Identification of a cytoplasmic, phorbol ester-inducible isoform of protein tyrosine phosphatase epsilon.

The protein-tyrosine phosphatase epsilon (PTP epsilon) is a transmembranal, receptor-type protein that possesses two phosphatase catalytic domains characteristic of transmembranal phosphatases. Here we demonstrate the existence of a nontransmembranal isoform of PTP epsilon, PTP epsilon-cytoplasmic. PTP epsilon-cytoplasmic and the transmembranal isoform of PTP epsilon have separate, nonoverlapping expression patterns. Further, the data clearly indicate that control of which of the two isoforms is to be expressed is initiated at the transcriptional level, suggesting that they have distinct physiological roles. PTP epsilon-cytoplasmic mRNA is the product of a delayed early response gene in NIH 3T3 fibroblasts, and its transcription is regulated through a pathway that requires protein kinase C. The human homologue of PTP epsilon-cytoplasmic has also been cloned and is strongly up-regulated in the early stages of phorbol 12-tetradecanoate 13-acetate-induced differentiation of HL-60 cells. Sequence analysis indicates and cellular fractionation experiments confirm that this isoform is a cytoplasmic molecule. PTP epsilon-cytoplasmic is therefore the initial example to our knowledge of a nontransmembranal protein-tyrosine phosphatase that contains two tandem of catalytic domains.

Capturing genes encoding membrane and secreted proteins important for mouse development.

A strategy based on the gene trap was developed to prescreen mouse embryonic stem cells for insertional mutations in genes encoding secreted and membrane-spanning proteins. The "secretory trap" relies on capturing the N-terminal signal sequence of an endogenous gene to generate an active beta-galactosidase fusion protein. Insertions were found in a cadherin gene, an unc6-related laminin (netrin) gene, the sek receptor tyrosine kinase gene, and genes encoding two receptor-linked protein-tyrosine phosphatases, LAR and PTP kappa. Analysis of homozygous mice carrying insertions in LAR and PTP kappa showed that both genes were effectively disrupted, but neither was essential for normal embryonic development.

Rescue, propagation, and partial purification of a helper virus-dependent adenovirus vector.

Adenoviral vectors are widely used as highly efficient gene transfer vehicles in a variety of biological research strategies including human gene therapy. One of the limitations of the currently available adenoviral vector system is the presence of the majority of the viral genome in the vector, resulting in leaky expression of viral genes particularly at high multiplicity of infection and limited cloning capacity of exogenous sequences. As a first step to overcome this problem, we attempted to rescue a defective human adenovirus serotype 5 DNA, which had an essential region of the viral genome (L1, L2, VAI + II, pTP) deleted and replaced with an indicator gene. In the presence of wild-type adenovirus as a helper, this DNA was packaged and propagated as transducing viral particles. After several rounds of amplification, the titer of the recombinant virus reached at least 4 x 10(6) transducing particles per ml. The recombinant virus could be partially purified from the helper virus by CsCl equilibrium density-gradient centrifugation. The structure of the recombinant virus around the marker gene remained intact after serial propagation, while the pBR sequence inserted in the E1 region was deleted from the recombinant virus. Our results suggest that it should be possible to develop a helper-dependent adenoviral vector, which does not encode any viral proteins, as an alternative to the currently available adenoviral vector systems.

NOX-driven ROS formation in cell transformation of FLT3-ITD positive AML

In different types of myeloid leukemia, increased formation of reactive oxygen species (ROS) has been noted and associated with aspects of cell transformation including the promotion of leukemic cell proliferation and migration, as well as DNA-damage and accumulation of mutations. Work reviewed in this article has shown the involvement of NADPH oxidase (NOX)-derived ROS downstream of oncogenic protein-tyrosine kinases in both processes, and the related pathways have been partially identified. FLT3-ITD, an important oncoprotein in a subset of AML, causes activation of AKT and subsequently stabilization of p22phox, a regulatory subunit for NOX1-4. This process is linked to ROS formation and DNA damage. Moreover, FLT3-ITD signaling through STAT5 enhances expression of NOX4, ROS formation and inactivation of the protein-tyrosine phosphatase DEP-1/PTPRJ, a negative regulator of FLT3 signaling, by reversible oxidation of its catalytic cysteine residue. Genetic inactivation of NOX4 restored DEP-1 activity and attenuated cell transformation by FLT3-ITD in vitro and in vivo. Future work is required to further explore these mechanisms and their causal involvement in leukemic cell transformation, which may result in the identification of novel candidate targets for therapy.

