Every country in the world has been affected by climate change. Global warming is considered a structural handicap for developed economies as well as developing economies. All the scientists have agreed that global warming can lower the pace of their growth and it can disrupt its financial stability. For some countries, this phenomenon can even worsen their financial instabilities. For these reasons, scientific research has been directed towards very advanced empirical studies linking the climate cycle with the economic cycle and these have been noticed by the development of the Integrated Assessment Models (IAM). This kind of model is considered as a macroeconomic model of climate change but in our case, we introduce this module in the Dynamic Stochastic General Equilibrium Model applied for the Tunisian economy. Our paper develops an environmental DSGE (E-DSGE) model whose objective is to try to sensitize political decision-makers as well as Tunisian financial decision-makers, to be more concerned about climate change in their economic policies from an evaluation of the effects of these climatic changes on financial stability in Tunisia. This study finds the negative effect of temperature on the whole of macroeconomic variables which led to the persistence of financial instability in Tunisia.
Background Cholangiocarcinoma (CCA) is still a deadly tumour. Histological and molecular aspects of thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats mimic those of human iCCA. Carcinogenic changes and therapeutic vulnerabilities in CCA may be captured by molecular investigations in bile, where we performed bile proteomic and metabolomic analyses that help discovery yet unknown pathways relevant to human iCCA. Methods Cholangiocarcinogenesis was induced in rats (TAA) and mice ( Jnk Δhepa + CCl 4 + DEN model). We performed proteomic and metabolomic analyses in bile from control and CCA-bearing rats. Differential expression was validated in rat and human CCAs. Mechanisms were addressed in human CCA cells, including Huh28-KRAS G12D cells. Cell signaling, growth, gene regulation and [U- ¹³ C]-D-glucose-serine fluxomics analyses were performed. In vivo studies were performed in the clinically-relevant iCCA mouse model. Results Pathways related to inflammation, oxidative stress and glucose metabolism were identified by proteomic analysis. Oxidative stress and high amounts of the oncogenesis-supporting amino acids serine and glycine were discovered by metabolomic studies. Most relevant hits were confirmed in rat and human CCAs (TCGA). Activation of interleukin-6 (IL6) and epidermal growth factor receptor (EGFR) pathways, and key genes in cancer-related glucose metabolic reprogramming, were validated in TAA-CCAs. In TAA-CCAs, G9a, an epigenetic pro-tumorigenic writer, was also increased. We show that EGFR signaling and mutant KRAS G12D can both activate IL6 production in CCA cells. Furthermore, phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in serine-glycine pathway, was upregulated in human iCCA correlating with G9a expression. In a G9a activity-dependent manner, KRAS G12D promoted PHGDH expression, glucose flow towards serine synthesis, and increased CCA cell viability. KRAS G12D CAA cells were more sensitive to PHGDH and G9a inhibition than controls. In mouse iCCA, G9a pharmacological targeting reduced PHGDH expression. Conclusions In CCA, we identified new pro-tumorigenic mechanisms: Activation of EGFR signaling or KRAS mutation drives IL6 expression in tumour cells; Glucose metabolism reprogramming in iCCA includes activation of the serine-glycine pathway; Mutant KRAS drives PHGDH expression in a G9a-dependent manner; PHGDH and G9a emerge as therapeutic targets in iCCA.
This work aims at obtaining a numerical approximation to the solution of a two-parameter singularly perturbed convection-diffusion-reaction system of partial differential equations with discontinuous coefficients. This discontinuity, together with small values of the perturbation parameters, causes interior and boundary layers to appear in the solution. To obtain appropriate point-wise accuracy, we have considered a central finite-difference approach in the space variable which is defined on a piecewise uniform Shishkin mesh and an implicit Euler scheme in the temporal variable defined on a uniform mesh. Some computational experiments have been performed, which confirm the theoretical findings.
This paper assesses the feasibility and robustness of an index-based insurance scheme against hydrological droughts under climate change. To this end, we develop a grand ensemble that samples both modeling and scenario uncertainty in the estimation of the insurance risk premium, so to reveal potential unfavorable surprises and minimize regret in the design of the proposed insurance scheme. The grand ensemble combines four mi-croeconomic models and seven GAMLSS models, which are run for three alternative climate change scenarios: stationary climate/no climate change, RCP 2.6, and RCP 8.5. Methods are illustrated with an application to the Cega River Sub-basin (CRS) in central Spain. Results indicate that for a conventional deductible of 30%, the proposed index-based insurance scheme would be actuarially feasible and affordable under all models for the stationary climate scenario (i.e., robust). For climate change scenarios RCP 2.6 and 8.5 and a 30% deductible, the suggested index-based insurance would be actuarially feasible under most models, albeit some outliers point towards potential unfavorable surprises. Lower deductibles decrease feasibility, particularly for deductibles <10%.
