On the Methyl-Transfer Reaction in Crystalline Methyl 2-(Methylthio)benzenesulfonate: a Thermally Induced Non-Topochemical Solid-State Reaction

The rearrangement of methyl 2-(methylthio)benzenesulfonate (1) to the zwitterionic 2-(dimethyl-sulfonium)benzenesulfonate (2) is known to proceed in solution by intermolecular Me transfers. The same rearrangement has been observed to occur in crystalline 1, but the crystal structure shows that the molecular packing is not conducive to intermolecular Me transfer. The reaction has been carried out with mixed crystals composed of 1 and deuteriomethylated (D6)-l. By fast-atom-bombardment mass spectroscopy, it has been shown that the product consists of a 1:2:1 mixture of the non-, tri-, and hexadeuterated species, the mixture expected, if the solid-state reaction proceeds by intermolecular Me transfers. From this result, together with the slower rates of conversion in the single crystal compared with the melt, it can be concluded that the reaction must occur not topochemically but rather at defects such as microcavities, surfaces, and other irregularities in the ordered crystal arrangement.

Autophagy in malignant transformation and cancer progression.

Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy.

Corporate aging and investment decisions

Paper I: Corporate aging and internal resource allocation Abstract Various observers argue that established firms are at a disadvantage in pursuing new growth opportunities. In this paper, we provide systematic evidence that established firms allocate fewer resources to high-growth lines of business. However, we find no evidence of inefficient resource allocation in established firms. Redirecting resources from high-growth to low-growth lines of business does not result in lower profitability. Also, resource allocation towards new growth opportunities does not increase when managers of established firms are exposed to takeover and product market threats. Rather, it seems that conservative resource allocation strategies are driven by pressures to meet investors’ expectations. Our empirical evidence, thus, favors the hypothesis that established firms wisely choose to allocate fewer resources to new growth opportunities as external pressures force them to focus on efficiency rather than novelty (Holmström 1989). Paper II: Corporate aging and asset sales Abstract This paper asks whether divestitures are motivated by strategic considerations about the scope of the firm’s activities. Limited managerial capacity implies that exploiting core competences becomes comparatively more attractive than exploring new growth opportunities as firms mature. Divestitures help stablished firms free management time and increase the focus on core competences. The testable implication of this attention hypothesis is that established firms are the main sellers of assets, that their divestiture activity increases when managerial capacity is scarcer, that they sell non-core activities, and that they return the divestiture proceeds to the providers of capital instead of reinvesting them in the firm. We find strong empirical support for these predictions. Paper III: Corporate aging and lobbying expenditures Abstract Creative destruction forces constantly challenge established firms, especially in competitive markets. This paper asks whether corporate lobbying is a competitive weapon of established firms to counteract the decline in rents over time. We find a statistically and economically significant positive relation between firm age and lobbying expenditures. Moreover, the documented age-effect is weaker when firms have unique products or operate in concentrated product markets. To address endogeneity, we use industry distress as an exogenous nonlegislative shock to future rents and show that established firms are relatively more likely to lobby when in distress. Finally, we provide empirical evidence that corporate lobbying efforts by established firms forestall the creative destruction process. In sum, our findings suggest that corporate lobbying is a competitive weapon of established firms to retain profitability in competitive environments.

Detecting outlying studies in meta-regression models using a forward search algorithm.

When considering data from many trials, it is likely that some of them present a markedly different intervention effect or exert an undue influence on the summary results. We develop a forward search algorithm for identifying outlying and influential studies in meta-analysis models. The forward search algorithm starts by fitting the hypothesized model to a small subset of likely outlier-free studies and proceeds by adding studies into the set one-by-one that are determined to be closest to the fitted model of the existing set. As each study is added to the set, plots of estimated parameters and measures of fit are monitored to identify outliers by sharp changes in the forward plots. We apply the proposed outlier detection method to two real data sets; a meta-analysis of 26 studies that examines the effect of writing-to-learn interventions on academic achievement adjusting for three possible effect modifiers, and a meta-analysis of 70 studies that compares a fluoride toothpaste treatment to placebo for preventing dental caries in children. A simple simulated example is used to illustrate the steps of the proposed methodology, and a small-scale simulation study is conducted to evaluate the performance of the proposed method. Copyright © 2016 John Wiley & Sons, Ltd.

