Tragedia intitulada: Sara Sampson: en cinco actos

En la port. sello: "Se hallara en la Imprenta de Orga, calle de las Barcas, en Valencia, nº 13"Nombre del autor tomado del "Catálogo de comedias sueltas conservadas en la Biblioteca de la Real Academia Española".Precede al tít. "N. 45"Los datos del pie de imprenta tomados del colofónSign.: A-D4Text a 2 col

Structural Ceramic Composites for Nuclear Applications

A research program has been established to investigate fiber reinforced ceramic composites to be used as control rod components within a Very High Temperature Reactor. Two candidate systems have been identified, carbon fiber reinforced carbon (Cf/C) and silicon carbide fiber reinforced silicon carbide (SiCf/SiC) composites. Initial irradiation stability studies to determine the maximum dose for each composite type have been initiated within the High Flux Isotope Reactor at Oak Ridge National Laboratory. Test samples exposed to 10 dpa irradiation dose have been completed with future samples to dose levels of 20 and 30 dpa scheduled for completion in following years. Mechanical and environmental testing is being conducted concurrently at the Idaho National Laboratory and at Pacific Northwest National Laboratory. High temperature test equipment, testing methodologies, and test samples for high temperature (up to 1600º C) tensile strength and long duration creep studies have been established. Specific attention was paid to the architectural fiber preform design as well as the materials used in construction of the composites. Actual testing of both tubular and flat, "dog-bone" shaped tensile composite specimens will begin next year. Since there is no precedence for using ceramic composites within a nuclear reactor, ASTM standard test procedures will be established from these mechanical and environmental tests. Close collaborations between the U.S. national laboratories and international collaborators (i.e. France and Japan) are being forged to establish both national and international test standards to be used to qualify ceramic composites for nuclear reactor applications

Polyglutamine Genes Interact to Modulate the Severity and Progression of Neurodegeneration in Drosophila

The expansion of polyglutamine tracts in a variety of proteins causes devastating, dominantly inherited neurodegenerative diseases, including six forms of spinal cerebellar ataxia (SCA). Although a polyglutamine expansion encoded in a single allele of each of the responsible genes is sufficient for the onset of each disease, clinical observations suggest that interactions between these genes may affect disease progression. In a screen for modifiers of neurodegeneration due to SCA3 in Drosophila, we isolated atx2, the fly ortholog of the human gene that causes a related ataxia, SCA2. We show that the normal activity of Ataxin-2 (Atx2) is critical for SCA3 degeneration and that Atx2 activity hastens the onset of nuclear inclusions associated with SCA3. These activities depend on a conserved protein interaction domain of Atx2, the PAM2 motif, which mediates binding of cytoplasmic poly(A)-binding protein (PABP). We show here that PABP also influences SCA3-associated neurodegeneration. These studies indicate that the toxicity of one polyglutamine disease protein can be dramatically modulated by the normal activity of another. We propose that functional links between these genes are critical to disease severity and progression, such that therapeutics for one disease may be applicable to others

The Nitric Oxide-Cyclic GMP Pathway Regulates FoxO and Alters Dopaminergic Neuron Survival in Drosophila

Activation of the forkhead box transcription factor FoxO is suggested to be involved in dopaminergic (DA) neurodegeneration in a Drosophila model of Parkinson's disease (PD), in which a PD gene product LRRK2 activates FoxO through phosphorylation. In the current study that combines Drosophila genetics and biochemical analysis, we show that cyclic guanosine monophosphate (cGMP)-dependent kinase II (cGKII) also phosphorylates FoxO at the same residue as LRRK2, and Drosophila orthologues of cGKII and LRRK2, DG2/For and dLRRK, respectively, enhance the neurotoxic activity of FoxO in an additive manner. Biochemical assays using mammalian cGKII and FoxO1 reveal that cGKII enhances the transcriptional activity of FoxO1 through phosphorylation of the FoxO1 S319 site in the same manner as LRRK2. A Drosophila FoxO mutant resistant to phosphorylation by DG2 and dLRRK (dFoxO S259A corresponding to human FoxO1 S319A) suppressed the neurotoxicity and improved motor dysfunction caused by co-expression of FoxO and DG2. Nitric oxide synthase (NOS) and soluble guanylyl cyclase (sGC) also increased FoxO's activity, whereas the administration of a NOS inhibitor L-NAME suppressed the loss of DA neurons in aged flies co-expressing FoxO and DG2. These results strongly suggest that the NO-FoxO axis contributes to DA neurodegeneration in LRRK2-linked PD

