Palladium Isotopic Evidence for Nucleosynthetic and Cosmogenic Isotope Anomalies in IVB Iron Meteorites

The origin of ubiquitous nucleosynthetic isotope anomalies in meteorites may represent spatial and/or temporal heterogeneity in the sources that supplied material to the nascent solar nebula, or enhancement by chemical processing. For elements beyond the Fe peak, deficits in s-process isotopes have been reported in some (e.g., Mo, Ru, W) but not all refractory elements studied (e.g., Os) that, among the iron meteorites, are most pronounced in IVB iron meteorites. Palladium is a non-refractory element in the same mass region as Mo and Ru. In this study, we report the first precise Pd isotopic abundances from IVB irons to test the mechanisms proposed for the origin of isotope anomalies. First, this study determined the existence of a cosmogenic neutron dosimeter from the reaction 103Rh(n, beta-)104Pd in the form of excess 104Pd, correlated with excess 192Pt, in IVB irons. Second, all IVB irons show a deficit of the s-process only isotope 104Pd (\varepsilon 104Pd = -0.48 ± 0.24), an excess of the r-only isotope 110Pd (\varepsilon 110Pd = +0.46 ± 0.12), and no resolvable anomaly in the p-process 102Pd (\varepsilon 102Pd = +1 ± 1). The magnitude of the Pd isotope anomaly is about half that predicted from a uniform depletion of the s-process yields from the correlated isotope anomalies of refractory Mo and Ru. The discrepancy is best understood as the result of nebular processing of the less refractory Pd, implying that all the observed nucleosynthetic anomalies in meteorites are likely to be isotopic relicts. The Mo-Ru-Pd isotope systematics do not support enhanced rates of the 22Ne(alpha,n)25Mg neutron source for the solar system s-process.

The Process of Starting a Business

Many students are inspired to start their own business venture after taking some courses in school or simply just taking an idea and turning it into a business. The beginning process is usually most difficult in terms of establishing a functioning business, getting the right connections, and avoiding discouragement to follow through with the business. That is why many businesses fall into the categories of starting, failing along the process, or failing to get started. There is a lot to be learned from the process of starting a business venture. In addressing this issue, some of the questions this research study aims to explore and study are how people go about their new venture efforts? Second, what steps they undertake? Third, from whom do they get information? And fourth, how do they use that information? This study will seek a variety of insights that can help answer these questions and improve our understanding of why some businesses fail, succeed, or never get started.

The Entrepreneurial Theory of the Firm and the Theory of the Entrepreneurial Firm

The entrepreneurial theory of the firm argues that entrepreneurship, properly understood, is a crucial but neglected element in explaining the nature and boundaries of the firm. By contrast, the theory of the entrepreneurial firm presumably seeks not to understand the nature and boundaries of "the firm" in general but rather to understand a particular type of firm: one that is entrepreneurial. This paper is an attempt to reconcile the two. After briefly delving for the concept of entrepreneurship in the work of Schumpeter, Kirzner, and (especially) Knight, the paper makes the case for the entrepreneurial theory of the firm. In such a theory, the firm exists as the solution to a coordination problem in a world of change and uncertainty, including Knightian or structural uncertainty. Taking a historical or developmental perspective, the paper then examines the changing nature of the entrepreneurial coordination problem over the life-cycle. In this formulation, "the entrepreneurial firm" is a nascent firm or proto-firm facing a problem of coordinating systemic change in economic capabilities. Lacking (by definition) adequate guidance from existing systems of rules of conduct embedded in markets or organizations, the entrepreneurial firm typically relies on a form of organization Max Weber called charismatic authority. In the end, although there is no such thing as a non-entrepreneurial firm, firms that must solve coordination problems in a world of novelty and systemic change ("entrepreneurial firms") are perhaps the purest case of the entrepreneurial theory of the firm.

Prières journalières à l'usage des juifs portugais ou espagnols : ce volume contient les Prières de tous les Jours Ouvriers, des Samedis, des Ros-Hodes, de Hanouca, de Pourim, avec leurs Paraschiot, du Jeûne particulier & autres Prières, traduites de l'Hébreu ; auxquelles on a ajouté des notes élémentaires, pour en faciliter l'intelligence

par Mardochée Venture

Molecular consequences of the loss of 3'→5' exonuclease activity of DNA polymerases delta and epsilon

