723 research outputs found

    Complex Adaptive Team Systems (CATS): Scaling of a Team Leadership Development Model

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    Complex adaptive systems (CAS) have been identified as being hard to comprehend, composed of multiple interacting components acting interdependently with overlapping functions aimed at adapting to external/environmental forces. The current theoretical model utilized the natural functions of teams, viewing teams as a complex adaptive system, to develop the structure of the theory of complex adaptive team systems (CATS). The CATS model was formulated around the components of complexity theory (interactions, nonlinearity, interdependency, heterogeneity, complex systems, emergence, self-organizing, and adaptability) to show its utility across multiple domains (the role of leadership, organizational learning, organizational change, collective cognitive structures, innovation, cross-business-unit collaborations). In theorizing the CATS model, a new level of analysis was implemented, the interactions between agents as a move toward emergence in complex systems. The CATS model ultimately provides a model for organizations/institutions to drive knowledge creation and innovation while operating in today’s complexity

    Improving the Inventory of Large Lunar Basins: Using LOLA Data to Test Previous Candidates and Search for New Ones

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    Topography and crustal thickness data from LOLA altimetry were used to test the validity of 98 candidate large lunar basins derived from photogeologic and earlier topographic and crustal thickness data, and to search for possible new candidates. We eliminate 23 previous candidates but find good evidence for 20 new candidates. The number of basins greater than 300 km diameter on the Moon is almost certainly a factor 2 (maybe 3?) larger than the number of named features having basin-like topography. Unified Lunar Control Net 2005 data [1] and model crustal thickness data [2] were previously used to search for possible previously unrecognized large lunar impact basins [3,4]. An inventory of 98 candidate topographic basins greater than 300 km in diameter was found [5]. This includes 33 named features (only those having basin-like topography) out of the 45 listed by Wilhelms [6], 38 additional Quasi-Circular Depressions (QCDs) found in the ULCN2005 topography, and 27 Circular Thin Areas (CTAs) found in model crustal thickness data [2]. Most named features and additional QCDs have strong CTA signatures, but there may be a class of CTAs that are not easily recognized in the old and low resolution ULCN2005 topography. Lunar Orbiter Laser Altimeter (LOLA) data have recently become publically available. We used these data to (a) refine the center and ring diameters of known basins, (b) test the viability of the candidate basins previously found (as described above), and (c) search for additional candidate basins not revealed by the earlier lower resolution data. We used the LOLA topography directly but also a recent new model crustal thickness data that includes Kaguya gravity data [7]. We repeated a Topographic Expression (TE) and a Crustal Thickness Expression (CTE) scoring exercise originally done with the basins found in ULCN and earlier model crustal thickness data [5]. Each candidate was scored on a scale from 0 (no topographic basin or circular thin area signature) to 5 (strong circular low or strong circular thin area signature). These were combined into a total score used to rank the probability for each candidate basin. We used the same GRIDVIEW software to stretch, contour and profile the LOLA and new crustal thickness data as was done with the ULCN2005 and older model crustal thickness data

    Systemic TLR2 agonist exposure regulates hematopoietic stem cells via cell-autonomous and cell-non-autonomous mechanisms

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    Toll-like receptor 2 (TLR2) is a member of the TLR family of receptors that play a central role in innate immunity. In addition to regulating effector immune cells, where it recognizes a wide variety of pathogen-associated and nonpathogen-associated endogenous ligands, TLR2 is expressed in hematopoietic stem cells (HSCs). Its role in HSCs, however, is not well understood. Furthermore, augmented TLR2 signaling is associated with myelodysplastic syndrome, an HSC disorder characterized by ineffective hematopoiesis and a high risk of transformation to leukemia, suggesting that aberrant signaling through this receptor may have clinically significant effects on HSCs. Herein, we show that systemic exposure of mice to a TLR2 agonist leads to an expansion of bone marrow and spleen phenotypic HSCs and progenitors, but a loss of HSC self-renewal capacity. Treatment of chimeric animals shows that these effects are largely cell non-autonomous, with a minor contribution from cell-autonomous TLR2 signaling, and are in part mediated by granulocyte colony-stimulating factor and tumor necrosis factor-α. Together, these data suggest that TLR2 ligand exposure influences HSC cycling and function via unique mechanisms from TLR4, and support an important role for TLR2 in the regulation of HSCs

