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The Chernobyl nuclear accident, and more recently the Fukushima accident, highlighted that the largest source of error on consequences assessment is the source term, including the time evolution of the release rate and its distribution between radioisotopes. Inverse modeling methods, which combine environmental measurements and atmospheric dispersion models, have proven efficient in assessing source term due to an accidental situation (Gudiksen, 1989; Krysta and Bocquet, 2007; Stohl et al., 2012a; Winiarek et al., 2012). Most existing approaches are designed to use air sampling measurements (Winiarek et al., 2012) and some of them also use deposition measurements (Stohl et al., 2012a; Winiarek et al., 2014). Some studies have been performed to use dose rate measurements (Duranova et al., 1999; Astrup et al., 2004; Drews et al., 2004; Tsiouri et al., 2012) but none of the developed methods were carried out to assess the complex source term of a real accident situation like the Fukushima accident. However, dose rate measurements are generated by the most widespread measurement system, and in the event of a nuclear accident, these data constitute the main source of measurements of the plume and radioactive fallout during releases. This paper proposes a method to use dose rate measurements as part of an inverse modeling approach to assess source terms. The method is proven efficient and reliable when applied to the accident at the Fukushima Daiichi Nuclear Power Plant (FD-NPP). The emissions for the eight main isotopes 133Xe, 134Cs, 136Cs, 137Cs, 137mBa, 131I, 132I and 132Te have been assessed. Accordingly, 105.9 PBq of 131I, 35.8 PBq of 132I, 15.5 PBq of 137Cs and 12 134 PBq of noble gases were released. The events at FD-NPP (such as venting, explosions, etc.) known to have caused atmospheric releases are well identified in the retrieved source term. The estimated source term is validated by comparing simulations of atmospheric dispersion and deposition with environmental observations. In total, it was found that for 80% of the measurements, simulated and observed dose rates agreed within a factor of 2. Changes in dose rates over time have been overall properly reconstructed, especially in the most contaminated areas to the northwest and south of the FD-NPP. A comparison with observed atmospheric activity concentration and surface deposition shows that the emissions of caesiums and 131I are realistic but that 132I and 132Te are probably underestimated and noble gases are likely overestimated. Finally, an important outcome of this study is that the method proved to be perfectly suited to emergency management and could contribute to improve emergency response in the event of a nuclear accident.

The cardiotoxic effects of adjuvant cancer treatments (i.e., chemotherapy and radiation treatment) have been well documented, but the effects on peripheral cardiovascular function are still unclear. We hypothesized that cancer survivors i) would have decreased resting endothelial function; and ii) altered muscle deoxygenation response during moderate intensity cycling exercise compared to cancer-free controls. A total of 8 cancer survivors (~70 months post-treatment) and 9 healthy controls completed a brachial artery FMD test, an index of endothelial-dependent dilation, followed by an incremental exercise test up to the ventilatory threshold (VT) on a cycle ergometer during which pulmonary V̇O2 and changes in near-infrared spectroscopy (NIRS)-derived microvascular tissue oxygenation (TOI), total hemoglobin concentration ([Hb]total), and muscle deoxygenation ([HHb] ≈ fractional O2 extraction) were measured. There were no significant differences in age, height, weight, and resting blood pressure between cancer survivors and control participants. Brachial artery FMD was similar between groups (P = 0.98). During exercise at the VT, TOI was similar between groups, but [Hb]total and [HHb] were significantly decreased in cancer survivors compared to controls (P < 0.01) The rate of change for TOI (ΔTOIΔ/V̇O2) and [HHb] (Δ[HHb]/ΔV̇O2) relative to ΔV̇O2 were decreased in cancer survivors compared to controls (P = 0.02 and P = 0.03 respectively). In cancer survivors, a decreased skeletal muscle microvascular function was observed during moderate intensity cycling exercise. These data suggest that adjuvant cancer therapies have an effect on the integrated relationship between O2 extraction, V̇O2 and O2 delivery during exercise.

