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This work presents the computational analysis of the sensitivity improvements that could be achieved in lithium formate monohydrate (LFM) electron paramagnetic resonance (EPR) dosemeters exposed to neutron beams. Monte Carlo (MC) simulations were performed on LFM pellets exposed to neutron beams with different energy spectra at various depths inside a water phantom. Various computations were carried out by considering different enrichments of 6Li inside the LFM matrix as well as addition of different amounts of gadolinium oxide inside the pellet blend. The energy released per unit mass was calculated with the aim of redicting the increase in dose achievable by the addition of sensitizers inside the pellets. As expected, a larger amount of 6Li induces an increase of energy released because of the charged secondary particles (i.e. 3H ions and α particles) produced after neutron capture. For small depths in water phantom and low-energy neutron spectra the dose increase due to 6Li enrichment is high (more than three orders of magnitude with respect to the case of with 7Li). In case of epithermal neutron beams the energy released in 6Li-enriched LFM compound is smaller but larger than in the case of fast neutron beams. On the other hand, the computational analysis evidenced that gadolinium is less effective than 6Li in improving neutron sensitivity of the LFM pellets. Discussion based on the features of MC transport code is provided. This result suggests that 6Li enrichment of LFM dosemeters would be more effective for neutron sensitivity improvement and these EPR dosemeters could be tested for dosimetric applications in Neutron Capture Therapy.

Acknowledgements IE has received funding from the postdoctoral fellowship programme Beatriu de Pinós (2019 BP00247), funded by the Secretary of Universities and Research (Government of Catalonia) and by the Horizon 2020 programme of research and innovation of the European Union under the Marie Skłodowska-Curie grant agreement No. 801370. Laboratory materials for sample processing at the University of Barcelona were funded by the Ministerio de Ciencia e Innovaci on - PID 2020-119773 GB-I00. Visit to the site for sampling collection for this study was sponsored by a NRF Y-Rated Research Grant (No. 116358) to DS. PdlP was supported by a Poroulis grant through Cambridge University. PdlP thanks the action PID 2019- 1049449 GB-I00 funded by Spanish FEDER/Ministry of Science and Innovation. LB was funded by a National Geographic Explorer grant (NGS-54810R-19), DSI-NRF Centre of Excellence in Palaeosciences (Genus) grant (CEOOP 2020-1), and NRF African Origins Platform grant (No. 98824). Research by FdE is funded by the Research Council of Norway (SFF Centre for Early Sapiens Behaviour- SapienCE-project 262618), the Talents program of the University of Bordeaux (n. 191022_001), and the program “Human Past”, funded by the same university.We are grateful to Amafa for issuing us with the excavation permit (SAH 15/7645), and to SAHRA for an export permit (CaseID 15987).We thank two anonymous reviewers for their helpful comments that significantly improved the manuscript., Supplementary data to this article can be found online at https://doi.org/10.1016/j.quascirev.2022.107898., Border Cave is a well-known South African Middle and Early Later Stone Age site located in KwaZulu-Natal. The site has exceptional plant preservation, unparalleled in the African Middle Stone Age archaeological record. This study focuses on the phytolith and FTIR analysis of two Members (2 BS and 2 WA) of the under-documented post-Howiesons Poort occupations dating to ∼60 ka. These members contain complex successions of vertically overlapping, interdigitating light brown sediments, plant bedding and combustion features of various sizes. The complexity and distinctiveness of these deposits provide an excellent opportunity for the study of plant exploitation strategies and their associated human behaviour. Our taphonomic assessment inferred, through the variability of phytolith properties and minerals composing archaeological layers, that specific occupations suffered more physical weathering than others, for example in the form of trampling. The preservation of fragile and highly soluble phytoliths (eudicot leaf phytoliths) and the high frequencies of articulated phytoliths indicates that some bedding deposits experienced little disturbance after their deposition. Not all bedding layers dating to ⁓60 ka show, from a phytolith perspective, the same plant composition, which could be explained in terms of changes in human preference for the use of plants over time to construct bedding or because distinct types of living floors are represented. Finally, the systematic application of phytoliths and FTIR to the complex archaeological sequence of Border Cave confirm these analyses can be used in the future to identify bedding deposits not visible to the naked eye, and behavioural patterns obscured by diagenetic or biased processes during sampling., Programme Beatriu de Pinós (2019 BP00247), funded by the Secretary of Universities and Research (Government of Catalonia), Horizon 2020 programme of research and innovation of the European Union under the Marie Skłodowska-Curie grant agreement No. 801370, Ministerio de Ciencia e Innovación - PID 2020-119773 GB-I00, NRF Y-Rated Research Grant (No. 116358), Action PID 2019- 1049449 GB-I00 funded by Spanish FEDER/Ministry of Science and Innovation, National Geographic Explorer grant (NGS-54810R-19), DSI-NRF Centre of Excellence in Palaeosciences (Genus) grant (CEOOP 2020-1), NRF African Origins Platform grant (No. 98824), Research Council of Norway (SFF Centre for Early Sapiens Behaviour- SapienCE-project 262618), Talents program of the University of Bordeaux (n. 191022_001), Program “Human Past” University of Bordeaux, SAH 15/7645, CaseID 15987

High levels of free D-aspartate (D-Asp) are present in vertebrate testis during post-natal development, coinciding with the onset of testosterone production, which suggests that this atypical amino acid might participate in the regulation of hormone biosynthesis. To elucidate the unknown role of D-Asp on testicular function, we investigated steroidogenesis and spermatogenesis in a one-month-old knockin mouse model with the constitutive depletion of D-Asp levels due to the targeted overexpression of D-aspartate oxidase (DDO), which catalyzes the deaminative oxidation of D-Asp to generate the corresponding α-keto acid, oxaloacetate, hydrogen peroxide, and ammonium ions. In the Ddo knockin mice, we found a dramatic reduction in testicular D-Asp levels, accompanied by a significant decrease in the serum testosterone levels and testicular 17β-HSD, the enzyme involved in testosterone biosynthesis. Additionally, in the testes of these Ddo knockin mice, the expression of PCNA and SYCP3 proteins decreased, suggesting alterations in spermatogenesis-related processes, as well as an increase in the cytosolic cytochrome c protein levels and TUNEL-positive cell number, which indicate an increase in apoptosis. To further investigate the histological and morphometric testicular alterations in Ddo knockin mice, we analyzed the expression and localization of prolyl endopeptidase (PREP) and disheveled-associated activator of morphogenesis 1 (DAAM1), two proteins involved in cytoskeletal organization. Our results showed that the testicular levels of DAAM1 and PREP in Ddo knockin mice were different from those in wild-type animals, suggesting that the deficiency of D-Asp is associated with overall cytoskeletal disorganization. Our findings confirmed that physiological D-Asp influences testosterone biosynthesis and plays a crucial role in germ cell proliferation and differentiation, which are required for successful reproduction.

