Optical in situ calibration of Sb to grow disordered GaInP by MOVPE

Reflectance anisotropy spectroscopy (RAS) was employed to determine the optimal specific molar flow of Sb needed to grow GaInP with a given order parameter by MOVPE. The RAS signature of GaInP surfaces exposed to different Sb/P molar flow ratios were recorded, and the RAS peak at 3.02 eV provided a feature that was sensitive to the amount of Sb on the surface. The range of Sb/P ratios over which Sb acts as a surfactant was determined using the RA intensity of this peak, and different GaInP layers were grown using different Sb/P ratios. The order parameter of the resulting layers was measured by PL at 20 K. This procedure may be extensible to the calibration of surfactant-mediated growth of other materials exhibiting characteristic RAS signatures.

Precios hedónicos para vinos españoles de calidad diferenciada en el mercado estadounidense

El sector del vino se enfrenta a nuevas oportunidades de mercado, debido a la creciente liberalización y globalización del comercio, a las que hay que unir mayores retos, como la competencia en aumento de nuevos actores y el descenso del consumo en los países productores tradicionales. Para hacer frente a esta competencia en mercados emergentes, así como a la saturación de los tradicionales, las estrategias de diferenciación se hacen cada vez más necesarias. La industria vitivinícola española, incluida en un modelo tradicional de producción, también ha sufrido con la aparición en el mercado internacional de nuevos países productores y requiere de procesos de reestructuración de la producción y estrategias innovadoras en el comercio. En España existe un claro desajuste entre oferta y demanda, con descensos en el consumo interno, que apenas cubre la sexta parte de la producción, con la eliminación de los apoyos públicos de regulación y con aumentos continuados de las cosechas. Por ello, la vía más relevante para mantener la rentabilidad del sector es la exportación, aumentando considerablemente el volumen exportado, pero también mejorando el valor de los envíos. Esta situación, sin duda, exige adaptar la oferta española a la demanda global y requiere del conocimiento de los mercados de destino y del diseño de estrategias adecuadas para alcanzar el objetivo marcado. Estados Unidos es un importador neto de vino, debido al incremento de la demanda, que desde 2013 le hizo convertirse en el mayor consumidor mundial en volumen. Este consumo en expansión no es cubierto por la producción interna, y los vinos importados adquieren un creciente interés para el consumidor estadounidense. España tiene tasas de incremento significativas en este destino, pero sus cuotas de mercado aún se sitúan en niveles inferiores a las de muchos países competidores y el consumidor medio estadounidense no tiene un elevado conocimiento del vino español, por lo que existe una gran capacidad de crecimiento. En este contexto, se plantea la necesidad de examinar el comportamiento de la demanda de EE.UU. frente a los atributos del vino español. Identificar y analizar las características que la demanda estadounidense, como mercado de exportación, considera relevantes en el vino español de calidad diferenciada, procedente de distintas regiones productoras, y posteriormente determinar su grado de importancia, de manera que se puedan plantear herramientas para la toma de decisiones empresariales y para la definición de estrategias comerciales, por parte de productores, exportadores y distribuidores vitivinícolas. El análisis de precios hedónicos, metodología ampliamente utilizada en el sector, trata de explicar la decisión de compra de determinado producto en base a una combinación de sus atributos, además de estimar el precio implícito de cada uno de ellos. Por tanto, este enfoque resulta indicado y ha sido el empleado para proporcionar a los operadores del lado de la oferta la posibilidad de comprobar los beneficios previstos de sus inversiones, comparándolos con los costes asociados a dicho esfuerzo inversor. La estimación hedónica se realiza sobre una muestra representativa de exportaciones de bodegas españolas, obtenida de una guía especializada de EE.UU. de amplia difusión en dicho mercado. Se realizan análisis tanto para el conjunto de la muestra, como para los distintos segmentos de precio (super premium, popular premium y ultra premium), y de ellos se deriva que seis grupos de variables presentan influencia sobre la apreciación del consumidor: añada, categoría comercial (grado de envejecimiento y vinos boutique), nota de calidad, origen, tipo de vino (según su color) y tamaño de la bodega. Cualquier decisión empresarial adoptada respecto a alguno de estos atributos es relevante respecto al posicionamiento del vino en el mercado estadounidense. Al margen de determinadas particularidades y del origen del vino, que presenta conductas diferentes según el segmento de precios, se observa un comportamiento similar de la demanda respecto a cada grupo de variables en los distintos tramos del mercado. Por otro lado, es necesario señalar que el rango super premium es el de mayor complejidad a la hora de tomar decisiones y en el que se dan un mayor número de posibilidades de actuación a la hora de posicionar el producto, ya que es en el que un mayor número de parámetros resulta de interés para el consumidor. El comprador estadounidense presta gran atención a la categoría del vino, siendo el factor más influyente sobre el precio de manera general. La demanda estadounidense valora de un modo