Convergent Approaches for the Synthesis of the Anti-tumoral Peptide, Kahalalide F. Study of Orthogonal Protecting Groups

Kahalalide compounds are peptides that are isolated from a Hawaiian herbivorous marine species of mollusc, Elysia rufescens, and its diet, the green alga Bryopsis sp. Kahalalide F and its synthetic analogues are the most promising compounds of the Kahalalide family because they show anti-tumoral activity. Linear solid-phase syntheses of Kahalalide F have been reported. Here we describe several new improved synthetic routes based on convergent approaches with distinct orthogonal protection schemes for the preparation of Kahaladide analogues. These strategies allow a better control and characterization of the intermediates because more reactions are performed in solution. Five derivatives of Kahalalide F were synthesized using several convergent approaches.

A parameterization method for the computation of invariant tori and their whiskers in quasi-periodic maps: explorations and mechanisms for the breakdown of hyperbolicity

In two previous papers [J. Differential Equations, 228 (2006), pp. 530 579; Discrete Contin. Dyn. Syst. Ser. B, 6 (2006), pp. 1261 1300] we have developed fast algorithms for the computations of invariant tori in quasi‐periodic systems and developed theorems that assess their accuracy. In this paper, we study the results of implementing these algorithms and study their performance in actual implementations. More importantly, we note that, due to the speed of the algorithms and the theoretical developments about their reliability, we can compute with confidence invariant objects close to the breakdown of their hyperbolicity properties. This allows us to identify a mechanism of loss of hyperbolicity and measure some of its quantitative regularities. We find that some systems lose hyperbolicity because the stable and unstable bundles approach each other but the Lyapunov multipliers remain away from 1. We find empirically that, close to the breakdown, the distances between the invariant bundles and the Lyapunov multipliers which are natural measures of hyperbolicity depend on the parameters, with power laws with universal exponents. We also observe that, even if the rigorous justifications in [J. Differential Equations, 228 (2006), pp. 530-579] are developed only for hyperbolic tori, the algorithms work also for elliptic tori in Hamiltonian systems. We can continue these tori and also compute some bifurcations at resonance which may lead to the existence of hyperbolic tori with nonorientable bundles. We compute manifolds tangent to nonorientable bundles.

Orthogonal protecting groups in the synthesis of tryptophanyl-hexahydropyrroloindoles

The synthesis of various polycyclic systems containing a C3a-Ni bond between a hexahydropyrrolo[2,3-b]indole and an indole tryptophan is described here. A series of experiments were performed to determine the best combination of five orthogonal protecting groups and the best reaction conditions for formation of said bond, which is a common feature among many recently discovered marine natural products.

The efficiency of indicator groups for the conservation of amphibians in the Brazilian Atlantic Forest

The adequate selection of indicator groups of biodiversity is an important aspect of the systematic conservation planning. However, these assessments differ in the spatial scale, in the methods used and in the groups considered to accomplish this task, which generally produces contradictory results. The quantification of the spatial congruence between species richness and complementarity among different taxonomic groups is a fundamental step to identify potential indicator groups. Using a constructive approach, the main purposes of this study were to evaluate the performance and efficiency of eight potential indicator groups representing amphibian diversity in the Brazilian Atlantic Forest. Data on the geographic range of amphibian species that occur in the Brazilian Atlantic Forest was overlapped to the full geographic extent of the biome, which was divided into a regular equal-area grid. Optimization routines based on the concept of complementarily were applied to verify the performance of each indicator group selected in relation to the representativeness of the amphibians in the Brazilian Atlantic Forest as a whole, which were solved by the algorithm"simulated annealing", through the use of the software MARXAN. Some indicator groups were substantially more effective than others in regards to the representation of the taxonomic groups assessed, which was confirmed by the high significance of data (F = 312.76; p < 0.01). Leiuperidae was considered as the best indicator group among the families analyzed, as it showed a good performance, representing 71% of amphibian species in the Brazilian Atlantic Forest (i.e. 290 species), which may be associated with the diffuse geographic distribution of its species. This study promotes understanding of how the diversity standards of amphibians can be informative for systematic conservation planning on a regional scale.

World Polarization in carbon emissions, potential conflict and groups: an updated revision

Typically, conflicts in world environmental negotiations are related, amongst other aspects, to the level of polarization of the countries in groups with conflicting interests. Given the predictable relationship between polarization and conflict, it would seem logical to evaluate the degree to which the distribution of countries – for example, in terms of their CO2 emissions per capita – would be structured through groups which in themselves are antagonistic, as well as their evolution over time. This paper takes the concept of polarization to explore this distribution for the period 1992-2010, looking at different analytic approaches related to the concept. Specifically, it makes a comparative evaluation of the results associated with endogenous multi-polarization measures (i.e. EGR and DER indices), exogenous measures (i.e. Z-K or multidimensional index) and strict bipolarization measures (i.e. Wolfson’s measure). Indeed, the interest lies not only in evaluating the global situation of polarization by comparing the different approaches and their temporal patterns, but also in examining the explanatory capacity of the different proxy groups used as a possible reference for designing global environmental policy from a group premise. JEL codes: D39; Q43; Q56. Key words: polarization; carbon emissions; conflict;

Versatile methodology to hydrate alkynes, in the presence of a wide variety of functional groups, with Mercury(II) p-Toluensulfonamidate, under catalytic, mild and neutral conditions

A method to generate carbonylic compounds from alkynes under mild and neutral conditions, with excellent functional group compatibility and high yields, is described. Hydration takes place under catalytic conditions by using from 0.1 to 0.2 equivalents of the easily available and inexpensive mercury(II) p-toluensulfonamidate in a hydroalcoholic solution. After use the catalyst is iner tized and/or recycled ...

