Copper(I) polypyridine complexes. the sensitizers of the future for dye-sensitized solar cells (DSSCs)

The thesis concerns the development of novel dyes for the photosensitization of titanium dioxide for incorporation into dyes-sensitized solar cells (DSSCs). The majority of dyes utilized to date are based upon heavy transition metals such as ruthenium. Although these are efficient (>10%), they have disadvantages in the cost of the materials and also in the availability of the very rare platinum group metals. The thesis investigates the use of copper(I) complexes of oligopyridines, which are known to have similar photophysical properties to ruthenium(II) tris(oligopyridine) species but which have not been widely used in solar cells. The labile nature of the copper(I) centre precluded previous systematic investigation of the complexes for this application. Synthetic methods for a series of carboxylate and phosphonate functionalized 2,2'- bipyridine ligands with substituents at the 6- and 6'-positions have been developed. The carboxylate or phosphonate functionality is required for the binding of the ligands and complexes to the titanium dioxide surface and the substituents adjacent to the nitrogen stabilise the photoexcited state with respect to quenching and oxidation. DSSCs were prepared using the basic protocols established for ruthenium dye-sensitizers, involving the doctor-blading of a TiO2 paste onto an ITO or FTO electrode followed by annealing, absorption of the dye and cell construction with conventional iodide-triiodide electrolyte. The cells were tested in Basel using a home-built cell tester or a modified scanning electrochemical microscope and in Lausanne at the EPFL in the laboratory of Prof. Michael Graetzel using an industry standard protocol. The surprising results were that the copper-functionalised DSSCs had efficiencies approaching 2.5% for the prototype compounds. The lability of the copper(I) complexes has allowed us to develop an entirely novel strategy for the design of solar cells in which the carboxylated or phosphonated ligand L is first attached to the TiO2 surface and subsequently metallated by reaction with any [CuL'2] complex to give a surface bound [CuLL'] species and the method is likely to lead to the future use of libraries of complexes to achieve full spectrum coverage rather than the design of "black" dyes

Determination of ethyl glucuronide and ethyl sulfate from dried blood spots

Background: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are non-oxidative minor metabolites of ethanol. They are detectable in various body fluids shortly after initial consumption of ethanol and have a longer detection time frame than the parent compound. They are regarded highly sensitive and specific markers of recent alcohol uptake. This study evaluates the determination of EtG and EtS from dried blood spots (DBS), a simple and cost-effective sampling method that would shorten the time gap between offense and blood sampling and lead to a better reflectance of the actual impairment. Methods: For method validation, EtG and EtS standard and quality control samples were prepared in fresh human heparinized blood and spotted on DBS cards, then extracted and measured by an LC-ESI-MS/MS method. Additionally, 76 heparinized blood samples from traffic offense cases were analyzed for EtG and EtS as whole blood and as DBS specimens. The results from these measurements were then compared by calculating the respective mean values, by a matched-paired t test, by a Wilcoxon test, and by Bland-Altman and Mountain plots. Results and discussion: Calibrations for EtG and EtS in DBS were linear over the studied calibration range. The precision and accuracy of the method met the requirements of the validation guidelines that were employed in the study. The stability of the biomarkers stored as DBS was demonstrated under different storage conditions. The t test showed no significant difference between whole blood and DBS in the determination of EtG and EtS. In addition, the Bland-Altman analysis and Mountain plot confirmed that the concentration differences that were measured in DBS specimens were not relevan

Inhibition of bacterial degradation of EtG by collection as dried urine spots (DUS)

Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are direct alcohol consumption markers widely used nowadays for clinical and forensic applications. They are detectable in blood and urine even after consumption of trace amounts of ethanol and for a longer time frame, being detectable even when no more ethanol is present. The instability of EtG against bacterial degradation in contaminated urine samples and/or the possible postcollection synthesis of this metabolite in samples containing, e.g., Escherichia coli and ethanol, may cause false identification of alcohol uptake. Therefore, it is of paramount importance to constrict these error sources by inhibition of any bacterial growth causing hydrolization or synthesis of EtG. This study evaluates a new method of collecting urine samples on filter paper, dried urine spots (DUS), for simultaneous detection of EtG, EtS and creatinine, having the great advantage of inhibiting bacterial activity. In addition, a method validation for the determination of EtG and EtS in DUS was performed according to the FDA guidelines. Sterile-filtered urine was spiked with EtG and EtS, inoculated with E. coli and incubated. Liquid and dried urine samples were collected after various time intervals up to 96h. Liquid samples were frozen immediately after collection, whereas aliquots for DUS were pipetted onto filter paper, allowed to dry and stored at RT until analysis 1week after. The specimens were analyzed by LC-ESI-MS/MS. As expected, degradation of EtG, but not of EtS, was observed in contaminated liquid urine samples. However, the specimens collected on filter paper and stored at RT showed no degradation during storage. Therefore, collecting urine samples on filter paper for EtG and EtS analysis turns out to be a reliable method to avoid bacterial degradation of EtG and EtS, and consequently, stabilization of these ethanol metabolites is achieved. In addition, simultaneous measurement of creatinine content as an indicator of urine dilution helps to interpret the results. Method validation for EtG and EtS in DUS was satisfactory, showing the linearity of the calibration curves in the studied concentration range, good precision, accuracy and selectivit

