Pablo Sackmann

Fil: López, Hugo Luis. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología Vertebrados; ArgentinaFil: Bastida, Ricardo. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología Vertebrados; ArgentinaFil: Bonetti, S.. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología Vertebrados; ArgentinaFil: Rouaux, Julia. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología Vertebrados; Argentin

Miristato de miristilo “100% natural”. Estudio del proceso de síntesis biocatalítica

El miristato de miristilo es uno de los ésteres cerosos másutilizados en las formulaciones cosméticas como emoliente.La legislación europea permite catalogar como productosnaturales a todos aquellos obtenidos directamente dela naturaleza o los sintetizados mediante procedimientosbiocatalíticos. En este contexto, el presente trabajo recogelos estudios realizados para optimizar la síntesis biocatalíticade miristato de miristilo con lipasa de Candida antarcticainmovilizada (Novozym® 435). Operando a 70ºC, avacío y con circulación de N2 seco, se ha podido obtener,en tan sólo 2 horas, un éster que presenta las mismas características (número ácido, valor de hidroxilo, índice deyodo e índice de saponificación), que los productos quese encuentran actualmente en el mercado, con la notableventaja de que este miristato de miristilo permite el etiquetadode los productos cosméticos que lo contienen como“100% natural”

Dual EGFR inhibition in combination with anti-VEGF treatment in colorectal cancer.

Preclinical studies demonstrate that epidermal growth factor receptor (EGFR) signals through both kinase-dependent and independent pathways and that combining a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is synergistic. We conducted a dose-escalation, phase I study combining erlotinib, cetuximab, and bevacizumab. The subset of patients with metastatic colorectal cancer was analyzed for safety and antitumor activity. Forty-one patients with heavily pretreated metastatic colorectal cancer received treatment on a range of dose levels. The most common treatment-related grade ≥2 adverse events were rash (68%), hypomagnesemia (37%), and fatigue (15%). Thirty of 34 patients (88%) treated at the full FDA-approved doses of all three drugs tolerated treatment without drug-related dose-limiting effects. Eleven patients (27%) achieved stable disease (SD) ≥6 months and three (7%) achieved a partial response (PR) (total SD>6 months/PR= 14 (34%)). Of the 14 patients with SD≥6 months/PR, eight (57%) had received prior sequential bevacizumab and cetuximab, two (5%) had received bevacizumab and cetuximab concurrently, and four (29%) had received prior bevacizumab but not cetuximab or erlotinib (though three had received prior panitumumab). The combination of bevacizumab, cetuximab, and erlotinib was well tolerated and demonstrated antitumor activity in heavily pretreated patients with metastatic colorectal cancer

Dual EGFR inhibition in combination with anti-VEGF treatment: a phase I clinical trial in non-small cell lung cancer.

BackgroundPreclinical data indicate EGFR signals through both kinase-dependent and independent pathways and that combining a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is synergistic in animal models.MethodsWe conducted a dose-escalation, phase I study combining erlotinib, cetuximab, and bevacizumab. The subset of patients with non-small cell lung cancer (NSCLC) was analyzed for safety and response.ResultsThirty-four patients with NSCLC (median four prior therapies) received treatment on a range of dose levels. The most common treatment-related grade ≥2 adverse events were rash (n=14, 41%), hypomagnesemia (n=9, 27%), and fatigue (n=5, 15%). Seven patients (21%) achieved stable disease (SD) ≥6 months, two achieved a partial response (PR) (6%), and two achieved an unconfirmed partial response (uPR) (6%) (total=32%). We observed SD≥6 months/PR/uPR in patients who had received prior erlotinib and/or bevacizumab, those with brain metastases, smokers, and patients treated at lower dose levels. Five of 16 patients (31%) with wild-type EGFR experienced SD≥6 months or uPR. Correlation between grade of rash and rate of SD≥6 months/PR was observed (p less than 0.01).ConclusionThe combination of erlotinib, cetuximab, and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with NSCLC

Development and economic evaluation of an eco-friendly biocatalytic synthesis of emollient esters.

©. This manuscript version is made available under the CC-BY-NC-ND license http://creativecommons.org/licenses/ccby-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in [Bioprocess and Biosystems Engineering]. To access the final edited and published work see [https://doi.org/ 10.1007/s00449-019-02243-1]During the last decades the understanding and prospects of enzyme-catalysed reactions have been massively widened and there are a number of implemented large-scale enzymatic processes mainly based in the use of commercial biocatalysts. As it might happen that the same process can be successfully carried out by different commercial lipases, the election of the biocatalyst must rely on productivity and economic considerations. This work presents productiveness and direct operation cost evaluation as a key tool for the selection between two commercial lipase catalysts, the versatile but expensive Novozym® 435 and a much more economical option, Lipozyme® TL IM, in the synthesis of spermaceti, a mixture of emollient esters with cosmetic applications. Proving that Novozym® 435 leads to minimum savings of 10% with respect to the cheapest immobilized derivative, biocatalyst cost does not appear to be the major contribution to the economics of the processes under study, due to their great capacity to be recovered and reused. At laboratory scale, the biggest economic investment is caused by substrates, which can be massively reduced at industrial scale by using bulk reagents. In such case, energy cost may be the major contribution to the process economy. This work proposes an optimized process ready to be scaled-up in order to accurately determine the energetic requirements of the possible industrial enzymatic synthesis

Green Production of a High-Value Branched-Chain Diester: Optimization Based on Operating Conditions and Economic and Sustainability Criteria

