María José Sanzo Pérez

Martensitic phase transformation in rapidly solidified Mn50Ni40In10 alloy ribbons

Heusler alloy Mn50Ni40In10 was produced as preferentially textured ribbon flakes by melt spinning, finding the existence of martensitic-austenic transformation with both phases exhibiting ferromagnetic ordering. A microcrystalline three-layered microstructure of ordered columnar grains grown perpendicularly to ribbon plane was formed between two thin layers of smaller grains. The characteristic temperatures of the martensitic transformation were MS=213K, Mf=173K, AS=222K, and Af=243K. Austenite phase shows a cubic L21 structure (a=0.6013(3)nm at 298K and a Curie point of 311K), transforming into a modulated fourteen-layer modulation monoclinic martensite.

Relative cooling power enhancement in magneto-caloric nanostructured Pr2Fe17

The magneto-caloric effect (MCE) of arc-melted bulk and 10 h ball-milled nanostructured Pr2Fe17 powders has been investigated. The maximum value for the magnetic entropy change, |�S M|, in the milled alloy is 4.5 J kg −1 K −1 for µ0H = 5 T, at around room temperature. The full width at half maximum, δTFWHM ,o f|�S M|(T ) for the nanostructured powders is about 60% greater than that of the starting bulk alloy, thus giving rise to large relative cooling power values of 573 J kg −1 (4.5 J cm −3 ) for µ0H = 5 T estimated from the product of |�S M| max × δTFWHM. These results have been compared with those of well-known magnetic materials that exhibit a large or giant MCE effect. The potential for using these low-cost iron based nanostructured Pr2Fe17 powders in magnetic refrigeration at room temperature is also discussed. (Some figures in this article are in colour only in the electronic version)

Deciphering Biosynthesis of the RNA Polymerase Inhibitor Streptolydigin and Generation of Glycosylated Derivatives

The biosynthetic gene cluster for the dienoyltetramic acid streptolydigin was identified and characterized from the producer organism Streptomyces lydicus NRRL2433. Sequence analysis of an 80.8 kb DNA region revealed the presence of 38 ORFs, 29 of which are probably involved in streptolydigin biosynthesis and would code for all activities required for its biosynthesis. Six insertional inactivation mutants were generated in the sequenced region to prove its involvement in streptolydigin biosynthesis, to define the boundaries of the cluster, to functionally characterize some genes, and to generate novel derivatives. A model for streptolydigin biosynthesis is proposed that includes a probable domain skipping in the streptolydigin PKS and the participation of a free-standing adenylation domain protein. Some bioactive derivatives of streptolydigin with altered glycosylation pattern have been produced by combinatorial biosynthesis showing a certain degree of flexibility of the L-rhodinosyl transferase SlgG for the recognition of 2,3,6-trideoxyhexoses and 2,6-dideoxyhexoses, both in D- and L-configuration.

Combining sugar biosynthesis genes for the generation of L- and D-amicetose and formation of two novel antitumor tetracenomycins

L- and D-stereoisomers of amicetose were generated by combining sugar biosynthesis genes from four different antibiotic gene clusters and both sugars were transferred to the elloramycin aglycone by the sugar flexible ElmGT glycosyltransferase.

Generation of new derivatives of the antitumor antibiotic mithramycin by altering the glycosylation pattern through combinatorial biosynthesis.

Mithramycin is an antitumor drug produced by Streptomyces argillaceus. It consists of a tricyclic aglycone and five deoxyhexoses that form a disaccharide and a trisaccharide chain, which are important for target interaction and therefore for the antitumor activity. Using a combinatorial biosynthesis approach, we have generated nine mithramycin derivatives, seven of which are new compounds, with alterations in the glycosylation pattern. The wild‐type S. argillaceus strain and the mutant S. argillaceus M7U1, which has altered D‐oliose biosynthesis, were used as hosts to express various “sugar plasmids”, each one directing the biosynthesis of a different deoxyhexose. The newly formed compounds were purified and characterized by MS and NMR. Compared to mithramycin, they contained different sugar substitutions in the second (D‐olivose, D‐mycarose, or D‐boivinose instead of D‐oliose) and third (D‐digitoxose instead of D‐mycarose) sugar units of the trisaccharide as well as in the first (D‐amicetose instead of D‐olivose) sugar unit of the disaccharide. All compounds showed antitumor activity against different tumor cell lines. Structure–activity relationships are discussed on the basis of the number and type of deoxyhexoses present in these mithramycin derivatives.

