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The state-of-the-art magnesia-based dry vibrateable tundish linings are predominantly bonded by resin. However, besides high energy consumption, the pyrolysis of the resin-containing lining during the tundish heat-up process generates hazardous gases and carbon residues, resulting in an unwanted carbon pick by the molten steel after the finished ladle treatment.Hence, the aim of this study was to develop novel carbon free binder system, therefore combine acid-based with thermally activated binder systems. Their influence on the physical and mechanical properties were investigated. Additionally, utilizing a unique steel casting simulator, the influence of newly developed lining compositions on the steel quality compared to a reference binder system was tested and analyzed. The influence on the inclusion population in the molten steel and the steel quality was evaluated.Newly developed compositions showed no significant influence on the steel cleanliness, only a minor change in the population could be detected.

Peatlands are one of the largest terrestrial carbon sinks on the planet, yet little is known about the carbon accumulation rates (CARs) of mountainous peatlands. The long-term variability in the size of the associated carbon sink and its drivers remain largely unconstrained, especially when the long-term anthropogenic impact is also considered. Here, we present a composite CAR record of nine peatlands from central–eastern Europe (Romania and Serbia) detailing variability in the rates of carbon accumulation during the Holocene. We show examples of extremely high long-term rates of carbon accumulation (LORCA>120 gCm-2yr-1), indicating that mountain peatlands constitute an efficient regional carbon sink at times. By comparing our data to modelled palaeoclimatic indices and to measures of anthropogenic impact we disentangle the drivers of peat carbon accumulation in the area. Variability in early- and mid-Holocene CARs is linked to hydroclimatic controls, with high CARs occurring during the early Holocene and lower CARs associated with the transition to cooler and moister mid-Holocene conditions. By contrast, after 4000 years (calibrated) before present (years BP), the trends in CARs indicate a divergence from hydroclimate proxies, suggesting that other processes became the dominant drivers of peat CARs. We propose that enhanced erosion following tree cover reduction as well as increased rates of long-distance atmospheric dust fallout might have played a role, as both processes would result in enhanced mineral and nutrient supply to bog surfaces, stimulating peatland productivity. Surprisingly though, for the last 1000 years, reconstructed temperature is significantly correlated with CARs, with rising temperatures linked to higher CARs. Under future climate conditions, which are predicted to be warmer in the region, we predict that peat growth may expand but that this is entirely dependent upon the scale of human impact directly affecting the sensitive hydrological budget of these peatlands.

Reconstructions of dust flux have been used to produce valuable global records of changes in atmospheric circulation and aridity. These studies have highlighted the importance of atmospheric dust in marine and terrestrial biogeochemistry and nutrient cycling. By investigating a 10 800-year-long paleoclimate archive from the Eastern Carpathians (Romania) we present the first peat record of changing dust deposition over the Holocene for the Carpathian–Balkan region. Using qualitative (X-ray fluorescence (XRF) core scanning) and quantitative inductively coupled plasma optical emission spectrometer(ICP-OES) measurements of lithogenic (K, Si, Ti) elements, we identify 10 periods of major dust deposition between 9500–9200, 8400–8100, 7720–7250, 6350–5950, 5450–5050, 4130–3770, 3450–2850, 2000–1450, 800–620, and 60 cal yr BP to present. In addition, we used testate amoeba assemblages preserved within the peat to infer local palaeohydroclimatic conditions. Our record highlights several discrepancies between eastern and western European dust depositional records and the impact of highly complex hydrological regimes in the Carpathian region. Since 6100 cal yr BP, we find that the geochemical indicators of dust flux have become uncoupled from the local hydrology. This coincides with the appearance of millennial-scale cycles in the dust input and changes in geochemical composition of dust. We suggest that this is indicative of a shift in dust provenance from local–regional (likely loess-related) to distal (Saharan) sources, which coincide with the end of the African Humid Period and the onset of Saharan desertification.

Here we present a speleothem isotope record (POM2) from Ascunsă Cave (Romania) that provides new data on past climate changes in the Carpathian–Balkan region from 8.2 ka until the present. This paper describes an approach to constrain the effect of temperature changes on calcite δ18O values in stalagmite POM2 over the course of the middle Holocene (6–4 ka), and across the 8.2 and 3.2 ka rapid climate change events. Independent pollen temperature reconstructions are used to this purpose. The approach combines the temperature-dependent isotope fractionation of rain water during condensation and fractionation resulting from calcite precipitation at the given cave temperature. The only prior assumptions are that pollen-derived average annual temperature reflects average cave temperature, and that pollen-derived coldest and warmest month temperatures reflect the range of condensation temperatures of rain above the cave site. This approach constrains a range of values between which speleothem δ18O changes should be found if controlled only by surface temperature variations at the cave site. Deviations of the change in δ18Ocspel values from the calculated temperature-constrained range of change are interpreted towards large-scale variability of climate–hydrology. Following this approach, we show that an additional ∼0.6‰ enrichment of δ18Oc in the POM2 stalagmite was caused by changing hydrological patterns in SW Romania across the middle Holocene, most likely comprising local evaporation from the soil and an increase in Mediterranean moisture δ18O. Further, by extending the calculations to other speleothem records from around the entire Mediterranean basin, it appears that all eastern Mediterranean speleothems recorded a similar isotopic enrichment due to changing hydrology, whereas all changes recorded in speleothems from the western Mediterranean are fully explained by temperature variation alone. This highlights a different hydrological evolution between the two sides of the Mediterranean. Our results also demonstrate that during the 8.2 ka event, POM2 stable isotope data essentially fit the temperature-constrained isotopic variability. In the case of the 3.2 ka event, an additional climate-related hydrological factor is more evident. This implies a different rainfall pattern in the Southern Carpathian region during this event at the end of the Bronze Age.

