41 research outputs found

    A study on the determinants of financial performance of U.S. agricultural cooperatives

    Get PDF
    A significant number of studies have been made in the area of agricultural economics; however, there is a paucity of work that investigates factors or determinants which influence the financial performance of agro cooperatives. This paper investigates determinants of financial performance for the United States (U.S.) agricultural cooperatives for the period 2009–2017. By using the United States Department of Agriculture (USDA) database, we created a sample of 37 U.S. agro cooperatives. For analysis, we used panel regression analysis as it is suitable to deal with fixed effect or random effect error component presented in the model. Finding states that the U.S. agro cooperatives are found highly sensitive to economic policy uncertainty. The results provide evidence of a negative relationship between size and profitability. Moreover, the impact of growth and capital intensity is also reflected in the return on asset (ROA). In this study, we considered ROA as a proxy for firm performance. Implications and suggestions for further new research are also discussed

    Erst verstehen, dann besiegen: Das Ubiquitin-aktivierende Enzym, ein vielversprechender Kandidat in der Krebstherapie

    No full text
    Ubiquitin is a 76 amino acid long polypeptide, which is present throughout eukaryotes in a highly conserved fashion. Ubiquitin can modify proteins by becoming covalently attached to them. Eukaryotic cells employ ubiquitin to maintain and regulate fundamental cellular processes like protein degradation, the immune response and transcriptional and translational regulation. Transfer of ubiquitin to the substrate is achieved by the catalysis of three classes of enzymes namely E1, E2 and E3. Together these enzymes form a pyramidal hierarchy, where E1 stands at the apex and E3 enzymes form the base of the pathway. The ubiquitin activating enzyme 1 (UBA1) plays a major role in ubiquitylation being the ubiquitin-dedicated E1 enzyme. In addition, it is the only enzyme in this pathway to use ATP as an energy source to catalyze two important reactions. The products of these reactions, ubiquitin adenylate and ubiquitin thioester, are the essential intermediate states of ubiquitin, for being conjugated to the target protein. With the help of X-ray crystallography and biochemical approaches, snapshots of multiple catalytic states of UBA1, where it is bound to Mg-ATP, ubiquitin and the E2 Ubc13 as substrates could be captured. With the help of these high-resolution crystal structures, deeper insights into the enzymatic mechanism of UBA1 could be attained. The resulting insights into the catalytic cycle were further validated by biochemical assays. It could be shown that ATP acts as a molecular switch to induce the enzyme’s open conformation. Ubiquitin-binding to the enzyme leads to domain rotations, which facilitate the recruitment of a cognate E2 enzyme. The interdomain communication as well as the cross-talk with the substrates and the products fuel the enzymatic cycle of UBA1. Due to the proven efficacy of proteasome inhibitors for cancer treatment, which block degradation of proteins labeled with ubiquitin, enzymes participating in the ubiquitylation cascade have been targeted by researchers for the development of novel anti-cancer therapeutics. UBA1 inhibition has been shown to preferentially induce cell death in malignant cells, and it can also be used as a strategy to overcome resistance against proteasome inhibitors. MLN7243, an adenosyl sulfamate inhibitor developed by Millenium Pharmaceutical to specifically target UBA1, is currently in Phase-I clinical trials for the treatment of solid tumors. UBA1 could be crystallized in complex with three adenosyl sulfamate inhibitors covalently linked to ubiquitin, which are promising drug candidates for cancer therapy. The inhibitors employed, MLN7243, MLN4924 and ABPA3, show distinct specificities towards different E1 enzymes. With the help of crystal structures the specificity determinants of these inhibitors could be deciphered, which were further confirmed by inhibition assays as well as molecular dynamics simulations. Together these crystal structures provide a starting point for developing E1-specific inhibitors, which, besides their potential for medicinal purposes, are important tools to better understand the function of the ubiquitin system as well as the action of ubiquitin-like proteins.Ubiquitin ist ein 76 Aminosäuren langes Polypeptid, das in allen Eukaryoten vorkommt und hoch konserviert ist. Ubiquitin kann Proteine modifizieren indem es mittels einer kovalente Bindung an diese angeheftet wird. Eukaryotische Zellen nutzen Ubiquitin, um fundamentale zelluläre Prozesse wie den Proteinabbau, die Immunantwort sowie die Regulation der Transkription und Translation aufrecht zu erhalten. Der Transfer von Ubiquitin auf das Substrat wird durch die Katalyse von drei Enzymklassen E1, E2 und E3 erreicht. Zusammen bilden diese Enzyme eine pyramidale Hierarchie in der das E1 an der Spitze steht und die E3 Enzyme die Basis bilden. Das Ubiquitin-aktivierende Enzym 1 (UBA1) ist das E1 Enzym für Ubiquitin und spielt somit eine Hauptrolle in der Ubiquitinierung. Weiterhin ist es das einzige Enzym dieses Stoffwechselweges, das ATP als Energie nutzt, um zwei wichtige Reaktionen zu katalysieren. Die Produkte dieser Reaktionen, Ubiquitin-Adenylat und thioesterifiziertes Ubiquitin, sind die essentiellen Ubiquitinintermediate für die Konjugation an das Zielprotein. Mit Hilfe der Röntgenstrukturanalyse und biochemischer Ansätze konnten für UBA1 Momentaufnahmen multipler katalytischer Zustände erfasst werden, in denen es an die Substrate Mg-ATP, Ubiquitin und dem E2 Enzym Ubc13 gebunden vorliegt. Mit Hilfe dieser hochaufgelösten Kristallstrukturen konnten tiefere Einblicke in den enzymatischen Mechanismus des Enzyms erzielt werden. Die gesammelten Erkenntnisse zum katalytischen Zyklus wurden mittels biochemischer Methoden validiert. Es konnte gezeigt werden, dass ATP als molekularer Schalter fungiert, um das Enzym in seine offene Konformation zu überführen. Die Bindung von Bindung an das Enzym führt zur Rotation einzelner Domänen welche die Rekrutierung des E2 Enzymes erleichtern. Die Interdomänen-Interaktion sowie molekulare Wechselwirkungen mit den Substraten und Produkten treiben den enzymatischen Zyklus von UBA1 an. Die Einsatz von Proteasominhibitoren, die den Abbau von Ubiquitin-markierten Proteinen blockieren, in der Krebstherapie weckte das Interesse von Forschern Enzyme, die an der Ubiquitinierungs-Kaskade beteiligt sind, als neue therapeutische Ziele zur Bekämpfung von Krebserkrankungen zu erschließen. Es konnte gezeigt werden, dass die Inhibierung von UBA1 bevorzugt den Tod maligner Zellen induziert und als Strategie für die Überwindung der Resistenz von Proteasominhibitoren genutzt werden kann. MLN7243, ein Adenosyl-Sulfamat Inhibitor, der von Millenium Pharmaceuticals entwickelt wurde und spezifisch UBA1 angreift, befindet sich gegenwärtig in klinischen Studien der Phase I mit dem Ziel einer Behandlung von soliden Tumoren. UBA1 konnte im Komplex mit drei an Ubiquitin gekoppelten Adenosyl-Sulfamat Inhibitoren, die vielversprechende Wirkstoffe in der Krebstherapie sind, kristallisiert werden. Die Inhibitoren MLN7243, MLN4924 und ABPA3 besitzen unterschiedliche Spezifitäten für verschiedene E1 Enzyme. Mit Hilfe von Kristallstrukturen konnten Spezifitätsfaktoren dieser Inhibitoren entschlüsselt werden, die im Weiteren mittels Inhibierungstests und molekulardynamischer Simulationen bestätigt werden konnten. Diese Kristallstrukturen lieferten ein klareres Bild für die Entwicklung E1-spezifischer Inhibitoren mit deren Hilfe, neben ihrer potentiellen medizinischen Anwendung, ein besseres Verständnis des Ubiquitinsystems und Ubiquitin-ähnlicher kovalenter Verknüpfungen gewonnen werden kann

