Modifications of Graphene Prepared by Chemical Vapor Deposition for Diagnostic Applications

xx, 186 p.El grafeno es un alótropo de carbono que ha demostrado tener excelentes propiedades electrónicas, mecánicas y térmicas. Gracias a ello, tiene un gran potencial en campos como biomedicina o electrónica. Entre sus distintos derivados, el grafeno crecido por deposición química de vapor (CVD) y transferido sobre superficie, ha demostrado ser un material idóneo para este tipo de aplicaciones debido a su elevada conductividad, carácter ambipolar de efecto campo, y una relación calidad/coste de producción conveniente. Sin embargo, la investigación del grafeno aún está en sus inicios y es necesaria una alta reproducibilidad de sus resultados para la futura comercialización y estandarización de los dispositivos de grafeno. Para ello, en esta tesis se ha desarrollado un protocolo de limpieza posterior al proceso de litografía con el fin de eliminar los residuos poliméricos de dicho proceso y obtener el mejor rendimiento electrónico. Además, la implementación de capacidades sensóricas sobre dispositivos electrónicos como los transistores de grafeno permite el desarrollo de herramientas para diagnóstico y tratamiento de diversas condiciones neurológicas como epilepsia o Parkinson. Con este propósito, el grafeno ha sido modificado covalentemente vía una adición radicalaria siguiendo diferentes estrategias compatibles con el diseño del dispositivo, con el fin de anclar los bio-receptores de interés. Como prueba de concepto, el sistema descrito se usó con un aptámero selectivo para trombina, demostrando resultados prometedores.Así mismo, se demostró por primera vez el uso del grafeno CVD en espectrometría de masas MALDI-TOF gracias a su capacidad de ionización/desorción. En concreto, se ha desarrollado un sistema compuesto por diferentes azucares modificados sobre grafeno como herramienta diagnóstica para la detección de proteínas. En este dispositivo se usó el grafeno como superficie asistente para la ionización/desorción láser en espectrometría de masas que, combinado al carácter conductor del grafeno, ha permitido reemplazar ITO como material de soporte y trabajar en condiciones de ausencia de matriz

Using machine learning methods to determine a typology of patients with HIV-HCV infection to be treated with antivirals

Several European countries have established criteria for prioritising initiation of treatment in patients infected with the hepatitis C virus (HCV) by grouping patients according to clinical characteristics. Based on neural network techniques, our objective was to identify those factors for HIV/HCV co-infected patients (to which clinicians have given careful consideration before treatment uptake) that have not being included among the prioritisation criteria. This study was based on the Spanish HERACLES cohort (NCT02511496) (April-September 2015, 2940 patients) and involved application of different neural network models with different basis functions (product-unit, sigmoid unit and radial basis function neural networks) for automatic classification of patients for treatment. An evolutionary algorithm was used to determine the architecture and estimate the coefficients of the model. This machine learning methodology found that radial basis neural networks provided a very simple model in terms of the number of patient characteristics to be considered by the classifier (in this case, six), returning a good overall classification accuracy of 0.767 and a minimum sensitivity (for the classification of the minority class, untreated patients) of 0.550. Finally, the area under the ROC curve was 0.802, which proved to be exceptional. The parsimony of the model makes it especially attractive, using just eight connections. The independent variable "recent PWID" is compulsory due to its importance. The simplicity of the model means that it is possible to analyse the relationship between patient characteristics and the probability of belonging to the treated group

Information and digital technologies of Industry 4.0 and Lean supply chain management: a systematic literature review

The purpose of this paper is to provide an overview of the current state of research and the key aspects and implications of the relationships between Information and Digital Technologies (IDT) of Industry 4.0 and Lean Supply Chain Management (LSCM), with the identification of the lines of research developed and an analysis of the main findings. A Systematic Literature Review methodology has been used for the identification, selection, and evaluation of the published research. A set of 78 papers deduced from the most relevant scientific databases, including Web of Science, Scopus, and ABI/Inform, from 1996 to December 2019, has been analyzed and synthesized. The analysis and evaluation of these papers has enabled a new classification of the literature to be offered that identifies four lines of research based on the Life Cycle of Technology: obsolete IDT in LSCM; mature IDT in LSCM; emerging IDT in LSCM; and an Information Systems and IDT general approach in LSCM. The paper goes on to discuss the gaps found in the literature and proposes new opportunities and challenges for future research. A series of implications are presented intended to be useful from not only an academic point-of-view but also from a management focus, including recommendations for industrial managers and policymakers

Charge Transfer-Induced SERS Enhancement of MoS2/Dopants Dependent on their Interaction Difference