Hamlet's Mobility: The Reception of Shakespeare's Tragedy in US-American and Canadian Narrative Fiction

This essay presents a comprehensive study of how Hamlet figures in North American fiction. Gabriele Rippl takes her cue from Stephen Greenblatt’s notion of Shakespeare’s ‘theatrical mobility’ (Greenblatt, Cultural Mobility. Cambridge University Press, 2010). This initial mobility, based on the playwright’s own borrowings, appears to facilitate, or even instigate further migrations. Rippl proceeds to give an overview of adaptations of Shakespeare’s Hamlet in the USA and Canada, thus providing an insight into the historical and cultural uses to which the play has been put by authors such as John Updike or Margaret Atwood. Phenomena such as the ‘republicanization’ of Shakespeare (James Fenimore Cooper), or his appropriation for a feminist counter-discourse in Canada circumscribe a space for the negotiation of cultural and political identities.

The physiological roles of ICAM-1 and ICAM-2 in neutrophil migration into tissues

PURPOSE OF REVIEW Neutrophil extravasation from the blood into tissues is initiated by tethering and rolling of neutrophils on endothelial cells, followed by neutrophil integrin activation and shear resistant arrest, crawling, diapedesis and breaching the endothelial basement membrane harbouring pericytes. Endothelial intercellular cell adhesion molecule (ICAM)-1 and ICAM-2, in conjunction with ICAM-1 on pericytes, critically contribute to each step. In addition, epithelial ICAM-1 is involved in neutrophil migration to peri-epithelial sites. The most recent findings on the role of ICAM-1 and ICAM-2 for neutrophil migration into tissues will be reviewed here. RECENT FINDINGS Signalling via endothelial ICAM-1 and ICAM-2 contributes to stiffness of the endothelial cells at sites of chronic inflammation and junctional maturation, respectively. Endothelial ICAM-2 contributes to neutrophil crawling and initiation of paracellular diapedesis, which then proceeds independent of ICAM-2. Substantial transcellular neutrophil diapedesis across the blood-brain barrier is strictly dependent on endothelial ICAM-1 and ICAM-2. Endothelial ICAM-1 or ICAM-2 is involved in neutrophil-mediated plasma leakage. ICAM-1 on pericytes assists the final step of neutrophil extravasation. Epithelial ICAM-1 rather indirectly promotes neutrophil migration to peri-epithelial sites. SUMMARY ICAM-1 and ICAM-2 are involved in each step of neutrophil extravasation, and have redundant but also distinct functions. Analysis of the role of endothelial ICAM-1 requires simultaneous consideration of ICAM-2.

The Old Ball Game: Organization of Nineteenth Century Professional Base Ball Clubs

The first professional base ball clubs came in two varieties: stock clubs, which paid their players fixed wages, and player cooperatives, in which players shared the proceeds after expenses. We argue that stock clubs were formed with players of known ability, while co-ops were formed with players of unknown ability. Although residual claimancy served to screen out players of inferior ability in co-ops, the process was imperfect due to the team production problem. Based on this argument, we suggest that co-ops functioned as an early minor league system where untried players could seek to prove themselves and eventually move up to wage teams. Empirical analysis of data on player performance and experience in early professional base ball provides support for the theory.

Regulation of myogenesis and suppression of {\it mck\/} 5$\sp\prime$ enhancer elements by TGF$\beta$ and RAS

The regulation of muscle differentiation, like cell differentiation in general, is only now beginning to be understood. Here are described several key features to myogenesis: a beginning, some intermediary events, and an endpoint. Muscle differentiation proceeds spontaneously when myoblasts are cultured in serum-poor medium. Transforming growth factor type $\beta$ (TGF$\beta$), a component of fetal serum, was found to potently suppress muscle differentiation. Prolonged blockade of differentiation required replenishing TGF$\beta$. When TGF$\beta$ was removed, cells rapidly differentiated. Both TGF$\beta$ and RAS, which also blocks myogenesis, suppress the genes for a series of muscle-specific proteins. Regions that regulate transcription of one such gene, muscle creatine kinase (mck), were located by linking progressively smaller parts of the mck 5$\sp\prime$ region to the marker gene cat and testing the constructs for regulated expression of cat in myoblasts and muscle cells. The mck promoter is not muscle-specific but requires activation. Two enhancers were found: a weak, developmentally regulated enhancer within the first intron, and a strong, compact, and tightly developmentally regulated enhancer about 1.2 Kb upstream of the transcription start site. Activity of this enhancer is eliminated by activated ras. Suppression of activated N-RAS restores potency to the upstream enhancer. Further deletion shows the mck 5$\sp\prime$ enhancer to contain an enhancer core with low but significant muscle-specific activity, and at least one peripheral element that augments core activity. The core and this peripheral element were comprised almost entirely of factor-binding motifs. The peripheral element was inactive as a single copy, but was constitutively active in multiple copies. Regions flanking the peripheral element augmented its activity and conferred partial muscle-specificity. The enhancer core is also modulated by its 5$\sp\prime$ flanking region in a complex manner. Site-specific mutants covering most of the enhancer core and interesting flanking sequences have been made; all mutants tested diminish the activity of the 5$\sp\prime$ enhancer. Alteration of the site to which MyoD1 is reported to bind completely inactivates the enhancer. A theoretical analysis of cooperativity is presented, through which the binding of a constitutively expressed nuclear factor is shown to have weak positive cooperativity. In summary, TGF$\beta$, RAS, and enhancer-binding factors are found to be initial, intermediary, and final regulators, respectively, of muscle differentiation. ^

