The Christian interpretation of history in Paul Tillich and Christopher Dawson

The preparation of this dissertation has been an engaging and rewarding project. There were difficulties, to be sure, chief among them being Tillich's highly individualistic vocabulary and compressed style which produced a certain initial apprehension. But this writer, for one, can testify to the transition (that is likely to come to anyone who will study Tillioh's thought) from bewilderment to profound admiration and appreciation. Dawson's thought presented no such initial complications due to his loud and arresting style. There were, however, difficulties to be encountered in attempting to uncover the basic philosophical and theological presuppositions in his thinking. It is regrettable that Tillich's second volume of his Systematic Theology is not yet in print. This hurdle, however, was not insurmountable, for Tillich has published, in mimeographed form, an outline of his forthcoming Systematics whioh is really an abstract of material to be covered in Volume II. (Quotations from this source are referred to in footnotes as The Propositions.

Convective scale interaction: Arc cloud lines and the development and evolution of deep convection

Information is used from satellite data and research aircraft data to provide new insights concerning the mesoscale development and evolution of deep convection in an atmosphere typified by weak synoptic-scale forcing. The importance of convective scale interaction in the development and evolution of deep convection is examined. This interaction is shown to manifest itself as the merger and intersection of thunderstorm outflow boundaries (arc cloud lines) with other convective lines, areas or boundaries. Using geostationary satellite visible and infrared data convective scale interaction is shown to be responsible for over 85 percent of the intense convection over the southeast U.S. by late afternoon, and a majority of that area's afternoon rainfall. The aircraft observations provided valuable information concerning critically important regions of the arc cloud line: (1) the cool outflow region, (2) the density surge line interface region; and (3) the sub-cloud region above the surge line. The observations when analyzed with rapid scan satellite data, helped in defining the arc cloud line's life cycle as 3 evolving stages

Do patients registered with CAM-trained GPs really use fewer health care resources and live longer? A response to Kooreman and Baars. Eur J Health Econ (2012). 13:469–776

Comment on Kooreman, P., Baars, E.W.: Patients whose GP knows complementary medicine tend to have lower costs and live longer. Eur. J. Health Econ.13(6), 769–776 (2012). doi:10.​1007/​s10198-011-0330-

Smoothed Particle Hydrodynamics Simulations of Apsidal and Nodal Superhumps

In recent years a handful of systems have been observed to show "negative" (nodal) superhumps, with periods slightly shorter than the orbital period. It has been suggested that these modes are a consequence of the slow retrograde precession of the line of nodes in a disk tilted with respect to the orbital plane. Our simulations confirm and refine this model: they suggest a roughly axisymmetric, retrogradely-precessing, tilted disk that is driven at a period slightly less than half the orbital period as the tidal field of the orbiting secondary encounters in turn the two halves of the disk above and below the midplane. Each of these passings leads to viscous dissipation on one face of an optically-thick disk -- observers on opposite sides of the disk would each observe one brightening per orbit, but 180 degrees out of phase with each other.Comment: 11 pages. Accepted for publication in The ApJ Letter

Carboxylate-assisted oxidative addition to aminoalkyl-Pd(II) complexes enables catalyzed C(sp3)-H arylation of alkylamines via distinct Pd(II)/Pd(IV) pathway

We report the discovery of an approach to functionalize secondary alkylamines using 2‐halobenzoic acids as aryl transfer reagents. These reagents promote an unusually mild carboxylate‐assisted oxidative addition to alkylamine‐derived palladacycles. In the presence of Ag(I) salts, a decarboxylative C(sp3)–C(sp2) bond reductive elimination leads to γ‐aryl secondary alkylamines and renders the carboxylate motif a traceless directing group. Stoichiometric mechanistic studies were effectively translated to a Pd‐catalyzed γ‐C(sp3)–H arylation process for secondary alkylamines.We are grateful to EPSRC (EP/N031792/1) and for a studentship (W.G.W.), AstraZeneca for a studentship (J.H.B.), the German Academic Exchange Service (DAAD) for a scholarship (G.N.H.), and the Royal Society for a Wolfson Merit Award (M.J.G.) for funding

