Thermoelectric Cooling: The Thomson Effect in Hybrid Two- Stage Thermoelectric Cooler Systems with Different Leg Geometric Shapes

This chapter aims to analyse the performance of hybrid two-stage thermoelectric cooler systems [two-stage thermoelectric cooling devices (TEC)], which are composed of different thermoelectric materials in each stage with different leg geometric shapes. If we consider a temperature gradient inside a two-stage TEC, then, besides Joule heat, also Thomson heat has to be taken into account. We discuss the out-of-equilibrium thermodynamics equations of a one-dimensional model to provide the performance expressions that govern the system. TEC system performance is analysed in function of the Thomson coefficients ratio of both stages. We describe a recent geometric optimization procedure that includes leg geometry parameters such as ratio of cross-sectional area and length of legs for each stage of the two-stage TEC

On the Use of Parametric Wind Models for Wind Wave Modeling under Tropical Cyclones

Wave and wind forces from tropical cyclones are one of the main design parameters of coastal and offshore infrastructure in tropical areas. The estimation of ocean waves parameters in the design of structures in tropical areas is difficult due to the complexity of wind fields associated with tropical cyclones. The use of numerical wave models, forced with parametric wind fields, is a common practice within the climatic characterization of extreme events. However, there is currently no consensus on the selection of parametric models for wave prediction due to the lack of a rigorous assessment of different models. In this study, six well-known parametric wind models were tested, compared, and applied in the Gulf of Mexico and the Caribbean Sea. Therefore, the evaluation and comparison of the resulting wind and wave fields are presented, showing that a particular model may best represent a specific event, but, when dealing with a large number of events, the choice of a particular parametric wind model or a combination of them does not guarantee greater accurac

The metasomatic enrichment of Li in psammopelitic units at San Jose-Valdeflorez, Central Iberian Zone, Spain: a new type of lithium deposit

A new type of Li mineralisation in hard rock has been found to occur in the Valdefórez area (Cáceres, Spain), where there is 111.3 Mt of resources and a mean value of 0.61 wt% of Li2O. Lithium is mainly held by very fne-grained micas, important constituents of Ordovician psammopelitic rocks belonging to the Palaeozoic metasedimentary sequence of the Cáceres syncline. The mineralised zone has an elliptical surface shape with a dimension of~ 700 × 500 m. Lithium-bearing rocks show a characteristic layered appearance, in which light grey quartz-micaceous laminae< 1 mm to some centimetres in thickness, with a variable ratio of quartz to mica, alternate with fne to very fne-grained, dark grey to black tourmalinite laminae parallel to the regional foliation. Subvertical quartz+ (montebrasite)-veins that cut the regional foliation at an extremely high angle are also common in this area. Mineralisation and the associated veins are likely to be linked to the intrusion of the nearby Cabeza de Araya pluton. The infltration of granite-derived Li-, F-, B- and P-rich aqueous fuids into the host rocks through fractures related to shearing processes is considered to be the cause of the formation of Li-rich micas and intense tourmalinisation at the expense of pre-existing phyllosilicates.Spanish Ministerio de Ciencia, Innovacion y Universidades RTI2018-094097-B-100Spanish Ministerio de Ciencia, Innovacion y Universidades (ERDF funds)University of Basque Country GIU18/08

Assessment of RGB vegetation indices to estimate chlorophyll content in sugar beet leaves in the final cultivation stage

Estimation of chlorophyll content with portable meters is an easy way to quantify crop nitrogen status in sugar beet leaves. In this work, an alternative for chlorophyll content estimation using RGB-only vegetation indices has been explored. In a first step, pictures of spring-sown ‘Fernanda KWS’ variety sugar beet leaves taken with a commercial camera were used to calculate 25 RGB indices reported in the literature and to obtain 9 new indices through principal component analysis (PCA) and stepwise linear regression (SLR) techniques. The performance of the 34 indices was examined in order to evaluate their ability to estimate chlorophyll content and chlorophyll degradation in the leaves under different natural light conditions along 4 days of the canopy senescence period. Two of the new proposed RGB indices were found to improve the already good performance of the indices reported in the literature, particularly for leaves featuring low chlorophyll contents. The 4 best indices were finally tested in field conditions, using unmanned aerial vehicle (UAV)-taken photographs of a sugar beet plot, finding a reasonably good agreement with chlorophyll-meter data for all indices, in particular for I2 and (R−B)/(R+G+B). Consequently, the suggested RGB indices may hold promise for inexpensive chlorophyll estimation in sugar beet leaves during the harvest time, although a direct relationship with nitrogen status still needs to be validated

Sugar beet agronomic performance evolution in NW Spain in future scenarios of climate change

