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Artykuły w czasopismach na temat "Global suppressor"
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Chattopadhyay, Gopinath, Jayantika Bhowmick, Kavyashree Manjunath, Shahbaz Ahmed, Parveen Goyal i Raghavan Varadarajan. "Mechanistic insights into global suppressors of protein folding defects". PLOS Genetics 18, nr 8 (29.08.2022): e1010334. http://dx.doi.org/10.1371/journal.pgen.1010334.
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Most amino acid substitutions in a protein either lead to partial loss of function or are near neutral. Several studies have shown the existence of second-site mutations that can rescue defects caused by diverse loss of function mutations. Such global suppressor mutations are key drivers of protein evolution. However, the mechanisms responsible for such suppression remain poorly understood. To address this, we characterized multiple suppressor mutations both in isolation and in combination with inactive mutants. We examined six global suppressors of the bacterial toxin CcdB, the known M182T global suppressor of TEM-1 β-lactamase, the N239Y global suppressor of p53-DBD and three suppressors of the SARS-CoV-2 spike Receptor Binding Domain. When coupled to inactive mutants, they promote increased in-vivo solubilities as well as regain-of-function phenotypes. In the case of CcdB, where novel suppressors were isolated, we determined the crystal structures of three such suppressors to obtain insight into the specific molecular interactions responsible for the observed effects. While most individual suppressors result in small stability enhancements relative to wildtype, which can be combined to yield significant stability increments, thermodynamic stabilisation is neither necessary nor sufficient for suppressor action. Instead, in diverse systems, we observe that individual global suppressors greatly enhance the foldability of buried site mutants, primarily through increase in refolding rate parameters measured in vitro. In the crowded intracellular environment, mutations that slow down folding likely facilitate off-pathway aggregation. We suggest that suppressor mutations that accelerate refolding can counteract this, enhancing the yield of properly folded, functional protein in vivo.
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Shortle, David, i Beth Lin. "GENETIC ANALYSIS OF STAPHYLOCOCCAL NUCLEASE: IDENTIFICATION OF THREE INTRAGENIC "GLOBAL" SUPPRESSORS OF NUCLEASE-MINUS MUTATIONS". Genetics 110, nr 4 (1.08.1985): 539–55. http://dx.doi.org/10.1093/genetics/110.4.539.
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ABSTRACT A collection of 77 unique missense mutations distributed across the gene encoding staphylococcal nuclease (nuc) has been assembled. These mutations were induced by random gap misrepair mutagenesis of the cloned gene and were identified in E. coli transformants expressing reduced levels of nuclease activity. Four nuc - mutations which alter amino acid residues at positions outside of the active site region of the enzyme were submitted to a second round of mutagenesis, and characterization of several independent NUC+ isolates lead to the identification of three second-site suppressor mutations within the protein-coding sequence of the nuc gene. On separation from the mutation originally suppressed and recombination with a number of other nuc - mutations, all three suppressors displayed the property of "global" suppression, i.e., phenotypic suppression of the nuclease-minus character of multiple different alleles. A simple and generally applicable strategy was used to obtain efficient homologous recombination between plasmids for purposes of mapping nuc - mutations, mapping second-site suppressors and constructing double mutant combinations from pairs of single mutations.
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Herring, Christopher D., i Frederick R. Blattner. "Global Transcriptional Effects of a Suppressor tRNA and the Inactivation of the Regulator frmR". Journal of Bacteriology 186, nr 20 (15.10.2004): 6714–20. http://dx.doi.org/10.1128/jb.186.20.6714-6720.2004.
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ABSTRACT Expression of an amber suppressor tRNA should result in read-through of the 326 open reading frames (ORFs) that terminate with amber stop codons in the Escherichia coli genome, including six pseudogenes. Abnormal extension of an ORF might alter the activities of the protein and have effects on cellular physiology, while suppression of a pseudogene could lead to a gain of function. We used oligonucleotide microarrays to determine if any effects were apparent at the level of transcription in glucose minimal medium. Surprisingly, only eight genes had significantly different expression in the presence of the suppressor. Among these were the genes yaiN, adhC, and yaiM, forming a single putative operon whose likely function is the degradation of formaldehyde. Expression of wild-type yaiN was shown to result in repression of the operon, while a suppression-mimicking allele lacking the amber stop codon and extended 7 amino acids did not. The operon was shown to be induced by formaldehyde, and the genes have been renamed frmR, frmA, and frmB, respectively.