Background Neuroinflammation contributes to the onset and progression of neurodegenerative diseases, but has not been specifically investigated in patients affected by severe and milder forms of spinal muscular atrophy (SMA). Methods In this two-center retrospective study, we investigated signatures of neuroinflammation in forty-eight pediatric male and female SMA1 (n = 18), male and female SMA2 (n = 19), and female SMA3 (n = 11) patients, as well as in a limited number of male and female non-neurological control subjects (n = 4). We employed a Bio-Plex multiplex system based on xMAP technology and performed targeted quantitative analysis of a wide range of pro- and anti-inflammatory cytokines (chemokines, interferons, interleukins, lymphokines and tumor necrosis factors) and neurotrophic factors in the cerebrospinal fluid (CSF) of the study cohort before and after Nusinersen treatment at loading and maintenance stages. Results We find a significant increase in the levels of several pro-inflammatory cytokines (IL-6, IFN-γ, TNF-α, IL-2, IL-8, IL-12, IL-17, MIP-1α, MCP-1, and Eotaxin) and neurotrophic factors (PDGF-BB and VEGF) in the CSF of SMA1 patients relative to SMA2 and SMA3 individuals, who display levels in the range of controls. We also find that treatment with Nusinersen significantly reduces the CSF levels of some but not all of these neuroinflammatory molecules in SMA1 patients. Conversely, Nusinersen increases the CSF levels of proinflammatory G-CSF, IL-8, MCP-1, MIP-1α, and MIP-1β in SMA2 patients and decreases those of anti-inflammatory IL-1ra in SMA3 patients. Conclusions These findings highlight signatures of neuroinflammation that are specifically associated with severe SMA and the neuro-immunomodulatory effects of Nusinersen therapy.

PURPOSE Automatizing the scoring of the cytokinesis-blocked micronucleus assay spares a lot of valuable time. The dose-effect relationship can be applied reliably for dose estimation if the quality of the slides is the same from the perspective of the used image processing algorithm. This aspect brings in additional requirements against the quality of the slides compared to the conventional visual scoring. MATERIALS AND METHODS An add-in software was created to the non-fluorescent RS-MN automatic MN scoring system which is capable of measuring quantitatively the degree of typical anomalies. The image processing is less reliable when the presence of these anomalies is more frequent. The behavior of the designed sample quality parameters (SQPs) was tested on in vitro irradiated peripheral blood samples (0, 1, and 2 Gy) obtained from a healthy donor and also on samples from patients undergoing low dose-rate brachytherapy. RESULTS We examined 20 different SQPs and identified two that are independent and correlate significantly with the error of the fully automatic MN frequency. One is related to the size of the cells and the other reflects the homogeneity of the environment. An equation was established which presents a connection between the error of the auto MN frequency and the SQPs. By adding a fourth cleaning step to the conventional sample preparation and changing the pre-dripping temperature of the slide, the SQP can be modified, and consequently, the sample quality can be improved. The gain in accuracy is 54 ± 10 MN per 1000 binucleated cells, which corresponds to the effects of 0.5 Gy. Around the lowest limit of detection (

Fully shaped, morphologically standardized bone tools are generally considered reliable indicators of the emergence of modern behavior. We report the discovery of 23 double-beveled bone tools from ~ 80,000–60,000-year-old archaeological layers at Sibudu Cave in KwaZulu-Natal, South Africa. We analyzed the texture of use-wear on the archaeological bone tools, and on bone tool replicas experimentally used in debarking trees, processing rabbit pelts with and without an ochre compound, digging in sediment in and outside a cave, and on ethnographic artefacts. Debarking trees and digging in humus-rich soil produce use-wear patterns closely matching those observed on most Sibudu tools. This tool type is associated with three different Middle Stone Age cultural traditions at Sibudu that span 20,000 years, yet they are absent at contemporaneous sites. Our results support a scenario in which some southern African early modern human groups developed and locally maintained specific, highly standardized cultural traits while sharing others at a sub-continental scale. We demonstrate that technological and texture analyses are effective means by which to infer past behaviors and assess the significance of prehistoric cultural innovations.

A database of 479 glass formulations used to immobilize radioactive wastes for facilities in a safe and resilient infrastructure was analyzed, searching for underlying statistical patterns and associated glass performance features. The analyzed data cover many oxides, including SiO2, B2O3, Na2O, Fe2O3, and some fluorides. Borosilicates were the most common glasses (60.1%), while silicates were only 11.9%. In addition to these two families, five radioactive waste vitrification matrices were identified: Boroaluminosilicates, iron phosphates, aluminosilicates, sodium iron phosphates, and boroaluminates, totaling seven glass families. Almost all compositions (97.7%) contained sodium oxide, followed by silica (91.4%), iron (82.7%), boron (73.7%), phosphorus (54.9%), and cesium oxides (26.1%). Multivariate exploratory methods were applied to analyze and classify glass compositions using hierarchical and non-hierarchical (K-means) clusters and principal component analysis. Four main clusters were observed, the largest comprising 417 formulations containing mainly silicates, borosilicates, aluminosilicates, and boroaluminosilicates; two principal components, representing 73.75% of all compositions, emerge from these four clusters derived from a covariance analysis. The principal components and four clusters may be associated with the following glass features in terms of glass compositions: liquidus temperature, glass transition temperature, density, resistivity, microhardness, and viscosity. Some general underlying properties emerged from our classification and are discussed.