2D transition metal dichalcogenide materials have attracted increasing attention as active surface-enhanced Raman spectroscopy (SERS) platforms. In this study, the influence of n- and p-type doping of exfoliated MoS2 (exMoS2) hybrids on the SERS performance is investigated, employing Rhodamine 6G (R6G) as a probe molecule. It is demonstrated that n-doped exMoS2 hybrids (exMoS2 mixed with C60, graphene, and sodium dodecyl sulfate) exhibit enhanced SERS intensities, while p-doping (exMoS2 mixed with TCNQ) resulted in inhibited SERS enhancement. A key discovery is the linear relationship between Raman enhancement of MoS2/dopant hybrids and the difference in their LUMO energy levels, which dictate the degree and direction of charge transfer. Interestingly, MC60-4, a C60-doped hybrid, deviates from the linear relationship, displaying remarkable SERS enhancement owing to its chemical interaction and unique Raman scattering activity. The findings provide critical insights into the SERS enhancement behavior of doped MoS2, facilitating precise tuning of SERS intensities by manipulating the MoS2 doping state.M.P. is the AXA Chair for Bionanotechnology (2016−2023). The authors gratefully acknowledge the financial support from the University of Trieste, INSTM, the Italian Ministry of Education MIUR (cofin Prot. 20228YFRNL), and the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (Grant No. MDM-2017-0720). H.-L.H. thanks MINECO for his research grant (Juan de la Cierva Incorporation/no. IJC-2018-037396-I). L. C. thanks financial support from the China Scholarship Council (202106140031). Financial support for this work was also provided by the Spanish Ministerio de Ciencia, Innovación y Universidades (MICIN/AEI/PID2019-104772GB-I00 and MCIN/AEI/RED2018-102387-T) and the Gobierno Vasco/Eusko Jaurlaritza (GV/EJ, Grant IT-1553-22). The authors acknowledge the computational resources, and technical and human support provided by the DIPC

Experience with the use of Rituximab for the treatment of rheumatoid arthritis in a tertiary Hospital in Spain: RITAR study

There is evidence supporting that there are no relevant clinical differences between dosing rituximab 1000 mg or 2000 mg per cycle in rheumatoid arthritis (RA) patients in clinical trials, and low-dose cycles seem to have a better safety profile. Our objective was to describe the pattern of use of rituximab in real-life practice conditions. Methods: Rituximab for RA in clinical practice (RITAR) study is a retrospective cohort study from 2005 to 2015. Eligibility criteria were RA adults treated with rituximab for active articular disease. Response duration was the main outcome defined as months elapsed from the date of rituximab first infusion to the date of flare. A multivariable analysis was performed to determine the variables associated with response duration. Results: A total of 114 patients and 409 cycles were described, 93.0% seropositive and 80.7% women. Rituximab was mainly used as second-line biological therapy. On demand retreatment was used in 94.6% of cases versus fixed 6 months retreatment in 5.4%. Median response duration to on demand rituximab cycles was 10 months (interquartile range, 7–13). Multivariable analysis showed that age older than 65 years, number of rituximab cycles, seropositivity, and first- or second-line therapy were associated with longer response duration. The dose administered at each cycle was not significantly associated with response duration. Conclusions: Our experience suggests that 1000 mg rituximab single infusion on demand is a reasonable schedule for long-term treatment of those patients with good response after the first cycles, especially in seropositive patients and when it is applied as a first- or second-line biological therap

The reactivity of reduced graphene depends on solvation

The reactivity of reduced graphene sheets (graphenide), obtained by dissolution of graphite intercalation compounds, in particular KC8, was systemically studied by covalent functionalization with 4-fluorobenzenediazonium tetrafluoroborate and 4-iodoaniline in different solvents (5 pure and 7 solvents with addition of K+ chelating agents). Interestingly, proper solvation of the potassium cations was beneficial to the covalent functionalization, while excessive solvation led to destabilization and flocculation, with decreased reactivity of graphenide. The results were confirmed by scanning Raman spectroscopy (SRS) and x-ray photoelectron spectroscopy (XPS)

Forecasting of poor visibility episodes in the vicinity of Tenerife Norte Airport