©. This manuscript version is made available under the CC-BY license http://creativecommons.org/licenses/by/4.0/ This document is the Published version of a Published Work that appeared in final form in [Applied Sciences]. To access the final edited and published work see [https://doi.org/ 10.3390/app13106177]Featured Application: In the last years, consumers’ and administrations’ demand for more sustainable products and processes has been increasing. This work develops a new sustainable way to obtain a branched ester for cosmetic applications (neopentylglycol dilaurate) and demonstrates that this new production route can be economically competitive. Branched-chain esters (BCEs) have found a large number of applications in cosmetics. Among them, neopentyl glycol dilaurate (NPGDL) stands out as an emollient, emulsifier, and skin-conditioning agent. This work presents the synthesis of NPGDL in a solvent-free medium using the two most common immobilized lipases: Novozym® 40086 (Rml) and Novozym® 435 (CalB). Results proved that the former biocatalyst has lower activity and certain temperature deactivation, although conversions ≥ 90% were obtained at 60 °C and 7.5% of catalyst. On the other hand, optimal reaction conditions for Novozym® 435 are 3.75% w/w of the immobilized derivative at 80 °C. Under optimal conditions, the process productivities were 0.105 and 0.169 kg NPGDL/L h, respectively. In order to select the best conditions for NPGDL production, studies on the reuse of the derivative and cost estimation have been performed. Economic study shows that biocatalytic processes can be competitive when lipases are reused for five cycles, yielding biocatalyst productivities of 56 and 122 kg NPGDL/kg biocatalyst using Novozym® 40086 and Novozym® 435, respectively. The final choice will be based on both economic and sustainability criteria. Green metric values using both biocatalysts are similar but the product obtained using Novozym® 40086 is 20% cheaper, making this alternative the best option

Esters in the Food and Cosmetic Industries: An Overview of the Reactors Used in Their Biocatalytic Synthesis

©2024. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the, Published, version of a Published Work that appeared in final form in Materials. To access the final edited and published work see https://doi.org/10.3390/ma17010268Esters are versatile compounds with a wide range of applications in various industries due to their unique properties and pleasant aromas. Conventionally, the manufacture of these compounds has relied on the chemical route. Nevertheless, this technique employs high temperatures and inorganic catalysts, resulting in undesired additional steps to purify the final product by removing solvent residues, which decreases environmental sustainability and energy efficiency. In accordance with the principles of “Green Chemistry” and the search for more environmentally friendly methods, a new alternative, the enzymatic route, has been introduced. This technique uses low temperatures and does not require the use of solvents, resulting in more environmentally friendly final products. Despite the large number of studies published on the biocatalytic synthesis of esters, little attention has been paid to the reactors used for it. Therefore, it is convenient to gather the scattered information regarding the type of reactor employed in these synthesis reactions, considering the industrial field in which the process is carried out. A comparison between the performance of the different reactor configurations will allow us to draw the appropriate conclusions regarding their suitability for each specific industrial application. This review addresses, for the first time, the above aspects, which will undoubtedly help with the correct industrial implementation of these processes

A Heuristically Optimized Complex Event Processing Engine for Big Data Stream Analytics

This paper describes a Big Data stream analytics platform developed within the DEWI project for processing upcoming events from wireless sensors installed in a truck. The platform consists of a Complex Event Processing (CEP) engine capable of triggering alarms from a predefined set of rules. In general these rules are characterized by multiple parameters, for which finding their opti- mal value usually yields a challenging task. In this paper we explain a methodol- ogy based on a meta-heuristic solver that is used as a wrapper to obtain optimal parametric rules for the CEP engine. In particular this approach optimizes CEP rules through the refinement of the parameters controlling their behavior based on an alarm detection improvement criterion. As a result the proposed scheme retrieves the rules parameterized in a detection-optimal fashion. Results for a cer- tain use case – i.e. fuel level of the vehicle – are discussed towards assessing the performance gains provided by our method

Sustainable Biocatalytic Synthesis of a Second-Generation Biolubricant

©. This manuscript version is made available under the CC-BY license http://creativecommons.org/licenses/by/4.0/ This document is the Published, version of a Published Work that appeared in final form in [Sustainability]. To access the final edited and published work see [https://doi.org/10.3390/su16041615]Background: Biolubricants represent a category of lubricating substances derived from sustainable sources such as vegetable oils, animal fats, and other bio-based materials. They are considered more environmentally friendly than mineral-based lubricants because they are biodegradable and nontoxic. Biolubricants derived from vegetable oils or animal fats were used as first-generation biolubricants. They have limited performance at extreme temperatures, both high and low, as well as low oxidative stability. Substitution of the double bonds by branching improves the performance and stability of the resulting second-generation biolubricants. Methods: In the past, the production of these compounds has relied on the chemical pathway. This method involves elevated temperatures and inorganic catalysts, leading to the necessity of additional purification steps, which decreases environmental sustainability and energy efficiency. A more environmentally friendly alternative, the enzymatic route, has been introduced, in accordance with the principles of “Green Chemistry”. Results: In this paper, the esterification of 2-methylhexanoic acid with 2-octyl-1-dodecanol and its optimization were developed for the first time. The synthesis was conducted within a jacketed batch reactor connected to a thermostatic bath in a solvent-free reaction medium and using Lipozyme® 435 as biocatalyst. Conclusions: The high viscosity index value of this new hyperbranched ester (>200, ASTM D2270) suggests that it may be an excellent biolubricant to be used under extreme temperature conditions. Regarding sustainability, the main green metrics calculated point to an environmentally friendly process