    Characterization of DNA Sequences that Confer Complement Resistance in \u3ci\u3eLeishmania chagasi\u3c/i\u3e

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    Serial passage of axenically cultured Leishmania chagasi promastigotes results in a progressive diminution in resistance to complement-mediated lysis (CML), whereas high CML resistance is seen in infectious metacyclic promastigotes from the sandfly vector as well as metacyclic-like promastigotes within low-passage cultures at stationary growth phase. As we previously reported, in a screen seeking to identify novel genes involved in CML resistance: (1) a genomic cosmid library derived from DNA of CML-resistant L. chagasi promastigotes was transfected into highpassage (constitutively CML-sensitive) L. chagasi promastigotes; (2) transformants were screened for acquisition of CML-resistance; (3) multiple cosmid-transfectants exhibited partial CML resistance; and (4) the sequence for one of the cosmids (Cosmid 51) was determined. This report extends the analysis of Cosmid 51, and identifies by deletion analysis a subregion of the cosmid insert that is critical to the CML-resistance phenotype of Cosmid 51 transformants. We also report the sequence determination and initial CML-resistance activity of another cosmid that also confers partial resistance to CML

    Potential Alzheimer’s Disease Therapeutics Among Weak Cysteine Protease Inhibitors Exhibit Mechanistic Differences Regarding Extent of Cathepsin B Up-Regulation and Ability to Block Calpain

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    Cysteine protease inhibitors have long been part of drug discovery programs for Alzheimer's disease (AD), traumatic brain injury (TBI), and other disorders. Select inhibitors reduce accumulating proteins and AD pathology in mouse models. One such compound, Z-Phe-Aladiazomethylketone (PADK), exhibits a very weak IC50 (9-11 μM) towards cathepsin B (CatB), but curiously PADK causes marked up-regulation of the Aβ-degrading CatB and improves spatial memory. Potential therapeutic and weak inhibitor E64d (14 μM IC50) also up-regulates CatB. PADK and E64d were compared regarding the blockage of calcium-induced cytoskeletal deterioration in brain samples, monitoring the 150-kDa spectrin breakdown product (SBDP) known to be produced by calpain. PADK had little to no effect on SBDP production at 10-100 μM. In contrast, E64d caused a dosedependent decline in SBDP levels with an IC50 of 3-6 μM, closely matching its reported potency for inhibiting μ-calpain. Calpain also cleaves the cytoskeletal organizing protein gephyrin, producing 49-kDa (GnBDP49) and 18-kDa (GnBDP18) breakdown products. PADK had no apparent effect on calcium-induced gephyrin fragments whereas E64d blocked their production. E64d also protected the parent gephyrin in correspondence with reduced BDP levels. The findings of this study indicate that PADK’s positive and selective effects on CatB are consistent with human studies showing exercise elevates CatB and such elevation correlates with improved memory. On the other hand, E64d exhibits both marginal CatB enhancement and potent calpain inhibition. This dual effect may be beneficial for treating AD. Alternatively, the potent action on calpain-related pathology may explain E64d’s protection in AD and TBI models

    iKanEat: Protocol for a randomized controlled trial of megestrol as a component of a pediatric tube weaning protocol

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    Background Although tube feeding routinely saves the lives of children who do not eat by mouth, chronic tube feeding can be a burden to patients, caregivers, and families. Very few randomized trials exist regarding the best methods for weaning children from their feeding tubes. Methods The current paper describes a randomized controlled trial of an empirically supported outpatient treatment protocol for moving children from tube to oral eating called iKanEat. Specifically, we describe the methods of randomized double-blind, placebo-controlled trial which includes a 4-week course of megestrol, the only medication used in the iKanEat protocol, to determine whether the addition of megestrol results in improved child outcomes. The primary and secondary aims are to assess the safety and efficacy of megestrol as part of the iKanEat protocol. The third aim is to provide critical information about the impact of the transition from tube to oral feeding on parent stress and parent and child quality of life. Discussion This trial will provide data regarding whether megestrol is a safe and effective component of the iKanEat tube weaning protocol, as well as important data on how the tube weaning process impacts parent stress and parent and child quality of life