The Ex Vivo Treatment of Donor T Cells with Cosalane, an HIV Therapeutic and Small-Molecule Antagonist of CC-Chemokine Receptor 7, Separates Acute Graft-versus-Host Disease from Graft-versus-Leukemia Responses in Murine Hematopoietic Stem Cell Transplantation Models

Despite recent advances in therapy, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option for a range of high-risk hematologic malignancies. However, acute graft-versus-host disease (aGVHD) continues to limit the long-term success of HSCT, and new therapies are still needed. We previously demonstrated that aGVHD depends on the ability of donor conventional T cells (Tcon s) to express the lymph node trafficking receptor, CC-Chemokine Receptor 7 (CCR7). Consequently, we examined the ability of cosalane, a recently identified CCR7 small-molecule antagonist, to attenuate aGVHD in mouse HSCT model systems. Here we show that the systemic administration of cosalane to transplant recipients after allogeneic HSCT did not prevent aGVHD. However, we were able to significantly reduce aGVHD by briefly incubating donor Tcons with cosalane ex vivo before transplantation. Cosalane did not result in Tcon toxicity and did not affect their activation or expansion. Instead, cosalane prevented donor Tcon trafficking into host secondary lymphoid tissues very early after transplantation and limited their subsequent accumulation within the liver and colon. Cosalane did not appear to impair the intrinsic ability of donor Tcon s to produce inflammatory cytokines. Furthermore, cosalane-treated Tcon s retained their graft-versus-leukemia (GVL) potential and rejected a murine P815 inoculum after transplantation. Collectively, our data indicate that a brief application of cosalane to donor Tcon s before HSCT significantly reduces aGVHD in relevant preclinical models while generally sparing beneficial GVL effects, and that cosalane might represent a viable new approach for aGVHD prophylaxis

An Improved Dynamical Model for the Microquasar XTE J1550-564

We present an improved dynamical model of the X-ray binary and microquasar XTE J1550-564 based on new moderate-resolution optical spectroscopy and near-infrared photometry. By combining our new radial velocity measurements with previous measurements obtained 2001 May at the 8.2m VLT and with light curves, we find an orbital period of P=1.5420333 +/- 0.0000024 days and a radial velocity semiamplitude of K_2=363.14 +/- 5.97$ km/sec, which together imply an optical mass function of f(M)=7.65 +/- 0.38 solar masses. We find that the projected rotational velocity of the secondary star is 55 +/- 5 km/sec, which implies a very extreme mass ratio of Q=M/M_2=30. Using a model of a Roche lobe-filling star and an azimuthally symmetric accretion disk, we fit simultaneously optical light curves from 2001, near-infrared light curves from 2008 and all of the radial velocity measurements to derive system parameters. We find an inclination of 74.7 +/- 3.8 deg and component masses of M_2=0.30 +/- 0.07 solar masses and M=9.10 +/- 0.61 solar masses for the secondary star and black hole, respectively. The radius of the secondary star for the adopted model is 1.75 +/- 0.12 solar radii. Using this radius, the average K_S magnitude, and an extinction of A_K=0.507 +/- 0.050 mag, we find a distance of 4.38^{+0.58}_{-0.41} kpc, which is in good agreement with a recent distance estimate based on HI absorption lines (abstract shortened).Comment: 29 pages, 11 figures, to appear in ApJ, figures 1 and 2 are compresse

Developing a framework for public involvement in mathematical and economic modelling : bringing new dynamism to vaccination policy recommendations