To date, not much research has been devoted to analyzing the impact of some corporate governance mechanisms (board diversity and CEO duality) on corporate risk. Consequently, we believe that it is necessary to study such topic in greater depth. The aim of this research is to provide further evidence of the impact that board diversity, specifically board specific skills, board tenure and board cultural diversity, as well as CEO duality, have on corporate risk. Additionally, our study also examines the moderating role of the state‐owned enterprises (SOEs) on the association between the three characteristics of board diversity and corporate risk, and between CEO duality and corporate risk. The theoretical framework used in this research is based on agency theory and resource dependence theory. The findings show that board specific skills and board cultural diversity have a negative effect on corporate risk, while board tenure does not affect it. On the other hand, CEO duality has a negative effect, which is against the prediction of our hypothesis. Our evidence also reveals a negative moderating effect of SOEs on the impact of board specific skills, board tenure and board cultural diversity on corporate risk. Additionally, SOEs do not moderate the negative impact of CEO duality on corporate risk. Our research contributes to past literature on corporate risk by concluding that some corporate governance mechanisms like board specific skills, board cultural diversity and CEO duality lessen it. The moderating role performed by SOEs with the relationship between board specific skills, board culture diversity, board tenure and corporate risk is also a relevant contribution.
Within the installation of a shallow geothermal system, the lack of information on the subsoil frequently leads to errors in the design of the geothermal wellfield. This research presents the application of geophysics, combining 2D and 3D electrical resistivity tomography surveys and the geological information of a certain area for defining the structural distribution of the underground. Processed electrical resistivity data allow elucidating possible geological units and the thermal behavior of the in-depth materials. Two different assumptions (with different locations of the wells) are designed by using the specific geothermal software GES-CAL. Results show, that Case 1 (based on the geophysical results, so avoiding complex areas) allows the reduction of the global drilling length, and hence, the general initial investment of the system (around 20% lower). Meanwhile, Case 2 (without considering the geophysics) is less economically advantageous and could also present technical difficulties during the drilling process, as well as the possible alteration to the normal system operation. The study highlights the benefits of geophysics as an effective approach to characterize the underground and to help to understand its thermal behavior, which is, in turn, crucial for a proper geothermal design.
This study examines the impact of international crude oil prices on quantiles of the distribution of stock market returns in Argentina, Brazil, Chile, and Mexico, from May 1, 2015 to January 15, 2021. For this purpose, quantile and ordinary least squares regression analysis methods were compared, controlling for the effects of autocorrelation, exchange rates, the S&P 500, and the COVID-19 pandemic period. We performed the analyses considering five quantiles associated with different states of stock market performance. The results showed that oil price fluctuations exhibited positive influences on Latin American stock markets, more prominent when oil prices were positive, as well as across all quantiles for the S&P 500 index. However, the exchange rate had a negative impact, except in Argentina. Asymmetric responses were found under negative and positive influences in previous trading sessions, as well for the pandemic period.
Light Steel Frame (LSF) walls are widely used in building structures, used as partition walls and load bearing walls. The LSF is usually protected by layers of homogeneous plates or composite plates, with or without insulation materials in the cavity. This investigation presents the simulation results of composite LSF walls in reduced scale and full scale, based on variable load levels (20 to 80%). The numerical model uses a hybrid model approximation, based on the experimental tests to accurately determine the temperature field. The numerical model is validated with experimental results, at reduced and full scale, both at room temperature and under fire conditions. This modelling technique can follow the thermal and mechanical degradation of the protection layers of the LSF wall and determine the fire rating for load bearing (R) and insulation (I). The fire resistance (R) decreases with the increase of the load level. The insulation ability is also predicted for different protection materials. Relevant conclusions are presented to increase the insulation ability of LSF walls, especially when using non combustible double protection layers. The insulation ability to sustain fire usually increases with the number of studs and with the application of insulation material in the cavity region. The ability to sustain the load under fire also increases with the number of studs, especially for higher load levels. The ability to sustain the load also increases with the number of protection layers, changing from 16% at 20% load level, to 42% at 50% load level. A new proposal is presented for the critical temperature of the LSF, based on the maximum temperature of the LSF during the fire, allowing the calculation of the critical temperature, based on the load level of the specimen. This relation can predict the fire resistance time, based on the preliminary thermal analysis of the specimen. The reduced scale specimens present higher critical temperatures when compared to the full scale specimens, due to the typical failure mode (local modes for the reduced scale and global modes for the large scale).
