Human urine certified reference material CZ 6010: creatinine and toluene metabolites (hippuric acid and o-cresol) and a benzene metabolite (phenol)

A reference material for the biological monitoring of occupational exposure to toluene, benzene and phenol was prepared. O-cresol and hippuric acid (metabolites of toluene) are used for the biological monitoring of occupational exposure to toluene. Phenol, a metabolite of benzene, is used for the biological monitoring of exposure to benzene, but phenol can of course also be used as an indicator of exposure to phenol as well. The reference material (RM) used for the determination of these metabolites was prepared by freeze-drying pooled urine samples obtained from healthy persons occupationally exposed to toluene and those taking part in an inhalation experiment. Tests for homogeneity and stability were performed by determining urine concentrations of o-cresol, hippuric acid, creatinine and phenol. To investigate the stability of the RM, the urinary concentrations of o-cresol and phenol were monitored for eighteen months using GC and HPLC, while those of hippuric acid and creatinine were followed for five and six years, respectively, using HPLC. Analysis of variance showed that the concentrations did not change. The certified concentration values (and their uncertainties) of the substances in this reference material (phenol concentration c=6.46+/-0.58 mg l(-1); o-cresol concentration c=1.17+/-0.15 mg l(-1); hippuric acid concentration c=1328+/-30 mg l(-1); creatinine concentration c=0.82+/-0.10 g l(-1)) were evaluated via the interactive statistical programme IPECA

Irradiation of luminescence dosimeters in pulsed mixed radiation fields

UHDpulse - Metrology for Advanced Radiotherapy using beams with Ultra-High Pulse Dose Rates is a European project aimed at developing novel dosimetry standards, as well as improving existing ones, for FLASH radiotherapy, very high energy electrons radiotherapy, and laser-driven medical accelerators. Within the scope of this project, Thermoluminescence (TL) and Optically Stimulated Luminescence (OSL) detectors are used to measure stray radiation fields. Experiments performed with conventional pulsed particle-beams allow to characterize the dosimeters in known and controllable radiation fields. In turn, this allows to develop models and predict their behavior in complex radiation fields, such as those at laser-driven and FLASH facilities. TL and OSL detectors were irradiated at the Microtron MT25 electron accelerator in Prague, Czech Republic. GAFChromicTM films and plastic nuclear track detectors were used to study the beam profile and the neutron background respectively. The responses of the different detector to the pulsed mixed radiation fields of the Microtron MT25 are compared among each other and presented in this paper

Structure of the human NK cell NKR-P1:LLT1 receptor:ligand complex reveals clustering in the immune synapse.

Signaling by the human C-type lectin-like receptor, natural killer (NK) cell inhibitory receptor NKR-P1, has a critical role in many immune-related diseases and cancer. C-type lectin-like receptors have weak affinities to their ligands; therefore, setting up a comprehensive model of NKR-P1-LLT1 interactions that considers the natural state of the receptor on the cell surface is necessary to understand its functions. Here we report the crystal structures of the NKR-P1 and NKR-P1:LLT1 complexes, which provides evidence that NKR-P1 forms homodimers in an unexpected arrangement to enable LLT1 binding in two modes, bridging two LLT1 molecules. These interaction clusters are suggestive of an inhibitory immune synapse. By observing the formation of these clusters in solution using SEC-SAXS analysis, by dSTORM super-resolution microscopy on the cell surface, and by following their role in receptor signaling with freshly isolated NK cells, we show that only the ligation of both LLT1 binding interfaces leads to effective NKR-P1 inhibitory signaling. In summary, our findings collectively support a model of NKR-P1:LLT1 clustering, which allows the interacting proteins to overcome weak ligand-receptor affinity and to trigger signal transduction upon cellular contact in the immune synapse

New Capabilities of the FLUKA Multi-Purpose Code

FLUKA is a general purpose Monte Carlo code able to describe the transport and interaction of any particle and nucleus type in complex geometries over an energy range extending from thermal neutrons to ultrarelativistic hadron collisions. It has many different applications in accelerator design, detector studies, dosimetry, radiation protection, medical physics, and space research. In 2019, CERN and INFN, as FLUKA copyright holders, together decided to end their formal collaboration framework, allowing them henceforth to pursue different pathways aimed at meeting the evolving requirements of the FLUKA user community, and at ensuring the long term sustainability of the code. To this end, CERN set up the FLUKA.CERN Collaboration1. This paper illustrates the physics processes that have been newly released or are currently implemented in the code distributed by the FLUKA.CERN Collaboration2 under new licensing conditions that are meant to further facilitate access to the code, as well as intercomparisons. The description of coherent effects experienced by high energy hadron beams in crystal devices, relevant to promising beam manipulation techniques, and the charged particle tracking in vacuum regions subject to an electric field, overcoming a former lack, have already been made available to the users. Other features, namely the different kinds of low energy deuteron interactions as well as the synchrotron radiation emission in the course of charged particle transport in vacuum regions subject to magnetic fields, are currently undergoing systematic testing and benchmarking prior to release. FLUKA is widely used to evaluate radiobiological effects, with the powerful support of the Flair graphical interface, whose new generation (Available at http://flair.cern) offers now additional capabilities, e.g., advanced 3D visualization with photorealistic rendering and support for industry-standard volume visualization of medical phantoms. FLUKA has also been playing an extensive role in the characterization of radiation environments in which electronics operate. In parallel, it has been used to evaluate the response of electronics to a variety of conditions not included in radiation testing guidelines and standards for space and accelerators, and not accessible through conventional ground level testing. Instructive results have been obtained from Single Event Effects (SEE) simulations and benchmarks, when possible, for various radiation types and energies. The code has reached a high level of maturity, from which the FLUKA.CERN Collaboration is planning a substantial evolution of its present architecture. Moving towards a modern programming language allows to overcome fundamental constraints that limited development options. Our long term goal, in addition to improving and extending its physics performances with even more rigorous scientific oversight, is to modernize its structure to integrate independent contributions more easily and to formalize quality assurance through state-of-the-art software deployment techniques. This includes a continuous integration pipeline to automatically validate the codebase as well as automatic processing and analysis of a tailored physics-case test suite. With regard to the aforementioned objectives, several paths are currently envisaged, like finding synergies with Geant4, both at the core structure and interface level, this way offering the user the possibility to run with the same input different Monte Carlo codes and crosscheck the results