Radiation Safety Engineering (United States)

BackgroundCTIM-76 is a Claudin 6 (CLDN6) x CD3 bispecific T cell-redirecting antibody that is in phase 1 clinical development. The minimal anticipated biological effect level (MABEL) approach is standard for determining the first-in-human dose potent of immune-activating drugs.MethodsAccordingly, we aimed to determine the first-in-human dose of CTIM-76 using both the MABEL and no observed adverse effect level (NOAEL) approaches. CTIM-76-induced lysis of OV-90 tumor cells was determined to be the most sensitive and pharmacologically relevant measure for MABEL calculations and resulted in a starting dose of 22.5 mcg.ResultsIn the 4-week GLP toxicology study in nonhuman primates the highest non-severely toxic dose (HNSTD) was 0.2 mg/kg. Based on ICH S9 guidance, this results in a maximum recommended starting dosage (MRSD) of 0.033 mg/kg. This is substantially higher than the proposed FIH dose of 22.5 mcg (0. 32 mcg/kg). Based on the predicted human PK, a 22.5 mcg dose would give a Cmax and AUC of 5.33 ng/mL and 206 hr*ng/mL, respectively, which would provide a Cmax approximately equivalent to the EC50 value from the OV-90 assay. This minimally pharmacologically active dose level is consistent with the dose proposed by the MABEL approach. The mean (SD) Cmax and AUC values, based on males and females combined, after repeat dosing (Day 29) of the HNSTD of 0.2 mg/kg, were 2460 (820) ng/mL and 80900 (37800) hr*ng/mL, respectively. Therefore, a 22.5 mcg dose in humans would have safety margins of 462 and 393 based on Cmax and AUC, respectively.ConclusionsThe weight of evidence of these data supports the safety of the proposed clinical starting dose of 22.5 mcg CTIM-76.

With the continuous development of port economy and the continuous promotion of industrial transformation and upgrading in China, the mode of gathering and distributing transportation in port area has gradually become the core factor to enhance the competitiveness of the whole logistics chain of port. It always play an important role in the port collection and distribution system. Especially for inland economic hinterland ports, it is of great significance to develop railway transportation and optimize port railway collection and distribution system. Based on the development and application of the theory of port railway transportation at home and abroad, this paper briefly analyzes the present situation and trend of port railway transportation mode. Combined with the demand characteristics of the current port railway transportation system and the problems that need to be further improved after the reform of freight organization, the form and task of optimizing the port railway transportation mode are clarified.

Pascal BOULET1, Bart MERCI2 and Patrick VAN HEES31Université de Lorraine, CNRS, LEMTA, France2Ghent University, Department of Fluid Mechanics, Heat and Combustion, Ghent, Belgium3Lund University, Division of Fire Safety Engineering, Lund, Swedenpascal.boulet@univ-lorraine.frEDITORIALThis special issue is based on the papers selected for presentation during the 3rd ESFSS (European Symposium on Fire Safety Science), held in Nancy (France) from 12 to 14 September 2018. Following the conference held in Cyprus (2015), the 3rd ESFSS was the third edition of a series of symposia organized in Europe, with the participation and support of the International Association for Fire Safety Science (IAFSS). The aim was to gather researchers from within Europe and beyond to have exchanges and discussions about fire safety science. In this frame, a workshop Agenda 2030 for a Fire Safe World was also organized by IAFSS on the afternoon of Tuesday, September 11, prior to the symposium, with the aim to discuss the definition of a Fire Safety Mission and the identification of specific topics for fire science research.Around 120 contributions have been received during the conference preparation, involving both submissions for oral and poster presentation. A selection, based on two peer-reviews of full papers, finally conducted to the acceptance of 35 contributions for oral presentation and 55 for poster presentation, plus 11 posters in a special session dedicated to work-in-progress.The conference was attended by 140 scientists, coming not only from Europe but from around the world, namely from Australia, Belgium, Canada, China, Czech Republic, Finland, France, Germany, India, Indonesia, Ireland, Japan, Portugal, Russia, Slovenia, Spain, Sweden, Turkey, United Kingdom, USA.List of Symposium chair and Scientific committee are available in this PDF.

Robust digital watermarking is an evolving research area that has received a large amount of attention and became a practical solution to copyright protection. This paper proposes a robust and imperceptible non-blind watermarking method for high rate embedding into 3D polygonal meshes. Our approach consists of partitioning, embedding and extracting steps. First, the mesh is partitioned into smaller sub-meshes, and then the watermark bits are embedded into each vertex in spatial domain. The main attractive features of this approach are flexibility in data embedding technique and fast computation compared to other recent techniques. The results showed that the proposed algorithm provides high robustness against the most common attacks. The applied attacks include the geometric transformations, adaptive random noise; mesh smoothing, mesh cropping and combinations of these attacks. The results of our approach are compared with recent published methods in terms of robustness, imperceptibility and payload. Moreover, the compared methods and the proposed one are evaluated according to a standard benchmark.