A Novel Mithramycin Analogue with High Antitumor Activity and Less Toxicity Generated by Combinatorial Biosynthesis

Mithramycin is an antitumor compound produced by Streptomyces argillaceus that has been used for the treatment of several types of tumors and hypercalcaemia processes. However, its use in humans has been limited because of its side effects. Using combinatorial biosynthesis approaches, we have generated seven new mithramycin derivatives, which differ from the parental compound in the sugar profile or in both the sugar profile and the 3-side chain. From these studies three novel derivatives were identified, demycarosyl-3D-β-d-digitoxosylmithramycin SK, demycarosylmithramycin SDK, and demycarosyl-3D-β-d-digitoxosylmithramycin SDK, which show high antitumor activity. The first one, which combines two structural features previously found to improve pharmacological behavior, was generated following two different strategies, and it showed less toxicity than mithramycin. Preliminary in vivo evaluation of its antitumor activity through hollow fiber assays, and in subcutaneous colon and melanoma cancers xenografts models, suggests that demycarosyl-3D-β-d-digitoxosylmithramycin SK could be a promising antitumor agent worthy of further investigation.

Combinatorial Biosynthesis of Antitumor Deoxysugar Pathways in Streptomyces griseus: Reconstitution of “Unnatural Natural Gene Clusters” for the Biosynthesis of Four 2,6-d-Dideoxyhexoses

ABSTRACT Combinatorial biosynthesis was applied to Streptomyces deoxysugar biosynthesis genes in order to reconstitute “unnatural natural gene clusters” for the biosynthesis of four d-deoxysugars (d-olivose, d-oliose, d-digitoxose, and d-boivinose). Expression of these gene clusters in Streptomyces albus 16F4 was used to prove the functionality of the designed clusters through the generation of glycosylated tetracenomycins. Three glycosylated tetracenomycins were generated and characterized, two of which (d-digitoxosyl-tetracenomycin C and d-boivinosyl-tetracenocmycin C) were novel compounds. The constructed gene clusters may be used to increase the capabilities of microorganisms to synthesize new deoxysugars and therefore to produce new glycosylated bioactive compounds.

Training in Small Business Retailing: Testing Human Capital Theory.

Analyses the training demand in the retail sector based on the study of a representative sample of small‐sized retailers. By means of probit models a set of hypotheses developed from the basic assumptions of the human capital theory are tested. Four models of training demand are considered: probability of attending a training course in the near future, probability of having attended in the past, probability of being willing to follow multimedia and correspondence courses, and probability of repeating the experience of attending another training course in the near future. In particular, we determined how the retailer’s age, sex, educational level and the business sector, location and size, the quality of training previously received, the suitability of the costs and scheduling of the training courses, among other variables, significantly influence the probability of small‐sized retailers attending training courses.

Kinetics of crystallization of FeB-based amorphous alloys studied by neutron thermo-diffractometry

Abstract Kinetics of crystallization of two amorphous alloys, Fe 70 Cr 10 B 20 and Fe 80 Zr 10 B 10 , have been followed up by neutron thermo-diffractometry experiments performed in the two axis diffractometer D20 (Institut Laue-Langevin, Grenoble). The structural changes are directly correlated with the temperature dependence of the magnetization. Fe 70 Cr 10 B 20 crystallizes following a two-step process: an eutectic crystallization of α-Fe (BCC) and the metastable tetragonal phase (Fe 0.8 Cr 0.2 ) 3 B followed by another eutectic transformation to the stable phase (Fe 0.75 Cr 0.25 ) 2 B and more segregation of α-Fe. These tetragonal phases are magnetically anisotropic, giving rise to a large increase of the coercivity. This behavior is similar to that of Fe 80 B 20 alloys, with Cr atoms replacing the Fe positions in both crystalline phases. Fe 80 Zr 10 B 10 shows also a two-step process in which two polymorphic transformations take place.

Annealing Effect on Martensitic Transformation and Magneto-Structural Properties of Ni-Mn-In Melt Spun Ribbons

We report the effect of a short-time vacuum annealing (1073 K during 10 minutes) on structural phase transition temperatures and magneto-structural properties of as-quenched ribbons of the Heusler alloy Ni50.6Mn34.5In14.9. This alloy crystallizes in a single phase cubic B2-type austenite with a Curie point of TCA=284 K that with the lowering in temperature transforms into a martensite with TCM185 K. The direct and reverse martensitic phase transition temperatures were MS=257 K, Mf = 221 K, AS = 239 K, and Af = 266 K. After annealing austenite shows the highly ordered L21-type structure while the average chemical composition as well as the structural and magnetic transition temperatures were shifted to Ni50.2Mn34.3In15.5 and MS = 253 K, Mf = 238 K, AS = 257 K, Af = 265 K, ΔT = 13 K, TCA = 299 K and TCM207 K. In the annealed samples the magnetization changes associated to the magnetic and structural transitions are more abrupt and magnetization isotherms in both the austenitic and martensitic existence region show higher initial magnetic susceptibility and faster approach to saturation. Field-cooled hysteresis loops at 10 K were shifted along the negative H-axis for both samples, but a significant anomaly was evident on the left side of the hysteresis loop for as-quenched ribbons.