An accurate and coherent chronological framework is essential for the interpretation of climatic and environmental records obtained from deep polar ice cores. Until now, one common ice core age scale had been developed based on an inverse dating method (Datice), combining glaciological modelling with absolute and stratigraphic markers between 4 ice cores covering the last 50 ka (thousands of years before present) (Lemieux-Dudon et al., 2010). In this paper, together with the companion paper of Veres et al. (2013), we present an extension of this work back to 800 ka for the NGRIP, TALDICE, EDML, Vostok and EDC ice cores using an improved version of the Datice tool. The AICC2012 (Antarctic Ice Core Chronology 2012) chronology includes numerous new gas and ice stratigraphic links as well as improved evaluation of background and associated variance scenarios. This paper concentrates on the long timescales between 120–800 ka. In this framework, new measurements of δ18Oatm over Marine Isotope Stage (MIS) 11–12 on EDC and a complete δ18Oatm record of the TALDICE ice cores permit us to derive additional orbital gas age constraints. The coherency of the different orbitally deduced ages (from δ18Oatm, δO2/N2 and air content) has been verified before implementation in AICC2012. The new chronology is now independent of other archives and shows only small differences, most of the time within the original uncertainty range calculated by Datice, when compared with the previous ice core reference age scale EDC3, the Dome F chronology, or using a comparison between speleothems and methane. For instance, the largest deviation between AICC2012 and EDC3 (5.4 ka) is obtained around MIS 12. Despite significant modifications of the chronological constraints around MIS 5, now independent of speleothem records in AICC2012, the date of Termination II is very close to the EDC3 one.

The deep polar ice cores provide reference records commonly employed in global correlation of past climate events. However, temporal divergences reaching up to several thousand years (ka) exist between ice cores over the last climatic cycle. In this context, we are hereby introducing the Antarctic Ice Core Chronology 2012 (AICC2012), a new and coherent timescale developed for four Antarctic ice cores, namely Vostok, EPICA Dome C (EDC), EPICA Dronning Maud Land (EDML) and Talos Dome (TALDICE), alongside the Greenlandic NGRIP record. The AICC2012 timescale has been constructed using the Bayesian tool Datice (Lemieux-Dudon et al., 2010) that combines glaciological inputs and data constraints, including a wide range of relative and absolute gas and ice stratigraphic markers. We focus here on the last 120 ka, whereas the companion paper by Bazin et al. (2013) focuses on the interval 120–800 ka. Compared to previous timescales, AICC2012 presents an improved timing for the last glacial inception, respecting the glaciological constraints of all analyzed records. Moreover, with the addition of numerous new stratigraphic markers and improved calculation of the lock-in depth (LID) based on δ15N data employed as the Datice background scenario, the AICC2012 presents a slightly improved timing for the bipolar sequence of events over Marine Isotope Stage 3 associated with the seesaw mechanism, with maximum differences of about 600 yr with respect to the previous Datice-derived chronology of Lemieux-Dudon et al. (2010), hereafter denoted LD2010. Our improved scenario confirms the regional differences for the millennial scale variability over the last glacial period: while the EDC isotopic record (events of triangular shape) displays peaks roughly at the same time as the NGRIP abrupt isotopic increases, the EDML isotopic record (events characterized by broader peaks or even extended periods of high isotope values) reached the isotopic maximum several centuries before. It is expected that the future contribution of both other long ice core records and other types of chronological constraints to the Datice tool will lead to further refinements in the ice core chronologies beyond the AICC2012 chronology. For the time being however, we recommend that AICC2012 be used as the preferred chronology for the Vostok, EDC, EDML and TALDICE ice core records, both over the last glacial cycle (this study), and beyond (following Bazin et al., 2013). The ages for NGRIP in AICC2012 are virtually identical to those of GICC05 for the last 60.2 ka, whereas the ages beyond are independent of those in GICC05modelext (as in the construction of AICC2012, the GICC05modelext was included only via the background scenarios and not as age markers). As such, where issues of phasing between Antarctic records included in AICC2012 and NGRIP are involved, the NGRIP ages in AICC2012 should therefore be taken to avoid introducing false offsets. However for issues involving only Greenland ice cores, there is not yet a strong basis to recommend superseding GICC05modelext as the recommended age scale for Greenland ice cores.

We compare a variety of methods for estimating the gas/ice depth offset (Δdepth) at EPICA Dome C (EDC, East Antarctica). (1) Purely based on modelling efforts, Δdepth can be estimated combining a firn densification with an ice flow model. (2) The diffusive column height can be estimated from δ15N and converted to Δdepth using an ice flow model and assumptions about past average firn density and thickness of the convective zone. (3) Ice and gas synchronisation of the EDC ice core to the GRIP, EDML and TALDICE ice cores shifts the ice/gas offset problem into higher accumulation ice cores where it can be more accurately evaluated. (4) Finally, the bipolar seesaw hypothesis allows us to synchronise the ice isotopic record with the gas CH4 record, the later being taken as a proxy of Greenland temperature. The general agreement of method 4 with methods 2 and 3 confirms that the bipolar seesaw antiphase happened during the last 140 kyr. Applying method 4 to the deeper section of the EDC core confirms that the ice flow is complex and can help to improve our reconstruction of the thinning function and thus, of the EDC age scale. We confirm that method 1 overestimates the glacial Δdepth at EDC and we suggest that it is due to an overestimation of the glacial lock-in depth (LID) by the firn densification model. In contrast, we find that method 1 very likely underestimates Δdepth during Termination II, due either to an underestimated thinning function or to an underestimated LID. Finally, method 2 gives estimates within a few metres of methods 3 and 4 during the last deglacial warming, suggesting that the convective zone at Dome C cannot have been very large at this time, if it existed at all.