Differentiation of bee pollen samples according to their intact-glucosinolate content using canonical discriminant analysis

Producción CientíficaA study is presented of the real possibilities of glucosinolate content and chemometrics (canonical discriminant analysis) to differentiate bee pollen samples from four different apiaries (Fuentelahiguera, Monte, Pistacho, Tío Natalio) located in the same geographical area. Fifteen intact-glucosinolates were quantified by means of ultraperformance liquid chromatography coupled to a quadrupole time-of-flight mass detector in forty-nine bee pollen samples. Glucosinolate residues were detected in most of the samples, and these differed in number and concentration. It was possible to directly differentiate one of the apiaries (Fuentelahiguera) from the other three (Monte, Pistacho y Tío Natalio) by comparing glucosinolate content. These three apiaries were differentiated by means of the first two canonical variables obtained from a canonical discriminant analysis. Following this analysis, more than 88% of the samples could be assigned correctly to the Pistacho and Monte apiaries, and 100% to the Tío Natalio apiary.Este trabajo forma parte de los proyectos de investigación financiados por el Ministerio de Economía y Competitividad e INIA-FEDER (RTA2015-00013-C03-01 y 03)

Molecular alterations in sporadic and sod1-als immortalized lymphocytes: Towards a personalized therapy

Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition where motor neurons (MNs) degenerate. Most of the ALS cases are sporadic (sALS), whereas 10% are hereditarily trans-mitted (fALS), among which mutations are found in the gene that codes for the enzyme superoxide dismutase 1 (SOD1). A central question in ALS field is whether causative mutations display selective alterations not found in sALS patients, or they converge on shared molecular pathways. To identify specific and common mechanisms for designing appropriate therapeutic interventions, we focused on the SOD1-mutated (SOD1-ALS) versus sALS patients. Since ALS pathology involves different cell types other than MNs, we generated lymphoblastoid cell lines (LCLs) from sALS and SOD1-ALS patients and healthy donors and investigated whether they show changes in oxidative stress, mito-chondrial dysfunction, metabolic disturbances, the antioxidant NRF2 pathway, inflammatory profile, and autophagic flux. Both oxidative phosphorylation and glycolysis appear to be upregulated in lymphoblasts from sALS and SOD1-ALS. Our results indicate significant differences in NRF2/ARE pathway between sALS and SOD1-ALS lymphoblasts. Furthermore, levels of inflammatory cytokines and autophagic flux discriminate between sALS and SOD1-ALS lymphoblasts. Overall, different molecular mechanisms are involved in sALS and SOD1-ALS patients and thus, personalized medicine should be developed for each case.This research was funded by Comunidad de Madrid (grant ELA_Madrid B2017/BMD-3813 and S2017/BMD-3688), European Commission MSCA-ITN-ETN (grant DRIVE GA: 765912), ISCiii (CIBERNED CB18/05/000 and CB06/05/0089), Fundela (2019/00325/001) for I.L.-B. and AEI (grant PID2019-105600RB-I00) for, A.M. and I.L.-B

Estudios históricos 8 : arquitectura y diseño

1 archivo PDF (157 páginas)Trabajo que se divide en tres apartados: arquitectura y ciudad; diseño gráfico e industrial; teoría; Al final se suma un apartado denominado "conferencias" que fueron impartidas por invitados de otros grupo académicos en el Seminario Anual de Historia del Diseño

Conventional type 1 dendritic cells protect against age-related adipose tissue dysfunction and obesity.

