94 research outputs found
sj-pdf-1-jcb-10.1177_0271678X231205661 - Supplemental material for [<sup>18</sup>F]LW223 has low non-displaceable binding in murine brain, enabling high sensitivity TSPO PET imaging
No full textSupplemental material, sj-pdf-1-jcb-10.1177_0271678X231205661 for [18F]LW223 has low non-displaceable binding in murine brain, enabling high sensitivity TSPO PET imaging by Agne Knyzeliene, Mark G MacAskill, Carlos J Alcaide-Corral, Timaeus EF Morgan, Martyn C Henry, Christophe Lucatelli, Sally L Pimlott, Andrew Sutherland and Adriana AS Tavares in Journal of Cerebral Blood Flow & Metabolism</p
Transformation and growth : the Davidic temple builder in Ephesians
No full textThe focus of this thesis is on the way in which the theology of the author of the Epistle to the Ephesians is both shaped by and shapes the appropriation of OT texts and themes, especially in Eph 2:11-22. This reveals an overarching theme, not only in 2:11-22, but in the whole letter, of the Davidic scion who builds his new temple consisting of Jews and Gentiles together. The creation and growth of this new humanity is expressed using temple imagery and by appropriating OT texts that are concerned with the eschatological pilgrimage of the Gentiles to Zion.
Ephesians is concerned with the transformed walking that is inherent to membership of the Messiah’s people. It is further concerned that this corporate entity should function as God’s dwelling place on earth; unity and loving relationships therefore being the burden of Ephesians’ paraenesis. This entire process is summed up at the gateway to the letter’s paraenesis in the phrase “learn the Messiah.” The discipleship thus conceived is about much more than (but not less than) individual transformation. The temple/dwelling place theme imparts a corporate dimension to growth that is crucial if the Messiah’s people are to function as they ought. This functioning is given further definition, however, by the expansionist element introduced by the temple theme and texts, as well as the framing of membership of the Messiah’s people in explicitly covenantal terms.
Ephesians may thus be seen as a letter whose purpose is to induct believers into the privileges and responsibilities of the Messiah’s new humanity, to give them the self understanding that they constitute corporately the new temple and to convince them that the manner of their “walking” is the means by which the unity and integrity of God’s dwelling place is both expressed and maintained
Quantification of Macrophage-Driven Inflammation During Myocardial Infarction with 18F-LW223, a Novel TSPO Radiotracer with Binding Independent of the rs6971 Human Polymorphism
No full textMyocardial infarction (MI) is one of the leading causes of death
worldwide, and inflammation is central to tissue response and patient
outcomes. The 18-kDa translocator protein (TSPO) has been used in
PET as an inflammatory biomarker. The aims of this study were to
screen novel, fluorinated, TSPO radiotracers for susceptibility to the
rs6971 genetic polymorphism using in vitro competition binding assays
in human brain and heart; assess whether the in vivo characteristics
of our lead radiotracer, 18F-LW223, are suitable for clinical
translation; and validate whether 18F-LW223 can detect macrophage-
driven inflammation in a rat MI model. Methods: Fifty-one
human brain and 29 human heart tissue samples were screened
for the rs6971 polymorphism. Competition binding assays were conducted
with 3H-PK11195 and the following ligands: PK11195, PBR28,
and our novel compounds (AB5186 and LW223). Na¨ıve rats and mice
were used for in vivo PET kinetic studies, radiometabolite studies, and
dosimetry experiments. Rats underwent permanent coronary artery
ligation and were scanned using PET/CT with an invasive input function
at 7 d after MI. For quantification of PET signal in the hypoperfused
myocardium, K1 (rate constant for transfer from arterial plasma
to tissues) was used as a surrogate marker of perfusion to correct the
binding potential for impaired radiotracer transfer from plasma to
tissue (BPTC). Results: LW223 binding to TSPO was not susceptible
to the rs6971 genetic polymorphism in human brain and heart samples.
In rodents, 18F-LW223 displayed a specific uptake consistent
with TSPO expression, a slow metabolism in blood (69% of parent at
120 min), a high plasma free fraction of 38.5%, and a suitable dosimetry
profile (effective dose of 20.5–24.5 μSv/MBq). 18F-LW223 BPTC
was significantly higher in the MI cohort within the infarct territory of
the anterior wall relative to the anterior wall of na¨ıve animals (32.7 ±
5.0 vs. 10.0 ± 2.4 cm3/mL/min, P # 0.001). Ex vivo immunofluorescent
staining for TSPO and CD68 (macrophage marker) resulted in
the same pattern seen with in vivo BPTC analysis. Conclusion: 18FLW223
is not susceptible to the rs6971 genetic polymorphism in in
vitro assays, has favorable in vivo characteristics, and is able to accurately
map macrophage-driven inflammation after MI.
