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Статті в журналах з теми "Activateur non essentiel"
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Noriega, Guillermo O., Adela A. Juknat, and Alcira M. del C. Batlle. "Non-Essential Activation of Rat Liver Porphobilinogen-Deaminase by Folic Acid." Zeitschrift für Naturforschung C 47, no. 5-6 (June 1, 1992): 416–19. http://dx.doi.org/10.1515/znc-1992-0616.
Повний текст джерелаАнотація:
This report demonstrates the ability of folic acid to activate rat liver porphobilinogen-deaminase (PBG -D). Lineweaver-Burk analysis revealed an increase in Vmax (38%) without affecting the Km. In the concentration range assayed, secondary replots of 1/Δslope and 1/Δintersect versus 1/[folic acid] yielded straight lines, indicating the binding of a single molecule of activator to the enzyme PBG-D , with a KA = 1.66 mᴍ. Results presented here show that folic acid acts as a non-essential activator (α = 1; β = 1.6). The activating effect of folic acid has been observed employing the 35-70% ammonium sulphate precipitated fraction, desalted by dialysis or gel filtration, whereas no action was detected when other partially purified PBG -D preparations were utilized as the enzyme source, suggesting either the presence of sites saturated for the activator, or the existence of a different structural protein conformation, or both.
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Gai, Lili, Yuting Zhu, Chun Zhang, and Xianfang Meng. "Targeting Canonical and Non-Canonical STAT Signaling Pathways in Renal Diseases." Cells 10, no. 7 (June 27, 2021): 1610. http://dx.doi.org/10.3390/cells10071610.
Повний текст джерелаАнотація:
Signal transducer and activator of transcription (STAT) plays an essential role in the inflammatory reaction and immune response of numerous renal diseases. STATs can transmit the signals of cytokines, chemokines, and growth factors from the cell membrane to the nucleus. In the canonical STAT signaling pathways, upon binding with their cognate receptors, cytokines lead to a caspase of Janus kinases (JAKs) and STATs tyrosine phosphorylation and activation. Besides receptor-associated tyrosine kinases JAKs, receptors with intrinsic tyrosine kinase activities, G-protein coupled receptors, and non-receptor tyrosine kinases can also activate STATs through tyrosine phosphorylation or, alternatively, other post-translational modifications. Activated STATs translocate into the nucleus and mediate the transcription of specific genes, thus mediating the progression of various renal diseases. Non-canonical STAT pathways consist of preassembled receptor complexes, preformed STAT dimers, unphosphorylated STATs (U-STATs), and non-canonical functions including mitochondria modulation, microtubule regulation and heterochromatin stabilization. Most studies targeting STAT signaling pathways have focused on canonical pathways, but research extending into non-canonical STAT pathways would provide novel strategies for treating renal diseases. In this review, we will introduce both canonical and non-canonical STAT pathways and their roles in a variety of renal diseases.
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Das-Panja, Kaberi, Vidya Jonnalagadda, and Sobhanaditya Jonnalagadda. "Orthophosphate is a non-essential activator of Vigna radiata flavokinase." IUBMB Life 47, no. 4 (April 1999): 547–54. http://dx.doi.org/10.1080/15216549900201583.
Повний текст джерела
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Künnapuu, Jaana, Honey Bokharaie, and Michael Jeltsch. "Proteolytic Cleavages in the VEGF Family: Generating Diversity among Angiogenic VEGFs, Essential for the Activation of Lymphangiogenic VEGFs." Biology 10, no. 2 (February 23, 2021): 167. http://dx.doi.org/10.3390/biology10020167.
Повний текст джерелаАнотація:
Specific proteolytic cleavages turn on, modify, or turn off the activity of vascular endothelial growth factors (VEGFs). Proteolysis is most prominent among the lymphangiogenic VEGF-C and VEGF-D, which are synthesized as precursors that need to undergo enzymatic removal of their C- and N-terminal propeptides before they can activate their receptors. At least five different proteases mediate the activating cleavage of VEGF-C: plasmin, ADAMTS3, prostate-specific antigen, cathepsin D, and thrombin. All of these proteases except for ADAMTS3 can also activate VEGF-D. Processing by different proteases results in distinct forms of the “mature” growth factors, which differ in affinity and receptor activation potential. The “default” VEGF-C-activating enzyme ADAMTS3 does not activate VEGF-D, and therefore, VEGF-C and VEGF-D do function in different contexts. VEGF-C itself is also regulated in different contexts by distinct proteases. During embryonic development, ADAMTS3 activates VEGF-C. The other activating proteases are likely important for non-developmental lymphangiogenesis during, e.g., tissue regeneration, inflammation, immune response, and pathological tumor-associated lymphangiogenesis. The better we understand these events at the molecular level, the greater our chances of developing successful therapies targeting VEGF-C and VEGF-D for diseases involving the lymphatics such as lymphedema or cancer.
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Inoue, Kazushi, and Elizabeth A. Fry. "Aberrant Expression of Cyclin D1 in Cancer." Signal Transduction Insights 4 (January 2015): STI.S30306. http://dx.doi.org/10.4137/sti.s30306.
Повний текст джерелаАнотація:
Cyclin D1 binds and activates cyclin-dependent kinases 4/6 (Cdk4/6) to phosphorylate the retinoblastoma (RB) family proteins, relieving E2F/DPs from the negative restraint of RB proteins and histone deacetylases (HDACs). The cyclin D-Cdk4/6 complexes activate cyclin E/Cdk2 through titration of the Cdk inhibitors p21Cip1/p27Kip1. Cyclin E/Cdk2 further phosphorylates RBs, thereby activating E2F/DPs, and cells enter the S-phase of the cell cycle. Cyclin D-Cdk4/6 also phosphorylates MEP50 subunit of the protein arginine methyltransferase 5 (PRMT5), which cooperates with cyclin D1 to drive lymphomagenesis in vivo. Activated PRMPT5 causes arginine methylation of p53 to suppress expression of proapoptotic and antiproliferative target genes, explaining the molecular mechanism for tumorigenesis. Cyclin D1 physically interacts with transcription factors such as estrogen receptor, androgen receptor, and Myb family proteins to regulate gene expression in Cdk-independent fashion. Dmp1 is a Myb-like protein that quenches the oncogenic signals from activated Ras or HER2 by inducing Arf/p53-dependent cell cycle arrest. Cyclin D1 binds to Dmp1 to activate both Arf and Ink4a promoters to induce cell cycle arrest or apoptosis in non-transformed cells to prevent them from neoplastic transformation. Dmp1deficiency significantly accelerates mouse mammary tumorigenesis with reduced apoptosis and increased metastasis. Cyclin D1 interferes with ligand activation of PPARγ involved in cellular differentiation; it also physically interacts with HDACs and p300 to repress gene expression. It has also been shown that cyclin D1 accelerates tumorigenesis through transcriptional activation of miR-17/20 and Dicer1 which, in turn, represses cyclin D1 expression. Identification of cyclin D1-binding proteins/promoters will be essential for further clarification of its biological activities.
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Jastrzebska, Beata, Yaroslav Tsybovsky, and Krzysztof Palczewski. "Complexes between photoactivated rhodopsin and transducin: progress and questions." Biochemical Journal 428, no. 1 (April 28, 2010): 1–10. http://dx.doi.org/10.1042/bj20100270.
Повний текст джерелаАнотація:
Activation of GPCRs (G-protein-coupled receptors) leads to conformational changes that ultimately initiate signal transduction. Activated GPCRs transiently combine with and activate heterotrimeric G-proteins resulting in GTP replacement of GDP on the G-protein α subunit. Both the detailed structural changes essential for productive GDP/GTP exchange on the G-protein α subunit and the structure of the GPCR–G-protein complex itself have yet to be elucidated. Nevertheless, transient GPCR–G-protein complexes can be trapped by nucleotide depletion, yielding an empty-nucleotide G-protein–GPCR complex that can be isolated. Whereas early biochemical studies indicated formation of a complex between G-protein and activated receptor only, more recent results suggest that G-protein can bind to pre-activated states of receptor or even couple transiently to non-activated receptor to facilitate rapid responses to stimuli. Efficient and reproducible formation of physiologically relevant, conformationally homogenous GPCR–G-protein complexes is a prerequisite for structural studies designed to address these possibilities.
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Vainchenker, William, Stefan N. Constantinescu, and Isabelle Plo. "Recent advances in understanding myelofibrosis and essential thrombocythemia." F1000Research 5 (April 19, 2016): 700. http://dx.doi.org/10.12688/f1000research.8081.1.