Convergent Approaches for the Synthesis of the Anti-tumoral Peptide, Kahalalide F. Study of Orthogonal Protecting Groups

Kahalalide compounds are peptides that are isolated from a Hawaiian herbivorous marine species of mollusc, Elysia rufescens, and its diet, the green alga Bryopsis sp. Kahalalide F and its synthetic analogues are the most promising compounds of the Kahalalide family because they show anti-tumoral activity. Linear solid-phase syntheses of Kahalalide F have been reported. Here we describe several new improved synthetic routes based on convergent approaches with distinct orthogonal protection schemes for the preparation of Kahaladide analogues. These strategies allow a better control and characterization of the intermediates because more reactions are performed in solution. Five derivatives of Kahalalide F were synthesized using several convergent approaches.

Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.

Genome-wide linkage studies have identified the 9q22 chromosomal region as linked with colorectal cancer (CRC) predisposition. A candidate gene in this region is transforming growth factor beta receptor 1 (TGFBR1). Investigation of TGFBR1 has focused on the common genetic variant rs11466445, a short exonic deletion of nine base pairs which results in truncation of a stretch of nine alanine residues to six alanine residues in the gene product. While the six alanine (*6A) allele has been reported to be associated with increased risk of CRC in some population based study groups this association remains the subject of robust debate. To date, reports have been limited to population-based case-control association studies, or case-control studies of CRC families selecting one affected individual per family. No study has yet taken advantage of all the genetic information provided by multiplex CRC families. Methods: We have tested for an association between rs11466445 and risk of CRC using several family-based statistical tests in a new study group comprising members of non-syndromic high risk CRC families sourced from three familial cancer centres, two in Australia and one in Spain. Results: We report a finding of a nominally significant result using the pedigree-based association test approach (PBAT; p = 0.028), while other family-based tests were non-significant, but with a p-value < 0.10 in each instance. These other tests included the Generalised Disequilibrium Test (GDT; p = 0.085), parent of origin GDT Generalised Disequilibrium Test (GDT-PO; p = 0.081) and empirical Family-Based Association Test (FBAT; p = 0.096, additive model). Related-person case-control testing using the 'More Powerful' Quasi-Likelihood Score Test did not provide any evidence for association (M-QL5; p = 0.41). Conclusions: After conservatively taking into account considerations for multiple hypothesis testing, we find little evidence for an association between the TGFBR1*6A allele and CRC risk in these families. The weak support for an increase in risk in CRC predisposed families is in agreement with recent meta-analyses of case-control studies, which estimate only a modest increase in sporadic CRC risk among 6*A allele carriers.

Recerca avaluativa sobre el programa “LÍMITS”

Des de la comunitat científica s’ha posat de manifest la necessitat d’avaluar els programes d’intervenció per a la millora de la parentalitat, especialment en el context de la infància i adolescència en risc. En aquesta recerca es presenten els resultats de l’avaluació del programa Límits aportant evidències d’eficàcia i efectivitat, que permeten identificar i descriure les seves fortaleses, així com també aquells elements que poden ser objecte de millora. El programa Límits és una proposta estructurada d’intervenció preventiva de caire selectiu amb grups de famílies de joves d’entre 14 i 18 anys que passen pel circuit de la justícia juvenil. El programa ha estat funcionant des del 2007, en diverses edicions, a tot el territori català aplegant una experiència i trajectòria remarcable que ha incidit en 351 persones i 245 famílies. El programa consta de vuit sessions en grup d’entre dotze i quinze participants, dinamitzat per dos monitors, en les que es treballen diferents estratègies a partir de l’abordatge de continguts relacionats amb les relacions i els lligams, la comunicació, els conflictes, l’establiment de normes i la disciplina. Per dur a terme l’avaluació del programa Límits s’ha partit d’un disseny quasi-experimental, pretest–postest aplicat a un grup programa (GP) i a grup col·laborador (GC) i de manera diferida (dos mesos després de la seva finalització) només al GP per constatar si s’han assolit els resultats previstos. Quan s’analitza l’evolució del GP s’observen millores en les habilitats d’autocontrol de les emocions, el reforç positiu i les relacions familiars. Tanmateix, des del punt de vista de les famílies no s’han observat canvis significatius en la millora de la percepció d’auto eficàcia del rol parental respecte el GC abans i després del programa. La percepció majoritària és que els objectius que planteja el programa són excessivament ambiciosos i en conseqüència, difícilment assolibles. Els responsables consideren que, en alguns casos, el perfil de famílies derivades al programa no és el més adequat perquè presenten problemàtiques molt més agudes a les desitjables per aquest tipus d’intervenció. Com a punts forts, es destaca que el programa és útil als ulls dels responsables i tècnics perquè genera una presa de consciència del problema i de la necessitat de canvi per part de les famílies. Els participants diuen transferir a la vida real algunes habilitats apreses especialment la comunicació i millora de les relacions familiars. Els tècnics aplicadors coincideixen amb la percepció de les famílies tot i declarar percentatges lleugerament inferiors. També és vist com un complement professional a la seva tasca que ajuda a fer un millor seguiment dels casos, i permet seguir treballant amb posterioritat amb les famílies.