The theory of convex mapping has a lot of applications in the field of applied mathematics and engineering. The fuzzy Riemann-Liouville fractional integrals are the most significant operator of fractional theory which permits to generalize the classical theory of integrals. This study considers the well-known Hermite-Hadamard type and associated inequalities. To full fill this mileage, some new versions of fuzzy Hermite-Hadamard type and Hermite-Hadamard-Fejér type inequalities for up and down convex fuzzy-number valued mappings have been obtained. Some new related fuzzy Hermite-Hadamard type inequalities are also obtained with the help of product of two up and down convex fuzzy-number valued mappings. Moreover, we have introduced some new important classes of fuzzy numbered valued convexity which are known as lower up and down convex (concave) and, upper up and down convex (concave) fuzzy numbered valued mappings by applying some mild restrictions on up and down convex (concave) fuzzy numbered valued mappings. By using these definitions, we have acquired many classical and new exceptional cases which can be viewed as applications of the main results. We also present three examples of fuzzy numbered valued convexity to demonstrate the validity of the fuzzy inclusion relations proposed in this paper.
Red Mediterranean Soils developed over carbonate rocks can precipitate pedogenic carbonates at the base of their profiles, forming an evolutionary stage of calcretes. We studied a 0.6 m deep soil profile in Dalmatia (Croatia) where the lowest section of the soil is a calcic horizon formed by diffuse calcite particles and small nodules. These nodules record different events of dissolution and precipitation. Using a 3-month period of soil environmental monitoring, where soil temperature, soil water content, soil bulk electrical conductivity and soil air CO2 were measured, we implemented a thermodynamic model for dissolution and precipitation of calcite in the soil. The simulation shows a stage dominated by calcite dissolution during spring and early summer followed by a stage dominated by calcite precipitation. Soil air CO2 is the main control of the calcite reactions, with concentration of solutes also being of some importance during the stage of calcite precipitation. Soil water content and temperature, both affect soil air CO2. Precipitation events also have high-frequency impact on soil air CO2, but the response is complex. The model enables soil water solutions to be supersaturated in relation to calcite without precipitation of that mineral. Simulated soil water reached variable values of supersaturation in relation to calcite before its precipitation was triggered, suggesting that there is no fixed threshold value for the precipitation of calcite in a particular soil. During the 3-month simulated period, 83% of the calcite dissolved was reprecipitated as pedogenic carbonate. Most of the initially dissolved calcite, was expected to be diffuse pedogenic carbonate particles, although nodules and bedrock at the base of the soil should also have contributed to the solutes dissolved. Therefore, karst landscapes where soils have pedogenic carbonates are expected to record less denudation rates than those regions without calcretes.
The archaeological investigations carried out in the last twenty years in the Lower Valley of the River Güeña (Asturias, central part of northern Spain) have documented different prehistoric sites, particularly with Middle and Upper Palaeolithic occupations. This paper presents the first results of the archaeological excavation carried out in the cave of La Cuevona de Avín. From the systematic study of the biotic and abiotic remains, a total of three occupation phases (Phases 1 to 3) have been determined, dated in the Late Pleistocene. The lithic studies indicate the use of local raw materials (mainly quartzite), but also regional ones (different types of flint) in the whole sequence. Retouched implements are typologically representative only during the Upper Magdalenian (Phase II) and use-wear analysis indicates the manufacture and use of artefacts in situ during this phase. Archaeozoological studies reveal continuity in subsistence strategies throughout the sequence, noting specialization in red deer hunting during the Azilian (Phase I), and more diversified prey in the older phases of the sequence.
The goal of this work is the photogrammetric reconstruction of a rocky outcrop with a panel decorated with palaeolithic engravings of the Siega Verde archaeological site (Salamanca, Spain) using photographs obtained with mobile phone cameras. The engravings present in this panel have been previously studied and published. The main objective of this work is the generation of 3D models by low-cost photogrammetry that allow the diffusion and study of the panel. The processing is approached at different quality levels with different photosets to provide the reconstruction of the complete rocky outcrop, the decorated wall, and the details of the engravings. The reconstruction of the rocky outcrop provides interactive 3D models useful to appreciate the morphology and the context of the engraved wall. The reconstruction of the decorated wall, after referencing, permits measurements with errors in the millimetre range and was used to obtain objective and subjective tracings of the engraved motifs. The highest quality level of photogrammetric processing makes it possible to determine the morphology, direction, and dimensions of the pecks and even depths and widths of the individual pecks.
