2,836 research outputs found

    Genetically Modified Crops, an Input Distance Function Approach

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    Our initial findings indicate that GM crops do not contribute to the decline of traditional family farms. We make a significant methodological impact by using the within transformation to remove unobserved individual effects and demonstrate that the within transformation results in ML estimates that are identical to OLS estimates.Production Economics, Genetically Modified Crops, Distance Function, Stochastic Frontier Analysis, Production Economics, Research Methods/ Statistical Methods,

    That’s Why I Don’t like You: An Investigation of Intergroup Disidentification in a Socialization Context

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    This study takes a social identity perspective to explain intergroup relationships within organizations. Specifically, I investigate how newcomers to an organization are socialized to an organization and why the sources of socialization can affect newcomers’ perceptions of their workgroup and other workgroups in the organization. Newcomers to organizations often face uncertainty in their new organization and receive information about organizational norms, rules, and procedures from various sources such as coworkers, supervisors, or organizational attempts to provide a socialization program. I propose that newcomers that receive socialization from proximal sources such as coworkers and supervisors will be more likely to disidentify from other workgroups within the organization. Additionally, I propose various individual-level moderators to this relationship. Subsequently, intergroup disidentification can result in various attitudinal and behavioral outcomes such as intergroup conflict, ingroup favoritism, outgroup derogation, interpersonal deviance, and intentions to leave the organization. To test my hypotheses I conducted a lab experiment to test socialization sources’ effects on intergroup disidentification and also the effects on ingroup/outgroup perceptions. I also conducted a field study to further test hypotheses related to intergroup behaviors as well as individual’s reactions to intergroup disidentification

    The San1 Ubiquitin Ligase Avidly Recognizes Misfolded Proteins Through Multiple Substrate Binding Sites

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    Cellular homeostasis depends on robust protein quality control (PQC) pathways that discern misfolded proteins from functional ones in the cell. One major branch of PQC involves the controlled degradation of misfolded proteins by the ubiquitin-proteasome system. Here ubiquitin ligases must recognize and bind to misfolded proteins with sufficient energy to form a complex and with an adequate half-life to achieve poly-ubiquitin chain formation, the signal for protein degradation, prior to its dissociation from the ligase. It is not well understood how PQC ubiquitin ligases accomplish these tasks. Employing a fully reconstituted enzyme and substrate system to perform quantitative biochemical experiments, we demonstrate that the yeast PQC ubiquitin ligase San1 contains multiple substrate binding sites along its polypeptide chain that appear to display specificity for unique misfolded proteins. The results are consistent with a model where these substrate binding sites enable San1 to bind to misfolded substrates avidly, resulting in high affinity ubiquitin ligase-substrate complexes

    Structure Previews Digging for Buried Amino Acids Unearths New Protein Quality Control Treasure

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    Proteins rely on three-dimensional structure for function, yet many proteins are marginally stable and prone to misfolding. In this issue of Structure, Brock et al. (2015) present a novel computational modeling method to gain insights into protein stability and misfolding. To function correctly, most proteins must adopt a proper three-dimensional structure that allows them to operate with high precision and fidelity. However, protein synthesis is not free of errors, and nascent proteins can initially misfold into defective structures. Even when a nascent protein folds properly, post-synthesis exposure to chemical or physical stresses can damage the functional structure and cause misfolding. The stochastic generation of misfolded proteins is a fundamental problem that all cells continuously face. If left unattended, misfolded proteins can form toxic aggregates that can ultimately lead to cell death. This dire consequence is underscored by the more than 50 human maladies causally linked with aggregation, which include devastating neurodegenerative disorders such as Alzheimer's, Parkinson's, Huntington's, and ALS Studying what features misfolded proteins present to PQC degradation systems in their abnormal state is a very difficult task. Misfolded proteins are highly recalcitrant to the biochemical and biophysical techniques typically used to probe the structural features of normally folded proteins. Just ask any protein biochemist-the bane of their existence is the aggregation that can occur during the purification of proteins for structural analyses. Yet, aggregation is the ''normal'' behavior of misfolded proteins that is important to understand for PQC biologists. An additional complicating feature is that when a pool of protein misfolds, different misfolded conformations will likely exist within the pool. This presents a considerable problem for biochemists using structural analyses that rely on a single uniform conformation within a protein pool. Given the difficulty of working with misfolded proteins by traditional means, it is useful to think outside the typical experimental toolkit used for probing the structure of normal proteins. Computational methods to predict protein structure have a long history; the Ramachandran plot is still used for theoretical models and validations of structure In this issue of Structure, The authors tested their method with the von Hippel-Lindau protein (VHL), which has been used as a model substrate for PQC because it is prone to misfolding when it does not interact with its partner proteins Structure 23, July 7