Changes in environmental conditions resulting from Climate Change are expected to have a major impact on crops. In order to foresee adaptation measures and to minimize yield decline, it is necessary to estimate the effect of those changes on the evapotranspiration and on the associated irrigation needs of crops. In the study presented herein, future conditions extracted from RCP4.5 scenario of IPCC, particularized for Castilla-y-León (Spain), were used as inputs for FAO crop simulation model (AquaCrop) to estimate sugar beet agronomic performance in the medium-term (2050 and 2070). A regional analysis of future trends in terms of yield, biomass and CO2 sequestration was carried out. An annual ET0 increase of up to 200 mm was estimated in 2050 and 2070 scenarios, with ETc increases of up to 40 mm/month. At current irrigation levels, temperature rise would be accompanied by a 9% decrease in yield and a ca. 6% decrease in assimilated CO2 in the 2050 and 2070 scenarios. However, it is also shown that the implementation of adequate adaptation measures, in combination with a more efficient irrigation management, may result in up to 17% higher yields and in the storage of between 9% and 13% higher amounts of CO2

Role of chemical structures and the 1331T>C bile salt export pump polymorphism in idiosyncratic drug-induced liver injury

Background & aims: Several pharmaceutical compounds have been shown to exert inhibitory effects on the bile salt export pump (BSEP) encoded by the ABCB11 gene. We analysed the combined effect on drug-induced liver injury (DILI) development of the ABCB11 1331T>C polymorphism and the presence of specific chemical moieties, with known BSEP inhibiting properties, in the causative drug. Methods: Genotyping using a TaqMan 5' allelic discrimination assay was performed in 188 Spanish DILI patients, 219 healthy controls and 91 sex-, age- and drug-matched controls. A chemical structure analysis was performed for each individual causative drug. Results: The CC genotype was significantly associated with hepatocellular damage [odds ratio (OR) = 2.1, P = 0.001], particularly in NSAID DILI cases (OR = 3.4, P = 0.007). In addition, the CC genotype was found to be significantly linked to DILI development from drugs causing C polymorphism in the absence of other BSEP inhibitory structures. Conclusion: Patients carrying the C allele in the ABCB11 1331T>C polymorphism are at increased risk of developing hepatocellular type of DILI, when taking drugs containing a carbocyclic system with aromatic rings

Selected ABCB1, ABCB4 and ABCC2 Polymorphisms Do Not Enhance the Risk of Drug-Induced Hepatotoxicity in a Spanish Cohort

[Background and Aims] Flawed ABC transporter functions may contribute to increased risk of drug-induced liver injury (DILI). We aimed to analyse the influence of genetic variations in ABC transporters on the risk of DILI development and clinical presentations in a large Spanish DILI cohort. [Methods] A total of ten polymorphisms in ABCB1 (1236T>C, 2677G>T,A, 3435T>C), ABCB4 (1954A>G) and ABCC2 (−1774G>del, −1549A>G, −24C>T, 1249G>A, 3972C>T and 4544G>A) were genotyped using Taqman 5′ allelic discrimination assays or sequencing in 141 Spanish DILI patients and 161 controls. The influence of specific genotypes, alleles and haplotypes on the risk of DILI development and clinical presentations was analysed. [Results] None of the individual polymorphisms or haplotypes was found to be associated with DILI development. Carriers homozygous for the ABCC2 −1774del allele were however only found in DILI patients. Hence, this genotype could potentially be associated with increased risk, though its low frequency in our Spanish cohort prevented a final conclusion. Furthermore, carriers homozygous for the ABCC2 −1774G/−1549A/−24T/1249G/3972T/4544G haplotype were found to have a higher propensity for total bilirubin elevations when developing DILI. [Conclusions] Our findings do not support a role for the analysed polymorphisms in the ABCB1, ABCB4 and ABCC2 transporter genes in DILI development in Spanish patients. The ABCC2 −1774deldel genotype was however restricted to DILI cases and could potentially contribute to enhanced DILI susceptibility.This study was supported, in part, by research grants from the Agencia Española del Medicamento and Fondo de Investigación Sanitaria (PS 09/01384). CIBERehd and Red Genómica del Cáncer are funded by Instituto de Salud Carlos III

Oxidative stress and mitochondrial dynamics malfunction are linked in Pelizaeus-Merzbacher disease

