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DNA replication is a complex process tightly regulated to ensure faithful genome duplication, and its perturbation leads to DNA damage and genomic instability. Replication stress is commonly associated with slow and stalled replication forks. Recently, accelerated replication has emerged as a non-canonical form of replication stress. However, the molecular basis underlying fork acceleration is largely unknown. Here, we show that mutated HRAS activation leads to increased topoisomerase 1 (TOP1) expression, causing aberrant replication fork acceleration and DNA damage by decreasing RNA-DNA hybrids or R-loops. In these cells, restoration of TOP1 expression or mild replication inhibition rescues the perturbed replication and reduces DNA damage. Furthermore, TOP1 or RNaseH1 overexpression induces accelerated replication and DNA damage, highlighting the importance of TOP1 equilibrium in regulating R-loop homeostasis to ensure faithful DNA replication and genome integrity. Altogether, our results dissect a mechanism of oncogene-induced DNA damage by aberrant replication fork acceleration.

We develop algorithms to analyze Information and Communication Technologies (ICT) data in order to estimate individuals’ mobility at different spatial scales. Specifically, we apply the algorithms to delineate airport catchment areas in the United Kingdom's Greater London region and to estimate ground access trip times from a very large ICT dataset. The spatial demand is regressed over demographic, socio-economic, airport-specific and ground access modal characteristics in order to determine the drivers of airport demand. Drawing on these insights, we develop a catchment area game inspired by Hotelling that analyzes the potential impact of collaboration between airports and airlines by integrating evidence of consumer behavior with producers’ financial data. We apply the game to a case study of two London airports with overlapping catchment areas for local residents. Our assessment of airline-airport vertical collusion and airport-airport horizontal collusion indicates that the former is beneficial to both producers and passengers. In contrast, whilst horizontal and vertical collusion is the equilibrium outcome in the analytic symmetric case, it is found to be less likely in the asymmetric case and the real-world, data-driven analysis, due to catchment area and cost asymmetries. Thus, such new datasets may enable regulators to overcome the long-standing information asymmetry issue that has yet to be resolved. Combining new data sources with traditional consumer surveys may provide more informed insights into both consumers’ and producers’ actions, which determines the need (or lack thereof) for regulatory intervention in aviation markets.

Multiple and heterogenous Earth observation (EO) platforms are broadly used for a wide array of applications, and the integration of these diverse modalities facilitates better extraction of information than using them individually. The detection capability of the multispectral unmanned aerial vehicle (UAV) and satellite imagery can be significantly improved by fusing with ground hyperspectral data. However, variability in spatial and spectral resolution can affect the efficiency of such dataset's fusion. In this study, to address the modality bias, the input data was projected to a shared latent space using cross-modal generative approaches or guided unsupervised transformation. The proposed adversarial networks and variational encoder-based strategies used bi-directional transformations to model the cross-domain correlation without using cross-domain correspondence. It may be noted that an interpolation-based convolution was adopted instead of the normal convolution for learning the features of the point spectral data (ground spectra). The proposed generative adversarial network-based approach employed dynamic time wrapping based layers along with a cyclic consistency constraint to use the minimal number of unlabeled samples, having cross-domain correlation, to compute a cross-modal generative latent space. The proposed variational encoder-based transformation also addressed the cross-modal resolution differences and limited availability of cross-domain samples by using a mixture of expert-based strategy, cross-domain constraints, and adversarial learning. In addition, the latent space was modelled to be composed of modality independent and modality dependent spaces, thereby further reducing the requirement of training samples and addressing the cross-modality biases. An unsupervised covariance guided transformation was also proposed to transform the labelled samples without using cross-domain correlation prior. The proposed latent space transformation approaches

[EN] A high-temperature solid-state synthesis is a widespread tool for the construction of metal-free materials, owing to its simplicity and scalability. However, no method is currently available for the synthesis of metal-free materials, which enables control over the atomic ratio and spatial organization of several heteroatoms. Here we report a general and large-scale synthesis of phosphorus-nitrogen-carbon (PNC) materials with highly controllable elemental composition and structural, electronic, and thermal stability properties. To do so, we designed four different crystals consisting of melamine and phosphoric acid with different monomers sequences as the starting precursors. The monomer sequence of the crystals is preserved upon calcination (up to 800 degrees C) to an unprecedented degree, which leads to precise control over the composition of the final PNC materials. The latter exhibit a remarkable stability up to 970 degrees C in air, positioning them as sustainable, lightweight supports for catalysts in high-temperature reactions as well as halogen-free fire-retardant materials.