BackgroundAdjuvant cancer treatments have been shown to decrease cardiac function. In addition to changes in cardiovascular risk, there are several additional functional consequences including decreases in exercise capacity and increased incidence of cancer‐related fatigue. However, the effects of adjuvant cancer treatment on peripheral vascular function during exercise in cancer survivors have not been well documented. We investigated the vascular responses to exercise in cancer survivors previously treated with adjuvant cancer therapies. Methods and ResultsPeripheral vascular responses were investigated in 11 cancer survivors previously treated with adjuvant cancer therapies (age 58±6 years, 34±30 months from diagnosis) and 9 healthy controls group matched for age, sex, and maximal voluntary contraction. A dynamic handgrip exercise test at 20% maximal voluntary contraction was performed with simultaneous measurements of forearm blood flow and mean arterial pressure. Forearm vascular conductance was calculated from forearm blood flow and mean arterial pressure. Left ventricular ejection time index (LVETi) was derived from the arterial pressure wave form. Forearm blood flow was attenuated in cancer therapies compared to control at 20% maximal voluntary contraction (189.8±53.8 vs 247.9±80.3 mL·min−1, respectively). Forearm vascular conductance was not different between groups at rest or during exercise. Mean arterial pressure response to exercise was attenuated in cancer therapies compared to controls (107.8±10.8 vs 119.2±16.2 mm Hg). LEVTi was lower in cancer therapies compared to controls. ConclusionsThese data suggest an attenuated exercise blood flow response in cancer survivors ≈34 months following adjuvant cancer therapy that may be attributed to an attenuated increase in mean arterial pressure.

Radical-polar crossover of organoborates is a poweful tool that enables the creation of two C-C bonds simultaneously. Small ring systems have become essential motifs in drug discovery and medicinal chemistry. However, step-economic methods for their selective functionalization remains scarce. Here we present a one-pot strategy that merges a simple preparation of strained organoboron species with the recently popularized polar radical crossover of borate derivatives to stereoselectively access tri-substituted azetidines, cyclobutanes and five-membered carbo- and heterocycles., (© 2024. The Author(s).)

Background: COVID-19 started to spread early in 2020, the precise year that lung cancer (LC) patients were recruited into the prospective epidemiological cohort KBP-2020-CPHG in French hospitals. This provides a unique opportunity to study COVID-19 incidence, survival risk factors, and overall prognosis., Methods: COVID data was collected before vaccination was made available. Clinical characteristics were compared (COVID vs non-COVID), incidence rate ratios were calculated based on clinical characteristics, survival (1 and 3 months) was estimated and the impact of COVID-19 on the overall prognosis of the cohort was studied., Results: In 2020, 285 out of 8,999 lung cancer patients were diagnosed with COVID-19. Diagnosis was mainly based on PCR tests (86.3 %). The annual incidence was 8.3 % (95 % CI [7.4, 9.3]); it was higher in former smokers and patients with squamous cell carcinoma or small cell carcinoma than in those with adenocarcinoma, in those with a PS score ≥2 versus 0-1, and with stages III-IV versus stages I-II. The incidence was reduced in patients who received chemotherapy or immunotherapy. 64.9 % of patients were hospitalized due to COVID-19. Risk factors for death at 1 and 3 months in COVID-19 patients were age, LC stage, and PS score. Multivariate analysis showed a major prognostic impact of COVID-19 on mortality of LC patients (hazard ratio: 4.12, 95 % CI [3.42, 4.97], p < 0.001)., Conclusions: This prospective study demonstrated the high incidence of COVID-19 in LC patients and identified as risk factors for COVID-19: smoking status, histology, PS, and stage. The impact of COVID-19 on lung cancer mortality appears major., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors have no financial or personal relationship with other people or organizations that could inappropriately bias this work. The scientific committee was fully independent from industrial sponsors., (Copyright © 2024 SPLF and Elsevier Masson SAS. All rights reserved.)

The addition of nucleophilic organometallic species onto in situ generated azabicyclobutanes enables the selective formation of 3-arylated azetidine intermediates through strain-release. Single pot strategies were further developed for the N -arylation of resulting azetidines, employing either S N Ar reactions or Buchwald-Hartwig couplings.