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Baroni, T. E., T. Wang, H. Qian, L. R. Dearth, L. N. Truong, J. Zeng, A. E. Denes, S. W. Chen i R. K. Brachmann. "A global suppressor motif for p53 cancer mutants". Proceedings of the National Academy of Sciences 101, nr 14 (22.03.2004): 4930–35. http://dx.doi.org/10.1073/pnas.0401162101.
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Csink, A. K., R. Linsk i J. A. Birchler. "Mosaic suppressor, a gene in Drosophila that modifies retrotransposon expression and interacts with zeste." Genetics 136, nr 2 (1.02.1994): 573–83. http://dx.doi.org/10.1093/genetics/136.2.573.
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Abstract A newly identified locus in Drosophila melanogaster, Mosaic suppressor (Msu), is described. This gene modifies the expression of white-apricot (wa), which is a copia retrotransposon-induced allele of the white gene. In addition to suppressing wa in a mosaic fashion, this mutation suppresses or enhances the expression of several other retrotransposon induced white alleles. Mutations in Msu alter copia transcript abundance and may regulate the expression of several other retrotransposons. While each of the two Msu isolates is homozygous lethal, heteroallelic escapers occur at a low frequency. These escapers act not only as strong suppressors of wa, but also as a recessive enhancer of synaptic-dependent gene expression at white. The mutation described here suggests a connection between the regulation of specific transcriptional units such as retrotransposons and more global synapsis dependent regulatory effects.
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Cheng, Chin Leng, Michael K. Wong i Mark Hochstrasser. "Yeast Nst1 is a novel component of P-bodies and is a specific suppressor of proteasome base assembly defects". Molecular Biology of the Cell 32, nr 20 (1.10.2021): ar6. http://dx.doi.org/10.1091/mbc.e21-04-0178.
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We identified negative salt tolerance 1 (Nst1) as a dosage suppressor of the temperature sensitivity and proteasome assembly defects in multiple base mutants. Both endogenous and overexpressed Nst1 could localize to processing bodies. Nst1 overexpression inhibited global protein translation that in turn suppressed aggregation and proteasome assembly defects in base assembly mutants.
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Huang, W., i T. Palzkill. "A natural polymorphism in -lactamase is a global suppressor". Proceedings of the National Academy of Sciences 94, nr 16 (5.08.1997): 8801–6. http://dx.doi.org/10.1073/pnas.94.16.8801.
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Irie, K., K. Yamaguchi, K. Kawase i K. Matsumoto. "The yeast MOT2 gene encodes a putative zinc finger protein that serves as a global negative regulator affecting expression of several categories of genes, including mating-pheromone-responsive genes". Molecular and Cellular Biology 14, nr 5 (maj 1994): 3150–57. http://dx.doi.org/10.1128/mcb.14.5.3150-3157.1994.
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The STE4 gene encodes the beta subunit of a heterotrimeric G protein that is an essential component of the pheromone signal transduction pathway. To identify downstream component(s) of Ste4, we sought pseudo-revertants that restored mating competence to ste4 mutants. The suppressor mot2 was isolated as a recessive mutation that restored conjugational competence to a temperature-sensitive ste4 mutant and simultaneously conferred a temperature-sensitive growth phenotype. The MOT2 gene encodes a putative zinc finger protein, the deletion of which resulted in temperature-sensitive growth, increased expression of FUS1 in the absence of pheromones, and suppression of a deletion of the alpha-factor receptor. On the other hand, sterility resulting from deletion of STE4 was not suppressed by the mot2 deletion. These phenotypes are similar to those associated with temperature-sensitive mutations in CDC36 and CDC39, which are proposed to encode general negative regulators of transcription rather than factors involved in the pheromone response pathway. Deletion of MOT2 also caused increased transcription of unrelated genes such as GAL7 and PHO84. Overexpression of MOT2 suppresses the growth defect of temperature-sensitive mutations in CDC36 and CDC39. These observations suggest that Mot2 functions as a general negative regulator of transcription in the same processes as Cdc36 and Cdc39.
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Irie, K., K. Yamaguchi, K. Kawase i K. Matsumoto. "The yeast MOT2 gene encodes a putative zinc finger protein that serves as a global negative regulator affecting expression of several categories of genes, including mating-pheromone-responsive genes." Molecular and Cellular Biology 14, nr 5 (maj 1994): 3150–57. http://dx.doi.org/10.1128/mcb.14.5.3150.
