Synthesis of New Analogues of the Bengamides: Peptidyl Bengamides and Molecular Probes

Isolated from sponges of the Jaspidae family, first members where discovered in 1986. The bengamides represent an interesting and unprecedented family of natural products that displayed striking antitumor activities [1]. The recognition of these natural products as antiangiogenic compounds, in virtue to their inhibition of methionine aminopeptidases, prompted intense research activities in the chemical and biological fields. In fact, the total synthesis of the natural products, together with an extensive variety of analogues, has been reported in the literature [2]. Particularly, we have recently developed a new synthetic methodology which allowed rapid and efficient access to the natural bengamide E (1), together with a wide library of analogues of which the cyclopentyl analogue 2 was identified as a more potent antitumor compound with respect to its natural congener [3]. As continuation of these synthetic efforts, with the objective of identifying new potent and promising analogues, we wish to report our recent synthetic studies directed to the synthesis of new bengamide analogues, featured by the replacement of the caprolactam fragment by a peptidyl residue (compounds type 3). On the other hand, in order to gain insight into the mechanism of the biological action of the bengamides, we describe the preparation of the N-alkyl derivatives 4 and 5, which represent interesting molecules that could be employed as suitable molecular probes.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Mass spectrometry imaging for plant biology: A review

Mass spectrometry imaging (MSI) is a developing technique to measure the spatio-temporal distribution of many biomolecules in tissues. Over the preceding decade, MSI has been adopted by plant biologists and applied in a broad range of areas, including primary metabolism, natural products, plant defense, plant responses to abiotic and biotic stress, plant lipids and the developing field of spatial metabolomics. This review covers recent advances in plant-based MSI, general aspects of instrumentation, analytical approaches, sample preparation and the current trends in respective plant research

SIT4 protein phosphatase is required for the normal accumulation of SWI4, CLN1, CLN2, and HCS26 RNAs during late G1

In Saccharomyces cerevisiae, the RNA levels of the G1 cyclins CLN1, CLN2, and HCS26 increase dramatically during the late G1 phase of the cell cycle. The SIT4 gene, which encodes a serine/threonine protein phosphatase, is required for the normal accumulation of CLN1, CLN2, and HCS26 RNAs during late G1. This requirement for SIT4 in normal G1 cyclin RNA accumulation is at least partly via SWI4. Strains containing mutations in SIT4 are sensitive to the loss of either CLN2 or CLN3 function. At the nonpermissive temperature, temperature-sensitive sit4 strains are blocked for both bud emergence and DNA synthesis. Heterologous expression of CLN2 in the absence of SIT4 function results in DNA synthesis, but most of the cells are still blocked for bud emergence. Therefore, SIT4 is required for at least two late G1 or G1/S functions: the normal accumulation of G1 cyclin RNAs (which is required for DNA synthesis) and some additional function that is required for bud emergence or cell cycle progression through late G1 or G1/S

Aerodynamic Performance and Static Stability and Control of Flat-Top Hypersonic Gliders at Mach Numbers from 0.6 to 18

A study is made of aerodynamic performance and static stability and control at hypersonic speeds. In a first part of the study, the effect of interference lift is investigated by tests of asymmetric models having conical fuselages and arrow plan-form wings. The fuselage of the asymmetric model is located entirely beneath the wing and has a semicircular cross section. The fuselage of the symmetric model was centrally located and has a circular cross section. Results are obtained for Mach numbers from 3 to 12 in part by application of the hypersonic similarity rule. These results show a maximum effect of interference on lift-drag ratio occurring at Mach number of 5, the Mach number at which the asymmetric model was designed to exploit favorable lift interference. At this Mach number, the asymmetric model is indicated to have a lift-drag ratio 11 percent higher than the symmetric model and 15 percent higher than the asymmetric model when inverted. These differences decrease to a few percent at a Mach number of 12. In the course of this part of the study, the accuracy to the hypersonic similarity rule applied to wing-body combinations is demonstrated with experimental results. These results indicate that the rule may prove useful for determining the aerodynamic characteristics of slender configurations at Mach numbers higher than those for which test equipment is really available. In a second part of the study, the aerodynamic performance and static stability and control characteristics of a hypersonic glider are investigated in somewhat greater detail. Results for Mach numbers from 3 to 18 for performance and 0.6 to 12 for stability and control are obtained by standard text techniques, by application of the hypersonic stability rule, and/or by use of helium as a test medium. Lift-drag ratios of about 5 for Mach numbers up to 18 are shown to be obtainable. The glider studied is shown to have acceptable longitudinal and directional stability characteristics through the range of Mach numbers studied. Some roll instability (negative effective dihedral) is found at Mach numbers near 12

Pleistocene climate fluctuations drove demographic history of African golden wolves (Canis lupaster)

