The Influence of Cicero on Newman\u27s Prose Style

No one can safely say that he is not in debt to anyone for some, at least, of his possessions, and this applies as well to intellectual achievements as to material goods. None of us knows, of course, just how far this debt extends in any individual case, but an analysis of any record of accomplishments shows that often so much must be attributed to that influence or this, that there is very little left to the individual\u27s personal credit. In some cases, however, the strong persona1ity of the individual considered so changes the influence, or so adapts it, that he seems not at all changed by it, but actively reaching out to grasp and assimilate to himself what it holds for him

Spectroscopic binaries with elliptical orbits

The radial velocity curves of many spectroscopic binaries (SBs) are perturbed by gas streams or proximity effects. For SBs with circular orbits, these perturbations can give rise to spurious orbital eccentricities of high statistical significance. But tests to identify such anomalous orbits can be constructed since perturbed velocity curves are in general no longer Keplerian. The derived tests are applied both to synthetic and to observed velocity curves.Comment: 9pages,3figures,accepted by A&

Recent advances in the development of tissue transglutaminase (TG2) inhibitors

Tissue transglutaminase (TG2) is a Ca2+-dependent enzyme and probably the most ubiquitously expressed member of the mammalian transglutaminase family. TG2 plays a number of important roles in a variety of biological processes. Via its transamidating function, it is responsible for the cross-linking of proteins by forming isopeptide bonds between glutamine and lysine residues. Intracellularly, Ca2+ activation of the enzyme is normally tightly regulated by the binding of GTP. However, upregulated levels of TG2 are associated with many disease states like celiac sprue, certain types of cancer, fibrosis, cystic fibrosis, multiple sclerosis, Alzheimer's, Huntington's and Parkinson's disease. Selective inhibitors for TG2 both cell penetrating and non-cell penetrating would therefore serve as novel therapeutic tools for the treatment of these disease states. Moreover, they would provide useful tools to fully elucidate the cellular mechanisms TG2 is involved in and help comprehend how the enzyme is regulated at the cellular level. The current paper is intended to give an update on the recently discovered classes of TG2 inhibitors along with their structure-activity relationships. The biological properties of these derivatives, in terms of both activity and selectivity, will also be reported in order to translate their potential for future therapeutic developments. © 2011 Springer-Verlag

Fine particulate matter pollution and risk of community-acquired sepsis

While air pollution has been associated with health complications, its effect on sepsis risk is unknown. We examined the association between fine particulate matter (PM2.5) air pollution and risk of sepsis hospitalization. We analyzed data from the 30,239 community-dwelling adults in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort linked with satellite-derived measures of PM2.5 data. We defined sepsis as a hospital admission for a serious infection with ≥2 systemic inflammatory response (SIRS) criteria. We performed incidence density sampling to match sepsis cases with 4 controls by age (±5 years), sex, and race. For each matched group we calculated mean daily PM2.5 exposures for short-term (30-day) and long-term (one-year) periods preceding the sepsis event. We used conditional logistic regression to evaluate the association between PM2.5 exposure and sepsis, adjusting for education, income, region, temperature, urbanicity, tobacco and alcohol use, and medical conditions. We matched 1386 sepsis cases with 5544 non-sepsis controls. Mean 30-day PM2.5 exposure levels (Cases 12.44 vs. Controls 12.34 µg/m3; p = 0.28) and mean one-year PM2.5 exposure levels (Cases 12.53 vs. Controls 12.50 µg/m3; p = 0.66) were similar between cases and controls. In adjusted models, there were no associations between 30-day PM2.5 exposure levels and sepsis (4th vs. 1st quartiles OR: 1.06, 95% CI: 0.85–1.32). Similarly, there were no associations between one-year PM2.5 exposure levels and sepsis risk (4th vs. 1st quartiles OR: 0.96, 95% CI: 0.78–1.18). In the REGARDS cohort, PM2.5 air pollution exposure was not associated with risk of sepsis

Impact of deprivation and comorbidity on outcomes in emergency general surgery : an epidemiological study

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Peer reviewedPublisher PD

Characterization of heparin-binding site of tissue transglutaminase:its importance in cell surface targeting, matrix deposition, and cell signaling

Tissue transglutaminase (TG2) is a multifunctional Ca2+ activated protein crosslinking enzyme secreted into the extracellular matrix (ECM), where it is involved in wound healing and scarring, tissue fibrosis, celiac disease and metastatic cancer. Extracellular TG2 can also facilitate cell adhesion important in wound healing through a non-transamidating mechanism via its association with fibronectin (FN), heparan sulphates (HS) and integrins. Regulating the mechanism how TG2 is translocated into the ECM therefore provides a strategy for modulating these physiological and pathological functions of the enzyme. Here, through molecular modelling and mutagenesis we have identified the HS binding site of TG2 202KFLKNAGRDCSRRSSPVYVGR222. We demonstrate the requirement of this binding site for translocation of TG2 into the ECM through a mechanism involving cell surface shedding of HS. By synthesizing a peptide NPKFLKNAGRDCSRRSS corresponding to the HS binding site within TG2, we also demonstrate how this mimicking peptide can in isolation compensate the RGD-induced loss of cell adhesion on FN via binding to syndecan-4, leading to activation of PKCa, pFAK-397 and ERK1/2 and the subsequent formation of focal adhesions and actin cytoskeleton organization. A novel regulatory mechanism for TG2 translocation into the extracellular compartment that depends upon TG2 conformation and the binding of HS is proposed