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The STE4 gene encodes the beta subunit of a heterotrimeric G protein that is an essential component of the pheromone signal transduction pathway. To identify downstream component(s) of Ste4, we sought pseudo-revertants that restored mating competence to ste4 mutants. The suppressor mot2 was isolated as a recessive mutation that restored conjugational competence to a temperature-sensitive ste4 mutant and simultaneously conferred a temperature-sensitive growth phenotype. The MOT2 gene encodes a putative zinc finger protein, the deletion of which resulted in temperature-sensitive growth, increased expression of FUS1 in the absence of pheromones, and suppression of a deletion of the alpha-factor receptor. On the other hand, sterility resulting from deletion of STE4 was not suppressed by the mot2 deletion. These phenotypes are similar to those associated with temperature-sensitive mutations in CDC36 and CDC39, which are proposed to encode general negative regulators of transcription rather than factors involved in the pheromone response pathway. Deletion of MOT2 also caused increased transcription of unrelated genes such as GAL7 and PHO84. Overexpression of MOT2 suppresses the growth defect of temperature-sensitive mutations in CDC36 and CDC39. These observations suggest that Mot2 functions as a general negative regulator of transcription in the same processes as Cdc36 and Cdc39.
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Nahar, Rahul, Parham Ramezani-Rad, Sinisa Dovat, Maike Buchner, Thomas G. Graeber i Markus Muschen. "Mechanisms of Ikaros-Mediated Tumor Suppression". Blood 118, nr 21 (18.11.2011): 408. http://dx.doi.org/10.1182/blood.v118.21.408.408.
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Abstract Abstract 408 Background: The Ikaros (IKZF1) tumor suppressor is deleted in >80% of the cases of Ph+ ALL. While Ikaros cooperates with pre-B cell receptor signaling to induce cell cycle exit in Ph+ ALL (Trageser et al., J Exp Med, 2009), the mechanism of Ikaros-mediated tumor suppression is poorly understood. Here we report on a series of genetic experiments that show that Ikaros (i) interferes with key survival pathways downstream of the BCR-ABL1 kinase, (ii) inhibits leukemia cell proliferation through interaction with the pre-B cell receptor signaling pathway and (iii) activates the tumor suppressors p53, p21 and p27. Results: To elucidate the mechanism of Ikaros-dependent tumor suppression in BCR-ABL1-driven B cell lineage leukemia, we studied regulation of critical phosphorylation events downstream of the BCR-ABL1 kinase as a central mediators of survival and proliferation. Reconstitution of Ikaros expression in BCR-ABL1-transformed pre-B ALL cells resulted in rapid and global dephosphorylation comparable to the effect of Imatinib. A detailed analysis showed that Ikaros-induced dephosphorylation events affect activation of Stat5 (Y694), AKT (S473), ERK1/2 (T202 and Y204) and SRC (Y416). Interestingly, both Imatinib-treatment and reconstitution of pre-B cell receptor signaling using retroviral vectors for expression of the m heavy chain or the BLNK adapter molecule have the same effects as reconstitution of Ikaros. In fact, a comprehensive gene expression analysis demonstrated that Ikaros reconstitution resulted in similar gene expression changes as reconstitution of pre-B cell receptor signaling (m heavy chain or BLNK), reconstitution of PAX5, Cre-mediated deletion of Stat5 or Myc, or treatment with Imatinib. The signature of common gene expression changes shared between reconstitution of Ikaros, Pax5, m heavy chain, BLNK and inducible deletion of Stat5 or Myc and Imatinib-treatment involves known tumor suppressors including SPIB, BTG1, and BTG2. These findings suggest that reconstitution of tumor suppressive transcription factor (Ikaros, Pax5) converges with pre-B cell receptor-mediated tumor suppression. To better understand how pre-B cell receptor signaling and Ikaros intersect, we combined reconstitution of Ikaros with genetic deletion of either the (more proximal) SYK kinase or the (more distal) BLNK adapter molecule. While inducible Cre-mediated deletion of Syk had no effect on Ikaros-mediated tumor suppression, deletion of the BLNK adapter compromised the ability of Ikaros to function as tumor suppressor. These findings were confirmed in an in vivo transplantation experiment. While mice transplanted with Ikaros+ BLNK+ leukemia cells survived indefinitely, mice transplanted with Ikaros- BLNK+, Ikaros+ BLNK- or Ikaros- BLNK- leukemia cells