This study aims at refining the synchronisation between the EPICA Dome C (EDC) and Vostok ice cores in the time interval 0–145 kyr BP by using the volcanic signatures. 102 common volcanic events were identified by using continuous electrical conductivity (ECM), di-electrical profiling (DEP) and sulfate measurements while trying to minimize the distortion of the glaciological chronologies. This is an update and a continuation of previous works performed over the 0–45 kyr interval that provided 56 tie points to the ice core chronologies (Udisti et al., 2004). This synchronisation will serve to establish Antarctic Ice Core Chronology 2012, the next synchronised Antarctic dating. A change of slope in the EDC-depth/Vostok-depth diagram is probably related to a change of accumulation regime as well as to a change of ice thickness upstream of the Lake Vostok, but we did not invoke any significant temporal change of surface accumulation at EDC relative to Vostok. No significant phase difference is detected between the EDC and Vostok isotopic records, but depth shifts between the Vostok 3G and 5G ice cores prevent from looking at this problem accurately. Three possible candidates for the Toba volcanic super-eruption ~73 kyr ago are suggested in the Vostok and EDC volcanic records. Neither the ECM, DEP nor the sulfate fingerprints for these 3 events are significantly larger than many others in the records.

The nanoscale spreading of a cationic polymer lubricant (CPL) film consisting of polydimethylsiloxane with quaternary ammonium salt side chains on a SiO2surface was studied with the disjoining pressure measurements using atomic force microscopy. CPL shows a monotonic decrease in disjoining pressure as the film thickness increases from 1.3 to 4.5 nm, which suggests stable spreading in this thickness range. Comparing the spreading rates calculated from disjoining pressure and the viscosity of CLP to the self-healing time after tribo-contacts revealed that the ionic form may not be the main mobile species. The X-ray photoelectron spectroscopy analysis found that the CPL film on SiO2has about 30% of the quaternary ammonium salts (cationic groups) reduced to tertiary amines (neutral groups). The reduced CPL polymer has much lower viscosity than the original CPL polymer and yields a spreading rate consistent with that measured at the macroscale. Thus, the mobile component in the CPL/SiO2film responsible for self-healing is concluded to be the reduced tertiary amine components of CPL. [ABSTRACT FROM AUTHOR]

Plant membrane transporters controlling metabolite distribution contribute key agronomic traits 1-6 . To eliminate anti-nutritional factors in edible parts of crops, the mutation of importers can block the accumulation of these factors in sink tissues 7 . However, this often results in a substantially altered distribution pattern within the plant 8-12 , whereas engineering of exporters may prevent such changes in distribution. In brassicaceous oilseed crops, anti-nutritional glucosinolate defence compounds are translocated to the seeds. However, the molecular targets for export engineering of glucosinolates remain unclear. Here we identify and characterize members of the USUALLY MULTIPLE AMINO ACIDS MOVE IN AND OUT TRANSPORTER (UMAMIT) family-UMAMIT29, UMAMIT30 and UMAMIT31-in Arabidopsis thaliana as glucosinolate exporters with a uniport mechanism. Loss-of-function umamit29 umamit30 umamit31 triple mutants have a very low level of seed glucosinolates, demonstrating a key role for these transporters in translocating glucosinolates into seeds. We propose a model in which the UMAMIT uniporters facilitate glucosinolate efflux from biosynthetic cells along the electrochemical gradient into the apoplast, where the high-affinity H + -coupled glucosinolate importers GLUCOSINOLATE TRANSPORTERS (GTRs) load them into the phloem for translocation to the seeds. Our findings validate the theory that two differently energized transporter types are required for cellular nutrient homeostasis 13 . The UMAMIT exporters are new molecular targets to improve nutritional value of seeds of brassicaceous oilseed crops without altering the distribution of the defence compounds in the whole plant., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The problem of soil degradation has accentuated over recent decades. Aspects related to soil erosion and its relation to changes in land use as well as anthropogenic influence constitute a topic of great interest. The current study is focused on a soil erosion assessment in relation to land use activities in the Pănăzii Lake catchment area. Fallout radionuclides were used to provide information on soil erosion as well as redistribution rates and patterns. Variations in the sedimentation rate of the lake were also investigated as these reflect periods in which massive erosion events occurred in the lake catchment area. The novelty of this study is the construction of a timescale with regard to the soil erosion events to better understand the relationship between soil erosion and land use activities. In this study, 10 soil profiles and one sediment core from the lake were taken. Soil parameters were determined for each sample. The activities of 210Pb, 137Cs and 226Ra were measured by gamma spectroscopy. For low 210Pb activities, measurements via 210Po using an alpha spectrometer were performed. Soil erosion rates were determined by the 137Cs method and the sedimentation rate calculated by the Constant Rate of Supply (CRS) model. A soil erosion rate of 13.5 t·ha-1·yr-1 was obtained. Three distinct periods could be observed in the evolution of the sedimentation rate. For the first period, between 1880 and 1958, the average deposition rate was 9.2 tons/year, followed by a high deposition period (1960-1991) of 29.6 tons/year and a third period, consisting of the last 30 years, during which the sedimentation rate was 15.7 tons/year. These sedimentation rates fluctuated depending on the main land use activity, which can also be seen in the soil erosion rates that had almost doubled by the time agricultural activities were performed in the area., Competing Interests: The authors have declared that no competing interests exist.