The simple expectation for safety would be "to prevent accidents". Accident is probabilistic concept. And there is no definitive way to prevent it. Therefore, instead of proactively avoiding by control, we have to take a method of stopping (function itself of original control) before accident (event), at least not to cause critical damage. The title theory (ex ante-safety control) is a system that ensures safety by stopping "before the accident". In this thesis, rather than positively preventing accidents, safety is to stop against accidents that can not be avoidable, at least to avoid causing critical damage. In this thesis, in advance safety theory fundamentally different from safety based on the probability theory so far is under consideration.

\nMayo Clinic Scottsdale (Scottsdale, Arizona) is building a cyclotron vault containing a cyclotron with adjacent targets and a beam line leading to an external target. The targets are irradiated by high energy (15 to 16.5 MeV) protons for the production of radioisotopes. We performed Monte Carlo radiation transport simulations to calculate the radiation dose outside of the vault during irradiation of the cyclotron and external targets. We present the Monte Carlo model including the geometry, sources, and variance reduction methods. Mesh tallies surrounding the vault show the external dose rate is within acceptable limits.\n

The bacterial NaK ion channel is distinctly different from other known ion channels due to its inherent non-selective feature. One of the unexplored and rather interesting features is its ability to permeate divalent metal ions (such as Ca2+ and Ba2+) and not monovalent alkali metal ions. Several intriguing questions about the energetics and structural aspects still remain unanswered. For instance, what causes Ca2+ to permeate as well as block the selectivity filter (SF) of the NaK ion channel and act as a "permeating blocker"? How and at what energetic cost does another chemical congener, Sr2+, as well as Ba2+, a potent blocker of the K+ ion channel, permeate through the SF of the NaK ion channel? Finally, how do their translocation energetics differ from those of monovalent ions such as K+? Here, in an attempt to address these outstanding issues, we elucidate the structure, binding and selectivity of divalent ions (Ca2+, Sr2+ and Ba2+) as they permeate through the SF of the NaK ion channel using all-atom molecular dynamics simulations and density functional theory based calculations. We unveil mechanistic insight into this translocation event using well-tempered metadynamics simulations in a polarizable environment using the mean-field model of water and incorporating electronic continuum corrections for ions via charge rescaling. The results show that, akin to K+ coordination, Sr2+ and Ba2+ bind at the SF in a very similar fashion and remain octa-coordinated at all sites. Interestingly, differing from its local hydration structure, Ca2+ interacts with eight carbonyls to remain at the middle of the S3 site. Furthermore, the binding of divalent metals at SF binding sites is more favorable than the binding of K+. However, their permeation through the extracellular entrance faces a considerably higher energetic barrier compared to that for K+, which eventually manifests their inherent blocking feature.

A study of numerous published rollover tests was conducted by reexamination of the original works, analysis of their data, and centralized compilation of their results. Instances were identified where the original reported results for trip speed were in error, requiring revision because the analysis technique employed extrapolation versus integration and lacked correction for offset errors that develop by placing the Global Positioning System (GPS) antenna away from the vehicle Center of Gravity (CG). An analysis was performed demonstrating revised results. In total, 81 dolly rollover crash tests, 24 naturally occurring rollover crash tests, and 102 reconstructed rollovers were identified. Of the 24 naturally occurring tests, 18 were steer-induced rollover tests. Distributions of the rollover drag factors are presented. The range of drag factors for all examined dolly rollovers was 0.38 g to 0.50 g with the upper and lower 15 percent statistically trimmed. The average drag factor for dolly rollovers was 0.44 g (standard deviation = 0.064) with a reported minimum of 0.31 g and a reported maximum of 0.61 g. After revisions, the range of drag factors for the set of naturally occurring rollovers was 0.39 g to 0.50 g with the upper and lower 15 percent statistically trimmed. The average drag factor for naturally occurring rollovers was 0.44 g (standard deviation = 0.063) with a reported minimum of 0.33 g and a reported maximum of 0.57 g. These results provide a more probable range of the drag factor for use in accident reconstruction compared to the often repeated assertion that rollover drag factors range between 0.4 g and 0.65 g.

Director, Radiation Safety; Drexel University; 1601 Cherry Street, Suite 10444; Philadelphia, PA 19102; [email protected] Presented toJAMES S. WILLISONat the 53rd Annual Meeting of the Health Physics Society, Pittsburgh, Pennsylvania 13–17 July 2008

Associate Editor, ORS; Mayo Clinic; Radiation Safety; 200 First Street SW; Rochester, MN 55905; [email protected]