The aim of this work is to evaluate the ability of terrestrial laser scanning technology to detect the moisture content in timber structures. For this purpose, an extensive experimental campaign was carried out under laboratory conditions. During the campaign, several wood samples were digitised using the Faro Focus 120 phase-shift laser scanner for which a radiometric calibration model is available. The digital level (intensity) of each 3D point cloud was then converted into reflectance values (0–1). These reflectance values were related to the moisture content of samples which was obtained using the oven-drying method and the resistive xylohygrometer device. Finally, a simple methodology based on experimental analytical equations was proposed. The results show that the laser scanner could be a potential non-destructive tool for the diagnosis of wooden construction systems, as it is not only able to detect deformations but also to infer the moisture content of specific areas in wood elements.
Phenolic compounds have attracted scientific interest due to their bioactive properties. Moreover, the environmental awareness has increased considerably and, with it, research into valorisation processes. Food waste is a source of bioactive compounds, however, the most common methods of extracting these compounds were polluting. Recently, the use of natural deep eutectic solvents (NADES) is being studied as a way to achieve a green extraction process. This article reviews the opportunities offered by some underexploited food by-products (potato peels, grape pomace, beetroot and olive leaves) as sources of phenolic compounds and discusses the possible application of NADES for extraction. The literature reviewed concludes that these by-products are a rich source of polyphenols and that natural solvents are a real alternative for their extraction. However, further research is needed to overcome the drawbacks of NADES, as well as to study the feasibility of the application of the extracts in the food industry.
Tree-growth-climate relationships are usually assumed to have a stationary character, i.e., continuous and/or time-independent, along the lifetime of the trees. The fact that non-stationarity, i.e., discontinuous and/or time-variable, is more likely to actually be their general rule, has been often neglected in dendrochronology. Nine silver fir, black pine and Scots pine residual ring-width index chronologies (RWIresidual) and five precipitation- and temperature-derived seasonal climatic variables, covering the 20th century and the beginning of the 21st one, were used in this study. Heat map analyses based on rolling window correlations, using corrected p-values in order to deal with the type I errors (i.e., the multiple testing or comparison problem) and reduce them, were conducted to evaluate the evolution and stability of tree-growth-climate relationships along the lifetime of the trees, i.e., their stationary and/or non-stationary character. The obtained results showed that stationary tree-growth-climate relationships were well conserved within trees belonging to a given genus: positive effects, both at young and mature stages, of Twinter (winter temperature) on the Abies trees and of Psprsum(t) (spring-summer precipitation of the current-to-growth year) on the Pinus trees. Non-stationary tree-growth-climate relationships were instead species- and site-dependent and stopped in the 1970s/1980s/1990s. Growth decoupling from seasonal climatic variables was linked in many cases with climatic anomalies but the obtained results did not yield a general rule in this regard. Heat map analyses based on rolling window correlations proved to be a powerful statistical tool in disentangling between the stationary and/or non-stationary character of the tree-growth-climate relationships. Summarizing, this study puts into perspective the critical aspect of looking at the stationary and/or non-stationary character of the tree-growth-climate relationships if we want to better predict the impact of climate change on the future forest tree growth and dynamics based on past tree-growth-climate relationships.
Background: Myelodysplastic syndromes (MDS) with isolated del(5q) represent a subtype defined by WHO with good prognosis. However, several studies have shown that the presence of somatic mutation, such as TP53, might have an impact on prognosis. In addition, recent publications suggest a role for SF3B1 in the poor outcome of some del(5q) MDS patients. Aims: Our aim was to validate the poor prognosis of SF3B1 mutations, present in patients with del(5q) MDS and to identify mutational profiles that could promote AML progression of patients del(5q) MDS. Methods: We performed a retrospective study including MDS patients with both isolated del(5q) and del(5q) with another alteration different from chromosome 7. We included 50 patients and a control group of 123 low-risk MDS patients with normal karyotype. Next-generation sequencing (NGS) data from bone marrow samples were analyzed using an in-house custom panel (>100 myeloid genes). Results: Median age at diagnosis was similar in del(5q) MDS and control group (72.9 and 71.8 years, respectively, p>0.05). The number of mutations per patient was significantly higher in the control group than in del(5q) (a mean of 3.16 against 1.7 for del(5q), p<0.0001). Despite a higher prevalence of somatic mutations in the control group, no differences were found in median overall survival (OS) (64.5 and 60.1 months for del(5q) MDS and control group respectively, p=0.413). However, when analyzing del(5q) patients individually, OS was significantly lower in those patients with either TP53 or SF3B1 mutation (64.5 vs. 28 months median) (p=0.031). Regarding progression to AML, patients with TP53 and/or DNMT3A mutations (n=14) had a shorter time to progression compared to patients without mutations in these genes, with a median of 13.6 months vs. 26.97 months (p=0.004). Median follow-up for these patients was 14.93 (0-170.30) months. Summary: MDS patients with del(5q) have a good prognosis and a higher time to progression to AML compared to other MDS subgroups. However, the mutational profile may modify this evolution. In our study, mutations in SF3B1 and DNMT3A may be involved in OS and transformation to AML (respectively), but a larger cohort of patients is needed to confirm that.