Fruit taste is determined by sugars, acids and in some species, bitter chemicals. Attraction of seed-dispersing organisms in nature and breeding for consumer preferences requires reduced fruit bitterness. A key metabolic shift during ripening prevents tomato fruit bitterness by eliminating α-tomatine, a renowned defence-associated Solanum alkaloid. Here, we combined fine mapping with information from 150 resequenced genomes and genotyping a 650-tomato core collection to identify nine bitter-tasting accessions including the 'high tomatine' Peruvian landraces reported in the literature. These 'bitter' accessions contain a deletion in GORKY, a nitrate/peptide family transporter mediating α-tomatine subcellular localization during fruit ripening. GORKY exports α-tomatine and its derivatives from the vacuole to the cytosol and this facilitates the conversion of the entire α-tomatine pool to non-bitter forms, rendering the fruit palatable. Hence, GORKY activity was a notable innovation in the process of tomato fruit domestication and breeding.

The advent of metal processing was one of the key technological evolutions presaging the development of modern society. However, the interplay between metal use and the long-term changes it induced in the development and functioning of past societies remains unclear. We present a compilation of global records of anthropogenic atmospheric lead (Pb) spanning the last 4000 years, an effective indirect proxy for reliably assessing Pb emissions directly linked to human activities. Separating this global Pb pollution signal into regionally representative clusters allows identification of regional differences in pollution output that reflect technological innovations, market demands, or demise of various human cultures for last 4000 years. Our European reconstruction traces well periods of intensive metal production such as the Roman and Medieval periods, in contrast to clusters from the Americas, which show low levels of atmospheric Pb until the Industrial Revolution. Further investigation of the European synthesis results displays clear regional variation in the timing and extent of past development of polluting activities. This indicates the challenges of using individual reconstructions to infer regional or global development in Pb output and related pollution.

A multiproxy approach including chironomid, diatom, pollen and geochemical analyses was applied on short gravitational cores retrieved from an alpine lake (Lacul Bâlea) in the Southern Carpathians (Romania) to unveil how this lake responded to natural and anthropogenic forcing over the past 500 years. On the basis of chironomid and diatom assemblage changes, and supported by sediment chemical data and historical information, we distinguished two main phases in lake evolution. Before 1926 the lake was dominated by chironomids belonging to Micropsectra insignilobus-type and benthic diatoms suggesting well-oxygenated oligotrophic environment with only small-scale disturbance. We considered this state as the lake's safe operational space. After 1926 significant changes occurred: Tanytarsus lugens-type and T. mendax-type chironomids took over dominance and collector filterers increased until 1970 pointing to an increase in available nutrients. The diatom community showed the most pronounced change between 1950 and 1992 when planktonic diatoms increased. The highest trophic level was reconstructed between 1970 and 1992, while the indicator species of increasing nutrient availability, Asterionella formosa spread from 1982 and decreased rapidly at 1992. Statistical analyses evidenced that the main driver of the diatom community change was atmospheric reactive nitrogen (Nr) fertilization that drastically moved the community towards planktonic diatom dominance from 1950. The transformation of the chironomid community was primarily driven by summer mean temperature increase that also changed the dominant feeding guild from collector gatherers to collector filterers. Our results overall suggest that the speed of ecosystem reorganisation showed an unprecedented increase over the last 100 years; biological systems in many cases underwent threshold type changes, while several system components displayed non-hysteretic change between alternating community composition. We conclude that Lake Bâlea is outside of its safe operating space today. The main trigger of changes since 1926 was climate change and human impact acting synergically., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Schizophrenia (SCH) and autism spectrum disorder (ASD) share several common aetiological and symptomatic features suggesting they may be included in a common spectrum. For example, recent results suggest that excitatory/inhibitory imbalance is relevant in the etiology of SCH and ASD. Numerous studies have investigated this imbalance in regions like the ventromedial and dorsolateral prefrontal cortex (DLPFC). However, relatively little is known about neuroanatomical changes that could reduce inhibition in subcortical structures, such as the caudate nucleus (CN), in neuropsychiatric disorders. We recently showed a significant decrease in calretinin-immunopositive (CR-ip) interneuronal density in the CN of patients with ASD without significant change in the density of neuropeptide Y-immunopositive (NPY-ip) neurons. These subtypes together constitute more than 50% of caudate interneurons and are likely necessary for maintaining excitatory/inhibitory balance. Consequently, and since SCH and ASD share characteristic features, here we tested the hypothesis, that the density of CR-ip neurons in the CN is decreased in patients with SCH. We used immunohistochemistry and qPCR for CR and NPY in six patients with schizophrenia and six control subjects. As expected, small, medium and large CR-ip interneurons were detected in the CN. We found a 38% decrease in the density of all CR-ip interneurons ( P < 0.01) that was driven by the loss of the small CR-ip interneurons ( P < 0.01) in patients with SCH. The densities of the large CR-ip and of the NPY-ip interneurons were not significantly altered. The lower density detected could have been due to inflammation-induced degeneration. However, the state of microglial activation assessed by quantification of ionized calcium-binding adapter molecule 1 (Iba1)- and transmembrane protein 119 (TMEM119)-immunopositive cells showed no significant difference between patients with SCH and controls. Our results warrant further studies focussing on the role of CR-ip neurons and on the striatum being a possible hub for information selection and regulation of associative cortical fields whose function have been altered in SCH., (Copyright © 2020 Adorjan, Sun, Feher, Tyler, Veres, Chance and Szele.)