    Integrity check of grounding grids at high voltage substations

    No full text
    The safety in the high voltage substations rely on the integrity of its grounding grid. A single discontinuity at any part of the grounding grid may cause a swell in touch or step potential that may expose the personnel to a hazard of critical electric shock. It may also lead to malfunction of the protection devices leading to erroneous tripping of circuit breakers. This report presents a cost-effective, reliable and precise way to investigate the integrity of grounding grid. An experimental setup was performed in the laboratory to inspect and corroborate the results; thereafter repeating and validating the experiment in a substation.Electrical Engineerin

    Pneumatic displacement and intravitreal bevacizumab: A new approach for management of submacular hemorrhage in choroidal neovascular membrane

    No full text
    Choroidal neovascular membrane (CNVM) is one of the most common causes of submacular hemorrhage (SMH). Conventional treatment involves management of the SMH with pneumatic displacement with or without tissue plasminogen activator (TPA) followed by intravitreal injection of bevacizumab in a second sitting. We decided to assess the efficacy of treating SMH secondary to CNVM with pneumatic displacement using sulphur hexafluoride (SF6) gas and intravitreal bevacizumab. Four patients with SMH secondary to CNVM were included in this study. Intravitreal bevacizumab, 0.05 ml, along with 0.5 ml of SF6 was injected through the pars plana into the vitreous cavity. Postoperative best corrected visual acuity improved in all eyes with complete or partial displacement of SMH out of the foveal area

    Rice mitogen activated protein kinase kinase and mitogen activated protein kinase interaction network revealed by in-silico docking and yeast two-hybrid approaches.