died after 24 to 31 days post transplantation. While these findings provide genetic evidence for collaboration between the Ikaros and pre-B cell receptor tumor suppressor pathways, Ikaros and pre-B cell receptor signaling differ with respect to activation of classical tumor suppressor pathways. While reconstitution of pre-B cell receptor signaling failed to activate Arf, p53 or p27, protein levels of all these molecules were strongly upregulated by Ikaros. In agreement with these findings, reconstitution of pre-B cell receptor signaling had the same tumor suppressive effect in wildtype leukemia cells as in Arf−/−, p53−/− as well as p27−/− leukemia cells. Conversely, deletion of Arf and p53 significantly diminished the ability of Ikaros to function as tumor suppressor. Conclusion: Ikaros deletion represents a near-obligatory lesion in the pathogenesis of Ph+ ALL. Here we provide genetic evidence for three novel pathways of Ikaros-mediated tumor suppression. Like PAX5, Ikaros reconstitution results in multiple dephosphorylation events (Stat5, AKT, ERK1/2 and SRC are affected). In collaboration with the pre-B cell receptor and its downstream adapter molecule BLNK, Ikaros suppressed MYC and inhibits cell cycle progression. Induction of the Arf/p53 pathway represents a distinct function of Ikaros, which is not shared with the pre-B cell receptor signaling pathway. Disclosures: No relevant conflicts of interest to declare.
Rozprawy doktorskie na temat "Global suppressor"
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Freter, Jan Rasmus Gerhard. "Adult stem cells exhibit global suppression of RNA polymerase II serine-2 phosphorylation". Kyoto University, 2011. http://hdl.handle.net/2433/135373.
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Mäkiranta, M. (Minna). "EEG and BOLD-contrast fMRI in brain:cerebrovascular reactivity, suppression of neuronal activity, global and local brain injury". Doctoral thesis, University of Oulu, 2004. http://urn.fi/urn:isbn:9514274296.
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Abstract
The purpose of the present study was to gain more insight into the blood oxygen level-dependent (BOLD)-contrast functional MRI (fMRI) in the brain and its connection to EEG, both in global and local scales of their temporal and spatial relations.
BOLD signal changes were studied during hyperventilation (HV) induced EEG reactivity of intermittent rhythmic delta activity (IRDA). The BOLD signal in gray matter decreased 30% more in subjects with IRDA (N = 4) than in controls (N = 4), during the first two minutes of HV. This difference disappeared during IRDA in EEG. BOLD signal changes may provide additional information about dynamic hemodynamic changes relative to HV induced EEG reactivity.
BOLD signal changes were investigated during sudden deepening of thiopental anesthesia into EEG burst-suppression level in pigs (N = 5). Positive (6–8%) or negative (-3– -8%) group average BOLD signal changes correlated to the thiopental bolus injection were seen. Positive and negative responses covered 1.6% and 2.3% of the brain voxels, respectively. BOLD signal changes in brain are associated with sudden deepening of thiopental anesthesia into EEG burst-suppression level, but they are spatially inconsistent and scarce.
Somatosensory BOLD response was studied in brain before and after globally induced methotrexate (MTX) exposition in pigs (N = 4). After the MTX exposure, reduced (from 2–4% to 0–1%) or negative (-2% to -3%) BOLD responses were detected. Somatosensory BOLD-contrast response shows a slight difference in brain before and after globally induced MTX exposition.
An experimental epilepsy model for development of simultaneous EEG and BOLD-contrast fMRI in the localization of epilepsy was developed and tested. Dynamic penicillin induced local epilepsy was applied in deep isoflurane anesthesia in pigs (N = 6). Relatively high (10–20%) and localized BOLD signal increase was found. The dynamic penicillin induced focal epilepsy model in deep isoflurane anesthesia with simultaneous EEG and BOLD-contrast fMRI is feasible for the development of these methods for localization of epileptic focus or foci.
In conclusion, with careful experimental design and analysis, BOLD-contrast fMRI with EEG provides a potential tool for monitoring and localising functional changes in the brain.
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Gabriel, André Filipe Gonçalves. "Suppression therapy of ß-thalassemia using Kanamycin and Gentamicin". Master's thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/17790.