importante el grado de envejecimiento de los vinos, así como su posicionamiento en precios altos que reflejen características específicas, como ocurre en los vinos boutique, especialmente apreciados en el segmento ultra premium. En este sentido, sería pertinente analizar los costes asociados a procurar a los vinos, en el caso de ser aptos para ello, un mayor envejecimiento o para elaborar un vino boutique dirigido a este mercado, o bien centrar las exportaciones en este tipo de vinos, para comprobar si se obtienen mayores beneficios con estas operaciones. Se presentan como excepción los vinos calificados como crianza que se equiparan a los vinos jóvenes o presentan peor apreciación, por lo que puede no resultar rentable un envejecimiento del vino hasta esa categoría. Por otro lado, se observa en los dos tramos inferiores de precio, que el consumidor estadounidense sabe apreciar las oportunidades de encontrar un vino de calidad en un precio inferior al esperado, por lo que aparecen oportunidades para establecer estrategias de comercialización, vía ofertas o promociones, para penetrar en el mercado. El factor exclusividad, medido a través del tamaño de la bodega, puede servir como instrumento de diferenciación comercial en EE.UU. al presentar valor añadido para la demanda, que aprecia en mayor medida los vinos elaborados por microempresas, frente a los de grandes empresas, que obtienen los peores resultados. En los vinos super premium crece la importancia de este factor, frente al tramo inferior donde el peso de las decisiones recae en otros parámetros. En ultra premium, la demanda relaciona más el factor exclusividad con la categoría boutique y no tanto con el menor tamaño de la empresa. En cuanto al tipo de vino, resulta el atributo menos relevante para el consumidor a la hora de tomar una decisión de compra, e incluso no es significativo en el segmento inferior de precios. Por tanto, las bodegas podrían tratar de introducirse en el mercado popular premium sin atender al color del vino como aspecto clave. De manera general, los vinos tintos presentan una mayor valoración frente a los blancos y rosados, teniendo estos últimos consideración negativa para el cliente. El origen del vino es relevante en las elecciones del consumidor y tiene utilidad como elemento diferenciador. Por tanto, la localización de una bodega puede favorecer o perjudicar su penetración en EE.UU. Resulta interesante que, en el tramo superior de precios, gran parte de las apreciaciones sobre los distintos orígenes son positivas, lo que va en favor de la asociación de los vinos españoles a un cierto factor prestigio y con la generación de una buena imagen general. Sin embargo, no hay muchas procedencias significativas en este estrato, por lo que son necesarios mayores esfuerzos promocionales y de posicionamiento, para ampliar el conocimiento y aceptación por el mercado de EE.UU. y mejorar así el citado factor prestigio. De manera global, la mejor valoración por la demanda se produce en los orígenes del norte de la península, mientras que la submeseta sur, zonas colindantes y Aragón tienen apreciaciones negativas. En este sentido, hay determinados orígenes, como Yecla, Utiel-Requena, Cariñena, Vinos de la Tierra de Castilla o, especialmente, Valdepeñas, que han de modificar sus estrategias de promoción, si existieran, o emprender trabajos intensos en esta línea. Por otro lado, se muestra que la mayor penetración de mercado ayuda a un mayor conocimiento y a una mejor valoración por parte del cliente. Las denominaciones de origen Rioja, Ribera de Duero, Priorat, Penedès, Rueda y Toro, orígenes con elevada presencia en la muestra, son reconocidas positivamente. Excepciones a esta afirmación, DO Navarra y Rías Baixas, deben aumentar la promoción y replantear las estrategias de posicionamiento, ya que el consumidor no parece predispuesto a comprar un vino de estas procedencias por encima de determinado nivel de precio. Finalmente, se destaca que hay orígenes, como DO Campo de Borja o IGP Vino de la Tierra de Castilla y León, con mayor valoración a mayor precio, por lo que deberían aprovechar esta percepción de buena calidad para penetrar en el mercado, especialmente en los tramos superiores de precio. En general, el consumidor estadounidense considera la añada como un factor de media relevancia en la toma de decisiones, con menos importancia en ultra premium que entre los vinos del segmento inferior y medio. En todos los análisis hay coincidencia en la mejor valoración de las últimas añadas, hecho que puede guardar relación con el aumento de la presencia y del mayor conocimiento de los vinos españoles en EE.UU. En cualquier caso, no resultaría interesante la exportación de vinos de años de cosecha antiguos, especialmente en los tramos más baratos de precios, dado que su valor puede no verse recompensado. Finalmente indicar que el mercado estadounidense tiene gran consideración, y de manera directamente proporcional, por la nota de calidad otorgada por expertos, más notablemente a medida que aumenta el precio, y la obtención de las máximas calificaciones puede suponer una apreciación significativa, mientras que una nota situada en los valores inferiores será considerada negativamente y prácticamente del mismo modo por el consumidor. Por tanto, para el elaborador del vino resultaría muy relevante obtener una de las máximas calificaciones, ya que sólo a partir de los 90 puntos se consigue un impacto positivo considerable, que permita rentabilizar los esfuerzos inversores realizados a tal fin.