From early April 2020, wildfires raged in the highly contaminated areas around the Chernobyl nuclear power plant (CNPP), Ukraine. For about 4 weeks, the fires spread around and into the Chernobyl exclusion zone (CEZ) and came within a few kilometers of both the CNPP and radioactive waste storage facilities. Wildfires occurred on several occasions throughout the month of April. They were extinguished, but weather conditions and the spread of fires by airborne embers and smoldering fires led to new fires starting at different locations of the CEZ. The forest fires were only completely under control at the beginning of May, thanks to the tireless and incessant work of the firefighters and a period of sustained precipitation. In total, 0.7-1.2 TBq 137 Cs were released into the atmosphere. Smoke plumes partly spread south and west and contributed to the detection of airborne 137 Cs over the Ukrainian territory and as far away as Western Europe. The increase in airborne 137 Cs ranged from several hundred μBq·m -3 in northern Ukraine to trace levels of a few μBq·m -3 or even within the usual background level in other European countries. Dispersion modeling determined the plume arrival time and was helpful in the assessment of the possible increase in airborne 137 Cs concentrations in Europe. Detections of airborne 90 Sr (emission estimate 345-612 GBq) and Pu (up to 75 GBq, mostly 241 Pu) were reported from the CEZ. Americium-241 represented only 1.4% of the total source term corresponding to the studied anthropogenic radionuclides but would have contributed up to 80% of the inhalation dose.

An alternative and complementary transformation for the synthesis of aryl- and heteroaryl-substituted alkynes is presented that relies on a chemoselective electrocoupling process. Tetraorganoborate substrates were logically designed and simply accessed by transmetalations using readily or commercially available organotrifluoroborate salts.

Strained ring systems have gained considerable importance over the last few years for their implication in natural product syntheses or in drug discovery programs. We present herein a recollection of our work on the construction and functionalization of unsaturated four-membered carbo- and heterocycles in the context of the literature, as well as their applications in further reactions., (© 2021 The Authors. Published by The Chemical Society of Japan & Wiley-VCH GmbH.)

The anatomy of sharks, rays, and chimaeras (chondrichthyans) is crucial to understanding the evolution of the cranial system in vertebrates due to their position as the sister group to bony fishes (osteichthyans). Strikingly different arrangements of the head in the two constituent chondrichthyan groups-holocephalans and elasmobranchs-have played a pivotal role in the formation of evolutionary hypotheses targeting major cranial structures such as the jaws and pharynx. However, despite the advent of digital dissections as a means of easily visualizing and sharing the results of anatomical studies in three dimensions, information on the musculoskeletal systems of the chondrichthyan head remains largely limited to traditional accounts, many of which are at least a century old. Here, we use synchrotron tomographic data to carry out a digital dissection of a holocephalan and an elasmobranch widely used as model species: the elephantfish, Callorhinchus milii, and the small-spotted catshark, Scyliorhinus canicula. We describe and figure the skeletal anatomy of the head, labial, mandibular, hyoid, and branchial cartilages in both taxa as well as the muscles of the head and pharynx. In Callorhinchus, we make several new observations regarding the branchial musculature, revealing several previously unreported or ambiguously characterized muscles, likely homologous to their counterparts in the elasmobranch pharynx. We also identify a previously unreported structure linking the pharyngohyal of Callorhinchus to the neurocranium. Finally, we review what is known about the evolution of chondrichthyan cranial muscles from their fossil record and discuss the implications for muscle homology and evolution, broadly concluding that the holocephalan pharynx is likely derived from a more elasmobranch-like form which is plesiomorphic for the chondrichthyan crown group. This dataset has great potential as a resource, particularly for researchers using these model species for zoological research, functional morphologists requiring models of musculature and skeletons, as well as for palaeontologists seeking comparative models for extinct taxa., (© 2021 Anatomical Society.)

Readily accessible tetraorganoborate salts undergo selective coupling reactions under blue light irradiation in the presence of catalytic amounts of transition-metal-free acridinium photocatalysts to furnish unsymmetrical biaryls, heterobiaryls and arylated olefins. This represents an interesting conceptual approach to forge C-C bonds between aryl, heteroaryl and alkenyl groups under smooth photochemical conditions. Computational studies were conducted to investigate the mechanism of the transformation., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

Non-natural azetidine-based amino acids (Aze) present interesting features in protein engineering. A simple organometallic route toward unsaturated carboxylic acid precursors is presented. Subsequent metal-catalyzed asymmetric reduction allowed for the synthesis of a new library of 2-azetidinylcarboxylic acids, which were finally employed in the formation of small peptide chains.