Conventional dendritic cells (cDCs) scan and integrate environmental cues in almost every tissue, including exogenous metabolic signals. While cDCs are critical in maintaining immune balance, their role in preserving energy homeostasis is unclear. Here, we showed that Batf3-deficient mice lacking conventional type 1 DCs (cDC1s) had increased body weight and adiposity during aging. This led to impaired energy expenditure and glucose tolerance, insulin resistance, dyslipidemia, and liver steatosis. cDC1 deficiency caused adipose tissue inflammation that was preceded by a paucity of NK1.1+ invariant NKT (iNKT) cells. Accordingly, among antigen-presenting cells, cDC1s exhibited notable induction of IFN-γ production by iNKT cells, which plays a metabolically protective role in lean adipose tissue. Flt3L treatment, which expands the dendritic cell (DC) compartment, mitigated diet-induced obesity and hyperlipidemia in a Batf3-dependent manner. This effect was partially mediated by NK1.1+ cells. These results reveal a new critical role for the cDC1-iNKT cell axis in the regulation of adipose tissue homeostasis.We are grateful to the Immunology, Ophthalmology, and ENT Department at the UCM for providing useful discussion and to Gillian Dunphy and Antonia Tomás for critically reading the manuscript. We thank the CNIC and UCM facilities. Funding: Work in the S.I. laboratory is funded by the Spanish Ministerio de Ciencia, Innovación (MICINN), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER), RTI2018-094484-BI00, and RYC-2016-19463. EHG is the recipient of an FPI fellowship (PRE2019-087509) from the Spanish Ministry of Science and Innovation. Work in the DS laboratory is funded by the CNIC; the European Research Council (ERC-2016-Consolidator Grant 725091); the MICINN, AEI and FEDER (PID2019-108157RB); Comunidad de Madrid (B2017/BMD-3733 Immunothercan-CM); Atresmedia (Constantes y Vitales prize); and Fundació La Marató de TV3 (201723). Work in the G.S. laboratory receives funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n° ERC 260464, EFSD/Lilly European Diabetes Research Programme GS, 2017 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation (Investigadores-BBVA-2017) IN[17]_BBM_BAS_0066, MINECO-FEDER SAF2016-79126-R, EUIN2017-85875, Comunidad de Madrid IMMUNOTHERCAN-CM S2010/BMD-2326 and B2017/BMD-3733 and Fundación AECC. IN receives funding from EFSD/Lilly (2019), EFSD Rising star (2019), and JdC— Incorporation (IJC2018-035390-I). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the MICINN, and the Pro CNIC Foundation.S

Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy

Cerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involvement with and without ataxia by exome sequencing or by a targeted panel with 363 genes involved in ataxia or spastic paraplegia. Novel variants were investigated by in silico or experimental approaches. Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD. The remaining three cases deserve special attention; they harbour variants in MAST1, PI4KA and CLK2 genes. MAST1 is responsible for an ultrarare condition characterised by global developmental delay and cognitive decline; our index case added ataxia to the list of concomitant associated symptoms. PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity. Finally, in a patient who suffers from mild ataxia with oculomotor apraxia, the de novo novel CLK2 c.1120T>C variant was found. The protein expression of the mutated protein was reduced, which may indicate instability that would affect its kinase activity

Estudios históricos 5 : arquitectura y diseño

1 archivo PDF (174 páginas)"El diseño en el periodo virreinal es un estudio que contempla una revisión histórico-artística de algunos de los acontecimientos más relevantes dentro del desarrollo urbano iberoamericano, por decirlo con un término aglutinador que lo identifique. La visión de un pasado común, con las actuales herramientas metodológicas que la interdisciplinariedad exige, es el resultado de una tarea viva y vigorosa que el presente libro entrega a los estudiosos del tema, fruto del trabajo en equipo del grupo de Historia del Diseño de la Universidad Autónoma Metropolitana Unidad Azcapotzalco"

Mesenchymal stromal cells (MSC) from JAK2+ myeloproliferative neoplasms differ from normal MSC and contribute to the maintenance of neoplastic hematopoiesis

[EN]There is evidence of continuous bidirectional cross-talk between malignant cells and bone marrow-derived mesenchymal stromal cells (BM-MSC), which favors the emergence and progression of myeloproliferative neoplastic (MPN) diseases. In the current work we have compared the function and gene expression profile of BM-MSC from healthy donors (HDMSC) and patients with MPN (JAK2V617F), showing no differences in the morphology, proliferation and differentiation capacity between both groups. However, BM-MSC from MPN expressed higher mean fluorescence intensity (MIF) of CD73, CD44 and CD90, whereas CD105 was lower when compared to controls. Gene expression profile of BM-MSC showed a total of 169 genes that were differentially expressed in BM-MSC from MPN patients compared to HD-MSC. In addition, we studied the ability of BM-MSC to support the growth and survival of hematopoietic stem/progenitor cells (HSPC), showing a significant increase in the number of CFU-GM colonies when MPN-HSPC were co-cultured with MPN-MSC. Furthermore, MPN-MSC showed alteration in the expression of genes associated to the maintenance of hematopoiesis, with an overexpression of SPP1 and NF-kB, and a downregulation of ANGPT1 and THPO. Our results suggest that BM-MSC from JAK2+ patients differ from their normal counterparts and favor the maintenance of malignant clonal hematopoietic cell