    Investıgatıon of Removal of Dye from Aqueous Solutıon by Advanced Treatment

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    The textile dyeing and finishing industry use a significant amount of water and produce water pollution. Conventional biological treatment processes have some difficulties for degradation of nonbiodegradable compounds. Dye-bearing wastewaters have high COD and colour. In this study, a photo reactor process was used to remove color from aqueous solution.Effects of pH on Reactive Red 4 and cationic dye removal using 1g/L TiO2, as catalyst were studied at constant inital dye concentration (25 mg/l). Cationic dye removal efficiency is better than Reactive dye removal efficiency for photocatalytic oxidation in this stud

    Recruitment and reach in a school-based pediatric obesity intervention trial in rural areas

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    Introduction: The purpose of this study is to evaluate two recruitment strategies on schools and participant participation rates and representativeness (reach) within a pediatric obesity treatment trial tailored for families who live in rural areas. Methods: Recruitment of schools was evaluated based on their progress toward enrolling participants. Recruitment and reach of participants were evaluated using (1) participation rates and (2) representativeness of demographics and weight status of participants compared to eligible participants (who did not consent and enroll) and all students (regardless of eligibility). School recruitment, as well as participant recruitment and reach, were evaluated across recruitment methods comparing opt-in (i.e., caregivers agreed to allow their child to be screened for eligibility) vs. screen-first (i.e., all children screened for eligibility). Results: Of the 395 schools contacted, 34 schools (8.6%) expressed initial interest; of these, 27 (79%) proceeded to recruit participants, and 18 (53%) ultimately participated in the program. Of schools who initiated recruitment, 75% of schools using the opt-in method and 60% of schools using the screen-first method continued participation and were able to recruit a sufficient number of participants. The average participation rate (number of enrolled individuals divided by those who were eligible) from all 18 schools was 21.6%. This percentage was higher in schools using the screen-first method (average of 29.7%) compared to schools using the opt-in method (13.5%). Study participants were representative of the student population based on sex (female), race (White), and eligibility for free and reduced-price lunch. Study participants had higher body mass index (BMI) metrics (BMI, BMIz, and BMI%) than eligible non-participants. Conclusions: Schools using the opt-in recruitment were more likely to enroll at least 5 families and administer the intervention. However, the participation rate was higher in screen-first schools. The overall study sample was representative of the school demographics

    Fnr (EtrA) acts as a fine-tuning regulator of anaerobic metabolism in Shewanella oneidensis MR-1

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    BackgroundEtrA in Shewanella oneidensis MR-1, a model organism for study of adaptation to varied redox niches, shares 73.6% and 50.8% amino acid sequence identity with the oxygen-sensing regulators Fnr in E. coli and Anr in Pseudomonas aeruginosa, respectively; however, its regulatory role of anaerobic metabolism in Shewanella spp. is complex and not well understood.ResultsThe expression of the nap genes, nrfA, cymA and hcp was significantly reduced in etrA deletion mutant EtrA7-1; however, limited anaerobic growth and nitrate reduction occurred, suggesting that multiple regulators control nitrate reduction in this strain. Dimethyl sulfoxide (DMSO) and fumarate reductase gene expression was down-regulated at least 2-fold in the mutant, which, showed lower or no reduction of these electron acceptors when compared to the wild type, suggesting both respiratory pathways are under EtrA control. Transcript analysis further suggested a role of EtrA in prophage activation and down-regulation of genes implicated in aerobic metabolism.ConclusionIn contrast to previous studies that attributed a minor regulatory role to EtrA in Shewanella spp., this study demonstrates that EtrA acts as a global transcriptional regulator and, in conjunction with other regulators, fine-tunes the expression of genes involved in anaerobic metabolism in S. oneidensis strain MR-1. Transcriptomic and sequence analyses of the genes differentially expressed showed that those mostly affected by the mutation belonged to the "Energy metabolism" category, while stress-related genes were indirectly regulated in the mutant possibly as a result of a secondary perturbation (e.g. oxidative stress, starvation). We also conclude based on sequence, physiological and expression analyses that this regulator is more appropriately termed Fnr and recommend this descriptor be used in future publications
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