This chapter highlights methodological challenges for an understanding of acculturation and creolization in early prehistory. The authors note that this is especially evident in situations such as the Châtelperronian where there is little chronological definition. In reference to the Châtelperronian, it is recognized as remarkable how such a restricted spectrum of evidence proves to be so incredibly agile, producing such outwardly conflicting and occasionally paradoxical models. It is also noted that concepts such as acculturation and creolization flounder when confronted with the period’s temporal resolution and lack of direct evidence for individual and group-level interactions. The authors recognize that the satisfactory furtherance of this research depends upon a thorough archaeological and taphonomic analysis of key sites.

Lanthanide-doped MgB4O7 is a potential dosimetric material due to its thermoluminescence (TL) and optically stimulated luminescence (OSL) properties. These properties have been largely reported, but there are few theoretical studies dedicated to understanding the materials defects. The aim of this work is to demonstrate that defects are a key issue to understand the luminescence mechanisms. A new set of interatomic potential parameters were obtained reproducing the MgB4O7 structure better than 2% and 4% for oxide precursors. The results showed that the O Frenkel defect is the most probable which can account for the intrinsic blue emission in the undoped material. Also, the extrinsic defect calculations demonstrated two possible doping schemes for lanthanide ions. One lanthanide dopant group prefers the direct substitution at the boron site with a molecular ion of (BO3)−3 moving to balance the strain caused by this substitution. Another prefers a substitution at the magnesium site with an MgB anti-site as the charge compensation defect.

The detailed dose analysis at the extremities remains a challenge, without affecting operators’ mobility and their tactile sense. Using films loaded with optically stimulated luminescence (OSL) crystals have been studied in order to overcome some of these challenges in 2D dosimetry. In this work, we investigated flexible polymeric films loaded with MgB4O7:Ce,Li to acquire a better understanding of the dependence of the dosimetric signal characteristics on the production process and the influence of using different powder grain sizes. In film production, five different solvents were used: acetone–benzene, dichloromethane, chloroform, tetrahydrofuran and formic acid. Our results indicate that acetone–benzene is the solvent mixture that less influences the signal emitted by treated crystals, in comparison with the signal emitted by the pristine crystal powder. Conversely, by using formic acid, the crystalline structure of the sample was most severely modified, leading to a drastic reduction of the emitted OSL signal. We found that the extent of the grain surface in contact with the solvent in the process is important and should be taken into consideration when choosing the proper grain size to be used. Highlights Polymeric films loaded with MgB4O7:Ce,Li crystals were produced using different solvents.Different effect on the OSL signal was found depending on the used solvent.Among the evaluated solvents, acetone–benzene was the one that less affected the OSL signal.

The formation of the coastal plain of the Brazilian sea is mainly due to the fluctuation of relative sea level in the past. Armacao dos Buzios or simply Buzios is a municipality in the microregion of lakes, in the state of Rio de Janeiro. In this region there is a lowland area about two meters above current sea level. This lowland area is also known as coastal plain of Una River. It is expected that during the Holocene period the sea level reached a maximum about 2.5 meters above the current level. During that time billions of mollusks lived and proliferated in the shallow waters around the coastal plain of the Una River. As they died their shells formed a layer in the soil including Malhada Marsh that belongs to the Una River plain. In this study, shells were collected from this region and dated using the techniques of Electronic Paramagnetic Resonance (EPR). Ages from 2480±130 to 4490±270 years were obtained. Radiocarbon dating were performed at the Beta Analytic Lab, USA for comparison with the EPR results. Shells ages obtained are compatible with geological data from the Holocene period relative to past sea level fluctuations.

The D-aspartate oxidase (DDO) gene encodes the enzyme responsible for the catabolism of D-aspartate, an atypical amino acid enriched in the mammalian brain and acting as an endogenous NMDA receptor agonist. Considering the key role of NMDA receptors in neurodevelopmental disorders, recent findings suggest a link between D-aspartate dysmetabolism and schizophrenia. To clarify the role of D-aspartate on brain development and functioning, we used a mouse model with constitutive Ddo overexpression and D-aspartate depletion. In these mice, we found reduced number of BrdU-positive dorsal pallium neurons during corticogenesis, and decreased cortical and striatal gray matter volume at adulthood. Brain abnormalities were associated with social recognition memory deficit at juvenile phase, suggesting that early D-aspartate occurrence influences neurodevelopmental related phenotypes. We corroborated this hypothesis by reporting the first clinical case of a young patient with severe intellectual disability, thought disorders and autism spectrum disorder symptomatology, harboring a duplication of a chromosome 6 region, including the entire DDO gene.

Homo sapiens was present in northern Asia by around 40,000 years ago, having replaced archaic populations across Eurasia after episodes of earlier population expansions and interbreeding1–4. Cultural adaptations of the last Neanderthals, the Denisovans and the incoming populations of H. sapiens into Asia remain unknown1,5–7. Here we describe Xiamabei, a well-preserved, approximately 40,000-year-old archaeological site in northern China, which includes the earliest known ochre-processing feature in east Asia, a distinctive miniaturized lithic assemblage with bladelet-like tools bearing traces of hafting, and a bone tool. The cultural assembly of traits at Xiamabei is unique for Eastern Asia and does not correspond with those found at other archaeological site assemblages inhabited by archaic populations or those generally associated with the expansion of H. sapiens, such as the Initial Upper Palaeolithic8–10. The record of northern Asia supports a process of technological innovations and cultural diversification emerging in a period of hominin hybridization and admixture2,3,6,11. Evidence for ochre processing Novel miniaturized lithics showing hafting Implications for cultural adaptations Methods