Pleistocene climate change impacted entire ecosystems throughout the world. In the northern hemisphere, the distribution of Arctic species expanded during glacial periods, while more temperate and mesic species contracted into climatic refugia, where isolation drove genetic divergence. Cycles of local cooling and warming in the Sahara region of northern Africa caused repeated contractions and expansions of savannah‐like environments which connected mesic species isolated in refugia during interglacial times, possibly driving population expansions and contractions; divergence and geneflow in the associated fauna. Here, we use whole genome sequences of African golden wolves (Canis lupaster), a generalist mesopredator with a wide distribution in northern Africa to estimate their demographic history and past episodes of geneflow. We detect a correlation between divergence times and cycles of increased aridity‐associated Pleistocene glacial cycles. A complex demographic history with responses to local climate change in different lineages was found, including a relict lineage north of the High Atlas Mountains of Morocco that has been isolated for more than 18,000 years, possibly a distinct ecotype.CS was supported by a PhD fellowship from Programa Internacional de Becas “La Caixa-Severo Ochoa” of the Spanish Ministerio de Economía y Competitividad and La Caixa bank (BES-2015-074331). This project was funded by the Frontera grant P18-FR-5099 from the Junta de Andalucia. EBD-CSIC received support from the Spanish Ministry of Economy and Competitiveness under the ‘Centro de Excelencia Severo Ochoa 2013-2017’ program, SEV-2012-0262

Desarrollo de herramientas de búsqueda en los archivos históricos de la CompañÍa de Jesús

El trabajo de los historiadores es pesado y difícil ya que consiste, fundamentalmente, en la localización, análisis e interpretación de documentos antiguos. Estos documentos, cuando están disponibles para su consulta, deben ser leídos uno por uno y todas las posibles referencias cruzadas, revisadas una por una. La Compañía de Jesús llegó a la Nueva España en el siglo XV y trabajó en colegios, misiones, parroquias y hospitales a lo largo de todo el continente hasta la expulsión de la Orden en 1767. Durante este tiempo, la Compañía de Jesús puso en marcha un sistema de comunicación conocido como las Cartas Anuales o Cartas Annuas que el Provincial enviaba al General de la Compañía en Roma. Cada una de las Cartas Anuales relataba las actividades llevadas a cabo por miembros de la Compañía. Para ayudarse a redactar cada Carta y con el fin de circular la información en toda la Provincia de la Nueva España, cada uno de los encargados de las obras enviaba al Provincial una o varias cartas conocidas como Puntos de Annua. La Compañía de Jesús, junto con el Archivo General de la Nación y el Instituto Nacional de Antropología e Historia se dio a la tarea de recopilar todas las Cartas Anuales escritas desde que los jesuitas llegaron a la Nueva España hasta su expulsión en 1767. Esta búsqueda resultó en más de 13000 folios que debieron paleografiarse para ayudar a la investigación histórica sobre la Compañía de Jesús. Como resultado de este trabajo de recuperación y paleografía y para facilitar el acceso y manejo de los documentos, se decidió crear una herramienta informática que ofreciera a los investigadores un motor de búsqueda para hacer referencias cruzadas rápida y fácilmente, así como el acceso a los documentos a través de índices temáticos. El desarrollo de esta herramienta presentó varios problemas técnicos que se han ido solucionando. Por ejemplo, la necesidad de que los documentos en formato electrónico siguieran fielmente las reglas de la paleografía. Este requerimiento hizo necesaria la realización de un filtro para manipular los archivos en formato XML. Se desarrolló también la interfaz gráfica para acceder a los índices temáticos y el motor de búsqueda para realizar referencias cruzadas en una o varias palabras, continuas o discontinuas en el texto del documento. La herramienta ha sido bien recibida por los investigadores y se ha decido aumentarla con algoritmos de Text-Mining para aumentar las capacidades de la búsqueda así como la generación de referencias cruzadas entre los documentos.ITESO, A.C

A Note on Combining Machine Learning with Statistical Modeling for Financial Data Analysis

This note revisits the ideas of the so-called semiparametric methods that we consider to be very useful when applying machine learning in insurance. To this aim, we first recall the main essence of semiparametrics like the mixing of global and local estimation and the combining of explicit modeling with purely data adaptive inference. Then, we discuss stepwise approaches with different ways of integrating machine learning. Furthermore, for the modeling of prior knowledge, we introduce classes of distribution families for financial data. The proposed procedures are illustrated with data on stock returns for five companies of the Spanish value-weighted index IBEX35.The authors thank the Institute and Faculty of Actuaries in the U.K. for funding their research through the grant “Minimizing Longevity and Investment Risk while Optimizing Future Pension Plans” and the Spanish Ministerio de Economía y Competitividad, Project ECO2016-76203-C2-1-P, for partial support of this work

Biovalorization of Brewery Waste by Applying Anaerobic Digestion

In the food industry, the brewing sector holds a strategic economic position: in the year 2013, the beer production of the EU-28 was equal to 383,553,000 hL. The brewing process includes chemical and biochemical reactions and solid-liquid separations, involving the generation of various residues and by-products, among which the major two fractions are brewer’s spent grain (BSG), and exhausted brewery yeast (BY). Although until today their main use has been for animal feed, in recent years, several studies have investigated the application of anaerobic digestion in order to revalue the brewery wastes. In this work, specific methane production (SMP) and first-order solubilisation (disintegration+ hydrolysis) rates (ksol) for BSG and BY were evaluated. Biomethanation tests were performed in 5-L fed-batch stirred reactors at several substrate/inoculum ratios. The obtained SMP ranged from 0.255 L CH4 g–1 COD for exhausted brewery yeast to 0.284 L CH4 g–1 COD for brewer’s spent grain. The estimated ksol values ranged from 0.224 d–1 for BSG to 0.659 d–1 for BY