A green light-triggerable RGD peptide for photocontrolled targeted drug delivery: synthesis and photolysis studies

We describe for the first time the synthesis and photochemical properties of a coumarin-caged cyclic RGD peptide and demonstrate that uncaging can be efficiently performed with biologically compatible green light. This was accomplished by using a new dicyanocoumarin derivative (DEAdcCE) for the protection of the carboxyl function at the side chain of the aspartic acid residue, which was selected on the basis of Fmoc-tBu SPPS compatibility and photolysis efficiency. The shielding effect of a methyl group incorporated in the coumarin derivative near the ester bond linking both moieties in combination with the use of acidic additives such as HOBt or Oxyma during the basic Fmoc-removal treatment were found to be very effective for minimizing aspartimide-related side reactions. In addition, a conjugate between the dicyanocoumarin-caged cyclic RGD peptide and ruthenocene, which was selected as a metallodrug model cargo, has been synthesized and characterized. The fact that green-light triggered photoactivation can be efficiently performed both with the caged peptide and with its ruthenocenoyl bioconjugate reveals great potential for DEAdcCE-caged peptide sequences as selective drug carriers in the context of photocontrolled targeted anticancer strategies

Análisis computacional de un generador termoeléctrico de estructura anular para la recuperación de energía térmica contenida en fluidos

Los dispositivos termoeléctricos se utilizan actualmente en aplicaciones que van desde sensores de termopar a generadores de energía, hasta acondicionadores de aire portátiles y refrigeradores. Con la demanda cada vez mayor de consumo de energía en todo el mundo y la necesidad de reducción de las emisiones de CO2, la conversión de energía termoeléctrica ha estado recibiendo gran atención como un posible candidato para la recuperación de calor residual, así como la capacidad de generación a partir de fuentes renovables. Hasta ahora, se ha puesto mucho énfasis en que la eficiencia en la conversión de la energía termoeléctrica dependía básicamente del rendimiento de los materiales y dispositivos termoeléctricos, sin embargo, aspectos como la geometría de los elementos P y N también afectan a la calidad de la energía producida. Prueba de ello son la poca variedad de módulos no planos o la gran cantidad de investigaciones centradas en la búsqueda de materiales con figuras de mérito mayor. En la conducción de fluidos, una de las geometrías más habituales es la tubular. Si lo que se desea es transferir energía a este fluido o a la inversa, el uso de módulos termoeléctricos planos con semiconductores habituales no resulta eficiente, aún incluso si se opta por hacer una modificación en la tubería y transformarla a rectangular. En este documento, se investiga el uso de semiconductores con estructura anular para la recuperación energética de fluidos en conductos tubulares. Se analiza la transferencia de calor en los materiales y dispositivos termoeléctricos, tanto fonones como electrones, con herramientas de simulación basadas en elementos finitos y se comparan los resultados obtenidos con los proporcionados en la teoría.Este trabajo ha sido parcialmente financiado por la Generalitat de Catalunya en la Ayuda Nov2014- SGR-36 y el MICINN-FEDER en la Ayuda No. FIS-2012-31307. Los autores les gustaría agradecer también a la Asociación de Ingenieros Industriales de Catalunya (AEIC) por su financiación parcial

Avances en la modelización del transporte térmico y eléctrico de generadores termoeléctricos longitudinales

Un sistema de recolección de energía termoeléctrica se aprovecha de cualquier diferencia de temperatura entre las superficies interior y exterior para producir electricidad por el efecto Seebeck. A menudo se utilizan como sistemas de recuperación de calor residual de los gases de escape en los motores de combustión interna. Para aumentar la potencia de salida, recolectores de energía a menudo están compuestos de varias matrices de TEG eléctricamente dispuestos en configuración serieparalelo. La forma en que TEG están conectados fuertemente afecta a las salidas electrotérmicos de cada TEG y toda la cosechadora también. Aunque muchos modelos TE coexisten en la literatura, no existe un modelo colector de energía termoeléctrica en cuenta este efecto. Por lo tanto, el propósito de este trabajo es mejorar la precisión de los modelos longitudinales colector de energía termoeléctrica (LTEH) introduciendo la predicción de los efectos de interconexión. La comparación de los resultados entre los datos teóricos y experimentales muestra una gran precisión y la posibilidad de ser utilizados como una herramienta de simulación.Este trabajo ha sido parcialmente financiado por la Generalitat de Catalunya en la Ayuda Nov2014- SGR-36 y el MICINN-FEDER en la Ayuda No. FIS-2012-31307. A los autores les gustaría agradecer a la Asociación de Ingenieros Industriales de Catalunya (AEIC) por su financiación parcial