Cell adhesion and the integrin-linked kinase regulate the LEF-1 and β-catenin signaling pathways

The integrin-linked kinase (ILK) is an ankyrin repeat containing serine-threonine protein kinase that can interact directly with the cytoplasmic domains of the β1 and β3 integrin subunits and whose kinase activity is modulated by cell–extracellular matrix interactions. Overexpression of constitutively active ILK results in loss of cell–cell adhesion, anchorage-independent growth, and tumorigenicity in nude mice. We now show that modest overexpression of ILK in intestinal epithelial cells as well as in mammary epithelial cells results in an invasive phenotype concomitant with a down-regulation of E-cadherin expression, translocation of β-catenin to the nucleus, formation of a complex between β-catenin and the high mobility group transcription factor, LEF-1, and transcriptional activation by this LEF-1/β-catenin complex. We also find that LEF-1 protein expression is rapidly modulated by cell detachment from the extracellular matrix, and that LEF-1 protein levels are constitutively up-regulated at ILK overexpression. These effects are specific for ILK, because transformation by activated H-ras or v-src oncogenes do not result in the activation of LEF-1/β-catenin. The results demonstrate that the oncogenic properties of ILK involve activation of the LEF-1/β-catenin signaling pathway, and also suggest ILK-mediated cross-talk between cell–matrix interactions and cell–cell adhesion as well as components of the Wnt signaling pathway.

Mitogenic and oncogenic properties of the small G protein Rap1b

It has been widely reported that the small GTP-binding protein Rap1 has an anti-Ras and anti-mitogenic activity. Thus, it is generally accepted that a normal physiological role of Rap1 proteins is to antagonize Ras mitogenic signals, presumably by forming nonproductive complexes with proteins that are typically effectors or modulators of Ras. Rap1 is activated by signals that raise intracellular levels of cAMP, a molecule that has long been known to exert both inhibitory and stimulatory effects on cell growth. We have now tested the intriguing hypothesis that Rap1 could have mitogenic effects in systems in which cAMP stimulates cell proliferation. The result of experiments addressing this possibility revealed that Rap1 has full oncogenic potential. Expression of Rap1 in these cells results in a decreased doubling time, an increased saturation density, and an unusual anchorage-dependent morphological transformation. Most significantly, however, Rap1-expressing cells formed tumors when injected into nude mice. Thus, we propose that the view that holds Rap1 as an antimitogenic protein should be restricted and conclude that Rap1 is a conditional oncoprotein.