El paisaje como patrimonio : paisaje costero del canal Zanjón Cacique Guaymallén : investigación, sistematización y propuesta

El objetivo del trabajo ha sido la revalorización del Canal Zanjón Cacique Guaymallén como un patrimonio cultural ambiental de los mendocinos. La metodología aplicada incluye el análisis de la trayectoria histórica del asentamiento del Gran Mendoza, el zanjón como parte de la cuenca del río Mendoza, como parte del sistema de drenaje, como parte del sistema de riego. Luego, el reconocimiento de los paisajes particulares del zanjón y una posterior catalogación y ordenación, con el fin de ser material útil al planificador territorial primero y al diseñador urbano después. A modo de conclusión el autor menciona la necesidad implícita de proteger, enriquecer e integrar a la vida y memoria urbanos el cauce, las márgenes, el entorno y el oasis al que da vida el zanjón; junto con la urgencia de proyectar a futuro nuevamente los cursos de agua como potenciales ordenadores del territorio y su rol central en la planificación urbana.

Carbonate mineralogical and isotopic analyses of TV-guided grab samples and TV-guided box corer samples from the Shumagin area

Methane seepage leads to Mg-calcite and aragonite precipitation at a depth of 4,850 m on the Aleutian accretionary margin. Stromatolitic and oncoid growth structures imply encrustation of microorganisms (microbial mats) in the host sediment with a unique growth direction downward into the sediment, forming crust-shaped lithologies. Biomarker investigations of the residue after carbonate dissolution show strong enrichments in crocetane and archaeol, which contain extremely low d13C values. This indicates the presence of methane-consuming archaea, and d13C values of -42 to -51 per mill PDB indicate that methane is the carbon source for the carbonate crusts. Thus, it appears that stromatolitic encrustations of methanotrophic anaerobic archaea probably occurs in a consortium with sulphate-reducing bacteria and that carbonate precipitation proceeds downward into the sediment, where ascending cold fluids provide a methane source. Strontium and oxygen isotope analyses as well as 14C ages of the carbonates suggest that the fluids come from deep within the sediment and that carbonate precipitation began about 3,000 years ago.

Apuntes sobre militancia, política, ocio y sociabilidad a través de la experiencia de izquierda y antifascista en el interior de la provincia de Buenos Aires en la época de la restauración conservadora (1932-1943)

El presente artículo reflexiona acerca de las relaciones existentes entre las esferas de la sociabilidad y la política desde el análisis de situaciones en que ellas confluyeron o se interpusieron en la práctica y los discursos de los dirigentes, militantes y simpatizantes izquierdistas y antifascistas en el interior de la Provincia de Buenos Aires durante los gobiernos de orientación conservadora surgidos en los años '30 y principios de los '40. Con información extraída mayoritariamente de la prensa del interior bonaerense, una fuente en general poco consultada, el texto se propone una mirada que se pose en la complejidad de las relaciones entre militancia, ocio, sociabilidad y política, que no centre únicamente en los aspectos ideológicos, la motorización y existencia de la sociabilidad política. Así, la hipótesis central que ha manejado esta investigación, es que las prácticas de sociabilidad y movilización políticas pueden analizarse en mutua correspondencia, sin remitir su construcción a una recepción unilateral y únicamente constreñida al plano ideológico y sin que su deriva se calque desde la imitación aséptica de los diseños que privilegiadamente proponen los diferentes cenáculos de la dirigencia que pretenden -fracasando necesariamente- conducir de manera total y verticalmente los múltiples fenómenos de actuación política.