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Mestrado em Biologia Molecular e CelularAs mutações nonsense são mutações pontuais que originam codões de terminação prematura (PTCs). A expressão de genes portadores de PTCs pode levar à síntese de proteínas truncadas. As proteínas truncadas caracterizam-se por serem menores e, na maioria das vezes, não possuem função biológica, apesar de poderem ter funções deletérias para a célula. Em condições normais, transcritos portadores de PTCs são degradados rapidamente através do processo de nonsense mediated mRNA decay (NMD). Quando um PTC atinge o sítio A ribossomal, os fatores de terminação da tradução ligam-se ao mesmo e a tradução termina imediatamente. A terapia de supressão consiste numa abordagem terapêutica que tem o objetivo de utilizar compostos de baixo peso molecular para induzir a incorporação de aminoacil-tRNAs quase cognatos, moléculas que possuem complementaridade para dois dos três nucleótidos de um códão de stop, quando o ribossoma atinge um PTC. Assim, a tradução não termina prematuramente. Estudos anteriores mostraram que alguns aminoglicósidos possuem a capacidade de suprimir PTCs responsáveis por doenças, como fibrose quística e distrofia muscular de Duchenne. Algumas mutações nonsense são responsáveis pela β-talassemia. Neste estudo foram utilizados dois aminoglicósidos, canamicina e gentamicina, de modo a avaliar a sua capacidade em aumentar a competitividade de tRNAs quase cognatos com os fatores de terminação da tradução pelo sítio A ribossomal, na presença de um PTC, evitando dessa forma a terminação prematura da tradução.
Nonsense mutations are point mutations that originate premature termination codons (PTCs). The expression of PTC-containing genes may lead to the synthesis of truncated proteins. Truncated proteins are shorter proteins that at most times do not have biological function, but may have deleterious functions for the cell. In regular conditions, PTC-containing transcripts are taken to rapid decay, through nonsense mediated mRNA decay (NMD). When a PTC reaches the ribosomal A-site, translation release factors bind it and translation immediately stops. Suppression therapy is a therapeutic approach that aims to suppress PTCs by using low molecular weight compounds to induce the incorporation of near cognate aminoacyl tRNAs, molecules that show complementarity to two of the three nucleotides of a stop codon, when the ribosome reaches a PTC. Thus, translation does not prematurely terminates. Previous studies have shown that some aminoglycosides have the ability to suppress PTCs responsible for diseases like cystic fibrosis and Duchenne muscular dystrophy. Some nonsense mutations are responsible for β-thalassemia disease. In this study two aminoglycoside compounds, kanamycin and gentamicin, were used in order to evaluate their capacity to increase the competition of near cognate aminoacyl tRNAs with translation release factors by the ribosomal A-site, when the ribosome reaches a PTC, therefore avoiding the premature termination of translation.
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Hérodin, Francis. "Contribution a l'etude des effets d'une reaction inflammatoire et d'une irradiation gamma ou neutron-gamma globale chez la souris". Paris 6, 1988. http://www.theses.fr/1988PA066295.
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Un modele de granulome inflammatoire induit chez la souris par injection souscutanee de microbilles de polyacrylamide est utilise pour etudier la physiopathologie de souris soumises, avant ou apres l'induction du processus inflammatoire local, a une exposition globale a des radiations ionisantes. L'effet suppresseur des radiations ionisantes. Une reaction inflammatoire locale induite depuis 24 h s'accompagne d'un effet radioprotecteur important, qui pourrait etre partiellement explique par une stimulation notable de la myelopoiese
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Desai, Megha. "Structural and Functional Characterization of the MBD2-NuRD Co-Repressor Complex". VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3617.
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The MBD2-NuRD co-repressor complex is an epigenetic regulator of the developmental silencing of embryonic and fetal β-type globin genes in adult erythroid cells as well as aberrant methylation-dependent silencing of tumor suppressor genes in neoplastic diseases. Biochemical characterization of the MBD2-NuRD complex in chicken erythroid cells identified RbAp46/48, HDAC1/2, MTA1/2/3, p66α/β, Mi2α/β and MBD2 to comprise this multi-protein complex.