Повний текст джерелаАнотація:
The classicBCR-ABL-negative myeloproliferative neoplasms (MPNs), a form of chronic malignant hemopathies, have been classified into polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). ET and PMF are two similar disorders in their pathogenesis, which is marked by a key role of the megakaryocyte (MK) lineage. Whereas ET is characterized by MK proliferation, PMF is also associated with aberrant MK differentiation (myelodysplasia), leading to the release of cytokines in the marrow environment, which causes the development of myelofibrosis. Thus, PMF is associated with both myeloproliferation and different levels of myelodysplastic features. MPNs are mostly driven by mutated genes called MPN drivers, which abnormally activate the cytokine receptor/JAK2 pathway and their downstream effectors. The recent discovery ofCALRmutations has closed a gap in our knowledge and has shown that this mutated endoplasmic reticulum chaperone activates the thrombopoietin receptor MPL and JAK2. These genetic studies have shown that there are two main types of MPNs: JAK2V617F-MPNs, including ET, PV, and PMF, and the MPL-/CALR-MPNs, which include only ET and PMF. These MPN driver mutations are associated with additional mutations in genes involved in epigenetics, splicing, and signaling, which can precede or follow the acquisition of MPN driver mutations. They are involved in clonal expansion or phenotypic changes or both, leading to myelofibrosis or leukemic transformation or both. Only a few patients with ET exhibit mutations in non-MPN drivers, whereas the great majority of patients with PMF harbor one or several mutations in these genes. However, the entire pathogenesis of ET and PMF may also depend on other factors, such as the patient’s constitutional genetics, the bone marrow microenvironment, the inflammatory response, and age. Recent advances allowed a better stratification of these diseases and new therapeutic approaches with the development of JAK2 inhibitors.
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Marschke, Keith, Deepa Rungta, Daniela A. Slavin, Jennifer Sanders, Steven L. Roach, Jason C. Pickens, Yixing Shen, et al. "Discovery of Non-Peptidyl Small-Molecule Human GCSF Receptor Agonists for the Potential Treatment of Neutropenia,." Blood 118, no. 21 (November 18, 2011): 3391. http://dx.doi.org/10.1182/blood.v118.21.3391.3391.
Повний текст джерелаАнотація:
Abstract Abstract 3391 Granulocyte colony stimulating factor (GCSF) is the essential cytokine for the regulation of neutrophilic granulocytes. Binding of GCSF to its receptor (GCSFR) triggers receptor dimerization, leading to activation of JAK1 and JAK2, phosphorylation of GCSFR, STAT3, STAT5, and Ras/mitogen-activated protein kinase (MAPK), and results in proliferation and differentiation of granulocytic cells. Recombinant human GCSF (rhGCSF) is used successfully to alleviate chemotherapy-induced neutropenia, neutropenia associated with hematopoietic stem cell transplantation, and severe chronic neutropenia. A small molecule oral GCSFR agonist may offer a safer and more convenient alternative to the current injectable rhGCSF therapy. Whereas a previous effort to identify small-molecule mimetics of GCSF found SB-247464 that selectively activated the murine GCSFR, no small-molecule human GCSF mimetics have been developed. Recently, we have discovered a series of novel non-peptidyl small molecules that selectively activate human GCSFR (hGCSFR) function, and may provide a significant innovation in the treatment of neutropenia. In cells transiently transfected with an hGCSFR expression vector and a STAT3-responsive luciferase reporter, a lead compound, LG7455, activates luciferase expression with an efficacy of 50% relative to rhGCSF, and potency (EC50) of 100 nM. LG7455 also activates luciferase expression in cells transfected with hGCSFR and a STAT5-responsive luciferase reporter (65%, 40 nM EC50). The activity of LG7455 is dependent on the expression of hGCSFR, and LG7455 is not active in luciferase assays when human thrombopoietin receptor (hTPOR) or erythropoietin receptor (hEPOR) is expressed. In UT-7 cells made responsive to GCSF by stable transfection of hGCSFR (UTP-hGCSFR), LG7455 stimulated cell growth and increased the phosphorylation of STAT3 and STAT5. LG7455 did not increase growth of TPO- or EPO-responsive UT-7 cells. In CD34 positive human bone marrow hematopoietic cells (BM-HCs), LG7455, increased the percentage of cells positive for the granulocyte-specific marker CD15 (FUT4). The effect of LG7455 in BM-HCs was additive to the effect of rhGCSF. LG7455 is active in luciferase assays with expressed cynomolgus monkey GCSFR, but not mouse, guinea pig or rabbit GCSFR. Similar to what has been demonstrated for small-molecule human TPOR agonists such as eltrombopag, the activity of LG7455 is dependent on a specific residue in the hGCSFR transmembrane domain. When histidine 627 (His-627) in hGCSFR is changed to asparagine present at a similar location in the mouse GCSFR (Asp-602), unlike rhGCSF, LG7455 is no longer active. LG7455 is active, however, on mouse GCSFR with Asp-602 replaced by His. In radioligand-binding experiments using UTP-hGCSFR cells, LG7455 did not displace [125I]rhGCSF, however binding of [125I]rhGCSF was augmented in a concentration dependent manner consistent with allosteric receptor modulation. These data demonstrate that LG7455 is a novel small-molecule selective hGCSFR agonist that activates the receptor in a manner distinct from GCSF and similar to the mechanism of small-molecule hTPOR agonists. Further optimization of the LG7455 chemical series should provide orally-available molecules to treat neutropenia with improved safety and convenience compared to current injectable rhGCSF. Disclosures: Marschke: Ligand Pharmaceuticals: Employment. Rungta:Ligand Pharmaceuticals: Employment. Slavin:Ligand Pharmaceuticals: Employment. Sanders:Ligand Pharmaceuticals: Employment. Roach:Ligand Pharmaceuticals: Employment. Pickens:Ligand Pharmaceuticals: Employment. Shen:Ligand Pharmaceuticals: Employment. van Oeveren:Ligand Pharmaceuticals: Employment. Hong:Ligand Pharmaceuticals: Employment. Sun:Ligand Pharmaceuticals: Employment. Bissonnette:Ligand Pharmaceuticals: Employment. Syka:Ligand Pharmaceuticals: Employment. Zhi:Ligand Pharmaceuticals: Employment.
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Działo, Edyta, Karolina Tkacz та Przemysław Błyszczuk. "Crosstalk between TGF-β and WNT signalling pathways during cardiac fibrogenesis". Acta Biochimica Polonica 65, № 3 (24 липня 2018): 341–49. http://dx.doi.org/10.18388/abp.2018_2635.
Повний текст джерелаАнотація:
Cardiac fibrosis is referred to as an excessive accumulation of stromal cells and extracellular matrix proteins in the myocardium. Progressive fibrosis causes stiffening of the cardiac tissue and affects conduction of electrical impulses, leading to heart failures in a broad range of cardiac conditions. At the cellular level, activation of the cardiac stromal cells and myofibroblast formation are considered as hallmarks of fibrogenesis. At the molecular level, transforming growth factor β (TGF-β) is traditionally considered as a master regulator of the profibrotic processes. More recently, the WNT signalling pathway has also been found to be implicated in the development of myocardial fibrosis. In this review, we summarize current knowledge on the involvement of TGF-β and WNT downstream molecular pathways to cardiac fibrogenesis and describe a crosstalk between these two profibrotic pathways. TGF-β and WNT ligands bind to different receptors and trigger various outputs. However, a growing body of evidence points to cross-regulation between these two pathways. It has been recognized that in cardiac pathologies TGF-β activates WNT/β-catenin signalling, which in turn stabilizes the TGF-β/Smad response. Furthermore both, the non-canonical TGF-β and non-canonical WNT signalling pathways, activate the same mitogen-activated protein kinases (MAPKs): the extracellular signal-regulated kinase (Erk), the c-Jun N-terminal kinases (JNKs) and p38. The cross-talk between TGF-β and WNT pathways seems to play an essential role in switching on the genetic machinery initiating profibrotic changes in the heart. Better understanding of these mechanisms will open new opportunities for development of targeted therapeutic approaches against cardiac fibrosis in the future.
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Guertin, Michael J., Xuesen Zhang, Scott A. Coonrod, and Gordon L. Hager. "Transient Estrogen Receptor Binding and p300 Redistribution Support a Squelching Mechanism for Estradiol-Repressed Genes." Molecular Endocrinology 28, no. 9 (September 1, 2014): 1522–33. http://dx.doi.org/10.1210/me.2014-1130.