Objectives The Mathematical and Economic Modelling for Vaccination and Immunisation Evaluation (MEMVIE) programme aimed to explore, capture and support the potential contribution of the public to mathematical and economic modelling, in order to identify the values that underpin public involvement (PI) in modelling and co-produce a framework that identifies the nature and type of PI in modelling and supports its implementation. Methods We established a PI Reference Group, who worked collaboratively with the academic contributors to create a deliberative knowledge space, which valued different forms of knowledge, expertise and evidence. Together, we explored the key steps of mathematical and economic methods in 21 meetings during 2015–2020. These deliberations generated rich discussion, through which we identified potential points of public contribution and the values that underpin PI in modelling. We iteratively developed a framework to guide future practice of PI in modelling. Results We present the MEMVIE Public Involvement Framework in two forms: a short form to summarise key elements, and a long form framework to provide a detailed description of each potential type of public contribution at each stage of the modelling process. At a macro level, the public can contribute to reviewing context, reviewing relevance, assessing data and justifying model choice, troubleshooting, and interpreting and reviewing outcomes and decision making. The underpinning values that drive involvement include the public contributing to the validity of the model, potentially enhancing its relevance, utility and transparency through diverse inputs, and enhancing the credibility, consistency and continuous development through scrutiny, in addition to contextualising the model within a wider societal view. Discussion and Conclusion PI in modelling is in its infancy. The MEMVIE Framework is the first attempt to identify potential points of collaborative public contribution to modelling, but it requires further evaluation and refinement that we are undertaking in a subsequent study

Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells

The MAPK/ERK1/2 serine kinases are primary mediators of the Ras mitogenic signaling pathway. Phosphorylation by MEK activates MAPK/ERK in the cytoplasm, and phospho-ERK is thought to enter the nucleus readily to modulate transcription.Here, however, we observe that in primary cultures of breast and ovarian epithelial cells, phosphorylation and activation of ERK1/2 are disassociated from nuclear translocalization and transcription of downstream targets, such as c-Fos, suggesting that nuclear translocation is limited in primary cells. Accordingly, in import assays in vitro, primary cells showed a lower import activity for ERK1/2 than cancer cells, in which activated MAPK readily translocated into the nucleus and activated c-Fos expression. Primary cells express lower levels of nuclear pore complex proteins and the nuclear transport factors, importin B1 and importin 7, which may explain the limiting ERK1/2 import found in primary cells. Additionally, reduction in expression of nucleoporin 153 by siRNA targeting reduced ERK1/2 nuclear activity in cancer cells.ERK1/2 activation is dissociated from nuclear entry, which is a rate limiting step in primary cells and in vivo, and the restriction of nuclear entry is disrupted in transformed cells by the increased expression of nuclear pores and/or nuclear transport factors

An Intermittent Live Cell Imaging Screen for siRNA Enhancers and Suppressors of a Kinesin-5 Inhibitor

Kinesin-5 (also known as Eg5, KSP and Kif11) is required for assembly of a bipolar mitotic spindle. Small molecule inhibitors of Kinesin-5, developed as potential anti-cancer drugs, arrest cell in mitosis and promote apoptosis of cancer cells. We performed a genome-wide siRNA screen for enhancers and suppressors of a Kinesin-5 inhibitor in human cells to elucidate cellular responses, and thus identify factors that might predict drug sensitivity in cancers. Because the drug's actions play out over several days, we developed an intermittent imaging screen. Live HeLa cells expressing GFP-tagged histone H2B were imaged at 0, 24 and 48 hours after drug addition, and images were analyzed using open-source software that incorporates machine learning. This screen effectively identified siRNAs that caused increased mitotic arrest at low drug concentrations (enhancers), and vice versa (suppressors), and we report siRNAs that caused both effects. We then classified the effect of siRNAs for 15 genes where 3 or 4 out of 4 siRNA oligos tested were suppressors as assessed by time lapse imaging, and by testing for suppression of mitotic arrest in taxol and nocodazole. This identified 4 phenotypic classes of drug suppressors, which included known and novel genes. Our methodology should be applicable to other screens, and the suppressor and enhancer genes we identified may open new lines of research into mitosis and checkpoint biology