Schizophrenia is a disorder of synaptic plasticity and aberrant connectivity in which a major dysfunction in glutamate synapse has been suggested. However, a multi-level approach tackling diverse clusters of interacting molecules of the glutamate signaling in schizophrenia is still lacking. We investigated in the post-mortem dorsolateral prefrontal cortex (DLPFC) and hippocampus of schizophrenia patients and non-psychiatric controls, the levels of neuroactive d- and l-amino acids (l-glutamate, d-serine, glycine, l-aspartate, d-aspartate) by HPLC. Moreover, by quantitative RT-PCR and western blotting we analyzed, respectively, the mRNA and protein levels of pre- and post-synaptic key molecules involved in the glutamatergic synapse functioning, including glutamate receptors (NMDA, AMPA, metabotropic), their interacting scaffolding proteins (PSD-95, Homer1b/c), plasma membrane and vesicular glutamate transporters (EAAT1, EAAT2, VGluT1, VGluT2), enzymes involved either in glutamate-dependent GABA neurotransmitter synthesis (GAD65 and 67), or in post-synaptic NMDA receptor-mediated signaling (CAMKIIα) and the pre-synaptic marker Synapsin-1. Univariable analyses revealed that none of the investigated molecules was differently represented in the post-mortem DLPFC and hippocampus of schizophrenia patients, compared with controls. Nonetheless, multivariable hypothesis-driven analyses revealed that the presence of schizophrenia was significantly affected by variations in neuroactive amino acid levels and glutamate-related synaptic elements. Furthermore, a Machine Learning hypothesis-free unveiled other discriminative clusters of molecules, one in the DLPFC and another in the hippocampus. Overall, while confirming a key role of glutamatergic synapse in the molecular pathophysiology of schizophrenia, we reported molecular signatures encompassing elements of the glutamate synapse able to discriminate patients with schizophrenia and normal individuals.

Schizophrenia (SCZ) is a mental illness characterized by aberrant synaptic plasticity and connectivity. A large bulk of evidence suggests genetic and functional links between postsynaptic abnormalities and SCZ. Here, we performed quantitative PCR and Western blotting analysis in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of SCZ patients to investigate the mRNA and protein expression of three key spine shapers: the actin-binding protein cyclase-associated protein 2 (CAP2), the sheddase a disintegrin and metalloproteinase 10 (ADAM10), and the synapse-associated protein 97 (SAP97). Our analysis of the SCZ post-mortem brain indicated increased DLG1 mRNA in DLPFC and decreased CAP2 mRNA in the hippocampus of SCZ patients, compared to non-psychiatric control subjects, while the ADAM10 transcript was unaffected. Conversely, no differences in CAP2, SAP97, and ADAM10 protein levels were detected between SCZ and control individuals in both brain regions. To assess whether DLG1 and CAP2 transcript alterations were selective for SCZ, we also measured their expression in the superior frontal gyrus of patients affected by neurodegenerative disorders, like Parkinson’s and Alzheimer’s disease. Interestingly, also in Parkinson’s disease patients, we found a selective reduction of CAP2 mRNA levels relative to controls but unaltered protein levels. Taken together, we reported for the first time altered CAP2 expression in the brain of patients with psychiatric and neurological disorders, thus suggesting that aberrant expression of this gene may contribute to synaptic dysfunction in these neuropathologies.

The PVA-GTA Fricke Gel is a three-dimensional tissue-equivalent dosimeter that can be analyzed with optical imaging techniques. In this work we demonstrate that the addition of silver nanoparticles to the gel reduces the diffusion effect.

This contribution focuses on the recently excavated lithic assemblage from Border Cave Members 1 RGBS, 3 BS, 2 WA and 2 BS. These members were attributed by Beaumont to the Howiesons Poort and post-Howiesons Poort Industries of the southern African Middle Stone Age. Here we consider lithics as indicators of cultural behaviour, site formation processes, and occupation intensity. As such, the assemblage is explored in depth through lithic technology attribute analysis, particle size distribution, and spatial analysis. These lines of inquiry follow the new allostratigraphic divisions proposed for the deposits by Stratford and colleagues. Results show that the lower members share a degree of similarity in terms of flaking strategies and raw material selection, whereas the upper members record a dissimilar set of features, with differentiation between them. The technological and spatial analyses suggest the sporadic presence of different groups at the site, each characterized by distinct sets of knapping techniques and methods but employing related knapping strategies and using similar raw materials. The interpretation of these members as a palimpsest of sporadic occupation is supported by the low number of archaeological finds by sediment volume. The evidence at hand does not support a Howiesons Poort attribution for the lowest members. The data show that lithics from part of Member 2 WA and 2 BS are in accordance with those of the recently defined Sibudan technocomplex.

Since the Fukushima Daiichi Nuclear Power Plant accident in March 2011, the technology available for unmanned aerial vehicles (UAVs) for radiation monitoring has improved greatly. Remote access to radiation-contaminated areas not only eliminates unnecessary exposure of civilians or military personnel, but also allows workers to explore inaccessible places. Hazardous levels of radioactive contamination can be expected as a result of accidents in the nuclear power industry or as a result of the intentional release of radioactive materials for terrorist purposes (dirty bombs, building contamination, etc.). The possibility to detect, identify, and characterize radiation and nuclear material using mobile and remote sensing platforms is a common requirement in the radiation sensing community. The technology has applications in homeland security and law enforcement, customs and border protection, nuclear power plant safety and security, nuclear waste monitoring, environmental recovery, and the military. In this work, the authors have developed, implemented, and characterized a gamma-ray detection and spectroscopy system capable of operating on a UAV. The system was mainly developed using open-source software and affordable hardware components to reduce development and maintenance costs and provide satisfactory performance as a detection instrument. The designed platform can be used to perform mapping or localization tasks to improve the risk assessment process for first responders during the management of radiological and nuclear incidents. First, the design process of the system is described; the result of the characterization of the platform is then presented together with the use of the prototype installed on a UAV in an exercise simulating a radiological and nuclear contamination scenario.