Повний текст джерелаАнотація:
Proper gene regulation is essential for proper organismal development and appropriate responses to external stimuli. Specialized factors, termed master regulators, are often responsible for orchestrating the molecular events that result from signaling cascades. Master regulators coordinate the activation and repression of specific gene classes. Estrogen receptor α (ER) precipitates the signaling cascade that results from endogenous or exogenous estrogen hormones. ER is a classic transcriptional activator and the mechanisms by which ER coordinates gene activation are well characterized. However, it remains unclear how ER coordinates the immediate repression of genes. We integrated genomic transcription, chromosome looping, transcription factor binding, and chromatin structure data to analyze the molecular cascade that results from estradiol (E2)-induced signaling in human MCF-7 breast cancer cells and addressed the context-specific nature of gene regulation. We defined a class of genes that are immediately repressed upon estrogen stimulation, and we compared and contrasted the molecular characteristics of these repressed genes vs activated and unregulated genes. The most striking and unique feature of the repressed gene class is transient binding of ER at early time points after estrogen stimulation. We also found that p300, a coactivator and acetyltransferase, quantitatively redistributes from non-ER enhancers to ER enhancers after E2 treatment. These data support an extension of the classic physiological squelching model, whereby ER hijacks coactivators from repressed genes and redistributes the coactivators to ER enhancers that activate transcription.
Дисертації з теми "Activateur non essentiel"
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Soualmia, Feryel. "Modulateurs synthétiques de la kallikréine 6, protéase à sérine impliquée dans les maladies neurodégénératives : identification, mécanisme d’action et validation de concept." Electronic Thesis or Diss., Paris 6, 2016. http://www.theses.fr/2016PA066755.
Повний текст джерелаАнотація:
La kallikréine humaine 6 (hK6) ou neurosine est la protéase à sérine la plus abondante du système nerveux central (SNC). Sa dualité de fonction dans les processus neurodégénératifs font d’elle une cible privilégiée pour la conception de modulateurs pharmacologiques de son activité. Cependant, il existe aujourd’hui très peu de composés répondant à cette attente. Aussi, le principal objectif de ces travaux de thèse a consisté à identifier des inhibiteurs et activateurs organiques de faible poids moléculaire (<500 Da) de la hK6, compatibles avec un développement clinique. L’étude de la hK6 sous ses différents aspects a permis d’établir son profil catalytique et dynamique et de mettre en évidence son rôle anti-agrégatif de l’α-synucléine endogène. L’exploration de diverses chimiothèques regroupant près de 1 200 molécules a permis d’identifier des molécules touches (hits) qui ont fait l’objet d’études mécanistiques approfondies. Des évaluations par modélisation moléculaire ont également été réalisées afin d’établir les bases structurales de la modulation et un profil de sélectivité de ces molécules vis-à-vis d’autres protéases à sérine concurrentes a pu être établi. Pour la première fois, un modulateur bimodal ainsi qu’un activateur, tous deux hautement sélectifs de la hK6, ont été identifiés et un modèle de régulation allostérique a pu être proposé. Plusieurs inhibiteurs originaux possédant un bon profil de sélectivité vis-à-vis de la hK6 ont également été sélectionnés. Ces molécules ne présentent pas d’effet cytotoxique sur des cultures primaires de neurones. Les composés identifiés au cours de cette thèse constituent ainsi une excellente base pour le développement d’agents pharmacologiques à visée neuroprotectrice et anti-inflammatoire et ouvre la voie à l’exploration de nouveaux sites allostériques au sein de cette enzyme et des protéases à sérine tryptiquesThe human kallikrein 6 (hK6) or neurosin is the most abundant serine protease of the central nervous system (CNS). Its dual implication in neurodegenerative processes makes it an emerging target for the design of pharmacological modulators of its activity. Yet today there are only very few compounds that meet this expectation. Thus, the main aim of these thesis was to identify organic low molecular weight (<500 Da) inhibitors and activators of hK6 compatible with clinical development. The study ofhK6 through various aspects has established its catalytic and dynamic profile and highlights its anti-aggregative role of endogenous α-synuclein. Exploring the diverse libraries comprising nearly 1 200molecules led to the identification of key compounds (hits) that have been subjected to extensive mechanistic studies. Assessments by molecular modeling were also carried out to establish the structural basis for activity modulation and selectivity profiling toward competing serine proteases has also been established. For the first time, a bimodal modulator as well as an activator, both highly selective to hK6, were identified and an allosteric regulatory model was proposed. Several original inhibitors having a good selectivity profile toward hK6 were also selected. Furthermore, these molecules do not exhibit any cytotoxic effect on primary neuronal cultures. The compounds identified in this thesis provide an excellent basis for the development of pharmacological agents with neuroprotective and anti-inflammatory properties and pave the way for the exploration of new allosteric sites in hK6 and tryptic serine proteases in general
Книги з теми "Activateur non essentiel"
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Voll, Reinhard E., and Barbara M. Bröker. Innate vs acquired immunity. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0048.
Повний текст джерелаАнотація:
The innate and the adaptive immune system efficiently cooperate to protect us from infections. The ancient innate immune system, dating back to the first multicellular organisms, utilizes phagocytic cells, soluble antimicrobial peptides, and the complement system for an immediate line of defence against pathogens. Using a limited number of germline-encoded pattern recognition receptors including the Toll-like, RIG-1-like, and NOD-like receptors, the innate immune system recognizes so-called pathogen-associated molecular patterns (PAMPs). PAMPs are specific for groups of related microorganisms and represent highly conserved, mostly non-protein molecules essential for the pathogens' life cycles. Hence, escape mutants strongly reduce the pathogen's fitness. An important task of the innate immune system is to distinguish between harmless antigens and potentially dangerous pathogens. Ideally, innate immune cells should activate the adaptive immune cells only in the case of invading pathogens. The evolutionarily rather new adaptive immune system, which can be found in jawed fish and higher vertebrates, needs several days to mount an efficient response upon its first encounter with a certain pathogen. As soon as antigen-specific lymphocyte clones have been expanded, they powerfully fight the pathogen. Importantly, memory lymphocytes can often protect us from reinfections. During the development of T and B lymphocytes, many millions of different receptors are generated by somatic recombination and hypermutation of gene segments making up the antigen receptors. This process carries the inherent risk of autoimmunity, causing most inflammatory rheumatic diseases. In contrast, inadequate activation of the innate immune system, especially activation of the inflammasomes, may cause autoinflammatory syndromes.
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Sullivan MD, PhD, Mark. From Patient to Agent. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780195386585.001.0001.
Повний текст джерелаАнотація:
In the 21st century, the primary challenge for health care is chronic illness. To meet this challenge, we need to think anew about the role of the patient in health and health care. There have been widespread calls for patient-centered care, but this model of care does not question deeply enough the goals of health care, the nature of the clinical problem, and the definition of health itself. We must instead pursue patient-centered health, which is a health perceived and produced by patients. We should not only respect, but promote patient autonomy as an essential component of this health. Objective health measures cannot capture the burden of chronic illness, so we need to draw on the patient's perspective to help define the clinical problem. We require a new definition of health as the capacity for meaningful action. It is recognized that patients play a central role in chronic illness care, but the concept of health behavior retards innovation. We seek not just an activated patient, but an autonomous patient who sets and pursues her own vital goals. To fully enlist patients, we must bridge the gap between impersonal disease processes and personal processes. This requires understanding how the roots of patient autonomy lie in the biological autonomy that allows organisms to carve their biological niche. It is time for us to recognize the patient as the primary customer for health care and the primary producer of health. Patient agency is both the primary means and primary end of health care.
Частини книг з теми "Activateur non essentiel"
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Danisi, Carmelo, Moira Dustin, Nuno Ferreira, and Nina Held. "The Decision-Making Procedure." In IMISCOE Research Series, 179–258. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-69441-8_6.
Повний текст джерелаАнотація:
AbstractWhereas in Chap. 10.1007/978-3-030-69441-8_5 we analysed pre-departure, journey and arrival experiences of SOGI claimants, we now turn our attention to the decision-making procedure. Whether they apply for asylum on arrival or later on, the initial screening is usually followed by a substantive interview. This is the essential moment when SOGI claimants have the opportunity to present their case. If the application is then refused, a judicial process is normally activated to appeal against the initial negative decision.
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Pavelkic, Vesna, Tanja Brdaric, and Kristina Gopcevic. "Aluminium - Non-Essential Activator of Pepsin: Kinetics and Thermodynamics." In Medicinal Chemistry and Drug Design. InTech, 2012. http://dx.doi.org/10.5772/35081.
Повний текст джерела
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Taofeek Popoola, Lekan, and Alhaji Shehu Grema. "Adsorption of Heavy Metals from Industrial Wastewater using Nanoparticles from Agro Wastes." In Nanopores [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.98241.