A 9-Month Hubble Space Telescope Near-UV Survey of M87. I. Light and Color Curves of 94 Novae, and a Re-determination of the Nova Rate

M87 has been monitored with a cadence of 5 days over a 9 month-long span through the near-ultraviolet (NUV:F275W) and optical (F606W) filters of the Wide Field Camera 3 (WFC3) of the Hubble Space Telescope. This unprecedented dataset yields the NUV and optical light and color curves of 94 M87 novae, characterizing the outburst and decline properties of the largest extragalactic nova dataset in the literature (after M31 and M81). We test and confirm nova modelers' prediction that recurrent novae cannot erupt more frequently that once every 45 days; show that there are zero rapidly recurring novae in the central ∼ 1/3 of M87 with recurrence times < 130 days; demonstrate that novae closely follow the K-band light of M87 to within a few arcsec of the galaxy nucleus; show that nova NUV light curves are as heterogeneous as their optical counterparts, and usually peak 5 to 30 days after visible light maximum; determine our observations' annual detection completeness to be 71 - 77\%; and measure the rate Rnova of nova eruptions in M87 as 352+37−37/yr. The corresponding luminosity-specific classical nova rate for this galaxy is 7.91+1.20−1.20/yr/1010L⊙,K. These rates confirm that ground-based observations of extragalactic novae miss most faint, fast novae and those near the centers of galaxies. An annual M87 nova rate of 300 or more seems inescapable. A luminosity-specific nova rate of ∼ 7−10/yr/1010L⊙,K in all types of galaxies is indicated by the data available in 2023

Internal representations of smell in the Drosophila brain

Recent advances in sensory neuroscience using Drosophila olfaction as a model system have revealed brain maps representing the external world. Once we understand how the brain's built-in capability generates the internal olfactory maps, we can then elaborate how the brain computes and makes decision to elicit complex behaviors. Here, we review current progress in mapping Drosophila olfactory circuits and discuss their relationships with innate olfactory behaviors

Simple model systems: a challenge for Alzheimer's disease

The success of biomedical researches has led to improvement in human health and increased life expectancy. An unexpected consequence has been an increase of age-related diseases and, in particular, neurodegenerative diseases. These disorders are generally late onset and exhibit complex pathologies including memory loss, cognitive defects, movement disorders and death. Here, it is described as the use of simple animal models such as worms, fishes, flies, Ascidians and sea urchins, have facilitated the understanding of several biochemical mechanisms underlying Alzheimer's disease (AD), one of the most diffuse neurodegenerative pathologies. The discovery of specific genes and proteins associated with AD, and the development of new technologies for the production of transgenic animals, has helped researchers to overcome the lack of natural models. Moreover, simple model systems of AD have been utilized to obtain key information for evaluating potential therapeutic interventions and for testing efficacy of putative neuroprotective compounds

Pro-Survival Role for Parkinson's Associated Gene DJ-1 Revealed in Trophically Impaired Dopaminergic Neurons

A mouse genetic study reveals a novel cell-survival role for the Parkinson's disease-associated gene DJ-1 in dopaminergic neurons that have reduced support from endogenous survival factors

Unique establishment of procephalic head segments is supported by the identification of cis-regulatory elements driving segment-specific segment polarity gene expression in Drosophila

Anterior head segmentation is governed by different regulatory mechanisms than those that control trunk segmentation in Drosophila. For segment polarity genes, both initial mode of activation as well as cross-regulatory interactions among them differ from the typical genetic circuitry in the trunk and are unique for each of the procephalic segments. In order to better understand the segment-specific gene network responsible for the procephalic expression of the earliest active segment polarity genes wingless and hedgehog, we started to identify and analyze cis-regulatory DNA elements of these genes. For hedgehog, we could identify a cis-regulatory element, ic-CRE, that mediates expression specifically in the posterior part of the intercalary segment and requires promoter-specific interaction for its function. The intercalary stripe is the last part of the metameric hedgehog expression pattern that appears during embryonic development, which probably reflects the late and distinct establishment of this segment. The identification of a cis-regulatory element that is specific for one head segment supports the mutant-based observation that the expression of segment polarity genes is governed by a unique gene network in each of the procephalic segments. This provides further indication that the anterior-most head segments represent primary segments, which are set up independently, in contrast to the secondary segments of the trunk, which resemble true repetitive units