Paint technology, namely paint preparation and application procedures, is an important aspect of painting traditions. With the expansion of archaeometric studies and in situ non-destructive analytical methods, a renewal of technological studies is being observed in rock art. In situ analyses have several limitations that are widely discussed in the literature, however. It is not yet clear whether they provide accurate information on paint technology, except under certain conditions. Here, we evaluated digital microscopic and pXRF in situ analyses for the characterisation of a large set of red and yellow paintings from the El Castillo cave, Cantabria, Spain. We have set experiments and used statistical methods to identify differences between paint components and determine factors impacting pXRF measurements. We found that the compositional heterogeneity of the paintings’ environment, especially variations in secondary deposits, was responsible for most of the differences observed between the pXRF signals recorded on the paintings. We concluded that the El Castillo cave environment is not suitable for non-destructive technological studies, but that more favourable contexts might exist. Following previous works and our own results, we advocate a combination of both in situ and laboratory invasive analyses for the study of paint composition and paint technology. Our research protocol, based on the comparison of rock paintings, their substrate, experimental paintings and Fe-normalisation of the signals can improve the reliability of pXRF results. We also propose to include more systematic characterisation of rock wall heterogeneity and the use of microscopic analyses in non-destructive approaches.

The aim of this work is to analyze the effects of ionizing radiation and radionuclides (like 137Cs) in several higher plants located around the Fukushima Dai-ichi Nuclear Power Plant (FNPP), evaluating both their adaptive processes and evolution. After the FNPP accident in March 2011 much attention was focused to the biological consequences of ionizing radiation and radionuclides released in the area surrounding the nuclear plant. This unexpected mishap led to the emission of radionuclides in aerosol and gaseous forms from the power plant, which contaminated a large area, including wild forest, cities, farmlands, mountains, and the sea, causing serious problems. Large quantities of 131I, 137Cs, and 134Cs were detected in the fallout. People were evacuated but the flora continued to be affected by the radiation exposure and by the radioactive dusts’ fallout. The response of biota to FNPP irradiation was a complex interaction among radiation dose, dose rate, temporal and spatial variation, varying radiation sensitivities of the different plants’ species, and indirect effects from other events. The repeated ionizing radiations, acute or chronic, guarantee an adaptation of the plant species, demonstrating a radio-resistance. Consequently, ionizing radiation affects the genetic structure, especially during chronic irradiation, reducing genetic variability. This reduction is associated with the different susceptibility of plant species to chronic stress. This would confirm the adaptive theory associated with this phenomenon. The effects that ionizing radiation has on different life forms are examined in this review using the FNPP disaster as a case study focusing the attention ten years after the accident.

Intrathecal delivery of Nusinersen–an antisense oligonucleotide that promotes survival motor neuron (SMN) protein induction–is an approved therapy for spinal muscular atrophy (SMA). Here, we employed nuclear magnetic resonance (NMR) spectroscopy to longitudinally characterize the unknown metabolic effects of Nusinersen in the cerebrospinal fluid (CSF) of SMA patients across disease severity. Modulation of amino acid metabolism is a common denominator of biochemical changes induced by Nusinersen, with distinct downstream metabolic effects according to disease severity. In severe SMA1 patients, Nusinersen stimulates energy-related glucose metabolism. In intermediate SMA2 patients, Nusinersen effects are also related to energy homeostasis but involve ketone body and fatty acid biosynthesis. In milder SMA3 patients, Nusinersen mainly modulates amino acid metabolism. Moreover, Nusinersen modifies the CSF metabolome of a more severe clinical group towards the profile of untreated SMA patients with milder disease. These findings reveal disease severity-specific neurometabolic signatures of Nusinersen treatment, suggesting a selective modulation of peripheral organ metabolism by this CNS-directed therapy in severe SMA patients.

Upper Palaeolithic sites in southwestern France attributed to the Upper Gravettian and the Solutrean yielded sub spherical gravels with a highly shiny appearance that have intrigued researchers since the 1930s. In this work, we analyze specimens from five sites, including the recently excavated Solutrean site of Landry, to establish whether their presence in archaeological layers and peculiar aspect are due to natural processes or human agency. We study the spatial distribution of gravels at Landry and submit archaeological gravels from the five sites, natural formations, Landry sediment sieving, and polishing experiments with a rotary tumbling machine to morphometric, colorimetric and textural analyses. Our results suggest that the lustrous gravels found at the five sites result from deliberate selection and their shiny appearance is the probable consequence of prolonged contact with a soft material such as animal skin. Ethnographic accounts indicate that these gravels may have been used for magico-religious ritual purposes (charms, sorcery, divination etc.), in games, as elements of musical instruments, and as items serving other social and personal purposes. We argue that these objects reflect a cultural innovation emerged during the Gravettian and continued into the Solutrean.

It has been suggested that engraved abstract patterns dating from the Middle and Lower Palaeolithic served as means of representation and communication. Identifying the brain regions involved in visual processing of these engravings can provide insights into their function. In this study, brain activity was measured during perception of the earliest known Palaeolithic engraved patterns and compared to natural patterns mimicking human-made engravings. Participants were asked to categorise marks as being intentionally made by humans or due to natural processes (e.g. erosion, root etching). To simulate the putative familiarity of our ancestors with the marks, the responses of expert archaeologists and control participants were compared, allowing characterisation of the effect of previous knowledge on both behaviour and brain activity in perception of the marks. Besides a set of regions common to both groups and involved in visual analysis and decision-making, the experts exhibited greater activity in the inferior part of the lateral occipital cortex, ventral occipitotemporal cortex, and medial thalamic regions. These results are consistent with those reported in visual expertise studies, and confirm the importance of the integrative visual areas in the perception of the earliest abstract engravings. The attribution of a natural rather than human origin to the marks elicited greater activity in the salience network in both groups, reflecting the uncertainty and ambiguity in the perception of, and decision-making for, natural patterns. The activation of the salience network might also be related to the process at work in the attribution of an intention to the marks. The primary visual area was not specifically involved in the visual processing of engravings, which argued against its central role in the emergence of engraving production.