Повний текст джерелаАнотація:
Effluents from essential industries have been characterized with heavy metals which are non-biodegradable in nature and also detrimental to health when accumulated in body tissues over long exposure. Adsorption was proved as the best efficient process amongst others to remove these heavy metals from industrial wastewater due to its excellent features. Activated carbons from nanoparticles of agricultural wastes such as pods, shells, husks, peels, shafts and many prepared via calcination process at high temperature can be used as active adsorbent for the industrial wastewater treatment involving heavy metals removal. This chapter discusses heavy metals in industrial wastewater effluents and potential agro wastes from which nanoparticles of activated carbon for industrial wastewater purification could be generated. The transformation of agro wastes nanoparticles into activated carbons via calcination and their applications for heavy metals removal from industrial wastewater via adsorption were examined. Various characterization techniques to study the effects of calcination on structural, morphological and textural properties of activated carbon prepared from agro waste nanoparticles were also discussed. Various isotherm, kinetics, mechanistic and thermodynamics models to investigate the adsorptive nature of the process were presented. Error functions and algorithms for both the linear and non-linear isotherm models regression to affirm their fitness for prediction were presented. Lastly, proposed adsorption mechanisms of heavy metals removal from industrial wastewater using activated carbons from nanoparticles of agro wastes were presented.
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Ježek, Petr, Blanka Holendová, Martin Jabůrek, Jan Tauber, Andrea Dlasková, and Lydie Plecitá-Hlavatá. "Redox Signaling is Essential for Insulin Secretion." In Type 2 Diabetes [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.94312.
Повний текст джерелаАнотація:
In this review, we place redox signaling in pancreatic β-cells to the context with signaling pathways leading to insulin secretion, acting for example upon the action of incretins (GLP-1, GIP) and the metabotropic receptor GPR40. Besides a brief description of ion channel participation in depolarization/repolarization of the plasma membrane, we emphasize a prominent role of the elevated glucose level in pancreatic β-cells during glucose-stimulated insulin secretion (GSIS). We focus on our recent findings, which revealed that for GSIS, not only elevated ATP synthesis is required, but also fundamental redox signaling originating from the NADPH oxidase 4- (NOX4-) mediated H2O2 production. We hypothesized that the closing of the ATP-sensitive K+ channel (KATP) is only possible when both ATP plus H2O2 are elevated in INS-1E cells. KATP alone or with synergic channels provides an element of logical sum, integrating both metabolic plus redox homeostasis. This is also valid for other secretagogues, such as branched chain ketoacids (BCKAs); and partly for fatty acids (FAs). Branched chain aminoacids, leucine, valine and isoleucine, after being converted to BCKAs are metabolized by a series of reactions resembling β-oxidation of FAs. This increases superoxide formation in mitochondria, including its portion elevated due to the function of electron transfer flavoprotein ubiquinone oxidoreductase (ETF:QOR). After superoxide conversion to H2O2 the oxidation of BCKAs provides the mitochondrial redox signaling extending up to the plasma membrane to induce its depolarization together with the elevated ATP. In contrast, experimental FA-stimulated insulin secretion in the presence of non-stimulating glucose concentrations is predominantly mediated by GPR40, for which intramitochondrial redox signaling activates phospholipase iPLA2γ, cleaving free FAs from mitochondrial membranes, which diffuse to the plasma membrane and largely amplify the GPR40 response. These events are concomitant to the insulin release due to the metabolic component. Hypothetically, redox signaling may proceed by simple H2O2 diffusion or via an SH-relay enabled by peroxiredoxins to target proteins. However, these aspects have yet to be elucidated.
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Enciso-Pablo, Óscar, Karina Angélica Méndez-Reséndiz, Tamara Rosenbaum, and Sara Luz Morales-Lázaro. "Nociceptive TRP Channels and Sex Steroids." In Reproductive Hormones. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.95552.
Повний текст джерелаАнотація:
Proteins belonging to Transient Receptor Potential (TRP) family are nonselective cation channels that play an essential role in mammalian physiology, functioning as transducers of several environmental signals including those of chemical, thermal and mechanical natures. A subgroup of these receptors is expressed in sensory neurons where they are activated by noxious stimuli and are key players of pain responses in the organism. Some TRP channels are molecular targets for the classical and non-classical effects of sex steroids. This chapter will describe the close relationship between nociceptive TRP channels and sex steroids as well as their impact on nociception and pain-related responses.
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Rana, Sukanta, and Jatindra Nath Bhakta. "Heavy Metal(loid) Remediation Using Bio-Waste." In Handbook of Research on Inventive Bioremediation Techniques, 394–415. IGI Global, 2017. http://dx.doi.org/10.4018/978-1-5225-2325-3.ch017.
Повний текст джерелаАнотація:
Heavy metal(loid)s are hazardous, biologically non-essential, non-biodegradable and persistent in nature, which can accumulate in plants and animals as well as in environment especially agri- and aqua- culture ecosystems. It is severely responsible for causing several health hazards problems in human, such as, cardiovascular, pulmonary, hepatic, nephrological, dermatological, neurological disorders as well as carcinogenic effects. Removal of these heavy metals from living systems is extensively expensive and also unsuccessful in sent percent removal. Therefore, in order to protect the environment, the removal of heavy metal(loid)s from polluted effluents is essential before discharging into environment. Besides various treatment technologies, sorption of metal(loid)s using bio-wastes are highly potent alternatives in recent years. The present chapter deals with the removal efficiencies of various bio-wastes, orange peels, waste tea leaves, rice husk, wheat stalk, sugar cane bagasse, coconut husk, sun flower stalk, corn cob, nut shell, water hyacinth, crab shell particle, activated carbons etc. The present discussion has also revealed that bio-waste could be a low-cost eco-friendly and green emerging alternative technology in treating the metal(loid)s contaminated environment without posing any further adverse environmental impacts.
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Rana, Sukanta, and Jatindra Nath Bhakta. "Heavy Metal(loid) Remediation Using Bio-Waste." In Waste Management, 754–74. IGI Global, 2020. http://dx.doi.org/10.4018/978-1-7998-1210-4.ch035.
Повний текст джерелаАнотація:
Heavy metal(loid)s are hazardous, biologically non-essential, non-biodegradable and persistent in nature, which can accumulate in plants and animals as well as in environment especially agri- and aqua- culture ecosystems. It is severely responsible for causing several health hazards problems in human, such as, cardiovascular, pulmonary, hepatic, nephrological, dermatological, neurological disorders as well as carcinogenic effects. Removal of these heavy metals from living systems is extensively expensive and also unsuccessful in sent percent removal. Therefore, in order to protect the environment, the removal of heavy metal(loid)s from polluted effluents is essential before discharging into environment. Besides various treatment technologies, sorption of metal(loid)s using bio-wastes are highly potent alternatives in recent years. The present chapter deals with the removal efficiencies of various bio-wastes, orange peels, waste tea leaves, rice husk, wheat stalk, sugar cane bagasse, coconut husk, sun flower stalk, corn cob, nut shell, water hyacinth, crab shell particle, activated carbons etc. The present discussion has also revealed that bio-waste could be a low-cost eco-friendly and green emerging alternative technology in treating the metal(loid)s contaminated environment without posing any further adverse environmental impacts.
8
Mabe, Michael R. "The Library as Lifeboat." In Advances in Library and Information Science, 494–515. IGI Global, 2016. http://dx.doi.org/10.4018/978-1-4666-8624-3.ch021.
Повний текст джерелаАнотація:
According to Hurricane Katrina: Lessons Learned (2006), emergency management professionals realized first-hand that preplanning and coordination is essential when mounting an effective reaction to natural disasters. This chapter describes how leaders in Chesterfield County, VA learned similar lessons in 2001 during Hurricane Irene. In comparison to Katrina the amount of damage caused by Irene was minimal but the impact on county leaders was severe. Based on lessons learned during Irene and an unexpected wind storm nine months later, Chesterfield County leaders now include the Chesterfield County Public (CCPL) in their official disaster relief plans. When activated, CCPL will serve as an information hub, double as a daytime relief shelter and participate in mass feeding if necessary. Selected library branches are available to be used as overnight relief shelters for mass care when the activation of a standard sized shelter facility is not warranted. These changes have made a notable difference.
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Mabe, Michael R. "The Library as Lifeboat." In Emergency and Disaster Management, 1513–35. IGI Global, 2019. http://dx.doi.org/10.4018/978-1-5225-6195-8.ch071.