In this chapter, we present an analysis of civic crowdfunding promoted by the Milan Municipality: it is the most systematic experience conducted in Italy thus far and the one that permits to draw some reflections, potentially useful also for other local authorities. The chapter is organised into paragraphs: the first one is an overview of civic crowdfunding in Italy; the second one discusses the crowdfunding initiative promoted by the Milan Municipality and the main elements emerging from the campaigns conducted so far; in the third one, we propose some interpretative hypotheses moving from fieldwork conducted through interviews to some actors involved; finally, the conclusions aim at reconnecting some evidence emerging from the Milan case to the wider international debate on civic crowdfunding as a form of social, economic, and political innovation.

This article investigates early Slavic exegesis and its influence on Slavic languages (and, more broadly, models for transferring Judeo-Christian thought onto the Slavic soil). The investigation is based on an example of a unique phenomenon related to the sacro-secular homonymy in the terminology defining the God of monotheistic religions. Out of all the languages of Christian civilization, only the languages belonging to Slavia Orthodoxa depart from this general pattern. The development of a dichotomy between the forms gospod’ (“lord”) and gospodin” (“master”) is connected with a particular translational exegesis unknown in other early ecclesiastical traditions. This therefore stands as a unique and, at any rate, independent Slavic innovation in the interpretation of the biblical text. This new Slavic dichotomy compensated for the ambiguous polysemy of the underlying Greek term, κύριος (kyrios), and restored a semantic distinction present in the original Biblical Hebrew text. This phenomenon represents one of the not yet completely elucidated and comprehended cases of independent Slavic exegetical thought, which at this early stage manifested itself not so much in the composition of biblical commentaries and theological works as in translational and editorial choices. It is also significant that certain processes in the allocation of meanings depending on the grammatical form, attested already in early Slavic biblical texts, are cognate with analogous processes in contemporary Slavic languages. Moreover, such semantic distinction between related and highly cognate forms has even enriched the modern Slavic languages connected to this tradition, thus creating means of artistic expression that remain impossible in most other languages of Christian civilization. DOI: 10.31168/2305-6754.2019.8.1.2, В статье рассматривается ранняя славянская экзегеза и ее влияние на славянские языки (и шире — модели перенесения иудео-христианского мышления на славянскую почву) на примере уникального феномена профанно-сакральной омонимии терминологии, определяющей Бога монотеистических религий, которая из всех языков христианской цивилизации снимается только в языках, принадлежащих к Slavia Orthodoxa. Развитие дихотомии форм господь и господинъ связано с переводческой экзегезой, неизвестной другим ранним церковным традициям и являющейся уникальной — и во всяком случае, самостоятельной — славянской инновацией в интерпретации библейского текста. Новая славянская дихотомия компенсировала многозначность стоящего за ней греческого термина κύριος и восстанавливала различение значений оригинального еврейского текста Библии. Это один из не вполне выявленных и осмысленных случаев самостоятельной славянской экзегетической мысли, на этом раннем этапе проявлявшейся не столько в сочинении библейских комментариев и богословских трудов, сколько в переводческом и редакторском выборе. Важно также, что некоторые процессы в распределении значений в зависимости от грамматической формы, зафиксированные в ранних славянских библейских текстах, сходны с аналогичными процессами в современных славянских языках. Кроме того, такое семантическое различение родственных и очень сходных форм обогатило и причастные к этой традиции современные славянские языки, создав средства художественного выражения, невозможные в большинстве других языков христианской цивилизации. DOI: 10.31168/2305-6754.2019.8.1.2