Conventional methods carrying out C(sp 2 )-C(sp 2 ) bond formations are typically mediated by transition-metal-based catalysts. Herein, we conceptualize a complementary avenue to access such bonds by exploiting the potential of electrochemistry in combination with organoboron chemistry. We demonstrate a transition metal catalyst-free electrocoupling between (hetero)aryls and alkenes through readily available alkenyl-tri(hetero)aryl borate salts (ATBs) in a stereoconvergent fashion. This unprecedented transformation was investigated theoretically and experimentally and led to a library of functionalized alkenes. The concept was then carried further and applied to the synthesis of the natural product pinosylvin and the derivatization of the steroidal dehydroepiandrosterone (DHEA) scaffold., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Thiete dioxide units have been employed as a template for further functionalization through C-H activation strategies. Using simple thiete dioxide building blocks, a new library of axially chiral molecules has been synthesized that owe their stability to electrostatic interactions in the solid state. Similar starting materials were further engaged in the formation of cyclic trimeric structures, opening the pathway to unprecedented macrocyclic ring systems., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

We report herein versatile, transition metal-free and additive-free (hetero)aryl-aryl coupling reactions promoted by the oxidative electrocoupling of unsymmetrical tetra(hetero)arylborates (TABs) prepared from ligand-exchange reactions on potassium trifluoroarylborates. Exploiting the power of electrochemical oxidations, this method complements the existing organoboron toolbox. We demonstrate the broad scope, scalability, and robustness of this unconventional catalyst-free transformation, leading to functionalized biaryls and ultimately furnishing drug-like small molecules, as well as late stage derivatization of natural compounds. In addition, the observed selectivity of the oxidative coupling reaction is related to the electronic structure of the TABs through quantum-chemical calculations and experimental investigations.

In October 2017 unusual 106 Ru detections across most of Europe prompted the Institut de Radioprotection et de Sûreté Nucléaire (IRSN) to analyze the event in order to locate the origin and identify the magnitude of the release. This paper presents the inverse modeling techniques used during the event to achieve this goal. The method is based on a variational approach and consists of using air concentration measurements with the ldX long-range dispersion model included in the IRSN's C3X operational platform. The method made it possible to quickly identify the southern Urals as the most likely geographical origin of the release. Despite uncertainties regarding the starting date of the release, calculations show that it potentially began on 23 September, while most of the release was emitted on 26 September. Among the nuclear plants identified in the southern Urals, the Mayak complex is that from which the dispersion of the 106 Ru plume is most consistent with observations. The reconstructed 106 Ru source term from Mayak is ∼250 TBq. In total, it was found that for 72% of the measurements simulated and observed air concentration agreed within a factor of 5. In addition, the simulated deposition of 106 Ru agrees with the observed deposition. Outside the southern Urals, the simulations indicate that areas with highest deposition values are located in southern Scandinavia and southeastern Bulgaria and are explained by rainfall events occurring while the plume was passing over., Competing Interests: The authors declare no competing interest., (Copyright © 2019 the Author(s). Published by PNAS.)

In the early phase of a nuclear reactor accident, in-vivo monitoring of impacted population would be highly useful to detect potential contamination during the passage of the cloud and to estimate the dose from inhalation of measured radionuclides. However, it would be important to take into account other exposure components: (1) inhalation of unmeasured radionuclides and (2) external irradiation from the plume and from the radionuclides deposited on the soil. This article presents a methodology to calculate coefficients used to convert in-vivo measurement results directly into doses, not only from the measured radionuclides but from all sources of exposure according to model-based projected doses. This early interpretation of in-vivo measurements will provide an initial indication of individual exposure levels. As an illustration, the methodology is applied to two scenarios of accidents affecting a nuclear power plant: a loss-of-coolant accident leading to core meltdown and a steam generator tube rupture accident., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Zweifel olefination is a catalyst-free reaction that serves alkene functionalization. While most methods employ commercially available boron pinacol esters, we have assembled a sequence in which the two partners of the formal coupling reaction are installed successively, starting from inexpensive boron alkoxides. The in situ formation of bisorganoborinates was accomplished by consecutive reaction of two different organometallic species. This single-pot procedure represents a great advancement in the generation of organoborinates and their involvement in C-C bond formation.