Pelizaeus-Merzbacher disease (PMD) is a fatal hypomyelinating disorder characterized by early impairment of motor development, nystagmus, choreoathetotic movements, ataxia and progressive spasticity. PMD is caused by variations in the proteolipid protein gene PLP1, which encodes the two major myelin proteins of the central nervous system, PLP and its spliced isoform DM20, in oligodendrocytes. Large duplications including the entire PLP1 gene are the most frequent causative mutation leading to the classical form of PMD. The Plp1 overexpressing mouse model (PLP-tg66/66 ) develops a phenotype very similar to human PMD, with early and severe motor dysfunction and a dramatic decrease in lifespan. The sequence of cellular events that cause neurodegeneration and ultimately death is poorly understood. In this work, we analyzed patient-derived fibroblasts and spinal cords of the PLP-tg66/66 mouse model, and identified redox imbalance, with altered antioxidant defense and oxidative damage to several enzymes involved in ATP production, such as glycolytic enzymes, creatine kinase and mitochondrial proteins from the Krebs cycle and oxidative phosphorylation. We also evidenced malfunction of the mitochondria compartment with increased ROS production and depolarization in PMD patient's fibroblasts, which was prevented by the antioxidant N-acetyl-cysteine. Finally, we uncovered an impairment of mitochondrial dynamics in patient's fibroblasts which may help explain the ultrastructural abnormalities of mitochondria morphology detected in spinal cords from PLP-tg66/66 mice. Altogether, these results underscore the link between redox and metabolic homeostasis in myelin diseases, provide insight into the pathophysiology of PMD, and may bear implications for tailored pharmacological intervention

Aberrant regulation of the GSK-3β/NRF2 axis unveils a novel therapy for adrenoleukodystrophy

The nuclear factor erythroid 2‐like 2 (NRF2) is the master regulator of endogenous antioxidant responses. Oxidative damage is a shared and early‐appearing feature in X‐linked adrenoleukodystrophy (X‐ALD) patients and the mouse model (Abcd1 null mouse). This rare neurometabolic disease is caused by the loss of function of the peroxisomal transporter ABCD1, leading to an accumulation of very long‐chain fatty acids and the induction of reactive oxygen species of mitochondrial origin. Here, we identify an impaired NRF2 response caused by aberrant activity of GSK‐3β. We find that GSK‐3β inhibitors can significantly reactivate the blunted NRF2 response in patients' fibroblasts. In the mouse models (Abcd1 − and Abcd1 −/Abcd2 −/− mice), oral administration of dimethyl fumarate (DMF/BG12/Tecfidera), an NRF2 activator in use for multiple sclerosis, normalized (i) mitochondrial depletion, (ii) bioenergetic failure, (iii) oxidative damage, and (iv) inflammation, highlighting an intricate cross‐talk governing energetic and redox homeostasis in X‐ALD. Importantly, DMF halted axonal degeneration and locomotor disability suggesting that therapies activating NRF2 hold therapeutic potential for X‐ALD and other axonopathies with impaired GSK‐3β/NRF2 axis. Keywords: adrenoleukodystrophy, dimethyl fumarate, GSK‐3, NRF2, oxidative stress Subject Categories: Genetics, Gene Therapy & Genetic Disease, Metabolism, Neuroscienc

Association of breast and gut microbiota dysbiosis and the risk of breast cancer: a case-control clinical study

We would like to thank M Luisa Puertas-Martin and Isabel Manzano-Jimenez, nurses at the Unit of Mammary Pathology, General Surgery Service, San Cecilio University Hospital (Granada), without whose enthusiasm the enrolment of participants in Granada would still be stalled. We are indebted to all the women taking part in the study.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Trial registration ClinicalTrials.gov NCT03885648, 03/25/2019. Retrospectively registered.Background Breast cancer ranks first in women, and is the second cause of death in this gender. In addition to genetics, the environment contributes to the development of the disease, although the factors involved are not well known. Among the latter is the influence of microorganisms and, therefore, attention is recently being paid to the mammary microbiota. We hypothesize that the risk of breast cancer could be associated with the composition and functionality of the mammary/gut microbiota, and that exposure to environmental contaminants (endocrine disruptors, EDCs) might contribute to alter these microbiota. Methods We describe a case-control clinical study that will be performed in women between 25 and 70 years of age. Cases will be women diagnosed and surgically intervened of breast cancer (stages I and II). Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment within a period of 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded. Controls will be women surgically intervened of breast augmentation or reduction. Women with oncological, gynecological or endocrine history, and those who have received antibiotic treatment within a period of 3 months prior to recruitment will also be excluded. Blood, urine, breast tissue and stool samples will be collected. Data regarding anthropometric, sociodemographic, reproductive history, tumor features and dietary habits will be gathered. Metabolomic studies will be carried out in stool and breast tissue samples. Metagenomic studies will also be performed in stool and breast tissue samples to ascertain the viral, fungal, bacterial and archaea populations of the microbiota. Quantitation of estrogens, estrogen metabolites and EDCs in samples of serum, urine and breast tissue will also be performed. Discussion: This is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study. Results obtained could contribute to elucidate risk factors, improve the prognosis, as well as to propose novel intervention studies in this disease.This work is funded by grants PI-0538-2017 (Junta de Andalucía, Spain, to LF) and Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP) of the Institute of Health Carlos III -supported by European Regional Development Fund/FEDER (FIS-PI16/01812) (to MFF)