Personal ornaments have become a key cultural proxy to investigate cognitive evolution, modern human dispersal, and population dynamics. Here, we reassess personal ornaments found at Zhoukoudian Upper Cave and compare them with those from other Late Paleolithic Northern Chinese sites. We reappraise the information provided by Pei Wen Chung on Upper Cave personal ornaments lost during World War II and analyze casts of 17 of them, along with two unpublished objects displayed at the Zhoukoudian Site Museum and three original perforated teeth rediscovered at the Zhoukoudian Site Museum. We apply archeozoological, technological and use-wear analyses to document variation in ornamental practices and their change throughout the site stratigraphy. Badger, fox, red deer, sika deer, marten, and tiger teeth as well as carp bone, bird bone, Anadara shell, limestone beads, and perforated pebble appear to have been the preferred objects used as ornaments by Upper Cave visitors. Multivariate analysis of technological data highlights a correspondence between cultural layers and perforation techniques, with radial incising being typical of layer L2 and bidirectional incising of L4. The three rediscovered badger canines display features suggesting they were sewed on clothing rather than suspended from necklaces or bracelets. Elemental scanning electron microscopy coupled with energy dispersive X-ray spectromety and mineralogical (μ-Raman) analyses of red residues adhering to the rediscovered teeth indicate these objects were originally coated with ochre and identify variations that match differences in technology. The two ornaments exhibited at the Zhoukoudian Site Museum are ancient teeth that were recently perforated and should be excluded from the Upper Cave assemblage. A seriation of Late Paleolithic ornaments found at Northern Chinese sites identifies a clear-cut difference in preferred ornament types between western and eastern sites, interpreted as reflecting two long-lasting traditions in garment symbolic codes. acceptedVersion

Schizophrenia (SCZ) is a mental illness characterized by aberrant synaptic plasticity and connectivity. A large bulk of evidence suggests genetic and functional links between postsynaptic abnormalities and SCZ. Here, we performed quantitative PCR and Western blotting analysis in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of SCZ patients to investigate the mRNA and protein expression of three key spine shapers: the actin-binding protein cyclase-associated protein 2 (

Lithic assemblages immediately following the Howiesons Poort, often loosely referred to as the ‘post- Howiesons Poort’ or MSA III, have attracted relatively little attention when compared to other wellknown phases of the South African Middle Stone Age (MSA) sequence. Current evidence from sites occurring in widely-differing environments suggests that these assemblages are marked by temporal and technological variability, with few features in common other than the presence of unifacial points. Here we present a technological and geometric morphometric analysis of ‘points’ from the new excavations of Members 2 BS, 2WA and the top of 3 BS members at Border Cave, KwaZulu-Natal, one of the key sites for studying modern human cultural evolution. Our complementary methodologies demonstrate that, at this site, hominins adopted a knapping strategy that primarily produced non-standardised unretouched points. Triangular morphologies were manufactured using a variety of reduction strategies, of which the discoidal and Levallois recurrent centripetal methods produced distinctive morphologies. We find technological and morphological variability increases throughout the post-Howiesons Poort sequence, with clear differences between and within chrono-stratigraphic groups. Finally, we assess the suitability of the ‘Sibudan’ cultural-technological typology proposed for post-Howiesons Poort assemblages at Sibhudu, another KwaZulu-Natal site, and find similarities in the morphological axes characterising the samples, despite differences in the shaping strategies adopted. Overall, our work contributes to the growing body of research that is helping to address historical research biases that have slanted our understanding of cultural evolution during the MSA of southern Africa towards the Still Bay and Howiesons Poort technocomplexes., UK Research & Innovation (UKRI), Arts & Humanities Research Council (AHRC) NGS-54810R-19, Wenner Gren Foundation CEOOP2020-1, Poroulis grant through Cambridge University, Spanish FEDER/Ministry of Science and Innovation 262618, National Geographic Explorer grant ANR-10-LABX-52, DSI- NRF Centre of Excellence in Palaeosciences grant 191022_001, Research Council of Norway through its Centres of Excellence funding scheme, LaScArBx research programme, Grand Programme de Recherche 'Human Past' of the Initiative d'Excellence (IdEx) of the Bordeaux University, Leakey Foundation (Movement, interaction, and structure: modelling population networks and cultural diversity in the African Middle Stone Age), Lithic Studies Society (Jacobi Bursary Awardee, 2020), SFF Centre for Early Sapiens Behaviour (SapienCE), Talents Programme AH/R012792/1 Gr. 10157 PID2019-1049449 GB-I00

Cueva de Ardales in Málaga, Spain, is one of the richest and best-preserved Paleolithic painted caves of southwestern Europe, containing over a thousand graphic representations. Here, we study the red pigment in panel II.A.3 of “Sala de las Estrellas,” dated by U-Th to the Middle Paleolithic, to determine its composition, verify its anthropogenic nature, infer the associated behaviors, and discuss their implications. Using optical microscopy, scanning electron microscopy coupled with energy dispersive X-ray spectroscopy, micro-Raman spectroscopy, and X-ray diffraction, we analyzed a set of samples from the panel and compared them to natural coloring materials collected from the floor and walls of the cave. The conspicuously different texture and composition of the geological samples indicates that the pigments used in the paintings do not come from the outcrops of colorant material known in the cave. We confirm that the paintings are not the result of natural processes and show that the composition of the paint is consistent with the artistic activity being recurrent. Our results strengthen the hypothesis that Neanderthals symbolically used these paintings and the large stalagmitic dome harboring them over an extended time span.

L- α -alanine has aroused considerable interest for use in radiation EPR dosimetry and has been formally accepted as a secondary standard for high-dose (kGy) and transfer dosimetry of high-energy photons and electrons. In this work, we extended the investigation of the energy response of alanine EPR films in the low energy range for X-photons (1–30 keV). Electron Paramagnetic Resonance (EPR) measurements were performed on Kodak BioMax alanine films exposed to low-energy X-rays from a Cu-, W- and Mo-targets tube operating at voltages up to 30 kV. Films were chosen because of the low penetration of the soft X-rays used. The response of alanine to low-energy X-rays was characterized experimentally and the relative response (with respect to high energy photons) was found to be between 0.8 and 0.9 for Cu- and W-tube X-rays, and 1.0 for Mo-tube X-rays. The attenuation profiles were investigated and it was found that 1 mm of film material reduces the intensity of the X-ray-beam by about 70%, 50% and 40% for Cu-, W- and Mo-tube X-rays, respectively. Monte Carlo simulations were performed to model the energy release as well as the depth dose profiles for the various radiation beams used. These data are considered relevant for dosimetric applications in low energy beams such the high-gradient treatment fields used in monoenergetic microbeam radiation therapy (MRT) with synchrotron radiation as well as in brachytherapy with low energy sources, for instance 169Yb.