BACKGROUND Empirical evidence showing higher survivorship in urban areas of sub-Saharan Africa (SSA) supports a theory of rural disadvantage. Yet this evidence mostly builds on infant or child mortality. There is practically no empirical evidence comparing adult mortality levels across urban and rural sectors. OBJECTIVE This study explores adult mortality differences by urban–rural residence across SSA for men and women. It considers whether existing differences across sectors vary over the course of development. METHODS The indirect orphanhood method is applied to 90 Demographic and Health Survey (DHS) datasets from 30 countries between 1991 and 2014. Conditional probabilities of dying between ages 15 and 60 (45q15) are separately estimated for rural and urban populations. RESULTS Based on country averages over all time periods, the mean 45q15 is 0.274 and 0.265 among adult women and 0.307 and 0.292 among adult men in urban and rural populations, respectively. The average urban to rural probability of dying ratio from the most recent data between 2000 and 2010 is 1.08 for females and 1.11 for males in SSA as a whole, indicating an urban penalty. Multiple checks highlight the robustness of our findings to methodological limitations inherent in the method. Multivariate regression models suggest that as countries develop, excess adult mortality is likely to shift from the urban to the rural sector. CONTRIBUTION We provide evidence that, unlike child mortality, adult mortality remains higher in the urban sector for many countries and for SSA as a whole. This finding has policy implications regarding the spatial provision of health services. Urban poor should be given more attention.

Population age structures act both to support and constrain key aspects of development, ranging from demographic dividends to civil violence. Despite recognition of the crucial role played by national age and sex structures, the rural/urban perspective remains sorely neglected. This study explores how differential rural/urban natural increase, interacting with rural-to-urban migration, creates profound gaps in population age and sex structures across sectors in Sub-Saharan Africa. We calculate sector-specific dependency and sex ratios using United Nations data from 45 Sub-Saharan African countries between 1980 and 2015 to probe the extent of the rural/urban age and sex structure gaps. Results indicate that these gaps are predictable by stage of demographic transition. Rural-to-urban migration of young adults plays an important role in explaining the gaps between the sectors. Our results highlight the value of accounting for local age and sex structures to better prepare for the consequences of demographic shifts in Sub-Saharan Africa.

Ephemeral rivers in dryland regions exhibit a high interannual variability of streamflow regime, mainly dominated by floods. In these environments, floods are a water resource and a potential hazard with important socioeconomic implications. The Fish River (86,600 km2) is the largest ephemeral stream in Namibia and, recently, also the focus of new development plans, including construction of the largest dam in Namibia. The hydrological analysis to support decisions implies large uncertainties owing to spatial-limited and short hydrological records (since 1962). Here we investigate the current and past patterns of extreme floods combining instrumental, historical, and palaeoflood records. Palaeoflood studies were performed at two reaches with preserved sedimentary evidence: at the upper sector (Vogelkranz) upstream of Hardap Dam (~13% catchment area) and in the lower part of the river, in the Fish River Canyon National Park (70% catchment area). In the Hardap reach, the palaeoflood record identified at least eight large floods during the last 350 years, with the largest flood reaching a minimum discharge of 4800 m3 s−1 (150-year return period). In the Fish River Canyon reach, the sedimentary record shows at least 12 large floods over the last 400 years, the largest with an estimated minimum discharge of 8700 m3 s−1. The elevation of alluvial surfaces without flood evidence provided an upper bound for flood stages, associated with discharges of 6400 m3 s−1 and 16,140 m3 s−1 for the upper and mid-lower Fish River respectively. In the upper reach, the flood frequency analysis (FFA) combining systematic and palaeoflood data provided lower discharges (~25%) of the flood quantiles than the ones using only systematic data sets. In the Fish River Canyon reach, incorporation of the palaeoflood data into the FFA results in slightly higher values in the magnitude of the higher flood quantiles (~4–7%). The FFA analysis using an upper limited lognormal distribution function (LN4)

info:eu-repo/semantics/nonPublished

The effects of free and bound water on the dielectric properties of rnicroemulsions prepared with the non-ionic surfactant Brij 97 were investigated. For the calculation of the relative amounts of free and bound water, a simple multi-layered dielectric model was applied. The model considers the microemulsion as a sum of three separate layers consisting of a 'dry' microemulsion, free water and bound water, respectively. The method is based on dielectric measurements of microemulsions at a frequency for which the dielectric permittivity and the dielectric losses for bound and free water have significantly different magnitudes. The dielectric contribution of free water to the relaxation spectrum of the microemulsion can be obtained, allowing both fractions be calculated. In contrast to the traditional procedures used for calculation of bound water from the relaxation spectrum, this method does not involve analyses of overlapping relaxation processes.