Executable Model Development from Architectural Description with Application to the Time Sensitive Target Problem

As the Department of Defense (DoD) moves to a capabilities-based approach for requirements definition and systems development, it has become necessary to conceptualize and evaluate our needs at the System of Systems (SoS) level. Desired capabilities are often achievable only through seamless integration of many different systems. As the classical systems engineering approaches are not suited to effectively handle the complexity of SoS level concepts, an architectures-driven approach has emerged as a way of defining and evaluating these new concepts. While the use of architectures for documenting and tracking interfaces and interoperability concerns is generally understood, architectural analysis and the use of executable models for evaluation of architectures remain an open area of research. With this purpose in mind, this thesis will apply architectural-based analysis to the proposed Time Sensitive Effect Operation (TSEO2012) scenario. This scenario will become the baseline for architectural analysis, and an excursion to this baseline will add a Weapon Born Battle Damage Assessment (WBBDA) capability. By creating an executable model, the two architectural concepts can be compared against each other. The addition of a WBBDA capability to the TSEO architecture improves the efficiency of the time sensitive target operations by shortening the decision cycle for target re-strike. While this effort was successful in obtaining an executable model directly from the architecture description, it highlighted the importance of having sufficient and correct information contained in the architecture products

Identification of two different 14-alpha sterol demethylase-related genes (cyp51A and cyp51B) in Aspergillus fumigatus and other Aspergillus species

Erratum in: J Clin Microbiol 2001 Nov;39(11):4225.Two cyp51-related genes (cyp51A and cyp51B) encoding 14-alpha sterol demethylase-like enzymes were identified in the opportunistic human pathogen Aspergillus fumigatus. PCR amplification using degenerate oligonucleotides based on conserved areas of cytochrome P450 demethylases of other filamentous fungi and yeasts allowed the cloning and sequencing of two different homologue genes in A. fumigatus. Southern analysis confirmed that both genes hybridized to distinct genomic loci and that both are represented as single copies in the genome. Comparison of the deduced Cyp51A and Cyp51B proteins with the CYP51 proteins from Penicillium italicum, Aspergillus nidulans, Erysiphe graminis, Uncinula necator, Botrytis cinerea, Ustilago maydis, Cryptococcus neoformans, Candida albicans, Saccharomyces cerevisiae, Candida tropicalis, and Candida glabrata showed that the percentages of identity of the amino acid sequences (range, 40 to 70%) were high enough to consider Cyp51A and Cyp51B to be members of the fungal CYP51 family. Fragments from both genes were also cloned from other Aspergillus spp. (A. flavus, A. nidulans, and A. terreus). Phylogenetic analysis showed that, at least in the most pathogenic species of Aspergillus, there are two fungal CYP51 proteins. This is the first report of the existence of two homologue genes coding for 14-alpha sterol demethylase in the fungal kingdom. This finding could provide insights into the azole resistance mechanisms operating in fungi. The primers used here may be useful molecular tools for facilitating the cloning of novel 14-alpha sterol demethylase genes in other filamentous fungi.This work was supported in part by grant 1078/99 from Instituto de Salud Carlos III. T.M.D.-G. is a fellow of the Instituto de Salud Carlos III

Star Formation Under the Outflow: The Discovery of a Non-Thermal Jet from OMC-2 FIR 3 and its Relationship to the Deeply Embedded FIR 4 Protostar

We carried out multiwavelength (0.7-5 cm), multiepoch (1994-2015) Very Large Array (VLA) observations toward the region enclosing the bright far-IR sources FIR 3 (HOPS 370) and FIR 4 (HOPS 108) in OMC-2. We report the detection of 10 radio sources, seven of them identified as young stellar objects. We image a well-collimated radio jet with a thermal free-free core (VLA 11) associated with the Class I intermediate-mass protostar HOPS 370. The jet presents several knots (VLA 12N, 12C, 12S) of non-thermal radio emission (likely synchrotron from shock-accelerated relativistic electrons) at distances of ~7,500-12,500 au from the protostar, in a region where other shock tracers have been previously identified. These knots are moving away from the HOPS 370 protostar at ~ 100 km/s. The Class 0 protostar HOPS 108, which itself is detected as an independent, kinematically decoupled radio source, falls in the path of these non-thermal radio knots. These results favor the previously proposed scenario where the formation of HOPS 108 has been triggered by the impact of the HOPS 370 outflow with a dense clump. However, HOPS 108 presents a large proper motion velocity of ~ 30 km/s, similar to that of other runaway stars in Orion, whose origin would be puzzling within this scenario. Alternatively, an apparent proper motion could result because of changes in the position of the centroid of the source due to blending with nearby extended emission, variations in the source shape, and /or opacity effects.Comment: 16 pages, 4 figures, accepted for publication in The Astrophysical Journa