In 2015, which marked 35 years since Beaumont had worked at the site, we renewed excavations at Border Cave. Our primary aims were to reassess the stratigraphic context of the sedimentary and cultural sequence, gain insight into site formation processes, make a detailed study of organic remains, identify long term cultural trends, and characterize expressions of complex behaviour and innovation. This contribution serves as an update on activities conducted in 2018 and 2019 and provides an overview of our research findings to date, placing them in the broader context of the Middle Stone Age in southern Africa. New luminescence ages based on feldspar grains in the sedimentary sequence are in broad agreement with the previous chronology established for the site. Geoarchaeology and faunal taphonomy have started to elucidate site formation processes, showing that the members should not be considered as homogeneous units, and that associated formation interpretations established by Beaumont are simplifications that are not representative of the diverse site formation processes active in the shelter. This finding is supported by lithic analysis of the Member 2 WA assemblage that shows differences in technology between artefacts from the top, middle, and lower part of the same member. In addition, the lithic artefacts from the middle and lower part of Member 2 WA show continuities with the lithics from the underlying Members 3 BS and 1 RGBS, which were attributed by Beaumont to a different industry. Grass mats/bedding layers are preserved throughout the sequence, the oldest of which dates to ∼200 ka. The use of ash and leaves with insecticidal properties in the bedding construction reflects complex cognition, as does the cooking of starchy rhizomes that come from layers dated to 170 ka. In addition to a rich mammal fauna found in all of the deposits, the remains of a new individual, a 3–4-year-old child, were recovered from Member 1 BS.LR C that has an ESR date of 42.6 ka.

Effective provisions of preparedness and response are necessary to protect human life, health, property, and the environment in any nuclear and radiological emergency. Recently, the International Commission on Radiological Protection recognized the need to provide more quantitative guidance on environmental radiation protection to integrate these analyses. A required assessment is a correlation between dose and its effects in non-human biota. Plants are highly sensitive environmental monitors for the assessment of potentially genotoxic agents and avoid the controversial use of animal models. The Allium test is commonly used to assess genotoxicity for a wide variety of chemical and physical factors, as it allows for estimates of possible DNA damage in eukaryotes in general, including humans. In this work, onion (Allium cepa) seedlings were exposed to 20–200 mGy of $$\alpha$$ -radiation. We studied the possibility of using cytogenetic analyses of irradiated onion cells to determine the biological dose. It was observed that the increase in the frequencies of chromosomal aberrations, mitotic abnormalities, and micronuclei occurred proportional to the radiation dose, but a reduction in cytological damage was observed from 100 mGy, suggesting the onset of cytotoxic activity. Our research shows the potential of Allium cepa as a sensitive support system for dosimetry, detection, and screening of cellular effects produced by low doses of environmental radiation.

Radiation-sensitive gels are among the most recent and promising developments for radiation therapy (RT) dosimetry. RT dosimetry has the twofold goal of ensuring the quality of the treatment and the radiation protection of the patient. Benchmark dosimetry for acceptance testing and commissioning of RT systems is still based on ionization chambers. However, even the smallest chambers cannot resolve the steep dose gradients of up to 30–50% per mm generated with the most advanced techniques. While a multitude of systems based, e.g., on luminescence, silicon diodes and radiochromic materials have been developed, they do not allow the truly continuous 3D dose measurements offered by radiation-sensitive gels. The gels are tissue equivalent, so they also serve as phantoms, and their response is largely independent of radiation quality and dose rate. Some of them are infused with ferrous sulfate and rely on the radiation-induced oxidation of ferrous ions to ferric ions (Fricke-gels). Other formulations consist of monomers dispersed in a gelatinous medium (Polyacrylamide gels) and rely on radiation-induced polymerization, which creates a stable polymer structure. In both gel types, irradiation causes changes in proton relaxation rates that are proportional to locally absorbed dose and can be imaged using magnetic resonance imaging (MRI). Changes in color and/or opacification of the gels also occur upon irradiation, allowing the use of optical tomography techniques. In this work, we review both Fricke and polyacrylamide gels with emphasis on their chemical and physical properties and on their applications for radiation dosimetry.

The origin and evolution of hominin mortuary practices are topics of intense interest and debate1–3. Human burials dated to the Middle Stone Age (MSA) are exceedingly rare in Africa and unknown in East Africa1–6. Here we describe the partial skeleton of a roughly 2.5- to 3.0-year-old child dating to 78.3 ± 4.1 thousand years ago, which was recovered in the MSA layers of Panga ya Saidi (PYS), a cave site in the tropical upland coast of Kenya7,8. Recent excavations have revealed a pit feature containing a child in a flexed position. Geochemical, granulometric and micromorphological analyses of the burial pit content and encasing archaeological layers indicate that the pit was deliberately excavated. Taphonomical evidence, such as the strict articulation or good anatomical association of the skeletal elements and histological evidence of putrefaction, support the in-place decomposition of the fresh body. The presence of little or no displacement of the unstable joints during decomposition points to an interment in a filled space (grave earth), making the PYS finding the oldest known human burial in Africa. The morphological assessment of the partial skeleton is consistent with its assignment to Homo sapiens, although the preservation of some primitive features in the dentition supports increasing evidence for non-gradual assembly of modern traits during the emergence of our species. The PYS burial sheds light on how MSA populations interacted with the dead. Primary and intentional deposit Burial versus funerary caching Taxonomic assessment Implications for human cultural evolution Online content

Ionizing radiation is ubiquitous in the environment. Its source can be natural, such as radioactive materials present in soil and cosmic rays, or artificial, such as the fuel for nuclear power plants. Overexposure to ionizing radiation may damage living tissue and could cause severe health problems (i.e., mutations, radiation sickness, cancer, and death). Cytogenetic bio-dosimetry has the great advantage to take into account the inter-individual variation, and it is informative even when physical dosimetry is not applicable; moreover, it is the definitive method to assess exposure to ionizing radiation recommended by the World Health Organization (WHO). Such a procedure involves counting the frequency of dicentric chromosomes (DCs), which are the most studied chromosomal aberrations used as absorbed radiation biomarkers, during the metaphase of cells. A set of algorithms, tested on different programming languages to automatically identify DCs, is analyzed by the authors together with an Automated Dicentric Chromosome Identifying software (ADCI) mostly based on OpenCV programming libraries. The purpose of this work is to review the main results regarding the correlation between ionizing radiation and dicentric chromosomes in cytogenetic bio-dosimetry.

