Abstract During pregnancy, several tightly coordinated and regulated processes take place to enable proper fetal development and gestational success. The formation and development of the placenta is ...one of these critical pregnancy events. This organ plays essential roles during gestation, including fetal nourishment, support and protection, gas exchange and production of several hormones and other mediators. Placental hormones are mainly secreted by the syncytiotrophoblast, in a highly and tightly regulated way. These hormones are important for pregnancy establishment and maintenance, exerting autocrine and paracrine effects that regulate decidualization, placental development, angiogenesis, endometrial receptivity, embryo implantation, immunotolerance and fetal development. In addition, because they are released into maternal circulation, the profile of their blood levels throughout pregnancy has been the target of intense research towards finding potential robust and reliable biomarkers to predict and diagnose pregnancy-associated complications. In fact, altered levels of these hormones have been associated with some pathologies, such as chromosomal anomalies or pre-eclampsia. This review proposes to revise and update the main pregnancy-related hormones, addressing their major characteristics, molecular targets, function throughout pregnancy, regulators of their expression and their potential clinical interest.
•A new leaching process based on Cu2+/HCl media for recovering Pd and Rh from spent autocatalytic converters is presented.•Palladium and rhodium were efficiently leached, with attained maximum yields ...of 95% and 86%, respectively.•Temperature, time, and HCl and Cu2+ concentrations were found to be significant factors in the leaching of Pd and Rh.
The recycling of platinum-group metals from wastes such as autocatalytic converters is getting growing attention due to the scarcity of these precious metals and the market pressure originated by increase of demand in current and emerging applications. Hydrometallurgical treatment of such wastes is an alternative way to the most usual pyrometallurgical processes based on smelter operations. This paper focuses on the development of a leaching process using cupric chloride as oxidising agent, in HCl media, for recovery of palladium and rhodium from a spent catalyst. The chloride media allows the adequate conditions for oxidising and solubilising the metals, as demonstrated by equilibrium calculations based on thermodynamic data. The experimental study of the leaching process revealed that Pd solubilisation is clearly easier than that of Rh. The factors temperature, time, and HCl and Cu2+ concentrations were significant regarding Pd and Rh leaching, the latter requiring higher factor values to achieve the same results. Leaching yields of 95% Pd and 86% Rh were achieved under optimised conditions (T=80°C, t=4h, HCl=6M, Cu2+=0.3M).
In 2005 and 2010 the Amazon basin experienced two strong droughts, driven by shifts in the tropical hydrological regime possibly associated with global climate change, as predicted by some global ...models. Tree mortality increased after the 2005 drought, and regional atmospheric inversion modelling showed basin-wide decreases in CO2 uptake in 2010 compared with 2011 (ref. 5). But the response of tropical forest carbon cycling to these droughts is not fully understood and there has been no detailed multi-site investigation in situ. Here we use several years of data from a network of thirteen 1-ha forest plots spread throughout South America, where each component of net primary production (NPP), autotrophic respiration and heterotrophic respiration is measured separately, to develop a better mechanistic understanding of the impact of the 2010 drought on the Amazon forest. We find that total NPP remained constant throughout the drought. However, towards the end of the drought, autotrophic respiration, especially in roots and stems, declined significantly compared with measurements in 2009 made in the absence of drought, with extended decreases in autotrophic respiration in the three driest plots. In the year after the drought, total NPP remained constant but the allocation of carbon shifted towards canopy NPP and away from fine-root NPP. Both leaf-level and plot-level measurements indicate that severe drought suppresses photosynthesis. Scaling these measurements to the entire Amazon basin with rainfall data, we estimate that drought suppressed Amazon-wide photosynthesis in 2010 by 0.38 petagrams of carbon (0.23-0.53 petagrams of carbon). Overall, we find that during this drought, instead of reducing total NPP, trees prioritized growth by reducing autotrophic respiration that was unrelated to growth. This suggests that trees decrease investment in tissue maintenance and defence, in line with eco-evolutionary theories that trees are competitively disadvantaged in the absence of growth. We propose that weakened maintenance and defence investment may, in turn, cause the increase in post-drought tree mortality observed at our plots.