Solid-phase approaches for labelling targeting peptides with far-red emitting coumarin fluorophores

Fluorophores based on organic molecules hold great potential for ligand-targeted imaging applications, particularly those operating in the optical window in biological tissues. In this work, we have developed three straightforward solid-phase approaches based on amide-bond formation or a Cu(I)-catalyzed azide-alkyne click (CuAAC) reaction for labeling an octreotide peptide with far-red emitting coumarin-based COUPY dyes. First, the conjugatable versions of COUPY fluorophores incorporating the required functional groups (e.g., carboxylic acid, azide, or alkyne) were synthesized and characterized. All of them were found fully compatible with Fmoc/tBu solid-phase peptide synthesis, which allowed for the labeling of octreotide either through amide-bond formation or by CuAAC reaction. A near quantitative conversion was obtained after only 1 h of reaction at RT when using CuSO4 and sodium ascorbate independently of the click chemistry approach used (azido-COUPY/alkynyl-peptide resin or alkynyl-COUPY/azido-peptide resin). COUPY-octreotide conjugates were found stable in cell culture medium as well as noncytotoxic in HeLa cells, and their spectroscopic and photophysical properties were found similar to those of their parent coumarin dyes. Finally, the potential bioimaging applications of COUPY-octreotide conjugates were demonstrated by confocal microscopy through the visualization of living HeLa cells overexpressing the somatostatin subtype-2 receptor

An integrin-targeted photoactivatable Pt(IV) complex as a selective anticancer pro-drug: synthesis and photoactivation studies

A new anticancer agent based on the conjugation of a photoactivatable Pt(IV) pro-drug to a cyclic RGD-containing peptide is described. Upon visible light irradiation, phototoxicity was induced preferentially in SK-MEL-28 melanoma cancer cells overexpressing alphaVbeta3 integrin compared to control DU-145 human prostate carcinoma cells

Efficient siRNA-peptide conjugation for specific targeted delivery into tumor cells

Despite the broad applicability of the Huisgen cycloaddition reaction, the click functionalization of RNAs with peptides remains still a challenge. Here we describe a straightforward method for the click functionalization of siRNAs with peptides of different size and complexity. Among them, a promising peptide carrier for the selective siRNA delivery into HER2+ breast cancer cell lines

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Electrically tunable thermal conductivity and exhaust heat recovery applications of thermoelectric materials

The current work is focused on two areas related to thermoelectricity: (i) the study of the capability of controlling the thermal conductivity of TEMs and (ii) the development, testing and improvement of an automotive thermoelectric generator (ATEG).The first part of the thesis proposes a novel approach to the use of thermoelectric couples, treating them as variable insulators in thermal systems.The second part of this investigation is focused on exhaust heat recovery development. In the first place, author describes a method to help ATEG design and to predict its performance in terms of fuel economyAquest treball se centra en dues àrees relacionades amb la termoelectricitat: (i) l'estudi de la capacitat de controlar la conductivitat tèrmica dels materials termoelèctrics i (ii) el desenvolupament, assaig i millora d'un generador termoelèctric per automoció (ATEG).La primera part de la tesi proposa un nou enfocament sobre l'ús dels materials termoelèctrics, tractant-los com a aïllaments variables en sistemes tèrmics.La segona part d'aquesta investigació se centra en el desenvolupament de la recuperació de calor en tubs d’escapamen

NOx Emissions below the Prospective EURO VII Limit on a Retrofitted Heavy-Duty Vehicle

In this study, a EURO VI heavy-duty vehicle (HDV) has been retrofitted with an exhaust gas heater (EGH) with the objective to reduce its NOx emissions below the current EURO VI and EURO VII limits. Results show that an EGH of 5 kW is enough to produce a significant NOx emissions abatement below the EURO VI and EURO VII limits. A conventional after-treatment system heated using a 5 kW EGH could work at its maximum catalytic conversion efficiency of 95% regardless of the engine operating speed. Consequently, exhaust gas heaters are a potential solution to high NOx emission at low engine regimes. With the use of an EGH, urea can be injected sooner, and catalytic reactions could cut much more NOx emissions. However, its incorporation would increase the vehicle’s fuel consumption by 1.47% if it is connected directly to the vehicle’s electrical system. Finally, it is also demonstrated that an automotive thermoelectric generator (ATEG) can supply the energy required by the EGH through the conversion of the waste heat from exhaust gases into electricity. This system could work electrically autonomous so there is no extra consumption of fuel