Regulatory impact of the C-terminal tail on charge transfer pathways in drosophila cryptochrome

Interconnected transcriptional and translational feedback loops are at the core of the molecular mechanism of the circadian clock. Such feedback loops are synchronized to external light entrainment by the blue light photoreceptor cryptochrome (CRY) that undergoes conformational changes upon light absorption by an unknown photoexcitation mechanism. Light-induced charge transfer (CT) reactions in Drosophila CRY (dCRY) are investigated by state-of-the-art simulations that reveal a complex, multi-redox site nature of CT dynamics on the microscopic level. The simulations consider redox-active chromophores of the tryptophan triad (Trp triad) and further account for pathways mediated by W314 and W422 residues proximate to the C-terminal tail (CTT), thus avoiding a pre-bias to specific W-mediated CT pathways. The conducted dissipative quantum dynamics simulations employ microscopically derived model Hamiltonians and display complex and ultrafast CT dynamics on the picosecond timescale, subtly balanced by the electrostatic environment of dCRY. In silicio point mutations provide a microscopic basis for rationalizing particular CT directionality and demonstrate the degree of electrostatic control realized by a discrete set of charged amino acid residues. The predicted participation of CT states in proximity to the CTT relates the directionality of CT reactions to the spatial vicinity of a linear interaction motif. The results stress the importance of CTT directional charge transfer in addition to charge transfer via the Trp triad and call for the use of full-length CRY models including the interactions of photolyase homology region (PHR) and CTT domains. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

IPC2010-31419 BALANCING PIPELINE SAFETY AND COST INTEGRITY MANAGEMENT THROUGH PERFORMANCE VALIDATION OF IN-LINE INSPECTION DATA

ABSTRACT In-Line Inspection (ILI) surveys are widely employed to identify potential threats by capturing changes in pipe condition such as metal loss, caused by corrosion. The better the performance and interpretation of these survey data, the higher the reliability of being able to predict the actual condition of the pipe and required remediation. Each ILI survey has a certain level of conservatism from the assessment equations such as B31G and sensitivity to ILI performance for measurement uncertainty. Multiple levels of conservatism intended to limit the possibility of a non-conservative assessment can result in a significant economic penalty and excessive digs without improving safety. A study was undertaken to evaluate the reliability of responses to ILI corrosion features through multiple case studies examining the effects of failure criteria and data analysis parameters. This paper discusses the effect of validated ILI performance on safety, and addresses the risk of false acceptance of corrosion indications at a prescribed safety factor. The cost of unnecessary excavations due to falsely rejecting ILI predictions is also discussed

Dense Gas in Nearby Galaxies: XVII. The Distribution of Ammonia in NGC253, Maffei2 and IC342

The central few 100 pc of galaxies often contain large amounts of molecular gas. The chemical and physical properties of these extragalactic star formation regions differ from those in galactic disks, but are poorly constrained. This study aims to develop a better knowledge of the spatial distribution and kinetic temperature of the dense neutral gas associated with the nuclear regions of three prototypical spiral galaxies, NGC253, IC342, and Maffei2. VLA CnD and D configuration measurements have been made of three ammonia (NH3) inversion transitions. The (J,K)=(1,1) and (2,2) transitions of NH3 were imaged toward IC342 and Maffei2. The (3,3) transition was imaged toward NGC253. The entire flux obtained from single-antenna measurements is recovered for all three galaxies observed. Derived lower limits to the kinetic temperatures determined for the giant molecular clouds in the centers of these galaxies are between 25 and 50K. There is good agreement between the distributions of NH3 and other H2 tracers, such as rare CO isotopologues or HCN, suggesting that NH3 is representative of the distribution of dense gas. The "Western Peak" in IC342 is seen in the (6,6) line but not in lower transitions, suggesting maser emission in the (6,6) transition.Comment: 13 pages, 8 figures, latex format, accepted by A&

Defining neurotrauma in administrative data using the International Classification of Diseases Tenth Revision

Abstract Background It is essential to use a definition that is precise and accurate for the surveillance of traumatic brain injuries (TBI) and spinal cord injuries (SCI). This paper reviews the International Classification of Diseases 10th revision (ICD-10) definitions used internationally to inform the definition for neurotrauma surveillance using administrative data in Ontario, Canada. Methods PubMed, Web of Science, Medline and the grey literature were searched for keywords "spinal cord injuries" or "brain injuries" and "international classification of diseases". All papers and reports that used an ICD-10 definition were included. To determine the ICD-10 codes for inclusion consensus across papers and additional evidence were sought to look at the correlation between the condition and brain or spinal injuries. Results Twenty-four articles and reports were identified; 15 unique definitions for TBI and 7 for SCI were found. The definitions recommended for use in Ontario by this paper are F07.2, S02.0, S02.1, S02.3, S02.7, S02.8, S02.9, S06, S07.1, T90.2, and T90.5 for traumatic brain injuries and S14.0, S14.1, S24.0, S24.1, S34.1, S34.0, S34.3, T06.0, T06.1 and T91.3 for spinal cord injuries. Conclusions Internationally, inconsistent definitions are used to define brain and spinal cord injuries. An abstraction study of data would be an asset in understanding the effects of inclusion and exclusion of codes in the definition. This paper offers a definition of neurotrauma for surveillance in Ontario, but the definition could be applied to other countries that have mandated administrative data collection

Defining Major Surgery: A Delphi Consensus Among European Surgical Association (ESA) Members

Background: Major surgery is a term frequently used but poorly defined. The aim of the present study was to reach a consensus in the definition of major surgery within a panel of expert surgeons from the European Surgical Association (ESA). Methods: A 3-round Delphi process was performed. All ESA members were invited to participate in the expert panel. In round 1, experts were inquired by open- and closed-ended questions on potential criteria to define major surgery. Results were analyzed and presented back anonymously to the panel within next rounds. Closed-ended questions in round 2 and 3 were either binary or statements to be rated on a Likert scale ranging from 1 (strong disagreement) to 5 (strong agreement). Participants were sent 3 reminders at 2-week intervals for each round. 70% of agreement was considered to indicate consensus. Results: Out of 305 ESA members, 67 (22%) answered all the 3 rounds. Significant comorbidities were the only preoperative factor retained to define major surgery (78%). Vascular clampage or organ ischemia (92%), high intraoperative blood loss (90%), high noradrenalin requirements (77%), long operative time (73%) and perioperative blood transfusion (70%) were procedure-related factors that reached consensus. Regarding postoperative factors, systemic inflammatory response (76%) and the need for intensive or intermediate care (88%) reached consensus. Consequences of major surgery were high morbidity (>30% overall) and mortality (>2%). Conclusion: ESA experts defined major surgery according to extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes

Time Resolved Photoelectron Spectroscopy of Thioflavin T Photoisomerization: A Simulation Study

The excited state isomerization of thioflavin T (ThT) is responsible for the quenching of its fluorescence in a non-restricted environment. The fluorescence quantum yield increases substantially upon binding to amyloid fibers. Simulations reveal that the variation of the twisting angle between benzothiazole and benzene groups (ϕ(1)) is responsible for the sub-picosecond fluorescence quenching. The evolution of the twisting process can be directly probed by photoelectron emission with energies ε ≥ 1.0 eV before the molecule reaches the ϕ(1)-twisted configuration (~300 fs)