The DNA replication polymerases δ and ϵ have an inherent proofreading mechanism in the form of a 3'→5' exonuclease. Upon recognition of errant deoxynucleotide incorporation into DNA, the nascent primer terminus is partitioned to the exonuclease active site where the incorrectly paired nucleotide is excised before resumption of polymerization. The goal of this project was to identify the cellular and molecular consequences of an exonuclease deficiency. The proofreading capability of model system MEFs with EXOII mutations was abolished without altering polymerase function.^ It was hypothesized that 3'→5' exonucleases of polymerases δ and ϵ are critical for prevention of replication stress and important for sensitization to nucleoside analogs. To test this hypothesis, two aims were formulated: Determine the effect of the exonuclease active site mutation on replication related molecular signaling and identify the molecular consequences of an exonuclease deficiency when replication is challenged with nucleoside analogs.^ Via cell cycle studies it was determined that larger populations of exonuclease deficient cells are in the S-phase. There was an increase in levels of replication proteins, cell population growth and DNA synthesis capacity without alteration in cell cycle progression. These findings led to studies of proteins involved in checkpoint activation and DNA damage sensing. Finally, collective modifications at the level of DNA replication likely affect the strand integrity of DNA at the chromosomal level.^ Gemcitabine, a DNA directed nucleoside analog is a substrate of polymerases δ and ϵ and exploits replication to become incorporated into DNA. Though accumulation of gemcitabine triphosphate was similar in all cell types, incorporation into DNA and rates of DNA synthesis were increased in exonuclease defective cells and were not consistent with clonogenic survival. This led to molecular signaling investigations which demonstrated an increase in S-phase cells and activation of a DNA damage response upon gemcitabine treatment.^ Collectively, these data indicate that the loss of exonuclease results in a replication stress response that is likely required to employ other repair mechanisms to remove unexcised mismatches introduced into DNA during replication. When challenged with nucleoside analogs, this ongoing stress response coupled with repair serves as a resistance mechanism to cell death.^

Regulation of the heat shock response by thiol-reactive compounds in the yeast Saccharomyces cerevisiae

Cells govern their activities and modulate their interactions with the environment to achieve homeostasis. The heat shock response (HSR) is one of the most well studied fundamental cellular responses to environmental and physiological challenges, resulting in rapid synthesis of heat shock proteins (HSPs), which serve to protect cellular constituents from the deleterious effects of stress. In addition to its role in cytoprotection, the HSR also influences lifespan and is associated with a variety of human diseases including cancer, aging and neurodegenerative disorders. In most eukaryotes, the HSR is primarily mediated by the highly conserved transcription factor HSF1, which recognizes target hsp genes by binding to heat shock elements (HSEs) in their promoters. In recent years, significant efforts have been made to identify small molecules as potential pharmacological activators of HSF1 that could be used for therapeutic benefit in the treatment of human diseases relevant to protein conformation. However, the detailed mechanisms through which these molecules drive HSR activation remain unclear. In this work, I utilized the baker's yeast Saccharomyces cerevisiae as a model system to identify a group of thiol-reactive molecules including oxidants, transition metals and metalloids, and electrophiles, as potent activators of yeast Hsf1. Using an artificial HSE-lacZ reporter and the glucocorticoid receptor system (GR), these diverse thiol-reactive compounds are shown to activate Hsf1 and inhibit Hsp90 chaperone complex activity in a reciprocal, dose-dependent manner. To further understand whether cells sense these reactive compounds through accumulation of unfolded proteins, the proline analog azetidine-2-carboxylic acid (AZC) and protein cross-linker dithiobis(succinimidyl propionate) (DSP) were used to force misfolding of nascent polypeptides and existing cytosolic proteins, respectively. Both unfolding reagents display kinetic HSP induction profiles dissimilar to those generated by thiol-reactive compounds. Moreover, AZC treatment leads to significant cytotoxicity, which is not observed in the presence of the thiol-reactive compounds at the concentrations sufficient to induce Hsf1. Additionally, DSP treatment has little to no effect on Hsp90 functions. Together with the ultracentrifugation analysis of cell lysates that detected no insoluble protein aggregates, my data suggest that at concentrations sufficient to induce Hsf1, thiol-reactive compounds do not induce the HSR via a mechanism based on accumulation of unfolded cytosolic proteins. Another possibility is that thiol-reactive compounds may influence aspects of the protein quality control system such as the ubiquitin-proteasome system (UPS). To address this hypothesis, β-galactosidase reporter fusions were used as model substrates to demonstrate that thiol-reactive compounds do not inhibit ubiquitin activating enzymes (E1) or proteasome activity. Therefore, thiol-reactive compounds do not activate the HSR by inhibiting UPS-dependent protein degradation. I therefore hypothesized that these molecules may directly inactivate protein chaperones, known as repressors of Hsf1. To address this possibility, a thiol-reactive biotin probe was used to demonstrate in vitro that the yeast cytosolic Hsp70 Ssa1, which partners with Hsp90 to repress Hsf1, is specifically modified. Strikingly, mutation of conserved cysteine residues in Ssa1 renders cells insensitive to Hsf1 activation by cadmium and celastrol but not by heat shock. Conversely, substitution with the sulfinic acid and steric bulk mimic aspartic acid led to constitutive activation of Hsf1. Cysteine 303, located in the nucleotide-binding/ATPase domain of Ssa1, was shown to be modified in vivo by a model organic electrophile using Click chemistry technology, verifying that Ssa1 is a direct target for thiol-reactive compounds through adduct formation. Consistently, cadmium pretreatment promoted cells thermotolerance, which is abolished in cells carrying SSA1 cysteine mutant alleles. Taken together, these findings demonstrate that Hsp70 acts as a sensor to induce the cytoprotective heat shock response in response to environmental or endogenously produced thiol-reactive molecules and can discriminate between two distinct environmental stressors.