Rsk-2 activity is necessary for epidermal growth factor-induced phosphorylation of CREB protein and transcription of c-fos gene

Activation by growth factors of the Ras-dependent signaling cascade results in the induction of p90 ribosomal S6 kinases (p90rsk). These are translocated into the nucleus upon phosphorylation by mitogen-activated protein kinases, with which p90rsk are physically associated in the cytoplasm. In humans there are three isoforms of the p90rsk family, Rsk-1, Rsk-2, and Rsk-3, which are products of distinct genes. Although these isoforms are structurally very similar, little is known about their functional specificity. Recently, mutations in the Rsk-2 gene have been associated with the Coffin–Lowry syndrome (CLS). We have studied a fibroblast cell line established from a CLS patient that bears a nonfunctional Rsk-2. Here we document that in CLS fibroblasts there is a drastic attenuation in the induced Ser-133 phosphorylation of transcription factor CREB (cAMP response element-binding protein) in response to epidermal growth factor stimulation. The effect is specific, since response to serum, cAMP, and UV light is unaltered. Furthermore, epidermal growth factor-induced expression of c-fos is severely impaired in CLS fibroblasts despite normal phosphorylation of serum response factor and Elk-1. Finally, coexpression of Rsk-2 in transfected cells results in the activation of the c-fos promoter via the cAMP-responsive element. Thus, we establish a link in the transduction of a specific growth factor signal to changes in gene expression via the phosphorylation of CREB by Rsk-2.

20-Hydroxyeicosatetraenoic acid mediates calcium/calmodulin-dependent protein kinase II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells

Norepinephrine (NE) and angiotensin II (Ang II), by promoting extracellular Ca2+ influx, increase Ca2+/calmodulin-dependent kinase II (CaMKII) activity, leading to activation of mitogen-activated protein kinase (MAPK) and cytosolic phospholipase A2 (cPLA2), resulting in release of arachidonic acid (AA) for prostacyclin synthesis in rabbit vascular smooth muscle cells. However, the mechanism by which CaMKII activates MAPK is unclear. The present study was conducted to determine the contribution of AA and its metabolites as possible mediators of CaMKII-induced MAPK activation by NE, Ang II, and epidermal growth factor (EGF) in vascular smooth muscle cells. NE-, Ang II-, and EGF-stimulated MAPK and cPLA2 were reduced by inhibitors of cytochrome P450 (CYP450) and lipoxygenase but not by cyclooxygenase. NE-, Ang II-, and EGF-induced increases in Ras activity, measured by its translocation to plasma membrane, were abolished by CYP450, lipoxygenase, and farnesyltransferase inhibitors. An AA metabolite of CYP450, 20-hydroxyeicosatetraenoic acid (20-HETE), increased the activities of MAPK and cPLA2 and caused translocation of Ras. These data suggest that activation of MAPK by NE, Ang II, and EGF is mediated by a signaling mechanism involving 20-HETE, which is generated by stimulation of cPLA2 by CaMKII. Activation of Ras/MAPK by 20-HETE amplifies cPLA2 activity and releases additional AA by a positive feedback mechanism. This mechanism of Ras/MAPK activation by 20-HETE may play a central role in the regulation of other cellular signaling molecules involved in cell proliferation and growth.

Subtraction hybridization identifies a transformation progression-associated gene PEG-3 with sequence homology to a growth arrest and DNA damage-inducible gene