Aviation safety is a priority that may be compromised by adverse weather conditions. This is the case for poor visibility in the vicinity of airports, which can pose a risk during takeoff and landing. For airports that are prone to fog because of their location, an accurate forecast of poor-visibility episodes is vital. However, the forecasting of low clouds is still a challenge in numerical weather prediction, especially when an airport is near complex terrain for which the use of non-hydrostatic mesoscale models is mandatory. All these factors are present at Tenerife Norte Airport, which is commonly affected by poor visibility from low clouds related to persistent trade winds and moist flows from the Atlantic Ocean. In this paper, several methods for estimating visibility based on mesoscale model outputs are tested. Use of the HARMONIE-AROME model is encouraged because of its excellent performance in the detection of poor-visibility episodes (False Alarm Ratio = 0.34–0.38; Frequency Of Misses = 0.22–0.38, depending on the model version and method used). In addition, the use of satellite application facilities is proposed for the nowcasting of low clouds affecting the airport area. Specifically, we used products that estimate cloud type, cloud top altitude, and integrated water vapor content in the boundary layer. Finally, an application is presented for the monitoring of weather conditions in real time to estimate poor-visibility risk.This work was supported by the Aeronautics Annual Plan 2018 of AEMET

The animal model determines the results on Aeromonas virulence factors.

The selection of an experimental animal model is of great importance in the study of bacterial virulence factors. Here, a bath infection of zebrafish larvae is proposed as an alternative model to study the virulence factors of Aeromonas hydrophila. Intraperitoneal infections in mice and trout were compared with bath infections in zebrafish larvae using specific mutants. The great advantage of this model is that bath immersion mimics the natural route of infection, and injury to the tail also provides a natural portal of entry for the bacteria. The implication of T3SS in the virulence of A. hydrophila was analyzed using the AH-1::aopB mutant. This mutant was less virulent than the wild-type strain when inoculated into zebrafish larvae, as described in other vertebrates. However, the zebrafish model exhibited slight differences in mortality kinetics only observed using invertebrate models. Infections using the mutant AH-11vapA lacking the gene coding for the surface S-layer suggested that this protein was not totally necessary to the bacteria once it was inside the host, but it contributed to the inflammatory response. Only when healthy zebrafish larvae were infected did the mutant produce less mortality than the wild-type. Variations between models were evidenced using the AH-11rmlB, which lacks the O-antigen lipopolysaccharide (LPS), and the AH-11wahD, which lacks the O-antigen LPS and part of the LPS outer-core. Both mutants showed decreased mortality in all of the animal models, but the differences between them were only observed in injured zebrafish larvae, suggesting that residues from the LPS outer core must be important for virulence. The greatest differences were observed using the AH- 11FlaB-J (lacking polar flagella and unable to swim) and the AH-1::motX (non-motile but producing flagella). They were as pathogenic as the wild-type strain when injected into mice and trout, but no mortalities were registered in zebrafish larvae. This study demonstrates that zebrafish larvae can be used as a host model to assess the virulence factors of A. hydrophila. This model revealed more differences in pathogenicity than the in vitro models and enabled the detection of slight variations in pathogenesis not observed using intraperitoneal injections of mice or fish

Cryptic splice-altering variants in MYBPC3 are a prevalent cause of hypertrophic cardiomyopathy

Research lette

Malondialdehyde serum levels in a full characterized series of 430 rheumatoid arthritis patients

Background. Oxidative stress has been involved in the pathogenesis of rheumatoid arthritis (RA). The serum malondialdehyde (MDA) level is a reliable biomarker of oxidative stress status. In the present work, we aimed to analyze how a comprehensive characterization of the disease characteristics in RA, including a lipid profile, insulin resistance, and subclinical atherosclerosis, relates to serum MDA levels. Methods. In a cross-sectional study that included 430 RA patients, serum MDA levels were evaluated. Multivariable analysis was performed to examine the relationship of MDA with disease activity scores and disease characteristics, including subclinical carotid atherosclerosis, a comprehensive lipid molecule profile, and indices of insulin resistance and beta cell function indices. Results. The erythrocyte sedimentation rate (ESR) showed a significant and positive relationship with MDA. However, this did not occur for other acute phase reactants such as C-reactive protein or interleukin-6. Although the DAS28-ESR score (Disease Activity Score in 28 joints) had a positive and significant association with MDA serum levels, other disease activity scores that do not use the erythrocyte sedimentation rate in their formula did not show a significant relationship with MDA. Other disease characteristics, such as disease duration and the existence of rheumatoid factor and antibodies against citrullinated protein, were not related to serum MDA levels. This also occurred for lipid profiles, insulin resistance indices, and subclinical carotid atherosclerosis, for which no associations with circulating MDA were found. Conclusions. The disease characteristics are not related to circulating MDA levels in patients with RA.Funding: This work was supported by a grant to I. Ferraz-Amaro from Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC) (grant number: PIFIISC23/07)