Structure-function analysis of human Integrator subunit-4

Structure-function analysis of human Integrator subunit 4 Anupama Sataluri Advisor: Eric. J. Wagner, Ph.D. Uridine-rich small nuclear RNAs (U snRNA) are RNA Polymerase-II (RNAPII) transcripts that are ubiquitously expressed and are known to be essential for gene expression. snRNAs play a key role in mRNA splicing and in histone mRNA expression. Inaccurate snRNA biosynthesis can lead to diseases related to defective splicing and histone mRNA expression. Although the 3′ end formation mechanism and processing machinery of other RNAPII transcripts such as mRNA has been well studied, the mechanism of snRNA 3′ end processing has remained a mystery until the recent discovery of the machinery that mediates this process. In 2005, a complex of 14 subunits (the Integrator complex) associated with RNA Polymerase-II was discovered. The 14subunits were annotated Integrator 1-14 based on their size. The subunits of this complex together were found to facilitate 3′ end processing of snRNA. Identification of the Integrator complex propelled research in the direction of understanding the events of snRNA 3’end processing. Recent studies from our lab confirmed that Integrator subunit (IntS) 9 and 11 together perform the endonucleolytic cleavage of the nascent snRNA 3′ end to generate mature snRNA. However, the role of other members of the Integrator complex remains elusive. Current research in our lab is focused on deciphering the role of each subunit within the Integrator complex This work specifically focuses on elucidating the role of human Integrator subunit 4 (IntS4) and understanding how it facilitates the overall function of the complex. IntS4 has structural similarity with a protein called “Symplekin”, which is part of the mRNA 3’end processing machinery. Symplekin has been thoroughly researched in recent years and structure-function correlation studies in the context of mRNA 3’end processing have reported a scaffold function for Symplekin due to the presence of HEAT repeat motifs in its N-terminus. Based upon the structural similarity between IntS4 and Symplekin, we hypothesized that Integrator subunit 4 may be behaving as a Symplekin-like scaffold molecule that facilitates the interaction between other members of the Integrator Complex. To answer this question, the two important goals of this study were to: 1) identify the region of IntS4, which is important for snRNA 3′ end processing and 2) determine binding partners of IntS4 which promote its function as a scaffold. IntS4 structurally consists of a highly conserved N-terminus with 8 HEAT repeats, followed by a nonconserved C- terminus. A series of siRNA resistant N and C-terminus deletion constructs as well as specific point mutants within its N-terminal HEAT repeats were generated for human IntS4 and, utilizing a snRNA transcriptional readthrough GFP-reporter assay, we tested their ability to rescue misprocessing. This assay revealed a possible scaffold like property of IntS4. To probe IntS4 for interaction partners, we performed co-immunoprecipitation on nuclear extracts of IntS4 expressing stable cell lines and identified IntS3 and IntS5 among other Integrator subunits to be binding partners which facilitate the scaffold like function of hIntS4. These findings have established a critical role for IntS4 in snRNA 3′ end processing, identified that both its N and C termini are essential for its function, and mapped putative interaction domains with other Integrator subunits.