Mark G. MacAskill, Agne Stadulyte, Lewis Williams, Timaeus E.F. Morgan, Nikki L. Sloan, Carlos J. Alcaide-
Corral, Tashfeen Walton, Catriona Wimberley, Chris-Anne McKenzie, Nick Spath, William Mungall,
Ralph BouHaidar, Marc R. Dweck, Gillian A. Gray, David E. Newby, Christophe Lucatelli, Andrew Sutherland,
Sally L. Pimlott, and Adriana A.S. Tavare
The soteriology of James in light of earlier Jewish Wisdom literature and the Gospel of Matthew
No full textThe epistle of James has been neglected in NT studies, caught between its
relationship with Paul and the claim that it has no theology. Even as it experiences a
resurgence of study, surprisingly no full-length survey exists on James as the epistle of
“faith and works.” Approaches to James have neglected its soteriology and, in
consequence, its theological themes have been separated or studied only in connection
with Paul. As “moral character,” however, “faith” and “works” fit within a coherent
theology of God’s mercy and judgment.
This study provides a sustained reading of James as a Jewish-Christian document.
Because James presents the “faith” and “works” discussion in context of “can such faith
save?” (2:14), the issue becomes one of soteriology and final judgment. Both the “law of
freedom” and the “word of truth” demand faithful obedience—the “works.” Moreover,
God’s character and deeds in election form the basis for human “works” of mercy and
humble obedience, while future judgment is in accordance with virtuous character.
It has been established that James shares methodology and concerns with prior
wisdom literature. This thesis therefore examines key ideas developing across the Jewish
literature and Jesus’ teaching as presented by Matthew, and highlights developing views of
God saving and judging his people. Within the first two chapters, James gives a high view
of God’s work in calling and redeeming, providing wisdom to his people, and instilling the
long-anticipated new covenant that they might live in obedience, humility and purity in
accordance with his character and will. Because of God’s saving work, he justly judges
those who fail to live mercifully, while his mercy triumphs for those who obey. God
begins the work and sustains those who ask; but only those who submit to the “perfect
law of freedom,” whose faith works, receive mercy when God enacts his final justice
Cognitive Therapy in Clinical Practice – An Illustrative Casebook. Edited by Jan Scott, J. Mark G. Williams and Aaron T. Beck London: Routledge. 1989. 255 pp. £10.99.
No full textTransformation and growth : the Davidic temple builder in Ephesians
No full textThe focus of this thesis is on the way in which the theology of the author of the Epistle to the Ephesians is both shaped by and shapes the appropriation of OT texts and themes, especially in Eph 2:11-22. This reveals an overarching theme, not only in 2:11-22, but in the whole letter, of the Davidic scion who builds his new temple consisting of Jews and Gentiles together. The creation and growth of this new humanity is expressed using temple imagery and by appropriating OT texts that are concerned with the eschatological pilgrimage of the Gentiles to Zion. Ephesians is concerned with the transformed walking that is inherent to membership of the Messiah’s people. It is further concerned that this corporate entity should function as God’s dwelling place on earth; unity and loving relationships therefore being the burden of Ephesians’ paraenesis. This entire process is summed up at the gateway to the letter’s paraenesis in the phrase “learn the Messiah.” The discipleship thus conceived is about much more than (but not less than) individual transformation. The temple/dwelling place theme imparts a corporate dimension to growth that is crucial if the Messiah’s people are to function as they ought. This functioning is given further definition, however, by the expansionist element introduced by the temple theme and texts, as well as the framing of membership of the Messiah’s people in explicitly covenantal terms. Ephesians may thus be seen as a letter whose purpose is to induct believers into the privileges and responsibilities of the Messiah’s new humanity, to give them the self understanding that they constitute corporately the new temple and to convince them that the manner of their “walking” is the means by which the unity and integrity of God’s dwelling place is both expressed and maintained.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Quantification of Macrophage-Driven Inflammation During Myocardial Infarction with 18F-LW223, a Novel TSPO Radiotracer with Binding Independent of the rs6971 Human Polymorphism