Повний текст джерелаАнотація:
According to Hurricane Katrina: Lessons Learned (2006), emergency management professionals realized first-hand that preplanning and coordination is essential when mounting an effective reaction to natural disasters. This chapter describes how leaders in Chesterfield County, VA learned similar lessons in 2001 during Hurricane Irene. In comparison to Katrina the amount of damage caused by Irene was minimal but the impact on county leaders was severe. Based on lessons learned during Irene and an unexpected wind storm nine months later, Chesterfield County leaders now include the Chesterfield County Public (CCPL) in their official disaster relief plans. When activated, CCPL will serve as an information hub, double as a daytime relief shelter and participate in mass feeding if necessary. Selected library branches are available to be used as overnight relief shelters for mass care when the activation of a standard sized shelter facility is not warranted. These changes have made a notable difference.
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Valverde-Pérez, Borja, Xavier Flores-Alsina, Anna Katrine Vangsgaard, and Miguel Mauricio-Iglesias. "Modelling and Control of Nitrogen and Phosphorus Removing Systems." In Technologies for the Treatment and Recovery of Nutrients from Industrial Wastewater, 174–201. IGI Global, 2017. http://dx.doi.org/10.4018/978-1-5225-1037-6.ch007.
Повний текст джерелаАнотація:
A wide variety of technologies addressing nutrient removal in wastewater treatment have been developed in the latest years. In order to be able to design, manage, operate, optimise and benchmark these novel technologies with potentially existing standard technologies, detailed modelling of nutrient removal becomes essential. Nutrient removal is prominently considered, with different degrees of complexity, in the commonly used Activated Sludge Models (ASM). However, the description of nutrient-related compounds in these standard models is not sufficiently detailed for novel and not so novel technologies. Furthermore, the environmental evaluation of a process, which includes an estimation of the greenhouse gas release, would require a more complex process to represent nitrogen removal. This chapter reviews the current state of nutrient removal modelling, with special focus on the needs created by emerging technologies in nitrogen and phosphorus removal, paying special attention to the objectives that must be evaluated for each technology.
Тези доповідей конференцій з теми "Activateur non essentiel"
1
Lambers, J. W. J., M. Cammenga, B. Konig, H. Pannekoek, and J. A. van Mourik. "ACTIVATION OF HUMAN ENDOTHELIAL TYPE PLASMINOGEN ACTIVATOR INHIBITOR (PAI-1) BY NEGATIVELY CHARGED PHOSPHOLIPIDS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642807.
Повний текст джерелаАнотація:
The endothelial cell type plasminogen activator inhibitor (PAI-1) may exist in an active, latent form that can be converted into an active form upon exposure to denaturants such as sodium dodecyl sulphate (SDS), guanidine-HCl or urea. Here we show that latent PAI-1 can be activated with lipid vesicles, consisting of the negatively charged phospholipids phosphatidylserine (PS) or phosphatidylinositol (PI). The presence of a net negative charge on the phospholipid headgroup is essential for activation. Incubation with lipid vesicles, consisting of the zwitterionic phospholipids phosphatidylcholine (PC) and phosphatidylethanol-amine (PE), does not result in activation of the inhibitor. In the presence of PS vesicles, the capacity of PAI-1 to inhibit tissue type plasminogen activator (t-PA) is 50-fold higher than that of the untreated protein. For comparison, the activity of PAI-1 was enhanced 25-fold by treatment of the protein with SDS. PS induces activation of the inhibitor at much lower concentrations than SDS. For example, to achieve 50% inhibition of t-PA with a more than 100-fold excess of PAI-1, 0.25 nmoles of PS are required, whereas L.60 nmoles of SDS are necessary to reach half maximal inactivation of t-PA. Activation of PAI-1 by PS can be reversed by the addition of Ca2+-ions, suggesting that Ca2+-ions interfere with the interaction of PAI-1 with the negatively charged lipid surface, thus preventing its activation. The lipid-induced activation of PAI-1 points to a possibly important role of phospholipids in fibrinolysis; regulation of the fibrinolytic activity in blood plasma may ultimately be determined by the extent to which these phospholipids activate the inhibitor of t-PA.This study was supported by the Netherlands Thrombosis Foundation.
2
Kanamori, Y., I. Yada, I. Yuasa, M. Kusagawa, and K. Deguchi. "PHYSIOLOGICAL ROLE OF THE ENHANCED FIBRINOLYTIC ACTIVITY DURING CARDIOPULMONARY BYPASS IN OPEN HEART SURGERY." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644658.
Повний текст джерелаАнотація:
Fibrinolytic activity is reportedly increased during cardiopulmonary bypass( CPB ), and this increase has been considered to be related to the bleeding complications in open heart surgery. The purpose of this study was to clarify the nature of the fibrinolytic activity duringCPB. Twenty patients with valve replacement or aortocoronary bypass surgery were examined. The following parameters were determined: fibrinogen, plasminogen, fibrinopeptide A( FPA ), fibrinopeptide B β 15-42 ( FPB β15-42 ), and tissue-type plasminogen activator ( t-PA ). For further characterization of the fibrinolytic activity, the fibrin plate method was used. Intrinsic fibrinolytic activity was determined by the assay of the fibrinolytic activity of the kaolin activatedeuglobulin. Extrinsic fibrinolyticactivity was estimated by the assayof Cl-inactivator resistant fibrinolytic activity as well as t-PA. Fibrinogen and plasminogen did not decrease except at the beginning of CPB. FPA was increased significantly during CPB. FPB3 15-42 was also increased to four times the preoperative value at 2 hrs of CPB. The intrinsic fibrinolytic system was activatedonly a short time after the startof CPB. The Cl-inactivator resistant fibrinolytic activity was activated gradually during CPB, reached a maximum level 1 hr after the start of CPB, and returned to the preoperative level within 1 hr after the end of CPB. The changes on t-PA paralleled the course of the Cl-inactivator resistant fibrinolytic activity, indicating that enhanced fibrinolytic activity during CPB is predominantly of extrinsic origin caused by t-PA. We conclude that thrombin activity continues during CPB despite the use of heparin, and thatthe enhanced fibrinolytic activity during CPB is essential because t-PA activates plasminogen predominantly at the sites where fibrin is formed, resulting in the dissolution of the microthrombi formed during CPB.
3
D'Angelo, A., F. Gilardoni, V. Toschi, C. Ciminiello, E. A. Sinico, and S. Viganò D'Angelo. "REDUCED PROTEIN S ANTICOAGULANT ACTIVITY IN ESSENTIAL MIXED CRYOGLOBULINEMIA." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644293.
Повний текст джерелаАнотація:
Protein S (PS) is found in two forms in plasma, as free PS, which functions as a cofactor for activated protein C, and in e-quimolar complex with C4b-binding protein (C4b-bp), an inhibitor of the complement system. The Kd of the PS-C4b-bp interaction is one order of magnitude lower than the plasma concentration of the two proteins; thus 55-60% of total PS circulates in the bound form. Evidence has been provided that in vitro complement activation does not affect the equilibrium between PS and C4b-bp; however in patients with systemic lupus erythematosus and low C4 levels, a shift from free to bound PS has been observed. To further evaluate the relationship between complement activation and PS distribution we have measured PS and C4b-bp levels in 21 patients with essential mixed cryoglobulinemia (EMC), an autoimmune disorder characterized by cryo-precitable circulating immunocomplexes and associated with vasculitis and thrombotic episodes. EMC patients had cryocrit rangin from 1 to 66% and greatly reduced complement components (Clq: 45%, C3: 71%, C4: 15% of normal). Mean PS activity was significantly reduced inpatients as compared to the control population consisting of 20 age-and sex-matched blood donors (69%, p< 0.001). Free PS was similar in patients and controls, but total PS was lower in EMC patients (82%, p<0.05). Seven EMC patients had C4b-bp levels be low 60%. Thus, reduction of PS activity in patients with EMC is not due to reduced free PS. Cultured endothelial cells synthesize and release PS with reduced specif ic activity. In EMC patients very high levels of von Willebrand factor (313%, p< 0.001) a protein released from endothelial cells, but not of ceruplasmin, another acute phase reactant protein, were observed.In vivo release of PS from en dothelial cells might contribute to reduced PS specific activity in EMC.
4
Lember, Erki, Karin Pachel, and Enn Loigu. "Adsorption of Diclofenac, Sulfamethoxazole and Levofloxacin with Powdered Activated Carbon." In Environmental Engineering. VGTU Technika, 2017. http://dx.doi.org/10.3846/enviro.2017.082.