In recent decades, the increasing threats associated with Chemical and Radiological (CR) agents prompted the development of new tools to detect and collect samples without putting in danger first responders inside contaminated areas. A particularly promising branch of these technological developments relates to the integration of different detectors and sampling systems with Unmanned Aerial Vehicles (UAV). The adoption of this equipment may bring significant benefits for both military and civilian implementations. For instance, instrumented UAVs could be used in support of specialist military teams such as Sampling and Identification of Biological, Chemical and Radiological Agents (SIBCRA) team, tasked to perform sampling in contaminated areas, detecting the presence of CR substances in field and then confirming, collecting and evaluating the effective threats. Furthermore, instrumented UAVs may find dual-use application in the civil world in support of emergency teams during industrial accidents and in the monitoring activities of critical infrastructures. Small size drones equipped with different instruments for detection and collection of samples may enable, indeed, several applications, becoming a tool versatile and easy to use in different fields, and even featuring equipment normally utilized in manual operation. The authors hereby present the design of miniaturized sensors for a mission-oriented UAV application and the preliminary results from an experimental campaign performed in 2020.

Altered glutamatergic neurotransmission is thought to play a crucial role in the progression of Alzheimer’s disease (AD). Accordingly, the identification of peculiar biochemical patterns reflecting AD-related synaptopathy in blood and cerebrospinal fluid (CSF) could have relevant diagnostic and prognostic implications. In this study, we measured by High-Performance Liquid Chromatography the amount of glutamate, glutamine and glycine in post-mortem brain samples of AD patients, as well as in CSF and blood serum of drug-free subjects encompassing the whole AD clinical spectrum (pre-clinical AD, n = 18, mild cognitive impairment-AD, n = 29, dementia AD, n = 30). Interestingly, we found that glutamate and glycine levels, as well as total tau protein content, were significantly reduced in the superior frontal gyrus of patients with AD, compared with non-demented controls. No significant change was also found in glutamate, glutamine and glycine CSF concentrations between AD patients and neurological controls. Remarkably, serum glutamate levels were significantly higher in patients affected by early AD phases compared to controls, and were negatively correlated with CSF total tau levels. Conversely, serum glutamine concentration was significantly increased in AD patients, with a negative correlation with MMSE performances. Finally, we reported a significant correlation between seruml-glutamate concentrations and CDR score in female but not in male cohort of AD subjects. Overall, our results suggest that serum glutamate and glutamine levels in AD patients could vary across disease stages, potentially reflecting the progressive alteration of glutamatergic signaling during neurodegenerative processes.

Unconventional scenarios with hazardous radioactive levels are expected as consequences of accidents in the industrial sector of the nuclear energy production or following intentional releases of radioactive materials for terrorist purposes (dirty bombs, indoor contaminations, etc.). Nowadays, the need to balance the high standards of safety and security through an effective detection network is a matter of paramount importance. In this work, the authors’ challenge has been to design, realize and test a low-cost gamma detection and spectroscopy system which may be used in unmanned vehicles in general and/or drones with low payload capabilities. The designed platform may be used to carry out mapping or localization operations in order to reduce the risk factor for first responders or for the population affected by radiological and nuclear events. In this paper, the design process of a gamma ray detection and spectroscopy system based on affordable and commercially available technologies is presented along with the results of our ongoing characterization of the prototype.

The risk associated with chemical, biological, radiological, nuclear, and explosive (CBRNe) threats in the last two decades has grown as a result of easier access to hazardous materials and agents, potentially increasing the chance for dangerous events. Consequently, early detection of a threat following a CBRNe event is a mandatory requirement for the safety and security of human operators involved in the management of the emergency. Drones are nowadays one of the most advanced and versatile tools available, and they have proven to be successfully used in many different application fields. The use of drones equipped with inexpensive and selective detectors could be both a solution to improve the early detection of threats and, at the same time, a solution for human operators to prevent dangerous situations. To maximize the drone’s capability of detecting dangerous volatile substances, fluid dynamics numerical simulations may be used to understand the optimal configuration of the detectors positioned on the drone. This study serves as a first step to investigate how the fluid dynamics of the drone propeller flow and the different sensors position on-board could affect the conditioning and acquisition of data. The first consequence of this approach may lead to optimizing the position of the detectors on the drone based not only on the specific technology of the sensor, but also on the type of chemical agent dispersed in the environment, eventually allowing to define a technological solution to enhance the detection process and ensure the safety and security of first responders.

The development of a tool to reduce the exposure of personnel in case of intentional or accidental toxic chemicals dispersion scenarios opens the field to new operational perspectives in the domain of operator safety and of critical infrastructure monitoring. The use of two sensors with different operating principles, metal oxide and photo-ionization detector, allows to confirm the presence of specific classes of chemicals in a contaminated area. All instruments are expected to be integrated into the payload of an unmanned aerial vehicle (UAV) and used for different purposes such as critical infrastructure surveillance focused on the volatile organic chemical and chemical warfare agents (CWA) detection and the post-incident of contamination level monitoring. In this paper, the authors presented the hardware set-up implemented and the test realized with CWAs simulants and will discuss the results obtained presenting advantages and disadvantages of this system in an application such as a UAV for the detection of chemical substances.