No full textMyocardial infarction (MI) is one of the leading causes of death worldwide, and inflammation is central to tissue response and patient outcomes. The 18-kDa translocator protein (TSPO) has been used in PET as an inflammatory biomarker. The aims of this study were to screen novel, fluorinated, TSPO radiotracers for susceptibility to the rs6971 genetic polymorphism using in vitro competition binding assays in human brain and heart; assess whether the in vivo characteristics of our lead radiotracer, 18F-LW223, are suitable for clinical translation; and validate whether 18F-LW223 can detect macrophage- driven inflammation in a rat MI model. Methods: Fifty-one human brain and 29 human heart tissue samples were screened for the rs6971 polymorphism. Competition binding assays were conducted with 3H-PK11195 and the following ligands: PK11195, PBR28, and our novel compounds (AB5186 and LW223). Na¨ıve rats and mice were used for in vivo PET kinetic studies, radiometabolite studies, and dosimetry experiments. Rats underwent permanent coronary artery ligation and were scanned using PET/CT with an invasive input function at 7 d after MI. For quantification of PET signal in the hypoperfused myocardium, K1 (rate constant for transfer from arterial plasma to tissues) was used as a surrogate marker of perfusion to correct the binding potential for impaired radiotracer transfer from plasma to tissue (BPTC). Results: LW223 binding to TSPO was not susceptible to the rs6971 genetic polymorphism in human brain and heart samples. In rodents, 18F-LW223 displayed a specific uptake consistent with TSPO expression, a slow metabolism in blood (69% of parent at 120 min), a high plasma free fraction of 38.5%, and a suitable dosimetry profile (effective dose of 20.5–24.5 μSv/MBq). 18F-LW223 BPTC was significantly higher in the MI cohort within the infarct territory of the anterior wall relative to the anterior wall of na¨ıve animals (32.7 ± 5.0 vs. 10.0 ± 2.4 cm3/mL/min, P # 0.001). Ex vivo immunofluorescent staining for TSPO and CD68 (macrophage marker) resulted in the same pattern seen with in vivo BPTC analysis. Conclusion: 18FLW223 is not susceptible to the rs6971 genetic polymorphism in in vitro assays, has favorable in vivo characteristics, and is able to accurately map macrophage-driven inflammation after MI. Mark G. MacAskill, Agne Stadulyte, Lewis Williams, Timaeus E.F. Morgan, Nikki L. Sloan, Carlos J. Alcaide- Corral, Tashfeen Walton, Catriona Wimberley, Chris-Anne McKenzie, Nick Spath, William Mungall, Ralph BouHaidar, Marc R. Dweck, Gillian A. Gray, David E. Newby, Christophe Lucatelli, Andrew Sutherland, Sally L. Pimlott, and Adriana A.S. TavaresMacAskill, Mark; Stadulyte, Agne; Morgan, Timaeus; Alcaide Corral, Carlos; Wimberley, Catriona; Tavares, Adriana A.S.. (2022). Quantification of Macrophage-Driven Inflammation During Myocardial Infarction with 18F-LW223, a Novel TSPO Radiotracer with Binding Independent of the rs6971 Human Polymorphism, [dataset]. University of Edinburgh. Centre for Cardiovascular Science. https://doi.org/10.7488/ds/3489
Chronopolitanism: political inclusion and the distant future
No full textAn area of recent philosophical interest concerns longtermism. Longtermism is the view that we should be particularly concerned with (even distant) future generations. It is sometimes strengthened in the form of strong longtermism, the view that the primary determinant of the moral value of our actions today is their effect on the long-term future. The long-term future, here, refers to a period of time surprisingly far into the future, such as 1,000 years from now. Progenitors of longtermism have characteristically been most concerned, morally, with the aggregate welfare of the long-term future, and practically, with work to reduce the risk of human extinction. I aim to broaden the scope of longtermist reflection, morally, by providing an analysis of a set of non-welfarist and non-consequentialist intergenerational ideals, and practically, by providing an analysis of a set of interventions which may rival extinction risk reduction in the value of their long-term effects.