Повний текст джерелаАнотація:
The presence of pharmaceutical residues in the receiving waterbodies of wastewater treatment plants (WWTP) and in the environment has become a global concern. We can now say for certain that, having metabolised in our bodies, partially modified or unmodified pharmaceuticals will reach WWTP. However, WWTP are not designed for the removal of such com-pounds. Only a small fraction of pharmaceuticals decompose during biological treatment or are adsorbed in sediment. There-fore, it is essential to find a treatment process that is capable of removing pharmaceutical residues. The aim of the present study was to research the removal of three pharmaceuticals found in the environment, namely diclofenac (DCF), sulfamethoxazole (SMX) and levofloxacin (LFX), through the use of powdered activated carbon (PAC). To this end, adsorption tests were con-ducted where the adsorption capacity was estimated according to the adsorbent dose and the residence time of the process. LFX had the highest adsorption rate: the removal effectiveness was 77% in a residence time of 5 minutes and in 60 minutes a stable indicator was achieved whereby 94% of LFX had become adsorbed. The worst adsorption property was observed for SMX, as 68% of SMX was adsorbed in a residence time of 60 minutes. According to the conducted tests, the Freundlich adsorption isotherms and constants characterising the adsorption were found where the DCF K was 23.8, the SMX K was 34.3 and the LFX K was 106.1. This test demonstrated that the pharmaceuticals selected for the experiment could easily be subjected to adsorption processes and could be removed by means of PAC.
5
Heo, Su-Jin, Tristan P. Driscoll, and Robert L. Mauck. "Dynamic Tensile Loading Activates TGF and BMP Signaling in Mesenchymal Stem Cells on Aligned Nanofibrous Scaffolds." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80706.
Повний текст джерелаАнотація:
Mesenchymal stem cells (MSCs) are a promising cell source for tissue engineering applications, given their ease of isolation and multi-potential differentiation capacity [1]. External mechanical cues directly influence MSC lineage commitment [2]. However, it is not yet clear how these physical cues are transduced to the cell nucleus, an understanding of which may prove essential for orthopaedic tissue engineering. Transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP), members of the TGF beta superfamily, regulate cellular processes including growth and differentiation [3, 4]. TGF and/or BMP ligand binding initiate SMAD phosphorylation, translocation to the nucleus, and transcriptional activation of target genes [4]. Additionally, both ligands can influence the organization of chromatin and the Lamin A/C (LMAC) nucleoskeletal network [5]. For example, we have recently shown that TGF-β3 leads to corticalized LMAC, marked increases in heterochromatin (HTC), and increased nuclear stiffness [6]. Interestingly, dynamic tensile stretch of MSCs on aligned nanofibrous scaffolds, in the absence of these differentiation factors, resulted in many of these same nuclear transformations [6, 7]. The objective of this study was to identify how dynamic tensile stress is transduced in MSCs on aligned nanofibrous scaffolds, and further, to ascertain whether these mechanoregulatory changes are coordinated through TGFβ/BMP signaling pathways.
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Brewer, Bryson M., Mingjian Shi, Yandong Gao, Donna J. Webb, Jon F. Edd, and Deyu Li. "Microfluidic Cell Co-Culture Platform With Liquid Fluorocarbon as the Cell Separator." In ASME 2012 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/imece2012-87601.
Повний текст джерелаАнотація:
Cell co-culture platforms are essential tools for investigating inter-cellular communication and cellular activities among different cell populations. Microfluidic cell co-culture platforms offer several advantages over their conventional counterparts, including precise control over the cellular microenvironment, low cost, and high throughput. Previously, we have developed microfluidic devices using a hydraulically/pneumatically controlled polydimethylsiloxane (PDMS) valve barrier to separate distinct cell populations in culture, providing a means for manipulation and specific treatment of each cell type with different reagents [1]. After releasing the barrier, different cell populations can interact with each other while being observed using real-time imaging. However, the solid PDMS valve barrier is not truly reversible, as any cells/cell processes underneath the barrier will likely undergo physical damage when the valve barrier is activated.
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Kaplan, L. K., T. Mather, L. DeMarco, and S. Solomon. "FIBRIN STIMULATION OF ENDOTHELIAL CELL (EC) PRODUCTION OF PGI AND TISSUE PLASMINOGEN ACTIVATOR (t-PA)." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644738.
Повний текст джерелаАнотація:
Many substances are known to stimulate EC production of PGI2 and t-PA. Additionally, it has been reported that fibrin can Be formed on the EC surface. In this study, the possibility that fibrin generated on the surface of cells can stimulate production of PGI2 and t-PA was examined. Human umbilical vein ECs were incubated for various time intervals with citrated human plasma clotted on the cells by the addition of CaCl2 . Control dishes contained plasma without Ca++ or serum. Time-dependent generation of PGI2 and t-PA was seen over 22-24 hours. Maximal production of PGI2 occurred when fibrin on the cells was formed from 10 to 50% plasma, with serum comprising the remainder of the incubation volume, while maximal t-PA production occurred with clots formed from 100% plasma. Fibrin I formed by addition of batroboxin to citrated plasma stimulated less synthesis of t-PA than did fibrin formed by thrombin action, and it did not stimulate PGI2 production. Thrombin clots were significantly more adherent to the cells than were batroboxin clots. PG^ synthesis induced by fibrin was fully inhibited by indomethacin, approximately 50% inhibited by actinomycin D and cycloheximide, and 20% inhibited by trifluoperazine, but was unaffected by cytochalasin D and vinblastine. Stimulation of t-PA synthesis by fibrin was unaffected by indomethacin, completely inhibited by actinomycin D and cycloheximide, and 60%, 80% and 40% blocked by cytochalasin D, vinblastine, and trifluoperazine, respectively. Thus, thrombin-induced fibrin clots stimulated PGI2 synthesis, and both thrombin and batroboxin clots stimulated t-PA synthesis. Protein and RNA synthesis were essential to stimulation of t-PA synthesis but inhibition of these processes only partially inhibited stimulation of PGI2 synthesis. Integrity of the cytoskeleton was necessary for full stimulation of t-PA synthesis, but not for stimulation of PGI2 synthesis. Thus the mechanisms of stimulation of these two cellular products were different. Increased PGI2 production could serve to limit further fibrin formation by preventing platelets from contributing to the coagulation process and increased t-PA could stimulate lysis of existing fibrin.
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DeLeo, Michael J., Matthew J. Gounis, Ajay K. Wakhloo, and Alexei A. Bogdanov. "Validation of Di-5-HT-Gd-DTPA, an Enzyme-Specific MR Contrast Agent for Myeloperoxidase, in the Rabbit Elastase Model of Cerebrovascular Aneurysm." In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-206346.
Повний текст джерелаАнотація:
Characterization of molecular imaging probes in multiple animal models of disease is essential to increase their diagnostic potential. For example, we recently demonstrated visualization of active inflammation in a rabbit model saccular aneurysm using clinical field strength MRI and the paramagnetic MR contrast agent di-5-HT-GdDTPA, which has been shown in vitro to be sensitive and specific for the enzyme myeloperoxidase (MPO). While the use of transgenic mice (MPO−/−) has demonstrated specificity of di-5-HT-GdDTPA for MPO in a model of myocardial infarction [1], MPO-deficient rabbits are not available. Therefore, in this study, we sought to validate di-5-HT-GdDTPA MPO specificity in the New Zealand white rabbit by comparing serial enhancement ratios of di-5-HT-GdDTPA to a structurally similar MR contrast agent, di-Tyr-GdDTPA, which is activated by peroxidases but not by MPO. Structural diagrams of the synthesis of the two agents are demonstrated in Figure 1 [2].
9
Smogeli, Øyvind, and Trond Augustson. "Third Party HIL Testing of Safety Critical Control System Software on Ships and Rigs." In ASME 2012 31st International Conference on Ocean, Offshore and Arctic Engineering. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/omae2012-84250.
Повний текст джерелаАнотація:
The drilling industry is characterized by a rapid and up front technology development to conquer larger water and drilling depths. The level of automation has been steadily increasing over several decades, growing from manually operated sledge-hammer technology to space-age computer-based integrated systems. Most of the automation systems on today’s vessels are put into operation without independent testing. This is a paradox considering that a single control system may be more complex than all the mechanical systems onboard. It is also a paradox that the automation systems often contain safety-critical failure handling functionality that may be difficult or dangerous to test onboard the real vessel, and therefore is not properly tested until it is activated during an emergency situation. These automation systems are essential for the safety, reliability, and performance of the vessels. Examples are the Dynamic Positioning (DP) systems, Power Management systems, Drilling Control Systems, BOP control systems, Managed Pressure Drilling (MPD) systems, and crane control systems. Hardware-In-the-Loop (HIL) testing is a well proven test methodology from automotive, avionics, and space industries, and is now also gaining recognition in the marine and offshore industries. The aim of this paper is to clarify what HIL testing is, how third party HIL testing can be applied to safety critical control system software on drilling ships and rigs, and why this is an important contribution to technical safety, reliability and profitability of offshore operations.
