1,008 research outputs found

    Session 5: Looking Beyond COVID-19

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    The recovery from COVID represents a unique opportunity for the aviation community. Airlines and Air Traffic are working together to take advantage of the modern aircraft capabilities and improved ATC procedures. Implementation now, during this downturn, assures seamless integration as air traffic resumes. Building back better, safer, and more efficient is the goal of all within the community. This segment will highlight some of the many activities to achieve this goal as well as identify new areas for improvement

    Mechanisms Regulating the Association of Protein Phosphatase 1 with Spinophilin and Neurabin

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    Protein phosphorylation is a key mediator of signal transduction, allowing for dynamic regulation of substrate activity. Whereas protein kinases obtain substrate specificity by targeting specific amino acid sequences, serine/threonine phosphatase catalytic subunits are much more promiscuous in their ability to dephosphorylate substrates. To obtain substrate specificity, serine/threonine phosphatases utilize targeting proteins to regulate phosphatase subcellular localization and catalytic activity. Spinophilin and its homologue neurabin are two of the most abundant dendritic spine-localized protein phosphatase 1 (PP1) targeting proteins. The association between spinophilin and PP1 is increased in the striatum of animal models of Parkinson's disease (PD). However, mechanisms that regulate the association of spinophilin and neurabin with PP1 are unclear. Here, we report that the association between spinophilin and PP1α or PP1γ1 was increased by CDK5 expression and activation in a heterologous cell system. This increased association is at least partially due to phosphorylation of PP1. Conversely, CDK5 expression and activation decreased the association of PP1 with neurabin. As with dopamine depletion, methamphetamine (METH) abuse causes persistent alterations in dopamine signaling which influence striatal medium spiny neuron function and biochemistry. Moreover, both METH toxicity and dopamine depletion are associated with deficits in motor control and motor learning. Pathologically, we observed a decreased association of spinophilin with PP1 in rat striatum evaluated one month following a binge METH paradigm. Behaviorally, we found that loss of spinophilin recapitulates rotarod pathology previously observed in dopamine-depleted and METH-treated animals. Together, these data have implications in multiple disease states associated with altered dopamine signaling such as PD and psychostimulant drug abuse and delineate a novel mechanism by which PP1 interactions with spinophilin and neurabin may be differentially regulated

    National Register of Historic Places Eligibility Testing of Site 41SM385 Within TxDOT\u27s Tyler District, Smith County, Texas

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    PBS&J, an Atkins company, was contracted by the North East Texas Regional Mobility Authority to conduct National Register of Historic Places eligibility testing of site 41SM385, a prehistoric campsite on a small rise above the floodplain of Indian Creek in western Smith County, Texas. Testing investigations were conducted during March and September 2009. The site was subjected to a systematic program of shovel testing, mechanical trenching, and hand excavation in an effort to identify cultural features or living surfaces and optimize recovery of diagnostic faunal, floral, and artifactual remains. The recovered cultural artifacts indicate that site 41SM385 represents a probable Woodland and Caddo‐aged occupation on a small rise on the creek floodplain. The Woodland component is based on recovered small Gary and Kent projectile points characteristic of Woodland culture of the region. The Caddo component is based on ceramic sherds of probable Early or Middle Caddo origin identified at the site. Radiocarbon dating of four ceramic sherds supports these assessments with three sherds dating to the Early to Middle Caddo periods and one sherd dating to the Woodland period. The lack of identified cultural features suggests that the Woodland component probably represents a series of ephemeral usages of the location, probably as short‐term campsites. The Caddo‐aged artifacts at the site probably represent a series of ephemeral usage of the location, either as a resource procurement locus ancillary to nearby site 41SM404 or as a short‐term campsite. The testing program failed to locate living surfaces or cultural features containing in situ artifactual or organic remains preserved on the site. The absence of cultural features and the paucity of lithic tools or ceramic remains make more‐meaningful functional interpretation infeasible. For this reason, the site lacks the data resources that would warrant National Register of Historic Places isting or designation as a State Archeological Landmark. No further work is recommended

    An ancient spliceosomal intron in the ribosomal protein L7a gene (Rpl7a) of Giardia lamblia

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    BACKGROUND: Only one spliceosomal-type intron has previously been identified in the unicellular eukaryotic parasite, Giardia lamblia (a diplomonad). This intron is only 35 nucleotides in length and is unusual in possessing a non-canonical 5' intron boundary sequence, CT, instead of GT. RESULTS: We have identified a second spliceosomal-type intron in G. lamblia, in the ribosomal protein L7a gene (Rpl7a), that possesses a canonical GT 5' intron boundary sequence. A comparison of the two known Giardia intron sequences revealed extensive nucleotide identity at both the 5' and 3' intron boundaries, similar to the conserved sequence motifs recently identified at the boundaries of spliceosomal-type introns in Trichomonas vaginalis (a parabasalid). Based on these observations, we searched the partial G. lamblia genome sequence for these conserved features and identified a third spliceosomal intron, in an unassigned open reading frame. Our comprehensive analysis of the Rpl7a intron in other eukaryotic taxa demonstrates that it is evolutionarily conserved and is an ancient eukaryotic intron. CONCLUSION: An analysis of the phylogenetic distribution and properties of the Rpl7a intron suggests its utility as a phylogenetic marker to evaluate particular eukaryotic groupings. Additionally, analysis of the G. lamblia introns has provided further insight into some of the conserved and unique features possessed by the recently identified spliceosomal introns in related organisms such as T. vaginalis and Carpediemonas membranifera