Recent decades have been marked by unprecendented environmental changes which threaten the integrity of freshwater systems and their ecological value. Although most of these changes can be attributed to human activities, disentagling natural and anthropogenic drivers remains a challenge. In this study, surface sediments from Lake Ighiel, a mid-altitude site in the Carpathian Mts (Romania) were investigated following high-resolution sedimentological, geochemical, environmental magnetic and diatom analyses supported by historical cartographic and documentary evidence. Our results suggest that between 1920 and 1960 the study area experienced no significant anthropogenic impact. An excellent correspondence is observed between lake proxy responses (e.g., growth of submerged macrophytes, high detrital input, shifts in diatom assemblages) and parameters tracking natural hydroclimate variability (e.g., temperature, NAO). This highlights a dominant natural hydroclimatic control on the lacustrine system. From 1960 however, the depositional regime shifted markedly from laminated to homogenous clays; since then geochemical and magnetic data document a trend of significant (and on-going) subsurface erosion across the catchment. This is paralleled by a shift in lake ecosystem conditions denoting a strong response to an intensified anthropogenic impact, mainly through forestry. An increase in detrital input and marked changes in the diatom community are observed over the last three decades, alongside accelerated sedimentation rates following enhanced grazing and deforestation in the catchment. Recent shifts in diatom assemblages may also reflect forcing from atmospheric nitrogen (N) deposition, a key recent drive of diatom community turnover in mountain lakes. In general, enhanced human pressure alongside intermittent hydroclimate forcing drastically altered the landscape around Lake Ighiel and thus, the sedimentation regime and the ecosystem's health. However, paleoenvironmental signals tracking natural hydroclimate variability are also clearly discernible in the proxy data. Our work illustrates the complex link between the drivers of catchment-scale impacts on one hand, and lake proxy responses on the other, highlighting the importance of an integrated historical and palaeolimnological approach to better assess lake system changes., Competing Interests: The authors have declared that no competing interests exist.

The loess-palaeosol sequence of Batajnica (Vojvodina region, Serbia) is considered as one of the most complete and thickest terrestrial palaeoclimate archives for the Middle and Late Pleistocene. In order to achieve a numerical chronology for this profile, four sets of ages were obtained on 18 individual samples. Equivalent doses were determined using the SAR protocol on fine (4-11 μm) and coarse (63-90 μm) quartz fractions, as well as on polymineral fine grains by using two elevated temperature infrared stimulation methods, pIRIR 290 and pIRIR 225 . We show that the upper age limit of coarse quartz OSL and polymineral pIRIR 290 and pIRIR 225 techniques is restricted to the Last Glacial/Interglacial cycle due to the field saturation of the natural signals. Luminescence ages on coarse quartz, pIRIR 225 and pIRIR 290 polymineral fine grains are in general agreement. Fine quartz ages are systematically lower than the coarse quartz and pIRIR ages, the degree of underestimation increasing with age. Comparison between natural and laboratory dose response curves indicate the age range over which each protocol provides reliable ages. For fine and coarse quartz, the natural and laboratory dose response curves overlap up to ~150 and ~250 Gy, respectively, suggesting that the SAR protocol provides reliable ages up to c . 50 ka on fine quartz and c.  100 ka on coarse quartz. Using the pIRIR 225 and pIRIR 290 protocols, equivalent doses up to ~400 Gy can be determined, beyond which in the case of the former the natural dose response curve slightly overestimates the laboratory dose response curve. Our results suggest that the choice of the mineral and luminescence technique to be used for dating loess sediments should take into consideration the reported limited reliability., (© 2020 The Authors. Boreas published by John Wiley & Sons Ltd on behalf of The Boreas Collegium.)

Millennial-scale palaeoclimate variability has been documented in various terrestrial and marine palaeoclimate proxy records throughout the Northern Hemisphere for the last glacial cycle. Its clear expression and rapid shifts between different states of climate (Greenland Interstadials and Stadials) represents a correlation tool beyond the resolution of e.g. luminescence dating, especially relevant for terrestrial deposits. Usually, comparison of terrestrial proxy datasets and the Greenland ice cores indicates a complex expression of millennial-scale climate variability as recorded in terrestrial geoarchives including loess. Loess is the most widespread terrestrial geoarchive of the Quaternary and especially widespread over Eurasia. However, loess often records a smoothed representation of millennial-scale variability without all fidelity when compared to the Greenland data, this being a relevant limiting feature in integrating loess with other palaeoclimate records. To better understand the loess proxy-response to millennial-scale climate variability, we simulate a proxy signal smoothing by natural processes through application of low-pass filters of δ 18 O data from Greenland, a high-resolution palaeoclimate reference record, alongside speleothem isotope records from the Black Sea-Mediterranean region. We show that low-pass filters represent rather simple models for better constraining the expression of millennial-scale climate variability in low sedimentation environments, and in sediments where proxy-response signals are most likely affected by natural smoothing (by e.g. bioturbation). Interestingly, smoothed datasets from Greenland and the Black Sea-Mediterranean region are most similar in the last ~15 ka and between ~50-30 ka. Between ~30-15 ka, roughly corresponding to the Last Glacial Maximum and the deglaciation, the records show dissimilarities, challenging the construction of robust correlative time-scales in this age range. From our analysis it becomes apparent that patterns of palaeoclimate signals in loess-palaeosol sequences often might be better explained by smoothed Greenland reference data than the original high-resolution Greenland dataset, or other reference data. This opens the possibility to better assess the temporal resolution and palaeoclimate potential of loess-palaeosol sequences in recording supra-regional climate patterns, as well as to securely integrate loess with other chronologically better-resolved palaeoclimate records.

The occurrence of heavy rainfall events is expected to undergo significant changes under increasing anthropogenic forcing. South-eastern Europe is reacting rapidly to such changes, therefore understanding and forecasting of precipitation variability is vital to better comprehending environmental changes in this area. Here we present a sub-decadal reconstruction of enhanced rainfall events for the past 2000 years from the Southern Carpathians, Romania using peat geochemistry. Five clear periods of enhanced rainfall are identified at 125-250, 600-900, 1050-1300, 1400-1575 and 1725-1980 CE. Significant runoff is observed during the second half of the Medieval Warm Period, whilst the Little Ice Age was characterised by significant variability. The North Atlantic Oscillation appears to be the main control on regional precipitation, but changes in solar irradiance also seem to play a significant role, together with the Siberian High. Comparison of the data presented here with model outputs confirms the ability of models to predict general trends, and major shifts, but highlights the complexity of the region's hydrological history.