In Chapter 1, I consider the prospects for extending the non-welfarist and (predominantly) nonconsequentialist ideals of political legitimacy to future generations, contrary to the tacit assumptions of political philosophers. I show that, among extant accounts of political legitimacy, the most promising accounts of the grounds of political legitimacy imply that States have duties of legitimacy to future generations as well as to present citizens. In Chapter 2, I analyse a set of interventions for improving the value of the far future through the amelioration of political short-termism, the excessive priority that political systems give to present net benefits at the cost of future ones. I show that one popular set of proposed interventions centred on youth empowerment is unlikely to significantly increase the time horizons of political systems, and propose a novel set of political institutions employing a novel system of retrospective accountability which shows much greater promise. In Chapter 3, I analyse a set of interventions for improving the value of the far future through a form of moral values change, specifically interventions which seek to improve the far future by shaping humanity’s moral attitudes towards nonhuman animals today. This set of interventions is initially promising, but its case hinges on highly controversial theory about consciousness, the persistence of changes to human values, and about the psychological relationship between our various moral attitudes.Ph.D.Includes bibliographical reference
"This word is the gospel preached to you" : ecclesiology and the Isaianic narrative in 1 Peter
No full textThe appropriation of Isaiah in 1 Peter occurs through explicit quotations, but also by means of subtle allusions and echoes. I propose that the ecclesiology of 1 Peter draws upon the narrative of the restoration of divine presence among the people of God despite present suffering, which is informed largely by the themes and images of Isaiah, so that the church is identified as participants in a scriptural narrative through its participation in Christ, who is
understood to be the Messiah of the scriptures.
This study explores the relationship between 1 Peter and the scriptures it employs along
several lines. First, comparison is made with available textual evidence to determine differences between the texts in 1 Peter and their Vorlagen. This helps determine the extent to which texts have been modified, the cause of modification, and any interpretive uses such modifications may
have occurred. Second, individual texts used in 1 Peter are correlated with the larger narrative of scripture. It is argued that the terms suffering and glory express this narrative in the language of the epistle as a present conflict and future resolution. Third, Isaiah informs the ecclesiology of
the letter, in harmony with other scriptural texts, so that the church is viewed as participating in the scriptural narrative of the restoration of divine presence. Finally, the narrative drawn from scripture provides comfort and consolation to Christians suffering in Asia Minor by showing
how present suffering is consistent with the experiences of God’s people in ages past and with the experience of Christ. Furthermore, the hope of future glory entails the vindication of present calamities and the reward of honorable conduct.
I conclude by showing how the Isaianic narrative has been formative for Peter’s
understanding of the church. In his address to the churches of Asia Minor, he builds an
argument from his reading of the Isaianic narrative that 1) indicates how the scriptures of Israel are the basis of gospel proclamation and community formation, 2) proposes a high ethical standard in the midst of suffering based on the pattern of Christ, and 3) depicts the vindication
of the suffering church at the revelation of Christ
Wisdom and apocalyptic in the Gospel of Matthew : a comparative study with 1 Enoch and 4QInstruction
No full textRecent scholarship has demonstrated that Matthew's gospel has significantly developed
both sapiential and apocalyptic elements within its narrative. Little attention has been paid,
however, to the question of how these two features of Matthew's gospel might relate to one
another. It is this gap in scholarly literature that the present study is intended to fill, by means of a
comparative study with two other texts of mixed genre: 1 Enoch and 4Qlnstruction.
An examination of these texts demonstrates that each is marked by an inaugurated
eschatology, within which the revealing of wisdom to an elect group, defined in distinction to the
Jewish parent group, serves as the pivotal moment of inauguration. In addition, within
4Qlnstruction the idea is developed that possession of this revealed wisdom allows the remnant
to live in fidelity to the will of the Creator and to the patterns built-in to the original creation.
Thus, possession of revealed wisdom facilitates a recovery of creation.
These findings provide lines of enquiry that may be brought to Matthew. Three sections
of the gospel are examined (chapters 5-7; 11-12; 24-25). It is argued that Jesus is presented as an
eschatological figure who reveals wisdom to an elect group. This wisdom cannot be reduced to
great moral insight or interpretation of Torah, but is presented as prophetic revelation, happening
in eschatological time. It remains the case, however, that Matthew presents it as wisdom and
presents Jesus as a sage.
More tentatively, it is suggested that creation provides the patterns for the ethical
requirements of Jesus' wisdom, thus indicating that the idea of restored creation is also at work in
Matthew. The fall of the temple may also be connected in Matthew's narrative to such a
restoration, but again, the evidence for this is not clear
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