    A Comprehensive Survey of Hydrogen Chloride in the Galaxy

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    We report new observations of the fundamental J=10J=1-0 transition of HCl (at 625.918GHz) toward a sample of 25 galactic star-forming regions, molecular clouds, and evolved stars, carried out using the Caltech Submillimeter Observatory. Fourteen sources in the sample are also observed in the corresponding H\tscl\ J=10J=1-0 transition (at 624.978GHz). We have obtained clear detections in all but four of the targets, often in emission. Absorptions against bright background continuum sources are also seen in nine cases, usually involving a delicate balance between emission and absorption features. From RADEX modeling, we derive gas densities and HCl column densities for sources with HCl emission. HCl is found in a wide range of environments, with gas densities ranging from 10510^5 to 10710^7~cm3^{-3}. The HCl abundance relative to H2_2 is in the range of (330)×1010(3-30)\times10^{-10}. Comparing with the chlorine abundance in the solar neighborhood, this corresponds to a chlorine depletion factor of up to \sim400, assuming that HCl accounts for one third of the total chlorine in the gas phase. The [\tfcl]/[\tscl] isotopic ratio is rather varied, from unity to \sim5, mostly lower than the terrestrial value of 3.1. Such variation is highly localized, and could be generated by the nucleosynthesis in supernovae, which predicts a \tscl\ deficiency in most models. The lower ratios seen in W3IRS4 and W3IRS5 likely confine the progenitors of the supernovae to stars with relatively large mass (\ga25M_\sun) and high metallicity (Z\sim0.02).Comment: 11 pages, 5 figures, accepted by Ap

    Structure of the Shroom-Rho Kinase Complex Reveals a Binding Interface with Monomeric Shroom That Regulates Cell Morphology and Stimulates Kinase Activity

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    Shroom-mediated remodeling of the actomyosin cytoskeleton is a critical driver of cellular shape and tissue morphology that underlies the development of many tissues including the neural tube, eye, intestines, and vasculature. Shroom uses a conserved SD2 domain to direct the subcellular localization of Rho-associated kinase (Rock), which in turn drives changes in the cytoskeleton and cellular morphology through its ability to phosphorylate and activate non-muscle myosin II. Here, we present the structure of the human Shroom-Rock binding module, revealing an unexpected stoichiometry for Shroom in which two Shroom SD2 domains bind independent surfaces on Rock. Mutation of interfacial residues impaired Shroom-Rock binding in vitro and resulted in altered remodeling of the cytoskeleton and loss of Shroom-mediated changes in cellular morphology. Additionally, we provide the first direct evidence that Shroom can function as a Rock activator. These data provide molecular insight into the Shroom-Rock interface and demonstrate that Shroom directly participates in regulating cytoskeletal dynamics, adding to its known role in Rock localization