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Gurewich, V., F. Emmons, and R. Pannell. "THE CONTRIBUTION OF ENDOGENOUS UROKINASE (UK) AND TISSUE PLASMINOGEN ACTIVATOR (t-PA) TO SPONTANEOUS CLOT LYSIS IN PLASMA." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643601.
Повний текст джерелаАнотація:
Spontaneous lysis of 125I-labeled clots was measured in order to study the relative contributions of pro-UK, t-PA and contact activation. Clots were made up from 0.3 ml plasma, platelet rich plasma (PRP) or 2% human fibrinogen (Kabi) and suspended in plasma (3 ml) prepared from blood freshly collected onto citrate. The clots were preincubated to inactivate any residual thrombin which could inactivate pro-UK. Antibiotics were added to suppress bacterial growth. Lysis was approximately linear and went to completion with plasma clots in 12-16 d. and with fibrinogen clots in 6-10 d. Spontaneous lysis was inhibited by aprotinin at >200 KlU/ml and by antibody to t-PA. When the latter was added at t 2-5 d., clot lysis was arrested at each time point suggesting that t-PA was predominantly responsible for the lysis and not just for its initiation. Addition of antibody to UK or immunodepletion of plasma had little effect on spontaneous lysis of plasma or of fibrinogen clots, but retarded lysis of PRP clots. Only after ≥20 ng/ml of pro-UK were added to plasma, was a dose-responsive acceleration of clot lysis observed. The addition of antibodies to t-PA inhibited clot lysis by the added pro-UK (20-80 ng/ml) and greatly prolonged the lag phase of clot lysis by higher concentrations of pro-UK (100-200 ng/ml). Contact activation by dextran sulfate (1-5 μM) had no effect on spontaneous clot lysis but potentiated the effect of > 20 ng/ml added pro-UK. It was concluded that 1) The UK content of resting plasma (3-5 ng/ml) contributes little to lysis of platelet-free clots. 2) The presence of physiological concentrations of t-PA is essential for lysis by endogenous UK and markedly potentiates fibrinolysis by added pro-UK (20-200 ng/ml). 3) For endogenous UK to contribute to fibrinolysis, some amplification of its effect by a cofactor other than t-PA seems to be required. The results indicate augmentation of endogenous pro-UK induced fibrinolysis by platelets and that contact activation stimulates clot lysis by added pro-UK.
Звіти організацій з теми "Activateur non essentiel"
1
Prusky, Dov, Nancy P. Keller, and Amir Sherman. global regulation of mycotoxin accumulation during pathogenicity of Penicillium expansum in postharvest fruits. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7600012.bard.
Повний текст джерелаАнотація:
Background to the topic- Penicilliumas a postharvest pathogen and producer of the mycotoxin PAT. Penicilliumspp. are destructive phytopathogens, capable of causing decay in many deciduous fruits, during postharvest handling and storage; and the resulting losses can amount to 10% of the stored produce and the accumulation of large amounts of the mycotoxinpatulin. The overall goal of this proposal is to identify critical host and pathogen factors that modulate P. expansummycotoxin genes and pathways which are required for PAT production and virulence. Our preliminary results indicated that gluconic acid are strongly affecting patulin accumulation during colonization. P. expansumacidifies apple fruit tissue during colonization in part through secretion of gluconic acid (GLA). Several publications suggested that GLA accumulation is an essential factor in P. expansumpathogenicity. Furthermore, down regulation of GOX2 significantly reduced PAT accumulation and pathogenicity. PAT is a polyketide and its biosynthesis pathway includes a 15-gene cluster. LaeA is a global regulator of mycotoxin synthesis. It is now known that patulin synthesis might be subjected to LaeA and sometimes by environmental sensing global regulatory factors including the carbon catabolite repressor CreA as well as the pH regulator factor PacC and nitrogen regulator AreA. The mechanisms by which LaeA regulates patulin synthesis was not fully known and was part of our work. Furthermore, the regulatory system that controls gene expression in accordance with ambient pH was also included in our work. PacC protein is in an inactive conformation and is unable to bind to the promoter sites of the target genes; however, under alkaline growth conditions activated PacC acts as both an activator of alkaline-expressed genes and a repressor of acid-expressed genes. The aims of the project- This project aims to provide new insights on the roles of LaeA and PacC and their signaling pathways that lead to GLA and PAT biosynthesis and pathogenicity on the host. Specifically, our specific aims were: i) To elucidate the mechanism of pH-controlled regulation of GLA and PAT, and their contribution to pathogenesis of P. expansum. We are interested to understanding how pH and/or GLA impact/s under PacC regulation affect PAT production and pathogenesis. ii) To characterize the role of LaeA, the global regulator of mycotoxin production, and its effect on PAT and PacC activity. iii) To identify the signaling pathways leading to GLA and PAT synthesis. Using state- of-the-art RNAseq technologies, we will interrogate the transcriptomes of laeAand pacCmutants, to identify the common signaling pathways regulating synthesis of both GLA and PAT. Major conclusions, solutions, achievements- In our first Aim our results demonstrated that ammonia secreted at the leading edge of the fungal colony induced transcript activation of the global pH modulator PacC and PAT accumulation in the presence of GLA. We assessed these parameters by: (i) direct exogenous treatment of P. expansumgrowing on solid medium; (ii) direct exogenous treatment on colonized apple tissue; (iii) growth under self-ammonia production conditions with limited carbon; and (iv) analysis of the transcriptional response to ammonia of the PAT biosynthesis cluster. Ammonia induced PAT accumulation concurrently with the transcript activation of pacCand PAT biosynthesis cluster genes, indicating the regulatory effect of ammonia on pacCtranscript expression under acidic conditions. Transcriptomic analysis of pH regulated processes showed that important genes and BARD Report - Project 4773 Page 2 of 10 functionalities of P. expansumwere controlled by environmental pH. The differential expression patterns of genes belonging to the same gene family suggest that genes were selectively activated according to their optimal environmental conditions to enable the fungus to cope with varying conditions and to make optimal use of available enzymes. Concerning the second and third Aims, we demonstrated that LaeA regulates several secondary metabolite genes, including the PAT gene cluster and concomitant PAT synthesis invitro. Virulence studies of ΔlaeAmutants of two geographically distant P. expansumisolates (Pe-21 from Israel and Pe-T01 from China) showed differential reduction in disease severity in freshly harvested fruit ranging from no reduction for Ch-Pe-T01 strains in immature fruit to 15–25% reduction for both strains in mature fruit, with the ΔlaeAstrains of Is-Pe-21 always showing a greater loss in virulence. Results suggest the importance of LaeA regulation of PAT and other secondary metabolites on pathogenicity. Our work also characterized for the first time the role of sucrose, a key nutritional factor present in apple fruit, as a negative regulator of laeAexpression and consequent PAT production in vitro. This is the first report of sugar regulation of laeAexpression, suggesting that its expression may be subject to catabolite repression by CreA. Some, but not all of the 54 secondary metabolite backbone genes in the P. expansumgenome, including the PAT polyketide backbone gene, were found to be regulated by LaeA. Together, these findings enable for the first time a straight analysis of a host factor that potentially activates laeAand subsequent PAT synthesis.
2
Makhachashvili, Rusudan K., Svetlana I. Kovpik, Anna O. Bakhtina, and Ekaterina O. Shmeltser. Technology of presentation of literature on the Emoji Maker platform: pedagogical function of graphic mimesis. [б. в.], July 2020. http://dx.doi.org/10.31812/123456789/3864.
Повний текст джерелаАнотація:
The article deals with the technology of visualizing fictional text (poetry) with the help of emoji symbols in the Emoji Maker platform that not only activates students’ thinking, but also develops creative attention, makes it possible to reproduce the meaning of poetry in a succinct way. The application of this technology has yielded the significance of introducing a computer being emoji in the study and mastering of literature is absolutely logical: an emoji, phenomenologically, logically and eidologically installed in the digital continuum, is separated from the natural language provided by (ethno)logy, and is implicitly embedded into (cosmo)logy. The technology application object is the text of the twentieth century Cuban poet José Ángel Buesa. The choice of poetry was dictated by the appeal to the most important function of emoji – the expression of feelings, emotions, and mood. It has been discovered that sensuality can reconstructed with the help of this type of meta-linguistic digital continuum. It is noted that during the emoji design in the Emoji Maker program, due to the technical limitations of the platform, it is possible to phenomenologize one’s own essential-empirical reconstruction of the lyrical image. Creating the image of the lyrical protagonist sign, it was sensible to apply knowledge in linguistics, philosophy of language, psychology, psycholinguistics, literary criticism. By constructing the sign, a special emphasis was placed on the facial emogram, which also plays an essential role in the transmission of a wide range of emotions, moods, feelings of the lyrical protagonist. Consequently, the Emoji Maker digital platform allowed to create a new model of digital presentation of fiction, especially considering the psychophysiological characteristics of the lyrical protagonist. Thus, the interpreting reader, using a specific digital toolkit – a visual iconic sign (smile) – reproduces the polylaterial metalinguistic multimodality of the sign meaning in fiction. The effectiveness of this approach is verified by the poly-functional emoji ousia, tested on texts of fiction.