Peptide Therapeutics and the Pharmaceutical Industry: Barriers Encountered Translating from the Laboratory to Patients

Peptides are receiving increasing interest as clinical therapeutics. These highly tunable molecules can be tailored to biocompatibility and biodegradability with simultaneously selective and potent therapeutic effects. Despite challenges regarding up-scaling and licensing of peptide products, their vast clinical potential is reflected in the 60 plus peptide-based therapeutics already on the market, and the further 500 derivatives currently in developmental stages. Peptides are proving effective for a multitude of disease states including: type 2 diabetes (controlled using the licensed glucagon-like peptide-1 receptor liraglutide); irritable bowel syndrome managed with linaclotide (currently at approval stages); acromegaly (treated with octapeptide somostatin analogues lanreotide and octreotide); selective or broad spectrum microbicidal agents such as the Gram-positive selective PTP-7 and antifungal heliomicin; anticancer agents including goserelin used as either adjuvant or for prostate and breast cancer,and the first marketed peptide derived vaccine against prostate cancer, sipuleucel-T. Research is also focusing on improving the biostability of peptides. This is achieved through a number of mechanisms ranging from replacement of naturally occurring L-amino acid enantiomers with D-amino acid forms, lipidation, peptidomimetics, N-methylation, cyclization and exploitation of carrier systems. The development of self-assembling peptides are paving the way for sustained release peptide formulations and already two such licensed examples exist, lanreotide and octreotide. The versatility and tunability of peptide-based products is resulting in increased translation of peptide therapies, however significant challenges remain with regard to their wider implementation. This review highlights some of the notable peptide therapeutics discovered to date and the difficulties encountered by the pharmaceutica lindustry in translating these molecules to the clinical setting for patient benefit, providing some possible solutions to the most challenging barriers. 

Konzeption und Untersuchung eines Konzeptes zur hochpräzisen Synchronisierung von verteilten Messsystemen in der Automation

Es werden die Anforderungen verschiedener Kommunikationslösungen in der Automation hinsichtlich der benötigten Synchronizität betrachtet. Im Anschluss wird ein Konzept erstellt und bewertet, welches die bisherigen netzwerkbasierten Synchronisationslösungen PTP und satellitengestütztes NTP anhand existierender Implementierungen kombiniert. Die gewonnenen Erkenntnisse werden mit den im Vorfeld ermittelten Anforderungen verglichen und bewertet. Es wird zu dem Schluss gekommen, dass das vorgestellte Konzept ausreicht, um Ereignisse aufeine Zykluszeit genau zuzuordnen.

Estimating the effect of state-level gun purchasing policy on county-level firearm suicide mortality

Thesis (Master's)--University of Washington, 2016-08

Global citizenship education: a sociological critique

This paper considers the recent focus on citizenship within education by taking curricular reform within Scottish secondary schooling as a case study. In Scotland the Curriculum for Excellence reform places citizenship as one of four main capacities that pupils must work towards as part of their education. A central theme in this reform is the need for students to take a global perspective and work across different disciplines. In this model of citizenship education learners are enabled to develop their sense of citizenship identity in response to a fast-paced world of innovation and change. Citizenship is therefore linked to a futurist agenda, where the learner-citizen is positioned as an ongoing project, as something to be worked at or perhaps worked on. However, this kind of notion of agency is an expression of an ideological construction of the citizen as a flexible resource for society. Such citizens are active in the sense of being adaptive to change through utilizing intellectual skills but without a sense of identity grounded in one's commitments or reflexive engagement with different forms of understanding. The paper offers a critical assessment of this learner-citizen discourse as focusing on ratiocination rather than relational identity.