Two speleothem stable isotope records from East-Central Europe demonstrate that Greenland Stadial 12 (GS12) and GS10-at 44.3-43.3 and 40.8-40.2 ka-were prominent intervals of cold and arid conditions. GS12, GS11, and GS10 are coeval with a regional pattern of culturally (near-)sterile layers within Europe's diachronous archeologic transition from Neanderthals to modern human Aurignacian. Sterile layers coeval with GS12 precede the Aurignacian throughout the middle and upper Danube region. In some records from the northern Iberian Peninsula, such layers are coeval with GS11 and separate the Châtelperronian from the Aurignacian. Sterile layers preceding the Aurignacian in the remaining Châtelperronian domain are coeval with GS10 and the previously reported 40.0- to 40.8-ka cal BP [calendar years before present (1950)] time range of Neanderthals' disappearance from most of Europe. This suggests that ecologic stress during stadial expansion of steppe landscape caused a diachronous pattern of depopulation of Neanderthals, which facilitated repopulation by modern humans who appear to have been better adapted to this environment. Consecutive depopulation-repopulation cycles during severe stadials of the middle pleniglacial may principally explain the repeated replacement of Europe's population and its genetic composition., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

The Balkans are considered the birthplace of mineral resource exploitation and metalworking in Europe. However, since knowledge of the timing and extent of metallurgy in southeastern Europe is largely constrained by discontinuous archaeological findings, the long-term environmental impact of past mineral resource exploitation is not fully understood. Here, we present a high-resolution and continuous geochemical record from a peat bog in western Serbia, providing a clear indication of the extent and magnitude of environmental pollution in this region, and a context in which to place archaeological findings. We observe initial evidence of anthropogenic lead (Pb) pollution during the earliest part of the Bronze Age [∼3,600 years before Common Era (BCE)], the earliest such evidence documented in European environmental records. A steady, almost linear increase in Pb concentration after 600 BCE, until ∼1,600 CE is observed, documenting the development in both sophistication and extent of southeastern European metallurgical activity throughout Antiquity and the medieval period. This provides an alternative view on the history of mineral exploitation in Europe, with metal-related pollution not ceasing at the fall of the western Roman Empire, as was the case in western Europe. Further comparison with other Pb pollution records indicates the amount of Pb deposited in the Balkans during the medieval period was, if not greater, at least similar to records located close to western European mining regions, suggestive of the key role the Balkans have played in mineral resource exploitation in Europe over the last 5,600 years., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Lead (Pb) isotopes provide valuable insights into the origin of Pb within a sample, typically allowing for reliable fingerprinting of their source. This is useful for a variety of applications, from tracing sources of pollution-related Pb, to the origins of Pb in archaeological artefacts. However, current approaches investigate source proportions via graphical means, or simple mixing models. As such, an approach, which quantitatively assesses source proportions and fingerprints the signature of analysed Pb, especially for larger numbers of sources, would be valuable. Here we use an advanced Bayesian isotope mixing model for three such applications: tracing dust sources in pre-anthropogenic environmental samples, tracking changing ore exploitation during the Roman period, and identifying the source of Pb in a Roman-age mining artefact. These examples indicate this approach can understand changing Pb sources deposited during both pre-anthropogenic times, when natural cycling of Pb dominated, and the Roman period, one marked by significant anthropogenic pollution. Our archaeometric investigation indicates clear input of Pb from Romanian ores previously speculated, but not proven, to have been the Pb source. Our approach can be applied to a range of disciplines, providing a new method for robustly tracing sources of Pb observed within a variety of environments.

Understanding the past dynamics of large-scale atmospheric systems is crucial for our knowledge of the palaeoclimate conditions in Europe. Southeastern Europe currently lies at the border between Atlantic, Mediterranean, and continental climate zones. Past changes in the relative influence of associated atmospheric systems must have been recorded in the region's palaeoarchives. By comparing high-resolution grain-size, environmental magnetic and geochemical data from two loess-palaeosol sequences in the Lower Danube Basin with other Eurasian palaeorecords, we reconstructed past climatic patterns over Southeastern Europe and the related interaction of the prevailing large-scale circulation modes over Europe, especially during late Marine Isotope Stage 3 (40,000-27,000 years ago). We demonstrate that during this time interval, the intensification of the Siberian High had a crucial influence on European climate causing the more continental conditions over major parts of Europe, and a southwards shift of the Westerlies. Such a climatic and environmental change, combined with the Campanian Ignimbrite/Y-5 volcanic eruption, may have driven the Anatomically Modern Human dispersal towards Central and Western Europe, pointing to a corridor over the Eastern European Plain as an important pathway in their dispersal.

Background and Aims: Ductular reaction is a standard component of fibrotic liver tissue but its function is largely unknown. It is supposed to interact with the matrix producing myofibroblasts and compensate the declining regenerative capacity of hepatocytes. The relationship between the extent of fibrosis-ductular reaction, proliferative activity of hepatocytes and ductular reaction were studied sequentially in experimental hepatic fibrosis models., Methods: Liver fibrosis/cirrhosis was induced in wild type and TGFβ overproducing transgenic mice by carbon tetrachloride and thioacetamide administration. The effect of thioacetamide was modulated by treatment with imatinib and erlotinib. The extent of ductular reaction and fibrosis was measured by morphometry following cytokeratin 19 immunofluorescent labeling and Picro Sirius staining respectively. The proliferative activity of hepatocytes and ductular reaction was evaluated by BrdU incorporation. The temporal distribution of the parameters was followed and compared within and between different experimental groups., Results: There was a strong significant correlation between the extent of fibrosis and ductular reaction in each experimental group. Although imatinib and erlotinib temporarily decreased fibrosis this effect later disappeared. We could not observe negative correlation between the proliferation of hepatocytes and ductular reaction in any of the investigated models., Conclusions: The stringent connection between ductular reaction and fibrosis, which cannot be influenced by any of our treatment regimens, suggests that there is a close mutual interaction between them instead of a unidirectional causal relationship. Our results confirm a close connection between DR and fibrogenesis. However, since the two parameters changed together we could not establish a causal relationship and were unable to reveal which was the primary event. The lack of inverse correlation between the proliferation of hepatocytes and ductular reaction questions that ductular reaction can compensate for the failing regenerative activity of hepatocytes. No evidences support the persistent antifibrotic property of imatinib or erlotinib.