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Philosoph-Hadas, Sonia, Peter Kaufman, Shimon Meir, and Abraham Halevy. Signal Transduction Pathway of Hormonal Action in Control and Regulation of the Gravitropic Response of Cut Flowering Stems during Storage and Transport. United States Department of Agriculture, October 1999. http://dx.doi.org/10.32747/1999.7695838.bard.
Повний текст джерелаАнотація:
Original objectives: The basic goal of the present project was to increase our understanding of the cellular mechanisms operating during the gravitropic response of cut flowers, for solving their bending problem without affecting flower quality. Thus, several elements operating at the 3 levels o the gravity-induced signal transduction pathway, were proposed to be examined in snapdragon stems according to the following research goals: 1) Signaling: characterize the signal transduction pathway leading to the gravitropic response, regarding the involvement of [Ca2+]cyt as a mediator of IAA movement and sensitivity to auxin. 2) Transduction by plant hormones: a) Examine the involvement of auxin in the gravitropic response of flower stems with regard to: possible participation of auxin binding protein (ABP), auxin redistribution, auxin mechanism of action (activation of H+-ATPase) mediation by changes in [Ca2+]cyt and possible regulation of auxin-induced Ca2+ action b: calmodulin-activated or Ca2+-activated protein kinases (PK). b) Examine the involvement of ethylene in the gravitropic response of flower stems with regard to auxin-induced ethylene production and sensitivity of the tissue to ethylene. 3) Response: examine the effect of gravistimulation on invertase (associated with growth and elongation) activity and invertase gene expression. 4) Commercial practice: develop practical and simple treatments to prevent bending of cut flowers grown for export. Revisions: 1) Model systems: in addition to snapdragon (Antirrhinum majus L.), 3 other model shoe systems, consisting of oat (Avena sativa) pulvini, Ornithogalun 'Nova' cut flowers and Arabidopsis thaliana inflorescence, were targeted to confirm a more general mechanism for shoot gravitropism. 2 Research topics: the involvement of ABP, auxin action, PK and invertase in the gravitropic response of snapdragon stems could not be demonstrated. Alternatively, the involvement in the gravity signaling cascade of several other physiological mediators apart of [Ca2+]cyt such as: IP3, protein phosphorylation and actin cytoskeleton, was shown. Additional topics introduced: starch statolith reorientation, differential expression of early auxin responsive genes, and differential shoot growth. Background to the topic: The gravitropic bending response of flowering shoots occurring upon their horizontal placement during shipment exhibits a major horticultural problem. In spite of extensive studies in various aboveground organs, the gravitropic response was hardly investigated in flowering shoots. Being a complex multistep process that requires the participation of various cellular components acting in succession or in parallel, analysis of the negative gravitropic response of shoot includes investigation of signal transduction elements and various regulatory physiological mediators. Major achievements: 1) A correlative role for starch statoliths as gravireceptors in flowering shoot was initially established. 2) Differentially phosphorylated proteins and IP3 levels across the oat shoe pulvini, as well as a differential appearance of 2 early auxin-responsive genes in snapdragon stems were all detected within 5-30 minutes following gravistimulation. 3) Unlike in roots, involvement of actin cytoskeleton in early events of the gravitropic response of snapdragon shoots was established. 4) An asymmetric IAA distribution, followed by an asymmetric ethylene production across snapdragon stems was found following gravistimulation. 5) The gravity-induced differential growth in shoots of snapdragon was derived from initial shrinkage of the upper stem side and a subsequent elongation o the lower stem side. 6) Shoot bending could be successfully inhibited by Ca2+ antagonists (that serve as a basis for practical treatments), kinase and phosphatase inhibitors and actin-cytoskeleton modulators. All these agents did not affect vertical growth. The essential characterization of these key events and their sequence led us to the conclusion that blocking gravity perception may be the most powerful means to inhibit bending without hampering shoot and flower growth after harvest. Implications, scientific and agriculture: The innovative results of this project have provided some new insight in the basic understanding of gravitropism in flower stalks, that partially filled the gap in our knowledge, and established useful means for its control. Additionally, our analysis has advanced the understanding of important and fundamental physiological processes involved, thereby leading to new ideas for agriculture. Gravitropism has an important impact on agriculture, particularly for controlling the bending of various important agricultural products with economic value. So far, no safe control of the undesired bending problem of flower stalks has been established. Our results show for the first time that shoot bending of cut flowers can be inhibited without adverse effects by controlling the gravity perception step with Ca2+ antagonists and cytoskeleton modulators. Such a practical benefit resulting from this project is of great economic value for the floriculture industry.
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Sessa, Guido, and Gregory Martin. A functional genomics approach to dissect resistance of tomato to bacterial spot disease. United States Department of Agriculture, January 2004. http://dx.doi.org/10.32747/2004.7695876.bard.
Повний текст джерелаАнотація:
The research problem. Bacterial spot disease in tomato is of great economic importance worldwide and it is particularly severe in warm and moist areas affecting yield and quality of tomato fruits. Causal agent of spot disease is the Gram-negative bacterium Xanthomonas campestris pv. vesicatoria (Xcv), which can be a contaminant on tomato seeds, or survive in plant debris and in association with certain weeds. Despite the economic significance of spot disease, plant protection against Xcvby cultural practices and chemical control have so far proven unsuccessful. In addition, breeding for resistance to bacterial spot in tomato has been undermined by the genetic complexity of the available sources of resistance and by the multiple races of the pathogen. Genetic resistance to specific Xcvraces have been identified in tomato lines that develop a hypersensitive response and additional defense responses upon bacterial challenge. Central goals of this research were: 1. To identify plant genes involved in signaling and defense responses that result in the onset of resistance. 2. To characterize molecular properties and mode of action of bacterial proteins, which function as avirulence or virulence factors during the interaction between Xcvand resistant or susceptible tomato plants, respectively. Our main achievements during this research program are in three major areas: 1. Identification of differentially expressed genes during the resistance response of tomato to Xcvrace T3. A combination of suppression subtractive hybridization and microarray analysis identified a large set of tomato genes that are induced or repressed during the response of resistant plants to avirulent XcvT3 bacteria. These genes were grouped in clusters based on coordinate expression kinetics, and classified into over 20 functional classes. Among them we identified genes that are directly modulated by expression of the type III effector protein AvrXv3 and genes that are induced also during the tomato resistance response to Pseudomonas syringae pv. tomato. 2. Characterization of molecular and biochemical properties of the tomato LeMPK3MAP kinase. A detailed molecular and biochemical analysis was performed for LeMPK3 MAP kinase, which was among the genes induced by XcvT3 in resistant tomato plants. LeMPK3 was induced at the mRNA level by different pathogens, elicitors, and wounding, but not by defense-related plant hormones. Moreover, an induction of LeMPK3 kinase activity was observed in resistant tomato plants upon Xcvinfection. LeMPK3 was biochemically defined as a dual-specificity MAP kinase, and extensively characterized in vitro in terms of kinase activity, sites and mechanism of autophosphorylation, divalent cation preference, Kₘand Vₘₐₓ values for ATP. 3. Characteriztion of molecular properties of the Xcveffector protein AvrRxv. The avirulence gene avrRxvis involved in the genetic interaction that determines tomato resistance to Xcvrace T1. We found that AvrRxv functions inside the plant cell, localizes to the cytoplasm, and is sufficient to confer avirulence to virulent Xcvstrains. In addition, we showed that the AvrRxv cysteine protease catalytic core is essential for host recognition. Finally, insights into cellular processes activated by AvrRxv expression in resistant plants were obtained by microarray analysis of 8,600 tomato genes. Scientific and agricultural significance: The findings of these activities depict a comprehensive and detailed picture of cellular processes taking place during the onset of tomato resistance to Xcv. In this research, a large pool of genes, which may be involved in the control and execution of plant defense responses, was identified and the stage is set for the dissection of signaling pathways specifically triggered by Xcv.