8+ CD70+ T cell number increased by 9-fold and 4-fold respectively during acute GvHD (aGvHD) and displayed an oligoclonal TCR repertoire. These cells expressed CCR4 and CCR6 chemokine receptors and were markedly increased in aGvHD tissue samples. Furthermore, CD70+ T cells demonstrated alloreactive specificity in vitro and proliferative and inflammatory cytokine responses were markedly attenuated by CD70 blockade. These findings identify CD70 as a marker of highly activated alloreactive T cells and reveal the potential therapeutic importance of inhibiting CD27-CD70 co-stimulation in both the prophylaxis and treatment of aGvHD

Reduction and Simultaneous Removal of 99Tc and Cr by Fe(OH)2(s) Mineral Transformation.

Technetium (Tc) remains a priority remediation concern due to persistent challenges, including mobilization due to rapid reoxidation of immobilized Tc, and competing comingled contaminants, e.g., Cr(VI), that inhibit Tc(VII) reduction and incorporation into stable mineral phases. Here Fe(OH)2(s) is investigated as a comprehensive solution for overcoming these challenges, by serving as both the reductant, (Fe(II)), and the immobilization agent to form Tc-incorporated magnetite (Fe3O4). Trace metal analysis suggests removal of Tc(VII) and Cr(VI) from solution occurs simultaneously; however, complete removal and reduction of Cr(VI) is achieved earlier than the removal/reduction of comingled Tc(VII). Bulk oxidation state analysis of the final magnetite solid phase by XANES shows that the majority of Tc is Tc(IV), which is corroborated by XPS measurements. Furthermore, EXAFS results show successful, albeit partial, Tc(IV) incorporation into magnetite octahedral sites. Cr XPS analysis indicates reduction to Cr(III) and the formation of a Cr-incorporated spinel, Cr2O3, and Cr(OH)3 phases. Spinel (modeled as Fe3O4), goethite (α-FeOOH), and feroxyhyte (δ-FeOOH) are detected in all reacted final solid phase samples analyzed by XRD. Incorporation of Tc(IV) has little effect on the spinel lattice structure. Reaction of Fe(OH)2(s) in the presence of Cr(III) results in the formation of a spinel phase that is a solid solution between magnetite (Fe3O4) and chromite (FeCr2O4)