Modelo de competencias en TIC para el personal de una organización del sector eléctrico

La presente investigación pretendió incorporar el uso intensivo de TIC en los procedimientos establecidos y necesarios en los procesos de generación, distribución y control de la energía, lo que se expresa en un manual para el sistema de gestión humana de la organización analizada. La investigación partió de un levantamiento de un estado del arte, continuó con la realización de un análisis de actitudes y aptitudes de los colaboradores, basado en propuestas teóricas y mejores prácticas existentes del medio, y, por último, concluyó con un manual de gestión humana en el que se indican las competencias en los diferentes perfiles de la organización para el uso de TIC y su aplicación, con el propósito de alinearse con las perspectivas y objetivos de la organización analizada al tener como base la perdurabilidad y la competitividad de la misma.

El mandato por el Agua y su aplicación a una organización colombiana

Actualmente las organizaciones en su búsqueda por ser ecoeficientes y generar una mejor practica en sus procesos productivos, ha buscado generar herramientas y mediciones que le permitan llevar a cabo una producción más limpia. Es por ello que en su afán han buscado una manera óptima de abordar un tema de preocupación mundial; el manejo del agua. Esta investigación tiene como eje central aterrizar al idioma español, el mandato por el agua un documento dado a conocer por el pacto global, el cual contiene herramientas, métricas y guías sobre el manejo del agua en las organizaciones. Adicional a esto la presente investigación pretende ver su pertinencia al contexto colombiano mediante la aplicación en a una organización.

Plan de negocio Aprisco JAM

El Aprisco JAM busca entrar en el mercado de lácteos y derivados con un producto que posee atributos nutricionales importantes al igual que provee la facilidad de ser consumido por cualquier persona, principalmente aquellas que no toleran la leche vacuna encontrando en nuestros productos una alternativa para el disfrute de estos sin comprometer su salud y bienestar. Encontramos así pues una demanda existente en donde ofrecemos como solución a las necesidades un producto nutritivamente saludable siendo recordados y diferenciados por este aspecto. Todo ello en base a una producción limpia y sostenible que permita un aprovechamiento y uso eficiente de los recursos naturales. Para lograr dicho objetivo es necesario una inversión inicial de $24.742.036 COP, proyectado a 3 años dicha inversión se recuperará a partir del 5 mes con un interés esperado de 35,6% EA que representa beneficios en valor actual de $90´628.858. Por otro lado genera una relación beneficio-costo de 4,66, esto quiere decir que por cada peso invertido se generan beneficios de 3,66 pesos.

Snackggies

Snackggies, es una empresa ubicada en la ciudad de Bogotá cuya actividad económica es la elaboración y distribución de Snacks. Esta pretende entrar al mercado con una línea de productos poco convencional. Su enfoque, es ofrecer alternativas a los niños y jóvenes para que consuman verduras de una manera diferente, rica y agradable. Esto se realizará por medio de la elaboración de chips de verduras con sabor naturales. Con estos productos se busca que los niños y jóvenes disfruten y se diviertan consumiéndolas, pues se conoce que ellos son la población que mayor inconveniente presenta al comerlas y por ende sus padres lo perciben de la misma manera. La característica principal de Snackggies es desarrollar productos saludables comparados con los Chips que ofrece el mercado, pues se usará materia prima de calidad y a esto se le suma la forma de cocción; ya que se utilizará tecnología de aire caliente o AirFryer, cuya función es freír alimentos con una porción mínima de aceite, aportando una cantidad reducida de calorías vacías y grasas trans a los alimentos. Además, son productos creados para la lonchera de los niños y con diseño atractivo para ellos. Para la empresa lanzar al mercado estos productos es muy significativo y gratificante, pues se ha desarrollado durante un año un estudio en el cual se ha venido conociendo tanto al cliente como el consumidor, con el fin de desarrollar un producto que cumpla con sus necesidades y se logre posicionar como una alternativa innovadora para el consumo de verduras.

Emprendimiento NORNA

La creación de Norna Ltda., motivada por la expansión mundial de la idea del cuidado por el planeta, junto con el avance económico de Colombia se implanta como la base de un movimiento social y cultural que pretende expandirse por el país. Para la empresa, el objetivo principal es realzar el valor de la conservación del medio ambiente, a través de un bien tangible, para evitar la perpetuación de la sostenibilidad ecológica e inclusión social como una idea impalpable. Para confrontar el Statu Quo de la moda rápida que regularmente se encuentra acompañada por condiciones laborales lamentables, Norna ltda., confecciona y distribuye chaquetas a base de algodón orgánico a través de su página virtual en Colombia.