Loess-palaeosol sequences are valuable archives of past environmental changes. Although regional palaeoclimatic trends and conditions in Southeastern Europe have been inferred from loess sequences, large scale forcing mechanisms responsible for their formation have yet to be determined. Southeastern Europe is a climatically sensitive region, existing under the strong influence of both Mediterranean and continental climates. Establishment of the spatial and temporal evolution and interaction of these climatic areas is essential to understand the mechanisms of loess formation. Here we present high-resolution grain-size, environmental magnetic, spectrophotometric and geochemical data from the Stalać section in the Central Balkans (Serbia) for the past ~350,000 years. The goal of this study is to determine the influence of the Mediterranean climate during this period. Data show that the Central Balkans were under different atmospheric circulation regimes, especially during Marine Isotope Stages 9 and 7, while continental climate prevailed further north. We observe a general weakening of the Mediterranean climate influence with time. Our data suggest that Marine Isotope Stage 5 was the first interglacial in the Central Balkans that had continental climate characteristics. This prominent shift in climatic conditions resulted in unexpectedly warm and humid conditions during the last glacial.

This study focuses on the determination of (210)Pb and (137)Cs fluxes from different areas in Transylvania, Romania and on the determination of transport and mass balance within the lacustrine system of Red Lake. In order to achieve this, samples were taken from six different locations (Bihor County area, Ighiel area, Red Lake area, Mluha Peatbog, Mohos Peatbog and Zanoaga Rosie Peat bog in the Semenic Mountains) throughout Romania, these being compared to the values of the Danube Delta area. The activity concentrations of the soil samples were measured by gamma spectrometry (HPGe detector) for both (210)Pbtotal, (210)Pbsup ((226)Ra) and (137)Cs, while peat samples were measured by both alpha ((210)Po) spectrometry (PIPS detectors) as well. The mean value for the (210)Pb flux was measured in the Danube Delta region (42±8Bqm(-2) yr(-1)), while the highest was measured in the Semenic Peatbog (227±54Bqm(-2) yr(-1)); the average being 132±8Bqm(-2) yr(-1). In case of (137)Cs the mean was 298±3Bqm(-2) yr(-1), maximum being 1683±15Bqm(-2) yr(-1) in case of Ighiel area and minimum being 32±1Bqm(-2) yr(-1) in the Danube Delta region. In case of the Red Lake, from the total inventory of 410±23Bqm(-2) yr(-1) in the sediments, the loss by outflows is 100±12Bqm(-2) yr(-1), the catchment to lake transfer factor being 0.84%., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Reproducible structural analysis was made on cirrhotic human liver samples in order to reveal potential connections between morphological and laboratory parameters., Material and Methods: Large histological samples were taken from segment VII of 56 cirrhotic livers removed in connection with liver transplantation. Picro Sirius red and immunohistochemically (smooth muscle actin [SMA], cytokeratin 7 [CK7], Ki-67) stained sections were digitalized and morphometric evaluation was performed., Results: The Picro Sirius-stained fibrotic area correlated with the average thickness of the three broadest septa, extent of SMA positivity, alkaline phosphatase (ALP) values and it was lower in the viral hepatitis related cirrhoses than in samples with non-viral etiology. The extent of SMA staining increased with the CK7-positive ductular reaction. The proliferative activity of the hepatocytes correlated positively with the Ki-67 labeling of the ductular cells and inversely with the septum thickness. These data support the potential functional connection among different structural components, for example, myofibroblasts, ductular reaction and fibrogenesis but challenges the widely proposed role of ductular cells in regeneration., Conclusion: Unbiased morphological characterization of cirrhotic livers can provide valuable, clinically relevant information. Similar evaluation of routine core biopsies may increase the significance of this 'Gold Standard' examination.

Transport engineering in bioengineering is aimed at efficient export of the final product to reduce toxicity and feedback inhibition and to increase yield. The ATP-binding cassette (ABC) transporters with their highly diverse substrate specificity and role in cellular efflux are potentially suitable in transport engineering approaches, although their size and high number of introns make them notoriously difficult to clone. Here, we report a novel in planta "exon engineering" strategy for cloning of full-length coding sequence of ABC transporters followed by methods for biochemical characterization of ABC exporters in Xenopus oocytes. Although the Xenopus oocyte expression system is particularly suitable for expression of membrane proteins and powerful in screening for novel transporter activity, only few examples of successful expression of ABC transporter has been reported. This raises the question whether the oocytes system is suitable to express and characterize ABC transporters. Thus we have selected AtABCG25, previously characterized in insect cells as the exporter of commercially valuable abscisic acid-as case study for optimizing of characterization in Xenopus oocytes. The tools provided will hopefully contribute to more successful transport engineering in synthetic biology., (© 2016 Elsevier Inc. All rights reserved.)