Cancer is a progressive multigenic disorder characterized by defined changes in the transformed phenotype that culminates in metastatic disease. Determining the molecular basis of progression should lead to new opportunities for improved diagnostic and therapeutic modalities. Through the use of subtraction hybridization, a gene associated with transformation progression in virus- and oncogene-transformed rat embryo cells, progression elevated gene-3 (PEG-3), has been cloned. PEG-3 shares significant nucleotide and amino acid sequence homology with the hamster growth arrest and DNA damage-inducible gene gadd34 and a homologous murine gene, MyD116, that is induced during induction of terminal differentiation by interleukin-6 in murine myeloid leukemia cells. PEG-3 expression is elevated in rodent cells displaying a progressed-transformed phenotype and in rodent cells transformed by various oncogenes, including Ha-ras, v-src, mutant type 5 adenovirus (Ad5), and human papilloma virus type 18. The PEG-3 gene is transcriptionally activated in rodent cells, as is gadd34 and MyD116, after treatment with DNA damaging agents, including methyl methanesulfonate and γ-irradiation. In contrast, only PEG-3 is transcriptionally active in rodent cells displaying a progressed phenotype. Although transfection of PEG-3 into normal and Ad5-transformed cells only marginally suppresses colony formation, stable overexpression of PEG-3 in Ad5-transformed rat embryo cells elicits the progression phenotype. These results indicate that PEG-3 is a new member of the gadd and MyD gene family with similar yet distinct properties and this gene may directly contribute to the transformation progression phenotype. Moreover, these studies support the hypothesis that constitutive expression of a DNA damage response may mediate cancer progression.

Revival of oscillation from mean-field-induced death : Theory and experiment

Submitted ACKNOWLEDGMENTS T. B. acknowledges the financial support from SERB, Department of Science and Technology (DST), India [Project Grant No.: SB/FTP/PS-005/2013]. D. G. acknowledges DST, India, for providing support through the INSPIRE fellowship. J. K. acknowledges Government of the Russian Federation (Agreement No. 14.Z50.31.0033 with Institute of Applied Physics RAS).

Do the recent severe droughts in the Amazonia have the same period of length?

5 figures Acknowledgments This work was partially supported by the NNSFC (Grant Nos. 11305062, 11135001), the DFG/FAPESP (Grant No. IRTG 1740/TRP 2011/50151-0), and Government of the Russian Federation (Agreement No. 14.Z50.31.0033 with Institute of Applied Physics RAS). All data for this paper is properly cited and referred to in the reference list.

Stability threshold approach for complex dynamical systems

Acknowledgments This paper was developed within the scope of the IRTG 1740/TRP 2011/50151-0, funded by the DFG/FAPESP, and supported by the Government of the Russian Federation (Agreement No. 14.Z50.31.0033 with the Institute of Applied Physics RAS). The first author thanks Dr Roman Ovsyannikov for valuable discussions regarding estimation of the mistake probability.

Complementation of sporulation and motility defects in a prokaryote by a eukaryotic GTPase

The complex prokaryote, Myxococcus xanthus, undergoes a program of multicellular development when starved for nutrients, culminating in sporulation. M. xanthus makes MglA, a 22-kDa, soluble protein that is required for both multicellular development and gliding motility. MglA is similar in sequence to the Saccharomyces cerevisiae SAR1 protein, a member of the Ras/Rab/Rho superfamily of small eukaryotic GTPases. The SAR1 gene, when integrated into the M. xanthus genome, complements the sporulation defect of a ΔmglA strain. A forward, second-site mutation on the M. xanthus chromosome, rpm, in combination with SAR1, restores fruiting body morphogenesis and gliding motility to a ΔmglA strain. The result that the rpm mutation suppresses the substitution of SAR1 for mglA suggests that Sar1p interacts with other M. xanthus proteins to control the motility-dependent aggregation of cells during development.

The signal recognition particle receptor of Escherichia coli (FtsY) has a nucleotide exchange factor built into the GTPase domain

Targeting of many secretory and membrane proteins to the inner membrane in Escherichia coli is achieved by the signal recognition particle (SRP) and its receptor (FtsY). In E. coli SRP consists of only one polypeptide (Ffh), and a 4.5S RNA. Ffh and FtsY each contain a conserved GTPase domain (G domain) with an α-helical domain on its N terminus (N domain). The nucleotide binding kinetics of the NG domain of the SRP receptor FtsY have been investigated, using different fluorescence techniques. Methods to describe the reaction kinetically are presented. The kinetics of interaction of FtsY with guanine nucleotides are quantitatively different from those of other GTPases. The intrinsic guanine nucleotide dissociation rates of FtsY are about 105 times higher than in Ras, but similar to those seen in GTPases in the presence of an exchange factor. Therefore, the data presented here show that the NG domain of FtsY resembles a GTPase–nucleotide exchange factor complex not only in its structure but also kinetically. The I-box, an insertion present in all SRP-type GTPases, is likely to act as an intrinsic exchange factor. From this we conclude that the details of the GTPase cycle of FtsY and presumably other SRP-type GTPases are fundamentally different from those of other GTPases.