In the work presented in Chapter 2, we have pursued biophysical and molecular studies to describe a previously uncharacterized domain of human MBD2 (MBD2IDR). Biophysical analyses show that MBD2IDR is an intrinsically disordered region (IDR). Despite this inherent disorder, MBD2IDR increases the overall binding affinity of MBD2 for methylated DNA. MBD2IDR also recruits the histone deacetylase core components (RbAp48, HDAC2 and MTA2) of NuRD through a critical area of contact requiring two contiguous amino acid residues, Arg286 and Leu287. Mutation of these critical residues abrogates interaction of MBD2 with the histone deacetylase core and impairs the ability of MBD2 to repress the methylated tumor suppressor gene Prostasin in MDA-MB-435 breast cancer cells. These findings expand our knowledge of the multi-dimensional interactions of the MBD2-NuRD complex that govern its function.
In Chapter 3, we have discussed a novel mechanism for MBD2-mediated silencing of the fetal γ-globin gene. Through microarray expression analyses in adult erythroid cells of MBD2-/- mice, we identified ZBTB32 and miR-210 as downstream targets of MBD2. Over-expression of ZBTB32 and miR-210 in adult erythroid cells causes increased expression of the silenced fetal γ-globin gene. Thus, our results indicate that MBD2 may regulate γ-globin gene expression indirectly though ZBTB32 and miR-210 in adult erythroid cells.
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Bhowmick, Jayantika. "CcdB : Stability, folding and application to design novel antibacterials". Thesis, 2020. https://etd.iisc.ac.in/handle/2005/5134.
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The primary amino acid sequence typically dictates the ultimate conformation of the protein. Mutations in the sequence demonstrate neutral, positive or negative effects on the structure-function relationship of the protein. Destabilising mutations often reduce the soluble levels of the protein in vivo, leading to complete or partial loss of its function. Global suppressors are diverse compensatory mutations that can alleviate the detrimental effects of multiple destabilised, inactive mutants, despite being physically distant from the site of the original inactive mutations. The molecular mechanisms responsible for suppression are still unknown, despite the characterisation of suppressors in several proteins since the late 1980s. Another modulator of a protein’s structure is the pH of the solution. It has long been known that proteins form molten globules at acidic pH conditions, which are compact denatured states with fluctuating tertiary structures. CcdB (Controller of Cell Division or Death B), a 101-residue homodimeric toxin which is a part of the CcdA:CcdB toxin:antitoxin module and poisons intracellular Gyrase, has been utilised as the model protein of choice in the course of the studies. Chapter 1 presents the importance of global suppressors, gives an overview of the role of pH on the protein’s structure and discusses various Gyrase inhibitors and outlines how the CcdB:Gyrase interaction can be utilised to design antibacterial peptides based on the toxin’s sequence. Chapter 2 provides a detailed thermodynamic and kinetic investigation of a global suppressor in CcdB. The studies show that the suppressor restores the stability and function of inactive mutants by marginally enhancing their apparent thermodynamic stabilities and lowering their unfolding rates. Chapter 3 shows the broad-spectrum antibacterial action of a novel CcdB-derived peptide on E.coli and pathogenic strains of S.aureus, S.Typhimurium, as well as a multi-drug resistant clinical isolate of A.baumannii. Chapter 4 reports a preliminary investigation of the low pH-induced molten globule-like state of CcdB using NMR spectroscopy.MHRD, India
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Wu, Chi Sheng, i 吳啟生. "Global Analysis of Methylated Genes in Gastric Cancer by Differential Methylation Hybridization and CpG DNA Microarray and Identification of Glutamate receptor, ionotropic, kainate 2 as a Potential Tumor Suppressor Gene in Gastric Cancer". Thesis, 2009. http://ndltd.ncl.edu.tw/handle/64139597679182429359.
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博士長庚大學
生物醫學研究所
98
Abstract Aberrant DNA methylation is considered as a major mechanism for silencing tumor suppressor genes in gastric cancer. Here, we used CpG microarray and differential methylation hybridization (DMH) strategies to identify potential tumor suppressor genes, and recovered glutamate receptor, ionotropic, kainate 2 (GRIK2) as a novel epigenetic target in gastric cancer. Additional experiments revealed that the promoter region of GRIK2 was hypermethylated in three out of the four tested gastric cancer cell lines, and its expression was restored by treatment of cells with the DNA methylation inhibitor, 5’-aza-dC. In clinical samples, the GRIK2 promoter was differentially hypermethylated in 27 paired tumor tissues compared to adjacent normal tissues (P<0.001), and this methylation was inversely correlated with the expression level of GRIK2 mRNA (r=-0.44). Functional studies further revealed that GRIK2-expressing gastric cancer cell lines showed decreased colony formation and cell migration. Taken together, these results suggest that GRIK2 may play a tumor suppressor role in gastric cancer. Future studies are warranted to examine whether DNA hypermethylation of the GRIK2 promoter can be used as a potential tumor marker for gastric cancer.