Investigación evaluativa sobre el programa "LÍMITES"

Desde la comunidad científica se ha puesto de manifiesto la necesidad de evaluar los programas de intervención para la mejora de la parentalidad, especialmente en el contexto de la infancia y la adolescencia en riesgo. En esta investigación se presentan los resultados de la evaluación del programa Límites aportando evidencias de eficacia y efectividad, que permiten identificar y describir sus fortalezas, así como también aquellos elementos que pueden ser objeto de mejora. El programa Límites es una propuesta estructurada de intervención preventiva de carácter selectivo, con grupos de familias de jóvenes de entre 14 y 18 años que pasan por el circuito de la justicia juvenil. El programa ha estado funcionando desde 2007 en todo el territorio catalán, y ha incidido en un total de 351 personas y 245 familias. El programa consta de ocho sesiones en grupo en las que se trabajan contenidos relacionados con las relaciones y los vínculos, la comunicación, los conflictos, el establecimiento de normas y la disciplina. Para llevar a cabo la evaluación del programa Límites se ha partido de un diseño cuasi-experimental, pretest-postest aplicado a un grupo programa (GP) y grupo colaborador (GC) y de manera diferida (dos meses después de su finalización) sólo en el GP, para constatar si se han alcanzado los resultados previstos. Cuando se analiza la evolución del GP se observan mejoras en las habilidades de autocontrol de las emociones, el refuerzo positivo y las relaciones familiares. Sin embargo, desde el punto de vista de las familias no se han observado cambios significativos en la mejora de la percepción de auto eficacia del rol parental respecto al GC antes y después del programa. La percepción mayoritaria es que los objetivos que plantea el programa son excesivamente ambiciosos y en consecuencia, difícilmente alcanzables. Los responsables consideran que, en algunos casos, el perfil de familias derivadas al programa no es el más adecuado puesto que presenten problemáticas mucho más agudas a las deseables para este tipo de intervención. Como puntos fuertes, se destaca que el programa es útil a los ojos de los responsables y técnicos porque genera una toma de conciencia del problema y de la necesidad de cambio por parte de las familias. Los participantes dicen transferir a la vida real algunas habilidades aprendidas, especialmente la comunicación y mejora de las relaciones familiares. Los técnicos aplicadores coinciden con la percepción de las familias, a pesar de declarar porcentajes ligeramente inferiores. También es visto como un complemento profesional a su tarea que ayuda a hacer un mejor seguimiento de los casos, y permite seguir trabajando con posterioridad con las familias.

Essential factors for control of the equilibrium in the reversible rearrangement of M3N@Ih-C80 fulleropyrrolidines: Exohedral functional groups versus endohedral metal clusters

The effects of exohedral moieties and endohedral metal clusters on the isomerization of M3N@Ih-C80 products from the Prato reaction through [1,5]-sigmatropic rearrangement were systematically investigated by using three types of fulleropyrrolidine derivatives and four different endohedral metal clusters. As a result, all types of derivatives provided the same ratios of the isomers for a given trimetallic nitride template (TNT) as the thermodynamic products, thus indicating that the size of the endohedral metal clusters inside C80 was the single essential factor in determining the equilibrium between the [6,6]-isomer (kinetic product) and the [5,6]-isomer. In all the derivatives, the [6,6]- and [5,6]-Prato adducts with larger metal clusters, such as Y3N and Gd3N, were equally stable, which is in good agreement with DFT calculations. The reaction rate of the rearrangement was dependent on both the substituent of exohedral functional groups and the endohedral metal-cluster size. Further DFT calculations and 13C NMR spectroscopic studies were employed to rationalize the equilibrium in the rearrangement between the [6,6]- and [5,6]-fulleropyrrolidines

The adequacy of different robust statistical tests in comparing two independent groups

In the current study, we evaluated various robust statistical methods for comparing two independent groups. Two scenarios for simulation were generated: one of equality and another of population mean differences. In each of the scenarios, 33 experimental conditions were used as a function of sample size, standard deviation and asymmetry. For each condition, 5000 replications per group were generated. The results obtained by this study show an adequate type error I rate but not a high power for the confidence intervals. In general, for the two scenarios studied (mean population differences and not mean population differences) in the different conditions analysed, the Mann-Whitney U-test demonstrated strong performance, and a little worse the t-test of Yuen-Welch.