The doctrines of hell and judgment and the need for personal conversion as an index to the development of liberal theology within the theological colleges of the Methodist church in England from 1907 to 1932

The first chapter of the thesis shows how the study was born in a local church where the preached message represented a difference from the beliefs of John Wesley. The second chapter shows how the doctrinal standards of Methodism are defined in terms of the Motes and Sermons o£ John Wesley. These works are examined, and detailed doctrines expounded of Jesus as judge, and the grounds for and nature and experience of his judgment as applied to the lives of men. The third chapter considers the Primitive Methodist Church and shows how a liberal Influence was felt at Hartley College, Manchester, through the dominant personality of A. S. Peake. Peak’s doctrine is expounded and the securing of his position by the philanthropist, W. Hartley, is described. The fourth chapter considers Ranmoor College, Sheffield ' ,and Victoria Park College, Manchester, of the United Methodist Church and highlights the major influence of A. S. Peake in that denomination also. Chapters five and six treat the colleges of Wesleyan Methodism, namely Didsbury, Richmond, Headingley, Handsworth and Cambridge. For these the period is divided into pre- and post- 1918. The doctrinal stance is shown to be more complex than for the other denominations and for each college the doctrinal position of each senior member of staff is expounded and the changing tenor of each college traced. The final chapter shows how by 1932 the theological education of Methodist ministers was heavily biased to a liberal attitude, and relates the findings of the thesis to the state of Methodism generally

Critical Space Infrastructure: A Complex System Governance Perspective

This paper examines the applicability of Complex System Governance (CSG) to advance the Critical Space Infrastructure field (CSI). CSI encompasses space related hardware, workforce, environment, facilities, and businesses that are necessary for societal well-being. CSI is increasing in importance as more societal serving systems are becoming dependent on CSI to operate. Given this increasing dependence on CSI, societal sectors are increasingly at risk should something go wrong with CSI upon which they depend. CSI has been developing is a fragmented way and lacks coherent organization. CSG is focused on design, execution, and evolution of system functions that provide for communications, control, coordination, and integration of complex systems. CSG provides structure and order to complex systems through a rigorous grounding in systems theory (the axioms and propositions that govern behavior, performance, and structure of complex systems), management cybernetics (the science of organizational structure), and system governance (focused on provision of direction, oversight, and accountability). In this paper the intersection of CSI and CSG is explored with respect to the value that can accrue to both fields through their intersection and joint development. The opportunities that lie at the intersection of these fields are examined. This paper concludes the exploration with a discussion of the implications for movement forward in bringing the value offered by CSG to the governance of space-based critical infrastructures

A Case Study of Laser Wind Sensor Performance Validation by Comparison to an Existing Gage

A case study concerning validation of wind speed measurements made by a laser wind sensor mounted on a 190 square foot floating platform in Muskegon Lake through comparison with measurements made by pre-existing cup anemometers mounted on a met tower on the shore line is presented. The comparison strategy is to examine the difference in measurements over time using the paired-t statistical method to identify intervals when the measurements were equivalent and to provide explanatory information for the intervals when the measurements were not equivalent. The data was partitioned into three sets: not windy (average wind speed measured by the cup anemometers ≤ 6.7m/s) windy but no enhanced turbulence (average wind speed measured by the cup anemometers \u3e 6.7m/s), and windy with enhanced turbulence associated with storm periods. For the not windy data set, the difference in the average wind speeds was equal in absolute value to the precision of the gages and not statistically significant. Similar results were obtained for the windy with no enhanced turbulence data set and the average difference was not statistically significant (α=0.01). The windy with enhanced turbulence data set showed significant differences between the buoy mounted laser wind sensor and the on-shore mast mounted cup anemometers. The sign of the average difference depended on the direction of the winds. Overall, validation evidence is obtained in the absence of enhanced turbulence. In addition, differences in wind speed during enhanced turbulence were isolated in time, studied and explained

Analogies Between Digital Radio and Chemical Orthogonality as a Method for Enhanced Analysis of Molecular Recognition Events