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Lu, Yen-Jung, i 陸燕榮. "Global Screening of Methylated Genes in Gastric Cancer by Differential Methylation Hybridization and CpG DNA Microarray and Identification of Low Density Lipoprotein Receptor-Related Protein 1B as a Potential Tumor Suppressor Gene in Gastric Cancer". Thesis, 2010. http://ndltd.ncl.edu.tw/handle/93497197014267446088.
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博士國立陽明大學
微生物及免疫學研究所
98
Gastric cancer is the second most common cancer worldwide, while in Taiwan it is the fifth leading cause of cancer-related death. Several factors have been implicated in the development of gastric cancer, including chromosomal instability, genetic and epigenetic alterations, Helicobacter pylori infection, and environmental factors such as diet and smoking. Among them, the aberrant methylation of CpG dinucleotides has been reported during tumorigenesis in gastric cancer. In this study, we used CpG island microarray and differential methylation hybridization (DMH) to identify novel epigenetic targets in gastric cancer. We identified 107 genes that were differentially hypermethylated in the four gastric cancer cell lines (AGS, AZ521, KATOIII and TMC1) but not in the two adult normal stomach tissue samples. Several tumor suppressor genes previously identified as being regulated by DNA methylation in gastric cancer were identified by our approach. One of the candidate genes, LRP1B, was hypermethylated in four gastric cancer cell lines and clinical samples (45 out of 74, 60.8%), and low LRP1B mRNA expression was associated with high methylation levels in gastric cancer cell lines. Addition of DNA methylation inhibitor (5-Aza-dC) can restore the mRNA expression of LRP1B in these cell lines, indicating that DNA methylation is involved in regulating LRP1B expression. In 15 out of 19 (78.9%) gastric tumor tissues, LRP1B mRNA expression was significantly lower than in adjacent normal tissues. In addition, ectopic expression of mLRP1B4 in gastric cancer cell lines suppressed cell growth, colony formation and tumor formation in nude mice. These results collectively indicate that LRP1B is a functional tumor suppressor gene in gastric cancer, and that is regulated by DNA methylation.
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Zhang, Peng. "An investigation of interocular suppression with a global motion task". Thesis, 2012. http://hdl.handle.net/10012/7128.
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Abstract
Purpose:
Interocular inhibitory interactions appear to underlie the establishment of ocular dominance. The inhibitory effect leads to suppression of the non dominant eye in certain conditions. While these processes are not fully understood, the relative differences in image contrast appear to be fundamental. By titrating the relative contrast presented to each eye, a balance in the relative inhibitory effects of each eye can be defined. This research looked at whether the interocular contrast ratio at perceptual balance could be used as an index of the ocular dominance in binocular normal population, and the suppression typically found in the amblyopic population. Contrast variation was compared to luminance variation as well as the application of neutral density filters.
Methods:
Balance point measures were obtained by varying the interocular levels of contrast for a global motion task viewed dichoptically. One eye received signal dots moving in a given direction while the other eye received noise dots moving randomly. Subjects were tasked with determining the direction of movement of the signal dots. Balanced dichoptic motion sensitivity was achieved under a specific contrast ratio (or the balance point), depending on the observer’s binocular functions. This test was conducted on a control group (n=23) having normal vision and a strabismic amblyopic group (n=10). In addition, a variation of this test was designed with interocular luminance (rather than interocular contrast) serving as the independent variable was conducted to both the control (n=5) and amblyopic groups (n=8). Concurrent eye tracking measures measured changes in eye alignment at the balance point.
Results:
Although most normal vision subjects showed a balance point at close to equal levels of contrast between the eyes, a minority of them were significantly imbalanced. The suppression measured in the strabismic amblyopic group was significantly greater than that of the control group. Varying the interocular luminance instead of contrast failed to affect the coherence motion thresholds. Ocular alignment was not changed when the balance point was reached.
Conclusion:
Consistent with the current model of binocular integration, interocular contrast are uniquely important in establishing sensory dominance and suppression. This suggests that the interocular suppression found in amblyopia could be attenuated by methods that allow the reduction of contrast to the fellow fixing eye. Amblyopia therapy might then be improved where such contrast balancing methods are employed instead of the complete patching of the fellow eye.