Context: Isolated trisomy 8 is a karyotypic abnormality frequently found in hematological neoplasms. It is found in 10% of myelodysplastic syndromes (MDS) with cytogenetic aberrations. It is classified as an intermediate risk subgroup in MDS IPSS-R (Revised International Prognostic Scoring System) because of the heterogeneous clinical course of the patients. Objective: The aim of this study was to determine whether mutational profile could be useful to improve the risk reclassification of MDS with isolated trisomy 8. Design: In a cohort of 591 MDS patients, we included 38 patients with isolated trisomy 8 confirmed through karyotype and FISH. We carried out next generation sequencing in bone marrow samples of these patients with an in-house custom panel with more than 100 myeloid-related genes. NGS files were processed with our own pipeline. Statistical analysis was performed with SPSS. Results: A total of 102 somatic mutations were found in our cohort. The most frequently mutated genes were TET2, STAG2, ASXL1 and SRSF2. Interestingly, the mutational profile allows the differentiation of two subtypes of isolated trisomy 8: patients with mutations in either SRSF2 or STAG2 (n=16), and those without mutations in these genes (n=22). Both groups presented similar clinical characteristics. However, patients with STAG2 and/or SRSF2 mutations had a shorter time to progression to AML and lower overall survival than patients without these mutations (p<0.05). Surprisingly, the risk for AML progression and the overall survival of patients with STAG2/SRSF2 alterations was similar to those MDS classified as high risk in IPSS-R (p>0.05). Similarly, patients with trisomy 8 without these mutations did not show significant differences in survival and progression to AML when compared to the group of MDS with low IPSS-R risk (p>0.05). Conclusions: This study demonstrates, for the first time, that mutational profile of MDS with isolated trisomy 8 allows these patients to be reclassified into two groups based on the presence or absence of mutations in STAG2 and/or SRSF2. These alterations are clearly associated with an adverse prognosis. Therefore, we suggest the need to study the mutational profile of these patients in order to reclassify them on the prognostic scale.
Platinum-based chemotherapeutic treatment of cancer patients is associated with debilitating adverse effects. Several adverse effects have been well investigated, and can be managed satisfactorily, but chemotherapy-induced peripheral neuropathy (CIPN) remains poorly treated. Our primary aim in this study was to investigate the neuroprotective effect of the immunomodulatory drug rapamycin in the mitigation of cisplatin-induced neurotoxicity. Pain assays were performed in vivo to determine whether rapamycin would prevent or significantly decrease cisplatin-induced neurotoxicity in adult male Balb/c mice. Neuropathic pain induced by both chronic and acute exposure to cisplatin was measured by hot plate assay, cold plate assay, tail-flick test, and plantar test. Rapamycin co-treatment resulted in significant reduction in cisplatin-induced nociceptive-like symptoms. To understand the underlying mechanisms behind rapamycin-mediated neuroprotection, we investigated its effect on certain inflammatory mediators implicated in the propagation of chemotherapy-induced neurotoxicity. Interestingly, cisplatin was found to significantly increase peripheral IL-17A expression and CD8- T cells, which were remarkably reversed by the pre-treatment of mice with rapamycin. In addition, rapamycin reduced the cisplatin-induced neuronal apoptosis marked by decreased neuronal caspase-3 activity. The rapamycin neuroprotective effect was also associated with reversal of the changes in protein expression of p21Cip1, p53, and PUMA. Collectively, rapamycin alleviated some features of cisplatin-induced neurotoxicity in mice and can be further investigated for the treatment of cisplatin-induced peripheral neuropathy.
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