The helical domain of a G protein α subunit is a regulator of its effector

The α subunit (Gα) of heterotrimeric G proteins is a major determinant of signaling selectivity. The Gα structure essentially comprises a GTPase “Ras-like” domain (RasD) and a unique α-helical domain (HD). We used the vertebrate phototransduction model to test for potential functions of HD and found that the HD of the retinal transducin Gα (Gαt) and the closely related gustducin (Gαg), but not Gαi1, Gαs, or Gαq synergistically enhance guanosine 5′-γ[-thio]triphosphate bound Gαt (GαtGTPγS) activation of bovine rod cGMP phosphodiesterase (PDE). In addition, both HDt and HDg, but not HDi1, HDs, or HDq attenuate the trypsin-activated PDE. GαtGDP and HDt attenuation of trypsin-activated PDE saturate with similar affinities and to an identical 38% of initial activity. These data suggest that interaction of intact Gαt with the PDE catalytic core may be caused by the HD moiety, and they indicate an independent site(s) for the HD moiety of Gαt within the PDE catalytic core in addition to the sites for the inhibitory Pγ subunits. The HD moiety of GαtGDP is an attenuator of the activated catalytic core, whereas in the presence of activated GαtGTPγS the independently expressed HDt is a potent synergist. Rhodopsin catalysis of Gαt activation enhances the PDE activation produced by subsaturating levels of Gαt, suggesting a HD-moiety synergism from a transient conformation of Gαt. These results establish HD-selective regulations of vertebrate retinal PDE, and they provide evidence demonstrating that the HD is a modulatory domain. We suggest that the HD works in concert with the RasD, enhancing the efficiency of G protein signaling.

Alternative genetic pathways in colorectal carcinogenesis

The comparative typing of matched tumor and blood DNAs at dinucleotide repeat (microsatellite) loci has revealed in tumor DNA the presence of alleles that are not observed in normal DNA. The occurrence of these additional alleles is possibly due to replication errors (RERs). Although this observation has led to the recognition of a subtype of colorectal cancer with a high incidence of RERs (caused by a deficiency in DNA mismatch repair), a thorough analysis of the RER frequency in a consecutive series of colorectal cancers had not been reported. It is shown here that the extensive typing of 88 colorectal tumors reveals a bimodal distribution for the frequency of RER at microsatellite loci. Within the major mode (75 tumors, RER− subtype), the probability that a locus exhibited instability did not differ significantly among loci and tumors, being 0.02. The subsequent development of a statistical test for an operational discrimination between the RER− and RER+ subtypes indicated that the probability of misclassification did not exceed 0.001 in this series. The frequency of K-ras mutation was found to be equivalent in the two subtypes. However, in the RER+ tumors, the p53 gene mutation was less frequently detected, the adenomatous polyposis coli (APC) mutation was rare, and the biallelic inactivation of either of these genes was not observed. Furthermore, the concomitant occurrence of APC and tumor growth factor β receptor type II gene alterations was found only once. These data suggest that the repertoires of genes that are frequently altered in RER+ and RER− tumors may be more different than previously thought.

Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK

A human fibroblast cDNA expression library was screened for cDNA clones giving rise to flat colonies when transfected into v-Ki-ras-transformed NIH 3T3 cells. One such gene, RECK, encodes a membrane-anchored glycoprotein of about 110 kDa with multiple epidermal growth factor-like repeats and serine-protease inhibitor-like domains. While RECK mRNA is expressed in various human tissues and untransformed cells, it is undetectable in tumor-derived cell lines and oncogenically transformed cells. Restored expression of RECK in malignant cells resulted in suppression of invasive activity with concomitant decrease in the secretion of matrix metalloproteinase-9 (MMP-9), a key enzyme involved in tumor invasion and metastasis. Moreover, purified RECK protein was found to bind to, and inhibit the proteolytic activity of, MMP-9. Thus, RECK may link oncogenic signals to tumor invasion and metastasis.