Susceptibility patterns and molecular identification of Trichosporon species

The physiological patterns, the sequence polymorphisms of the internal transcriber spacer (ITS), and intergenic spacer regions (IGS) of the rRNA genes and the antifungal susceptibility profile were evaluated for their ability to identify Trichosporon spp. and their specificity for the identification of 49 clinical isolates of Trichosporon spp. Morphological and biochemical methodologies were unable to differentiate among the Trichosporon species. ITS sequencing was also unable to differentiate several species. However, IGS1 sequencing unambiguously identified all Trichosporon isolates. Following the results of DNA-based identification, Trichosporon asahii was the species most frequently isolated from deep sites (15 of 25 strains; 60%). In the main, other Trichosporon species were recovered from cutaneous samples. The majority of T. asahii, T. faecale, and T. coremiiforme clinical isolates exhibited resistance in vitro to amphotericin B, with geometric mean (GM) MICs >4 mug/ml. The other species of Trichosporon did not show high MICs of amphotericin B, and GM MICs were <1 mug/ml. Azole agents were active in vitro against the majority of clinical strains. The most potent compound in vitro was voriconazole, with a GM MIC </=0.14 mug/ml. The sequencing of IGS correctly identified Trichosporon isolates; however, this technique is not available in many clinical laboratories, and strains should be dispatched to reference centers where these complex methods are available. Therefore, it seems to be more practical to perform antifungal susceptibility testing of all isolates belonging to Trichosporon spp., since correct identification could take several weeks, delaying the indication of an antifungal agent which exhibits activity against the infectious strain.S

Terapia celular “neuro-restauradora” en la enfermedad de Parkinson: un debate pendiente

Existe en la actualidad un gran entusiasmo sobre las perspectivas derivadas de la denominada terapia celular en la enfermedad de Parkinson. Este entusiasmo ha sobrepasado la esfera de la comunidad médica, llegando hasta el público general, y se ha venido alimentando de un considerable debate ético y político, hurtándose en todo momento la necesidad de un análisis realmente científico sobre las cualidades y limitaciones reales del tratamiento con células madre en las enfermedades neurodegenerativas. La enfermedad de Parkinson con frecuencia se observa desde una perspectiva simplista, como una mera neurodegeneración de la vía dopaminérgica nigroestriada, punto de vista bajo el que se colocan diferentes diseños tendentes a reemplazar la falta de dopamina en el estriado, mediante el empleo de distintos tipos de terapia celular. En este sentido, es necesario señalar por un lado la naturaleza multisistémica y generalizada de la enfermedad, y por otro lado el carácter progresivo del proceso neurodegenerativo de la enfermedad de Parkinson. Bajo este enfoque, pretender que el mero reemplazo de la dopamina estriatal mediante terapia celular sustitutiva, pueda corregir el carácter generalizado y progresivo de la enfermedad es una aspiración quimérica, que únicamente contribuye a generar expectativas infundadas en el público general. Este artículo pretende argumentar desde un punto de vista puramente científico las dudas sobre las expectativas creadas con estos nuevos diseños terapéuticos.At present there is great enthusiasm over the perspectives deriving from so-called cell therapy in Parkinson’s disease. This enthusiasm has spread beyond the ambit of the medical community, reaching the general public, and has been fuelled by a considerable ethical and political debate, sidestepping the need for a really scientific analysis of the real qualities and limitations of treatment with stem-cells in neurodegenerative diseases. Parkinson’s disease is frequently observed from a simplistic perspective, as a mere neurodegeneration of the nigrostriatal dopaminergic pathway. This viewpoint encompasses different designs that tend to replace the lack of dopamine in the striatum through the use of different types of cell therapy. In this respect, it is important to indicate, on the one hand, the multisystemic and generalised nature of the disease and, on the other, the progressive character of the neurodegenerative process of Parkinson’s disease. With this approach, to claim that the mere replacement of striatal dopamine through replacement cell therapy can correct the generalised and progressive character of the disease is a fanciful aspiration, which can only contribute to generating unfounded expectations in the general public. This article attempts to set out from a purely scientific point of view the doubts over the expectations created by these new therapeutic designs