Geochemistry of the oldest Atlantic oceanic crust

Controversy has surrounded the issue of whether mantle plume activity was responsible for Pangaean continental rifting and massive flood volcanism (resulting in the Central Atlantic Magmatic Province or CAMP, emplaced around 200 Ma) preceding the opening of the central Atlantic Ocean in the Early Mesozoic. Our new Sr-Nd-Pb isotopic and trace element data for the oldest basalts sampled from central Atlantic oceanic crust by deep-sea drilling show that oceanic crust generated from about 160 to 120 Ma displays clear isotopic and chemical signals of plume contamination (e.g., 87Sr/86Sr(i) = 0.7032-0.7036, epsilonNd(t) =+6.2 to +8.2, incompatible element patterns with positive Nb anomalies), but these signals are muted or absent in crust generated between 120 and 80 Ma, which resembles young Atlantic normal mid-ocean ridge basalt. The plume-affected pre-120 Ma Atlantic crustal basalts are isotopically similar to lavas from the Ontong Java Plateau, and may represent one isotopic end-member for CAMP basalts. The strongest plume signature is displayed near the center of CAMP magmatism but the hotspots presently located nearest this location in the mantle reference frame do not appear to be older than latest Cretaceous and are isotopically distinct from the oldest Atlantic crust. The evidence for widespread plume contamination of the nascent Atlantic upper mantle, combined with a lack of evidence for a long-lived volcanic chain associated with this plume, leads us to propose that the enriched signature of early Atlantic crust and possibly the eruption of the CAMP were caused by a relatively short-lived, but large volume plume feature that was not rooted at a mantle boundary layer. Such a phenomenon has been predicted by recent numerical models of mantle circulation.

Determinación del coeficiente de nascencia en coberturas cespitosas : oasis del Norte de Mendoza (Argentina)

Uno de los principales problemas que se presenta para la investigación en césped acerca de la adaptabilidad de diferentes especies y sus mezclas o la introducción de otras nuevas, consiste en la dificultad de calcular la densidad de plantas, en forma lo suficientemente aproximada a los resultados reales como para permitir comparaciones estadísticamente válidas de la calidad o usos del cultivo resultante. Se propone una nueva metodología para reemplazar aquella tradicional de cálculo de necesidades de semilla por peso, con densidades determinadas por prueba y error según el resultado final por aspecto y corrección de cantidad de mezcla sólo por valor cultural. La propuesta considera cálculos matemáticos para determinar la cantidad exacta de semillas a emplear para obtener una densidad final de siembra controlada, teniendo en cuenta peso específico de la semilla y valor cultural, afectando el dato resultante por un factor de corrección (CN) que relaciona el valor teórico obtenido con la respuesta a campo. Es decir que la cantidad de semilla a emplear debe calcularse en función de la densidad de plantas deseada. En el presente trabajo el factor CN se determina para diferentes especies. Se parte de la hipótesis que es posible mejorar las formas de selección de especies y preparación de mezclas a través del cálculo de la necesidad de semillas por cm2 y que algunas de las especies utilizadas poseen baja eficiencia en la relación semilla-planta, por lo que se debería ajustar su proporción en las mezclas comerciales locales según este factor de cultivo. Como metodología se propone: a. análisis de poder germinativo, pureza y peso específico de semillas comerciales; b. con cuatro repeticiones, en bloques al azar, realizar siembras individuales de las especies en condiciones ideales de sustrato, iluminación y humedad, y siembra en las mismas condiciones de campo que un cultivo tradicional en condiciones de especie pura y consociadas (mezclas); c. conteo del número de plántulas obtenidas en cada caso por método propuesto por Lush y Franz; d. con los resultados, estimar los coeficientes (CN) promedio y sus respectivos intervalos de confianza. Esta nueva manera de calcular las cantidades exactas de cada componente de una mezcla para césped abre un campo muy importante a la investigación de especies más adecuadas a cada ambiente, dado que el método tradicional conduce a resultados muy ambiguos y de difícil comparación.

De la España africana a la América teocrática : notas sobre el ideario de Simón Bolívar

Las ideas de Simón Bolívar sobre América y sobre Europa han recibido alguna atención de los investigadores. Mucho menos las que expresó sobre Asia y África. Aunque fueron marginales a su pensamiento, la reunión de sus alusiones al respecto permite arrojar alguna luz sobre la reflexión de la Independencia y sobre los cambios que el Libertador experimentó en su percepción del naciente mundo que aparecía ante sus ojos. Partiendo de una actitud orientalista y despectiva inicial, con el tiempo llegó a pensar que el Oriente no podía descartarse como influencia en las instituciones americanas.

Características de la estructura del sector industrial en la provincia de Mendoza al inicio del siglo XXI.

Luego de un período de desmantelamiento de la estructura productiva nacional desde fines de 2002 la economía argentina comenzó lentamente a recuperarse, con una incipiente revitalización de la industria. En este escenario, el trabajo describe el perfil y las características de la estructura industrial de la provincia de Mendoza con el fin de trazar el punto de partida para el potencial desarrollo económico local, en relación con la distribución geográfica de las unidades productivas, los sectores más dinámicos y su concentración, diferenciando a aquellas según tamaño definido por cantidad de ocupados. Los datos analizados provienen del Censo Industrial Provincial, 2002/2003.