From Silos to Systems: Leveraging Visualization Tools to Map and Navigate the Complex Terrain of Health Professions Education

Rationale: Health Professions Education (HPE) programs are diverse and founded with varied goals, missions, and pedagogical approaches. Navigation of this complex system requires an understanding of the components and connections that form HPE programs. Educators need shared maps that match this system to facilitate communication, progress, and efficiency. Systems maps are useful for describing shared mental models and delineating educational processes and goals; they are particularly effective for revealing unproductive tendencies toward siloing. In ‘The Seven Silos of Accountability,’ Joshua Brown presents a model of accountability silos in higher education that is applicable to HPE. The seven silos are assessment, accreditation, institutional research, institutional effectiveness, program evaluation, educational measurement, and higher education public policy. Specialized stakeholders may lack understanding of this broad network, leaving leadership in the difficult position of ‘pulling it all together’ with limited backup and support. One approach for enhancing integration, communication, and efficiency across silos is visualizing components of systems as a mechanism for identifying and solving system-level challenges. These visualizations result in a process map that reflects the terrain of an organization called an Organigraph. Organigraphs are practical tools that can be used to orient those new to HPE, facilitate systems-level improvements, and identify opportunities to streamline effort and innovation. In this panel, members of four institutions will present an emerging collaborative effort to support HPE programs. We have designed an organigraph of the common organizational silos in UME as well as a user-sourced, interactive visualization of organizational silos to aid in orientation to HPE programs. Learning Objectives: 61 words At the end of this session, participants will be able to: Identify three advantages of visualizing an organizational process map of the Health Professions education. Describe three examples of how a systems approach can address silo-driven challenges in the academic program environment. Demonstrate how systems visualization tools can be used to map accreditation needs across silos. Discuss pain points of silos in a Health Professions education context and reflect on systems-based solutions. Session Methods and Format: 109 words Introduction and definition of 1) Silos in medical education, and 2) Organigraphs, followed by a presentation of current silos in UME, including examples of use cases from multiple institutions. (25 minutes) Interactive reflection on silos in HPE: Structured large group discussion. (15 minutes) Presentation of 1) an Organigraph that maps the silos and shows how they interact in the functional landscape of UME, 2) an interactive dashboard on these silos, and 3) how this visualization can be sourced by stakeholders. (25 minutes) Interactive reflection on Organigraphs and visualization of silos in HPE: Structured large group discussion. (15 minutes) Concluding remarks and Q&A session with the audience. (10 minutes

Isopeptidase activity of human transglutaminase 2:disconnection from transamidation and characterization by kinetic parameters

Transglutaminase 2 (TG2) is a multifunctional protein with diverse catalytic activities and biological roles. Its best studied function is the Ca2+-dependent transamidase activity leading to formation of γ-glutamyl-ε-lysine isopeptide crosslinks between proteins or γ-glutamyl-amine derivatives. TG2 has a poorly studied isopeptidase activity cleaving these bonds. We have developed and characterised TG2 mutants which are significantly deficient in transamidase activity while have normal or increased isopeptidase activity (W332F) and vice versa (W278F). The W332F mutation led to significant changes of both the Km and the Vmax kinetic parameters of the isopeptidase reaction of TG2 while its calcium and GTP sensitivity was similar to the wild type enzyme. The W278F mutation resulted in six times elevated amine incorporating transamidase activity demonstrating the regulatory significance of W278 and W332 in TG2 and that mutations can change opposed activities located at the same active site. The further application of our results in cellular systems may help to understand TG2 -driven physiological and pathological processes better and lead to novel therapeutic approaches where an increased amount of cross-linked proteins correlates with the manifestation of degenerative disorders

The Australian Space Eye: studying the history of galaxy formation with a CubeSat

The Australian Space Eye is a proposed astronomical telescope based on a 6U CubeSat platform. The Space Eye will exploit the low level of systematic errors achievable with a small space based telescope to enable high accuracy measurements of the optical extragalactic background light and low surface brightness emission around nearby galaxies. This project is also a demonstrator for several technologies with general applicability to astronomical observations from nanosatellites. Space Eye is based around a 90 mm aperture clear aperture all refractive telescope for broadband wide field imaging in the i and z bands.Comment: 19 pages, 14 figures, submitted for publication as Proc. SPIE 9904, 9904-56 (SPIE Astronomical Telescopes & Instrumentation 2016