    Galaxies in Southern Bright Star Fields I. Near-infrared imaging

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    As a prerequisite for cosmological studies using adaptive optics techniques, we have begun to identify and characterize faint sources in the vicinity of bright stars at high Galactic latitudes. The initial phase of this work has been a program of K_s imaging conducted with SOFI at the ESO NTT. From observations of 42 southern fields evenly divided between the spring and autumn skies, we have identified 391 additional stars and 1589 galaxies lying at separations 60" from candidate guide stars in the magnitude range 9.0 R 12.4. When analyzed as a "discrete deep field" with 131 arcmin^2 area, our dataset gives galaxy number counts that agree with those derived previously over the range 16 K_s 20.5. This consistency indicates that in the aggregate, our fields should be suitable for future statistical studies. We provide our source catalogue as a resource for users of large telescopes in the southern hemisphere.Comment: 10 pages, 7 figures, accepted by A&A; Table 3 is available at http://www.rzg.mpg.de/~ajb/data.html pending upload to CD

    Investigation of HNF-1B as a diagnostic biomarker for pancreatic ductal adenocarcinoma

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    Background: Diagnosing pancreatic ductal adenocarcinoma (PDAC) in the setting of metastasis with an unknown primary remains very challenging due to the lack of specific biomarkers. HNF-1B has been characterized as an important transcription factor for pancreatic development and was reported as a biomarker for clear cell subtype of PDAC. Methods: To investigate the diagnostic role of HNF-1B for PDAC, we used tissue microarray (TMA) and immunohistochemistry (IHC) to characterize HNF-1B expression in a large cohort of carcinomas, including 127 primary PDACs, 47 biliary adenocarcinomas, 17 metastatic PDACs, and 231 non-pancreaticobiliary carcinomas. Results: HNF-1B was expressed in 107 of 127 (84.3%) of PDACs, 13 of 15 (86.7%) of cholangiocarcinomas, 13 of 18 (72%) of ampullary carcinomas, and 13 of 14 (92.9%) of gallbladder adenocarcinomas. Notably, HNF-1B was expressed in 16 of 17 (94.1%) of metastatic PDACs. Among the non-pancreaticobiliary cancers, HNF-1B was expressed in ~ 77% clear cell carcinomas of the kidney and ovarian clear cell carcinomas. Gastroesophageal, lung, and prostate adenocarcinomas occasionally expressed HNF-1B in up to 37% cases. HNF-1B was completely negative in hepatocellular, colorectal, breast, and lung squamous cell carcinomas. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of HNF-1B for primary pancreaticobiliary carcinoma is 84, 68, 66, 85, and 75%, respectively. HNF-1B expression was not significantly associated with overall survival in patients with PDAC, but tumor size \u3e /=2 cm and high tumor grade were significantly associated with worse overall survival in multivariate analyses. Conclusions: HNF-1B may be used in surgical pathology to aid the diagnosis of metastatic pancreatic and biliary carcinoma with a panel of other markers to exclude lung, kidney, prostate, and Mullerian origins

    Out-Life Characteristics of IM7/977-3 Composites

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    The capability to manufacture large structures leads to weight savings and reduced risk relative to joining smaller components. However, manufacture of increasingly large composite components is pushing the out-time limits of epoxy/ carbon fiber prepreg. IM7/977-3 is an autoclave processable prepreg material, commonly used in aerospace structures. The out-time limit is reported as 30 days by the manufacturer. The purpose of this work was to evaluate the material processability and composite properties of 977-3 resin and IM7/977-3 prepreg that had been aged at room temperature for up to 60 days. The effects of room temperature aging on the thermal and visco-elastic properties of the materials were investigated. Neat resin was evaluated by differential scanning calorimetry to characterize thermal properties and change in activation energy of cure. Neat resin was also evaluated by rheometry to characterize its processability in composite fabrication. IM7/977-3 prepreg was evaluated by dynamic mechanical analysis to characterize the curing behavior. Prepreg tack was also evaluated over 60 days. The overall test results suggested that IM7/977-3 was a robust material that offered quality laminates throughout this aging process when processed by autoclave
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