    Evaluation of an ambulatory system for the quantification of cough frequency in patients with chronic obstructive pulmonary disease

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    BACKGROUND: To date, methods used to assess cough have been primarily subjective, and only broadly reflect the impact of chronic cough and/or chronic cough therapies on quality of life. Objective assessment of cough has been attempted, but early techniques were neither ambulatory nor feasible for long-term data collection. We evaluated a novel ambulatory cardio-respiratory monitoring system with an integrated unidirectional, contact microphone, and report here the results from a study of patients with COPD who were videotaped in a quasi-controlled environment for 24 continuous hours while wearing the ambulatory system. METHODS: Eight patients with a documented history of COPD with ten or more years of smoking (6 women; age 57.4 ± 11.8 yrs.; percent predicted FEV(1 )49.6 ± 13.7%) who complained of cough were evaluated in a clinical research unit equipped with video and sound recording capabilities. All patients wore the LifeShirt(Âź )system (LS) while undergoing simultaneous video (with sound) surveillance. Video data were visually inspected and annotated to indicate all cough events. Raw physiologic data records were visually inspected by technicians who remained blinded to the video data. Cough events from LS were analyzed quantitatively with a specialized software algorithm to identify cough. The output of the software algorithm was compared to video records on a per event basis in order to determine the validity of the LS system to detect cough in COPD patients. RESULTS: Video surveillance identified a total of 3,645 coughs, while LS identified 3,363 coughs during the same period. The median cough rate per patient was 21.3 coughs·hr(-1 )(Range: 10.1 cghs·hr(-1 )– 59.9 cghs·hr(-1)). The overall accuracy of the LS system was 99.0%. Overall sensitivity and specificity of LS, when compared to video surveillance, were 0.781 and 0.996, respectively, while positive- and negative-predictive values were 0.846 and 0.994. There was very good agreement between the LS system and video (kappa = 0.807). CONCLUSION: The LS system demonstrated a high level of accuracy and agreement when compared to video surveillance for the measurement of cough in patients with COPD

    The association of spinophilin with disks large-associated protein 3 (SAPAP3) is regulated by metabotropic glutamate receptor (mGluR) 5

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    Spinophilin is the most abundant protein phosphatase 1 targeting protein in the postsynaptic density of dendritic spines. Spinophilin associates with myriad synaptic proteins to regulate normal synaptic communication; however, the full complement of spinophilin interacting proteins and mechanisms regulating spinophilin interactions are unclear. Here we validate an association between spinophilin and the scaffolding protein, disks large-associated protein 3 (SAP90/PSD-95 associated protein 3; SAPAP3). Loss of SAPAP3 leads to obsessive-compulsive disorder (OCD)-like behaviors due to alterations in metabotropic glutamate receptor (mGluR) signaling. Here we report that spinophilin associates with SAPAP3 in the brain and in a heterologous cell system. Moreover, we have found that expression or activation of group I mGluRs along with activation of the mGluR-dependent kinase, protein kinase C ÎČ, enhances this interaction. Functionally, global loss of spinophilin attenuates amphetamine-induced hyperlocomotion, a striatal behavior associated with dopamine dysregulation and OCD. Together, these data delineate a novel link between mGluR signaling, spinophilin, and SAPAP3 in striatal pathophysiology

    Gratitude and Happiness: The Causes and Consequences of Gratitude

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    In this chapter, we review recent research on the relationship between gratitude and happiness. First, we show how gratitude is a critical component of the good life. Because gratitude is vital to wellbeing, it is important to establish the causes of state and trait gratitude. We explain an appraisal approach to grateful emotion and show how certain benefit interpretations are critical to the experience of gratitude. In this context, we describe an encouraging new paradigm that has been applied to the study of gratitude: cognitive bias modification. This experimental approach has helped to establish the causal status of interpretations to gratitude, and we describe how this methodology should help to understand gratitude in future research. Recent research on the cognitive antecedents of gratitude has shown that the nature of the benefactor matters to experiences of gratitude, and in this regard, a divine benefactor may create a unique experience of gratitude. Gratitude scholars have now turned to the question: How does gratitude enhance happiness? We present research and theories that have attempted to speak to this issue. Finally, we explore the question: Who benefits most from gratitude interventions? Research has supplied some surprising answers to this question

    A Survey for Circumstellar Disks Around Young Substellar Objects

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    (Abridged) We have completed the first systematic survey for disks around spectroscopically identified young brown dwarfs and very low mass stars. We have obtained L'-band (3.8 um) imaging for 38 very cool objects in IC 348 and Taurus. Our targets span spectral types from M6 to M9.5 (~100 to ~15 Mjup). Using the objects' measured spectral types and extinctions, we find that most of our sample (77%+/-15%) possess intrinsic IR excesses, indicative of disks. Because the excesses are modest, conventional analyses using only IR colors would have missed most of the sources with excesses. The observed IR excesses are correlated with Halpha emission, consistent with a common accretion disk origin. The excesses can be explained by disk reprocessing of starlight alone; the implied accretion rates are at least an order of magnitude below typical values for classical T Tauri stars. The observed distribution of IR excesses suggests the presence of inner disk holes. The disk frequency appears to be independent of the mass and age. In the same star-forming regions, disks around brown dwarfs are at least as long-lived (~3 Myr) as disks around the T Tauri stars. Altogether, the frequency and properties of young circumstellar disks appear to be similar from the stellar regime down to the substellar and planetary-mass regime. This provides prima facie evidence of a common origin for most stars and brown dwarfs.Comment: ApJ, in press, 28 pages. Minor change to the online, abridged version of the abstract. No change to the actual pape
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