•We study a real-world scheduling problem from the pharmaceutical industry.•We develop a hybrid genetic algorithm equipped with a double encoding scheme.•We compare the proposed approach with other ...metaheuristic techniques.•An experimental validation emphasizes the effectiveness of the proposed approach.
In today’s manufacturing outlook, production planning and scheduling may represent a leading leverage to enhance the competitiveness of firms which aim to address the new challenge coming from emerging markets and globalization. In this paper a real-world parallel machines scheduling problem from the pharmaceutical environment has been tackled. Though in the last decades literature extensively approached such an issue, a set of constraints and compulsory dispositions strongly increase the complexity of the level of the problem in hand; thus, in order to fulfill the firm’s objectives in terms of production rate increase and rapidity of solution, a dedicated hybrid genetic algorithm equipped with a two-stage encoding and a proper local search has been developed. A twofold validation procedure has been adopted for the proposed optimization technique. First, it was compared with a set of meta-heuristic algorithms on the basis of a real-world data set. Once the outperformance of the proposed genetic optimization was demonstrated, a further comparison with a set of empirical schedules, manually performed by the production supervisor, had been carried out.
Targeting replication stress in cancer therapy da Costa, Alexandre André B A; Chowdhury, Dipanjan; Shapiro, Geoffrey I ...
Nature reviews. Drug discovery,
01/2023, Letnik:
22, Številka:
1
Journal Article
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Replication stress is a major cause of genomic instability and a crucial vulnerability of cancer cells. This vulnerability can be therapeutically targeted by inhibiting kinases that coordinate the ...DNA damage response with cell cycle control, including ATR, CHK1, WEE1 and MYT1 checkpoint kinases. In addition, inhibiting the DNA damage response releases DNA fragments into the cytoplasm, eliciting an innate immune response. Therefore, several ATR, CHK1, WEE1 and MYT1 inhibitors are undergoing clinical evaluation as monotherapies or in combination with chemotherapy, polyADP-ribosepolymerase (PARP) inhibitors, or immune checkpoint inhibitors to capitalize on high replication stress, overcome therapeutic resistance and promote effective antitumour immunity. Here, we review current and emerging approaches for targeting replication stress in cancer, from preclinical and biomarker development to clinical trial evaluation.
Since Italian liver allocation policy was last revised (in 2012), relevant critical issues and conceptual advances have emerged, calling for significant improvements. We report the results of a ...national consensus conference process, promoted by the Italian College of Liver Transplant Surgeons (for the Italian Society for Organ Transplantation) and the Italian Association for the Study of the Liver, to review the best indicators for orienting organ allocation policies based on principles of urgency, utility, and transplant benefit in the light of current scientific evidence. MELD exceptions and hepatocellular carcinoma were analyzed to construct a transplantation priority algorithm, given the inequity of a purely MELD‐based system for governing organ allocation. Working groups of transplant surgeons and hepatologists prepared a list of statements for each topic, scoring their quality of evidence and strength of recommendation using the Centers for Disease Control grading system. A jury of Italian transplant surgeons, hepatologists, intensivists, infectious disease specialists, epidemiologists, representatives of patients’ associations and organ‐sharing organizations, transplant coordinators, and ethicists voted on and validated the proposed statements. After carefully reviewing the statements, a critical proposal for revising Italy's current liver allocation policy was prepared jointly by transplant surgeons and hepatologists.
The authors present a critical proposal for the implementation of the current liver allocation policy in Italy developed following the results of a national Consensus Conference process aimed to revise, on the basis of scientific evidence, the best indicators for guiding organ allocation policies in the urgency, utility, and benefit models. See the editorial from Berg on page 2537.