The Campanian Ignimbrite (CI) volcanic eruption was the most explosive in Europe in the last 200,000 years. The event coincided with the onset of an extremely cold climatic phase known as Heinrich Event 4 (HE4) approximately 40,000 years ago. Their combined effect may have exacerbated the severity of the climate through positive feedbacks across Europe and possibly globally. The CI event is of particular interest not only to investigate the role of volcanism on climate forcing and palaeoenvironments, but also because its timing coincides with the arrival into Europe of anatomically modern humans, the demise of Neanderthals, and an associated major shift in lithic technology. At this stage, however, the degree of interaction between these factors is poorly known, based on fragmentary and widely dispersed data points. In this study we provide important new data from Eastern Europe which indicate that the magnitude of the CI eruption and impact of associated distal ash (tephra) deposits may have been substantially greater than existing models suggest. The scale of the eruption is modelled by tephra distribution and thickness, supported by local data points. CI ashfall extends as far as the Russian Plain, Eastern Mediterranean and northern Africa. However, modelling input is limited by very few data points in Eastern Europe. Here we investigate an unexpectedly thick CI tephra deposit in the southeast Romanian loess steppe, positively identified using geochemical and geochronological analyses. We establish the tephra as a widespread primary deposit, which blanketed the topography both thickly and rapidly, with potentially catastrophic impacts on local ecosystems. Our discovery not only highlights the need to reassess models for the magnitude of the eruption and its role in climatic transition, but also suggests that it may have substantially influenced hominin population and subsistence dynamics in a region strategic for human migration into Europe.

Application of porphyrins as photosensitizers is based on their light-triggered generation of reactive oxygen species (ROS) that may cause oxidative tissue damage and ultimately kill cells. Cellular membranes are the action grounds of many sensitizers due to their hydrophobic or amphiphilic character as well as the location of many of the targets attacked by ROS. Hence, the binding ability and location of porphyrins in liposomes as simple models of cellular membranes are of outstanding interest. Here we compare mesoporphyrin IX dimethyl ester (MPE) and its nonesterified form, mesoporphyrin IX dihydrochloride (MPCl). Monocomponent small unilamellar vesicles formed of various saturated phosphatidylcholines with incorporated mesoporphyrins were investigated. We determined the binding parameters and the inhomogeneous distribution functions (IDFs) by different fluorescence techniques. We found in general that the binding ability of MPE is considerably greater than that of MPCl. In the case of MPCl, the IDFs suggest that only one of the two binding site types identified earlier for MPE ("site II") exists; the other one ("site I") vanishes while a new one appears ("site III"). We can confirm that "site I" is located between the two lipid layers, "site II" is situated between the hydrocarbon chains, while the location of the novel "site III" is along the outer part of the hydrocarbon chains partially inserted between the lipid head groups.

Binding of photosensitizers to target cells is a crucial step during the photodynamic effect. Sensitizer distribution is a good indication of whether the chemical is a good candidate for perturbing cell membrane integrity. Hence, the photophysical properties of porphyrinoid sensitizers in microheterogeneous systems such as liposomes are of outstanding interest. Here we present a site-selective fluorescence study of liposome systems. Monocomponent, small unilamellar vesicles formed of different phosphatidylcholines with incorporated mesoporphyrin were investigated. The size distribution of liposomes was measured by dynamic light scattering after each step of the experiment. On the basis of fluorescence line narrowing spectra of mesoporphyrin, the inhomogeneous distribution function was determined in order to characterize the photosensitizer location. The dual character of the functions revealed two different locations. Decomposition of the inhomogeneous distribution functions into Gaussians and the analysis of the fit results suggest that one of the locations for mesoporphyrin is between the two lipid layers, and the other one is between the hydrocarbon chains of the lipid molecules.

Background: The skin is repeatedly exposed to solar UV radiation. Long-term photodamage is a consequence of cumulative UV radiation injury. Hence an examination of the repetitive effects of UV exposure is more likely to yield clues to the early alterations that lead to photoaged skin than a single exposure., Objective: We examined the effects of repetitive low-dose UV irradiation on human skin with the aim of identifying UVA-induced effects that may have a different wavelength dependence than acute erythema., Methods: Areas on the lower part of the back were each exposed to a suberythemal dose (0.5 minimal erythema dose [MED]) of solar simulated radiation (290 to 400 nm) and of UVA (320 to 400 nm) once daily, 5 days a week, for 28 doses. One site was also treated daily with a sunscreen having a sun protection factor of 22 and then exposed to 11 MEDs of solar simulated radiation for the same duration. Epidermal and dermal changes were analyzed and quantified by histochemical stains in combination with computer-assisted image analysis of tissue sections., Results: At equal 0.5 MED doses, UVA induced greater cumulative changes than solar simulated radiation, as assessed by development of a greater cumulative erythema response in the first week of treatment, the presence of epidermal hyperplasia and stratum corneum thickening, depletion of Langerhans cells, dermal inflammatory infiltrates, and deposition of lysozyme on elastin fibers. These changes were not prevented by the sunscreen. A single short-term dose of UVA did not elicit these changes., Conclusion: These findings suggest that UVA may contribute significantly to long-term actinic damage and that the spectral dependence for cumulative damage does not parallel the action spectrum for acute injury (erythema) in human beings.

The wavelength dependence for immediate pigment darkening (IPD) was investigated by exposing the midback skin of volunteers to a series of incremental fluences of narrow waveband radiation isolated by band-pass filters in the 310-400 nm region. The threshold IPD fluence for each waveband was determined by visual assessment of the skin responses immediately after each exposure. The action spectrum, constructed from the mean threshold fluences, was broad and extended from 320 nm to 400 nm with a peak at around 340 nm. No IPD could be evoked at 310 nm, even after erythemogenic fluences. The spectrum was similar in each of the three skin types investigated (III, IV, V). The broad nature of the action spectrum within the UVA region suggests that IPD may serve as an alternative endpoint for measuring photoprotection against these wavelengths.