    Get PDF
    Protein-protein interaction is one of the crucial ways to decipher the functions of proteins and to understand their role in complex pathways at cellular level. Such a protein-protein interaction network in many crop plants remains poorly defined owing largely to the involvement of high costs, requirement for state of the art laboratory, time and labour intensive techniques. Here, we employed computational docking using ZDOCK and RDOCK programmes to identify interaction network between members of Oryza sativa mitogen activated protein kinase kinase (MAPKK) and mitogen activated protein kinase (MAPK). The 3-dimentional (3-D) structures of five MAPKKs and eleven MAPKs were determined by homology modelling and were further used as input for docking studies. With the help of the results obtained from ZDOCK and RDOCK programmes, top six possible interacting MAPK proteins were predicted for each MAPKK. In order to assess the reliability of the computational prediction, yeast two-hybrid (Y2H) analyses were performed using rice MAPKKs and MAPKs. A direct comparison of Y2H assay and computational prediction of protein interaction was made. With the exception of one, all the other MAPKK-MAPK pairs identified by Y2H screens were among the top predictions by computational dockings. Although, not all the predicted interacting partners could show interaction in Y2H, yet, the harmony between the two approaches suggests that the computational predictions in the present work are reliable. Moreover, the present Y2H analyses per se provide interaction network among MAPKKs and MAPKs which would shed more light on MAPK signalling network in rice

    Structures of UBA6 explain its dual specificity for ubiquitin and FAT10

    No full text
    The covalent modification of target proteins with ubiquitin or ubiquitin-like modifiers is initiated by E1 activating enzymes, which typically transfer a single modifier onto cognate conjugating enzymes. UBA6 is an unusual E1 since it activates two highly distinct modifiers, ubiquitin and FAT10. Here, we report crystal structures of UBA6 in complex with either ATP or FAT10. In the UBA6-FAT10 complex, the C-terminal domain of FAT10 binds to where ubiquitin resides in the UBA1-ubiquitin complex, however, a switch element ensures the alternate recruitment of either modifier. Simultaneously, the N-terminal domain of FAT10 interacts with the 3-helix bundle of UBA6. Site-directed mutagenesis identifies residues permitting the selective activation of either ubiquitin or FAT10. These results pave the way for studies investigating the activation of either modifier by UBA6 in physiological and pathophysiological settings

    Not Available

    No full text
    Not AvailableClimate change and the growing population are major challenges in the global agriculture scenario. High-quality crop genotypes are essential to counter the challenges. In plant breeding, phenotypic trait measurement is necessary to develop improved crop varieties. Plant phenotyping refers to studying the plant's morphological and physiological characteristics. Plant phenotypic traits like the number of spikes/panicle in cereal crops and senescence quantification play an important role in assessing functional plant biology, growth analysis, and net primary production. However, conventional plant phenotyping is time-consuming, labor-intensive, and error-prone. Computer vision-based techniques have emerged as an efficient method for non-invasive and non-destructive plant phenotyping over the last two decades. Therefore to measure these traits in high-throughput and non-destructive way, computer vision-based methodologies are proposed. For recognition and counting of number of spikes from visual images of wheat plant, a deep learning-based encoder-decoder network is developed. The precision, accuracy, and robustness (F1-score) of the approach for spike recognition are found as 98.97%, 98.07%, and 98.97%, respectively. For spike counting, the average precision, accuracy, and robustness are 98%, 93%, and 97%, respectively. The performance of the approach demonstrates that the encoder-decoder network-based approach is effective and robust for spike detection and counting. For senescence quantification, machine learning-based approach has been proposed which segments the wheat plant into different senescence and greenness classes. Six machine learning-based classifiers: decision tree, random forest, KNN, gradient boosting, naïve Bayes, and artificial neural network (ANN) are trained to segment the senescence portion from wheat plants. All the classifiers performed well, but ANN outperformed with 97.28% accuracy. After senescence segmentation, percentage of senescence area is also calculated. A GUI-based desktop application, m—Senescencica has been developed, which processes the input images and generates output for senescence percentage, plant height, and plant area.Not Availabl

    Effectiveness of a 1-day workshop on scientific writing conducted by the Indian journal of rheumatology

    No full text
    Background: Writing a scientific manuscript is an important skill to acquire for junior doctors considering the mandatory requirement of research publications during post-graduate training and for career advancement in India. Methods: We conducted a one-day workshop on scientific writing and publication at Udaipur in November 2017, comprising both didactic lectures as well as hands-on evaluation of a dummy manuscript, and evaluated structured questionnaires filled pre- and post-workshop. Results: There were 120 attendees, most of whom were junior doctors with little or no prior experience in writing a scientific paper. A significant baseline knowledge deficit regarding the principles and processes of scientific writing (ranging from 20.9% to 77.3% participants for the different questions asked) could be identified before the workshop. This knowledge deficit was significantly improved in most areas as assessed after the workshop. We identified the need to discuss predatory publishing in greater detail in subsequent workshops, as 20.8% of respondents after the workshop professed that they might consider publishing in a predatory journal. As expressed in participant feedback, longer, more-specialized or advanced level workshops on scientific writing in the future could also consider including more details on appropriate statistical presentation and pictorial representation of data as well as longer time spent on hands-on exercises. Conclusion: There remains a need to conduct more scientific writing workshops by national societies and journals all over the country

    Verification of 3D structures of rice MAPKs and MAPKKs.

    No full text
    <p>DOPE–Discrete Optimized Protein Energy, PDF–Probability Density Function.</p
    corecore