Described is the in situ formation of triorganocerium reagents and their application in catalyst-free Zweifel olefinations. These unique cerium species were generated through novel exchange reactions of organohalides with n-Bu 3 Ce reagents. The adequate electronegativity of cerium allowed for compensating the disadvantages of both usually functional-group-sensitive organolithium species and less reactive organomagnesium reagents. Exchange reactions were performed on aryl and alkenyl bromides, enabling enantiospecific transformations of chiral boron pinacol esters. Finally, these new organocerium species were engaged in selective 1,2-additions onto enolisable and sterically hindered ketones., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

By combining efficient methodologies for the preparation of substituted azetines and thietes with a highly regio- and diastereoselective [3 + 2]-cycloaddition, a straightforward pathway for the synthesis of fused isoxazoline azetidines and thietanes has been designed. With minimal steps and starting from commercial sources, a new library of elaborated architectures was synthesized opening up a new class of molecules with large potential in pharmacology. Finally, a retro [2 + 2]-cycloaddition leading to substituted isoxazoles is described.

For the 53rd time, the Bürgenstock Conference gathered some of the most gifted scientists and rising stars in organic, physical, and bioorganic chemistry. Orchestrated by Ilan Marek (President) and his successor, Véronique Gouverneur, the synergy between art and science took place in Brunnen, Switzerland, with a beatiful view over Lake Lucerne., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

For the first time, an approach to 3,4-disubstituted thietes was developed through two complementary paths. While the first one relies on α-metalation, the second is based on direct C-H functionalization. A new library of sophisticated sulfur-containing four-membered rings is described, paving the way to new bioactive analogues and small heterocycle incorporation.

An original oxidative ring contraction of easily accessible cyclobutene derivatives for the selective formation of cyclopropylketones (CPKs) under atmospheric conditions is reported. Comprehensive mechanistic studies are proposed to support this novel, yet unusual, rearrangement. Insights into the mechanism ultimately led to simplification and generalization of the ring contraction of cyclobutenes using mCPBA as an oxidant. This unique and functional group tolerant transformation proceeds under mild conditions at room temperature, providing access to a new library of polyfunctionalized motifs. With CPKs being attractive and privileged pharmacophores, the elaboration of such a simple and straightforward strategy represents a highly valuable tool for drug discovery and medicinal chemistry. Additionally, the described method was employed to generate a pool of bioactive substances and key precursors in a minimum number of steps.

Several approaches using organozirconocene species for the remote cleavage of strained three-membered ring carbocycles are described. ω-Ene polysubstituted cyclopropanes, alkylidenecyclopropanes, ω-ene spiro[2.2]pentanes, and ω-ene cyclopropyl methyl ethers were successfully transformed into stereodefined organometallic intermediates, allowing an easy access to highly stereoenriched acyclic scaffolds in good yields and, in most cases, excellent selectivities. DFT calculations and isotopic labeling experiments were performed to delineate the origin of the obtained chemo- and stereoselectivities, demonstrating the importance of microreversibility.

Following recent advances in the generalization and simplification of 2H-azetine synthesis, a regiodivergent approach to fused 2- and 3-alkylideneazetines was designed via the intermediate formation of unprecedented vinylazetine structures. Concise sequences to the latter are described from which an expected unsaturated fused ring system was isolated with very high yields and regio- and stereoselectivities by [4 + 2] cycloadditions.

Spurred on by the recent emerging interest from the chemical community for unsaturated four-membered heterocycles, an unprecedented approach to nitrogen-containing four-membered rings has been designed. 3,4-Disubstituted 2-azetines were synthesized from commercially available substrates, allowing for a straightforward access to a new library of chiral functionalized azetidines and amino alcohols. This original approach was applied to efficiently prepare functionalized azobenzenes, an emerging class of molecules with a large potential in photopharmacology.

Alkylidenecyclobutanes (ACBs) containing all-carbon quaternary stereocenters were simply and efficiently synthesized by combining boron-homologation and γ-selective cross-coupling strategies. This unique sequence led to excellent regio- and diastereoselectivities in the generation of targeted four-membered rings with up to 99% enantiomeric excess using chiral substrates. In addition to the original synthesis of ACBs, the first asymmetric catalytic formation of quaternary stereocenters based on γ-selective cross-coupling reactions is finally shown.

Combining an efficient preparation of cyclobutenylmetal species, high-yielding cross-coupling reactions, and highly diastereoselective [4 + 2]-cycloaddition led to opening a new route toward the synthesis of fused alkylidenecyclobutanes containing up to five consecutive stereocenters. New complex architectures, analogues to protoilludane skeletons, were obtained in a very efficient manner and with a minimum number of steps starting from commercial sources and were tested for their cytotoxicity against leukemia cell lines HL60.