Striatal expression of GDNF and differential vulnerability of midbrain dopaminergic cells

Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-beta superfamily that when exogenously administrated exerts a potent trophic action on dopaminergic (DA) cells. Although we know a lot about its signalling mechanisms and pharmacological effects, physiological actions of GDNF on the adult brain remain unclear. Here, we have used morphological and molecular techniques, and an experimental model of Parkinson's disease in rats, to investigate whether GDNF constitutively expressed in the adult mesostriatal system plays a neuroprotective role on midbrain DA cells. We found that although all midbrain DA cells express both receptor components of GDNF (GFRalpha1 and Ret), those in the ventral tegmental area (VTA) and rostromedial substantia nigra (SNrm) also contain GDNF but not GDNFmRNA. The levels of GDNFmRNA are significantly higher in the ventral striatum (vSt), the target region of VTA and SNrm cells, than in the dorsal striatum (dSt), the target region of DA cells in the caudoventral substantia nigra (SNcv). After fluoro-gold injection in striatum, VTA and SNrm DA cells show triple labelling for tyrosine hydroxylase, GDNF and fluoro-gold, and after colchicine injection in the lateral ventricle, they become GDNF-immunonegative, suggesting that GDNF in DA somata comes from their striatal target. As DA cells in VTA and SNrm are more resistant than those in SNcv to intracerebroventricular injection of 6-OHDA, as occurs in Parkinson's disease, we can suggest that the fact that they project to vSt, where GDNF expression is significantly higher than in the dSt, is a neuroprotective factor involved in the differential vulnerability of midbrain DA neurons

Actividad ovicida de la lavandina sobre huevos de Aedes aegypti (diptera: culicidae)

Introducción: Diversos productos de uso doméstico pueden ayudar en el saneamientode nuestro hábitat. Algunos autores señalan la efectividad del cloro puro en laremoción del corion del huevo de Aedes aegypti, produciéndose una menor eclosión alaplicarlo sobre las paredes de los contenedores donde son depositados. Objetivo:evaluar la susceptibilidad de huevos de Ae. aegypti a diferentes concentraciones delavandina, para valorar su actividad ovicida. Materiales y método: Se utilizó agualavandina concentrada (AYUDIN, 2,2 %, 55g Cl/ 1l), en cuatro concentraciones: L1(100 %), L2 (50 %), L3 (25 %) y L4 (12,5 %). Se trataron 40 huevos para cada unidady, luego de 48 hs, inundaron con agua declorada para inducir la eclosión. Paraobservar diferencias entre el control y el tratamiento, se realizó un test de KruskalWallis y un Boxplot, utilizando la plataforma R-medic. Resultados: Se observarondiferencias significativas (p< 0.001) con el control (Me= 95.8), registrándose unaelevada mortalidad de huevos al aplicar lavandina, sin importar la concentración usada(Me≤ 2.5). L4 fue la única dosis que registró supervivencia (Me= 2.5). Conclusiones:Estos resultados pueden ser útiles en la lucha antivectorial contra Ae. aegypti,reforzando las acciones comunitarias durante las campañas de fumigación ysaneamiento ambiental para la prevención de las enfermedades transmitidas por él.Consideramos que recomendar el empleo de la lavandina para el lavado de losrecipientes vacíos, enfatizando en la limpieza de las paredes, puede ayudar a ladisminución de las poblaciones del vector, especialmente durante los periodosinterepidémicos, ideales para la aplicación de medidas de control vectorial.Fil: Rodriguez, Gabriela Alejandra. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Superior de Entomología; ArgentinaFil: Herrera, V. G.. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Pomares, M. A.. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Fuenzalida, Ana Denise. Secretaria de Gobierno de Salud. Instituto Nacional de Medicina Tropical. Instituto Nacional de Medicina Tropical - Sede Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Superior de Entomología; ArgentinaFil: Direni Mancini, José Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Superior de Entomología; ArgentinaFil: Diaz Briz, L. M.. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Superior de Entomología; ArgentinaFil: Claps, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Superior de Entomología; ArgentinaFil: Quintana, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Superior de Entomología; Argentina. Secretaria de Gobierno de Salud. Instituto Nacional de Medicina Tropical. Instituto Nacional de Medicina Tropical - Sede Tucumán; ArgentinaXIV Jornadas Internas de Comunicaciones en Investigación, Docencia y ExtensiónSan Miguel de TucumánArgentinaUniversidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lill