Extracellular vesicles (EVs) are a heterogeneous group of natural particles that are relevant to the treatment of cardiovascular diseases. These endogenous vesicles have certain properties that allow ...them to survive in the extracellular space, bypass biological barriers and deliver their biologically active molecular cargo to recipient cells. Moreover, EVs can be bioengineered to increase their stability, bioactivity, presentation to acceptor cells and capacity for on-target binding at both cell-type-specific and tissue-specific levels. Bioengineering of EVs involves the modification of the donor cell before EV isolation or direct modification of the EV properties after isolation. The therapeutic potential of native EVs and bioengineered EVs has been only minimally explored in the context of cardiovascular diseases. Efforts to harness the therapeutic potential of EVs will require innovative approaches and a comprehensive integration of knowledge gathered from decades of research into molecular-compound delivery. In this Review, we outline the endogenous properties of EVs that make them natural delivery agents as well as the features that can be improved by bioengineering. We also discuss the therapeutic applications of native and bioengineered EVs to cardiovascular diseases and examine the opportunities and challenges that need to be addressed to advance this research area, with an emphasis on clinical translation.
A wide range of microorganisms produce extracellular polymeric substances (EPS), highly hydrated polymers that are mainly composed of polysaccharides, proteins, and DNA. EPS are fundamental for ...microbial life and provide an ideal environment for chemical reactions, nutrient entrapment, and protection against environmental stresses such as salinity and drought. Microbial EPS can enhance the aggregation of soil particles and benefit plants by maintaining the moisture of the environment and trapping nutrients. In addition, EPS have unique characteristics, such as biocompatibility, gelling, and thickening capabilities, with industrial applications. However, despite decades of research on the industrial potential of EPS, only a few polymers are widely used in different areas, especially in agriculture. This review provides an overview of current knowledge on the ecological functions of microbial EPSs and their application in agricultural soils to improve soil particle aggregation, an important factor for soil structure, health, and fertility.
The Total Grain-Size Distribution (TGSD) of tephra deposits is crucial for hazard assessment and provides fundamental insights into eruption dynamics. It controls both the mass distribution within ...the eruptive plume and the sedimentation processes and can provide essential information on the fragmentation mechanisms. TGSD is typically calculated by integrating deposit grain-size at different locations. The result of such integration is affected not only by the number, but also by the spatial distribution and distance from the vent of the sampling sites. In order to evaluate the reliability of TGSDs, we assessed representative sampling distances for pyroclasts of different sizes through dedicated numerical simulations of tephra dispersal. Results reveal that, depending on wind conditions, a representative grain-size distribution of tephra deposits down to ∼100 μm can be obtained by integrating samples collected at distances from less than one tenth up to a few tens of the column height. The statistical properties of TGSDs representative of a range of eruption styles were calculated by fitting the data with a few general distributions given by the sum of two log-normal distributions (bi-Gaussian in Φ-units), the sum of two Weibull distributions, and a generalized log-logistic distribution for the cumulative number distributions. The main parameters of the bi-lognormal fitting correlate with height of the eruptive columns and magma viscosity, allowing general relationships to be used for estimating TGSD generated in a variety of eruptive styles and for different magma compositions. Fitting results of the cumulative number distribution show two different power law trends for coarse and fine fractions of tephra particles, respectively.
Our results shed light on the complex processes that control the size of particles being injected into the atmosphere during volcanic explosive eruptions and represent the first attempt to assess TGSD on the basis of pivotal physical quantities, such as magma viscosity and plume height. Our empirical method can be used to assess the main features of TGSD necessary for numerical simulations aimed to real-time forecasting and long-term hazard assessment when more accurate field-derived TGSDs are not available.
•We analysed tephra total grain-size distributions derived from field data.•The dataset was described using general statistical distributions.•We found statistical parameters correlate with eruption intensity and magma viscosity.•We propose an empirical method to assess tephra total grain-size distributions.
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