Ciudadanos, administración pública y control

Este trabajo responde al propósito de reflexionar acerca de las formas que toma el control de la administración pública en nuestro país, ahondando especialmente en el control social. El recorrido y análisis de diversas normas y programas, además de su cruce con las distintas modalidades del control, muestran diferentes instancias de participación que constituyen nuevos campos de intervención ciudadana. En todas y cada una de ellas, el acceso a la información pública aparece como auténtico presupuesto de la participación. Nuevos instrumentos y modalidades en los que, sin embargo, debemos resaltar el carácter de no vinculante que tienen las audiencias públicas y el escaso margen generado para la participación activa en los distintos programas. De todas maneras esos instrumentos son perfectibles y a futuro habrá de pensarse en el modo de transformar esta incipiente participación en una intervención activa y vigorosa que defina una nueva relación Estado/sociedad.

CaCO3 content and bulk densitiy of east equatorial Pacific Ocean sediment cores

Nine piston cores and six triggerweight cores retrieved from the eastern equatorial Pacific Ocean during the Venture 1 expedition were analyzed for dry-bulk density (DBD) and CaCO3 content. Sites are located along a north-south transect at 110°W from 11°N to 3°S and along an east-west transect from 110° to 90°W, at approximately 3°S. The data reveal two DBD-CaCO3 relationships and four patterns of CaCO3 abundance.

Discursos de poder en el fitness : El comercio de los entrenamientos que duelen

Investigar las prácticas del fitness puede suponer adentrarse en un camino incierto. La configuración histórica de este puzzle se constituye a partir de la comercialización de la gimnasia aeróbica. A partir de este modo de hacer gimnasia se construye un negocio en torno a diferentes productos, vestimentas, equipamientos, etc. Asimismo, para legitimar estas prácticas fue necesario utilizar los estudios e investigaciones que realizan las ciencias médicas. A través de estas ciencias la gimnasia aeróbica, y años más tarde, las clases de fitness grupal, se consideran válidas en el imaginario social de los clientes. Las empresas encargadas de comercializar estas clases pre-coreografiadas de fitness grupal, a través de estudios de marketing y de la veracidad de los estudios de las ciencias legitimadoras, intentan posicionarse en el mercado, aumentar el capital y continuar desplegando el negocio

Detener el mar con un haz de juncos : La religión en la filosofía de David Hume

No resulta fácil desentrañar el pensamiento de un escéptico acerca de temas sobre los que prefiere abstenerse de formular juicios. Es el caso de David Hume y la religión.El filósofo escocés nacido en 1711 dejó varios escritos aludiendo al fenómeno, es decir, a la religión tal como existe de hecho, y manifestó su opinión crítica acerca de las distintas posturas intelectuales de su tiempo en torno a cuestiones religiosas. Pero siempre fue ambiguo e irónico cuando le tocó dejar asentado su propio juicio con respecto a este tema. La dificultad principal reside en que, para Hume, a quien podríamos considerar un ?escéptico mitigado?, los juicios correctos son aquellos que se ajustan a la estrecha capacidad del entendimiento humano, que no va más allá de los límites de la experiencia de la vida cotidiana. Muchos aspectos vinculados a la religión ?tales como la posibilidad de conocer de la esencia y los atributos divinos- exceden nuestras limitadas facultades y, si nos aventuramos a argumentar en ese ámbito, corremos el riesgo de caer en el error y la irracionalidad. Nuestra propuesta consiste en examinar cuál es la postura de Hume sobre los distintos problemas que presentan el conocimiento y la práctica vinculados con la religión. Respecto del conocimiento, las dificultades se plantean a la hora de determinar qué estatuto otorgarle a las creencias religiosas, cuál es el origen en nuestra mente de la religiosidad y cómo justificar por medio de argumentos la existencia y atributos de la divinidad. En cuanto a la práctica, Hume formula una serie de críticas a las actitudes e instituciones religiosas tal como se han dado históricamente a partir del análisis de las consecuencias que observa en la sociedad, de las que surge una contradicción entre un conjunto de principios respetables y un sinnúmero de acciones deplorables. Para examinar estas cuestiones es necesario tener en cuenta el punto de vista desde el que efectúa su análisis, que se vincula, como acabamos de mencionar, con el escepticismo mitigado. Finalmente, evaluaremos si es posible proponer alguna forma de religión que tenga el visto bueno de Hume y, en ese caso, qué características debería revestir. Para lograrlo, deberemos abrirnos paso entre su inteligente ironía y su excesiva prudencia.