"El azúcar se forma en el campo" : El papel de las agencias estatales en la modernización de la agricultura cañera tucumana (1880-1910)

Nos proponemos analizar el rol desempeñado por las agencias estatales en el proceso de modernización de la agricultura cañera en Tucumán. Centraremos nuestra atención en la labor desarrollada por el Departamento Nacional de Agricultura (posteriormente convertido en Ministerio) y en el accionar de las oficinas públicas provinciales en la creación de instituciones educativas y experimentales como base para el desarrollo agroindustrial. Como complemento, estudiaremos la interacción entre el Estado y el sector privado (tanto cañeros, industriales, como personal científico involucrado en la actividad) frente a las reformas propuestas para incorporar la agricultura 'científica' en el espacio rural tucumano.

Apuntes sobre militancia, política, ocio y sociabilidad a través de la experiencia de izquierda y antifascista en el interior de la provincia de Buenos Aires en la época de la restauración conservadora (1932-1943)

El presente artículo reflexiona acerca de las relaciones existentes entre las esferas de la sociabilidad y la política desde el análisis de situaciones en que ellas confluyeron o se interpusieron en la práctica y los discursos de los dirigentes, militantes y simpatizantes izquierdistas y antifascistas en el interior de la Provincia de Buenos Aires durante los gobiernos de orientación conservadora surgidos en los años '30 y principios de los '40. Con información extraída mayoritariamente de la prensa del interior bonaerense, una fuente en general poco consultada, el texto se propone una mirada que se pose en la complejidad de las relaciones entre militancia, ocio, sociabilidad y política, que no centre únicamente en los aspectos ideológicos, la motorización y existencia de la sociabilidad política. Así, la hipótesis central que ha manejado esta investigación, es que las prácticas de sociabilidad y movilización políticas pueden analizarse en mutua correspondencia, sin remitir su construcción a una recepción unilateral y únicamente constreñida al plano ideológico y sin que su deriva se calque desde la imitación aséptica de los diseños que privilegiadamente proponen los diferentes cenáculos de la dirigencia que pretenden -fracasando necesariamente- conducir de manera total y verticalmente los múltiples fenómenos de actuación política.

"El azúcar se forma en el campo" : El papel de las agencias estatales en la modernización de la agricultura cañera tucumana (1880-1910)

Nos proponemos analizar el rol desempeñado por las agencias estatales en el proceso de modernización de la agricultura cañera en Tucumán. Centraremos nuestra atención en la labor desarrollada por el Departamento Nacional de Agricultura (posteriormente convertido en Ministerio) y en el accionar de las oficinas públicas provinciales en la creación de instituciones educativas y experimentales como base para el desarrollo agroindustrial. Como complemento, estudiaremos la interacción entre el Estado y el sector privado (tanto cañeros, industriales, como personal científico involucrado en la actividad) frente a las reformas propuestas para incorporar la agricultura 'científica' en el espacio rural tucumano.

Apuntes sobre militancia, política, ocio y sociabilidad a través de la experiencia de izquierda y antifascista en el interior de la provincia de Buenos Aires en la época de la restauración conservadora (1932-1943)

El presente artículo reflexiona acerca de las relaciones existentes entre las esferas de la sociabilidad y la política desde el análisis de situaciones en que ellas confluyeron o se interpusieron en la práctica y los discursos de los dirigentes, militantes y simpatizantes izquierdistas y antifascistas en el interior de la Provincia de Buenos Aires durante los gobiernos de orientación conservadora surgidos en los años '30 y principios de los '40. Con información extraída mayoritariamente de la prensa del interior bonaerense, una fuente en general poco consultada, el texto se propone una mirada que se pose en la complejidad de las relaciones entre militancia, ocio, sociabilidad y política, que no centre únicamente en los aspectos ideológicos, la motorización y existencia de la sociabilidad política. Así, la hipótesis central que ha manejado esta investigación, es que las prácticas de sociabilidad y movilización políticas pueden analizarse en mutua correspondencia, sin remitir su construcción a una recepción unilateral y únicamente constreñida al plano ideológico y sin que su deriva se calque desde la imitación aséptica de los diseños que privilegiadamente proponen los diferentes cenáculos de la dirigencia que pretenden -fracasando necesariamente- conducir de manera total y verticalmente los múltiples fenómenos de actuación política.