Acoustic wave biosensors are a real-time, label-free biosensor technology, which have been exploited for the detection of proteins and cells. One of the conventional biosensor approaches involves the immobilization of a monolayer of antibodies onto the surface of the acoustic wave device for the detection of a specific analyte. The method described within includes at least two immobilizations of two different antibodies onto the surfaces of two separate acoustic wave devices for the detection of several analogous analytes. The chemical specificity of the molecular recognition event is achieved by virtue of the extremely high (nM to pM) binding affinity between the antibody and its antigen. In a standard ELISA (Enzyme-Linked ImmunoSorbent Assay) test, there are multiple steps and the end result is a measure of what is bound so tightly that it does not wash away easily. The fact that this “gold standard” is very much not real time, masks the dance that is the molecular recognition event. X-Ray Crystallographer, Ian Wilson, demonstrated more than a decade ago that antibodies undergo conformational change during a binding event[1, 2]. Further, it is known in the arena of immunochemistry that some antibodies exhibit significant cross-reactivity and this is widely termed antibody promiscuity. A third piece of the puzzle that we will exploit in our system of acoustic wave biosensors is the notion of chemical orthogonality. These three biochemical constructs, the dance, antibody promiscuity and chemical orthogonality will be combined in this paper with the notions of in-phase (I) and quadrature (Q) signals from digital radio to manifest an approach to molecular recognition that allows a level of discrimination and analysis unobtainable without the aggregate. As an example we present experimental data on the detection of TNT, RDX, C4, ammonium nitrate and musk oil from a system of antibody-coated acoustic wave sensors

Deregulation of DUX4 and ERG in acute lymphoblastic leukemia

Chromosomal rearrangements deregulating hematopoietic transcription factors are common in acute lymphoblastic leukemia (ALL).1,2 Here, we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG are hallmarks of a subtype of B-progenitor ALL that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression was present in all cases, and was accompanied by transcriptional deregulation of ERG, expression of a novel ERG isoform, ERGalt, and frequent ERG deletion. ERGalt utilizes a non-canonical first exon whose transcription was initiated by DUX4 binding. ERGalt retains the DNA-binding and transactivating domains of ERG, but inhibits wild-type ERG transcriptional activity and is transforming. These results illustrate a unique paradigm of transcription factor deregulation in leukemia, in which DUX4 deregulation results in loss-of-function of ERG, either by deletion or induction of expression of an isoform that is a dominant negative inhibitor of wild type ERG function

HIV-1 Envelope Subregion Length Variation during Disease Progression

The V3 loop of the HIV-1 Env protein is the primary determinant of viral coreceptor usage, whereas the V1V2 loop region is thought to influence coreceptor binding and participate in shielding of neutralization-sensitive regions of the Env glycoprotein gp120 from antibody responses. The functional properties and antigenicity of V1V2 are influenced by changes in amino acid sequence, sequence length and patterns of N-linked glycosylation. However, how these polymorphisms relate to HIV pathogenesis is not fully understood. We examined 5185 HIV-1 gp120 nucleotide sequence fragments and clinical data from 154 individuals (152 were infected with HIV-1 Subtype B). Sequences were aligned, translated, manually edited and separated into V1V2, C2, V3, C3, V4, C4 and V5 subregions. V1-V5 and subregion lengths were calculated, and potential N-linked glycosylation sites (PNLGS) counted. Loop lengths and PNLGS were examined as a function of time since infection, CD4 count, viral load, and calendar year in cross-sectional and longitudinal analyses. V1V2 length and PNLGS increased significantly through chronic infection before declining in late-stage infection. In cross-sectional analyses, V1V2 length also increased by calendar year between 1984 and 2004 in subjects with early and mid-stage illness. Our observations suggest that there is little selection for loop length at the time of transmission; following infection, HIV-1 adapts to host immune responses through increased V1V2 length and/or addition of carbohydrate moieties at N-linked glycosylation sites. V1V2 shortening during early and late-stage infection may reflect ineffective host immunity. Transmission from donors with chronic illness may have caused the modest increase in V1V2 length observed during the course of the pandemic