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Wang, Chia-Hung, i 王嘉宏. "Global Screening of Antiviral Genes that Suppress Baculovirus Transgene Expression in Mammalian Cells". Thesis, 2017. http://ndltd.ncl.edu.tw/handle/c48yu9.
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博士國立陽明大學
生命科學系暨基因體科學研究所
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Although baculovirus has been used as a safe and convenient gene delivery vector in non-mammalian host cells, baculovirus-mediated transgene expression is less effective in various mammalian cell lines. Identification of the negative regulators in host cells is necessary to improve baculovirus-based expression systems. Here, we performed high-throughput shRNA library screening, targeting 176 antiviral innate immune genes, and identified 43 host restriction factor genes in a human A549 lung carcinoma cell line. Among them, suppression of receptor interaction protein kinase 1 (RIP1, alias RIPK1) significantly increased baculoviral transgene expression without resulting in significant cell death. Silencing of RIP1 did not affect viral entry or cell viability, but it did inhibit nuclear translocation of IRF3 and NF-κB transcription factors. Also, activation of downstream signaling mediators (such as TBK1 and IRF7) was affected, and subsequent interferon and cytokine gene expression levels were abolished. Further, Necrostatin-1 (Nec-1)—an inhibitor of RIP1 kinase activity—dramatically increased baculoviral transgene expression in RIP1-silenced cells. Using baculovirus as a model system, this study has presented an initial investigation of large numbers of human cell antiviral innate immune response factors against a "nonadaptive virus". In addition, our study has made baculovirus a more efficient gene transfer vector for some of the most frequently used mammalian cell systems.
Książki na temat "Global suppressor"
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Burson, Jeffrey D., i Jonathan Wright, red. The Jesuit Suppression in Global Context. Cambridge: Cambridge University Press, 2015. http://dx.doi.org/10.1017/cbo9781139344135.
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Beyond suppression: Global perspectives on youth violence. Santa Barbara, Calif: Praeger, 2011.
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J, Blakeslee Richard, i United States. National Aeronautics and Space Administration., red. Comment on "Current budget of the atmospheric electric global circuit" by Heinz W. Kasemir. [Washington, DC: National Aeronautics and Space Administration, 1996.
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United States. Congress. House. Committee on International Relations. Subcommittee on Asia and the Pacific, red. The Internet in China: A tool for freedom or suppression? : joint hearing before the Subcommittee on Africa, Global Human Rights, and International Operations and the Subcommittee on Asia and the Pacific of the Committee on International Relations, House of Representatives, One Hundred Ninth Congress, second session, February 15, 2006. Washington: U.S. G.P.O., 2006.
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Jesuit Suppression in Global Context: Causes, Events, and Consequences. University of Cambridge ESOL Examinations, 2015.
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Wright, Jonathan, i Jeffrey D. Burson. Jesuit Suppression in Global Context: Causes, Events, and Consequences. Cambridge University Press, 2015.
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Wright, Jonathan, i Jeffrey D. Burson. Jesuit Suppression in Global Context: Causes, Events, and Consequences. Cambridge University Press, 2015.
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Taylor, Natalie Greene, Karen Kettnich, Ursula Gorham i Paul T. Jaeger, red. Libraries and the Global Retreat of Democracy: Confronting Polarization, Misinformation, and Suppression. Emerald Publishing Limited, 2021. http://dx.doi.org/10.1108/s0065-2830202150.
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Jaeger, Paul T., Natalie Greene Taylor, Ursula Gorham i Karen Kettnich. Libraries and the Global Retreat of Democracy: Confronting Polarization, Misinformation, and Suppression. Emerald Publishing Limited, 2021.
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Jaeger, Paul T., Natalie Greene Taylor, Ursula Gorham i Karen Kettnich. Libraries and the Global Retreat of Democracy: Confronting Polarization, Misinformation, and Suppression. Emerald Publishing Limited, 2021.
Znajdź pełny tekst źródłaCzęści książek na temat "Global suppressor"
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Shardina, Kseniya, Valeriya Timganova, Mariya Bochkova i Sofya Uzhviyuk. "Generation of Human Myeloid-Derived Suppressor Cells from CD11b+ Cells in Vitro". W Science and Global Challenges of the 21st Century – Innovations and Technologies in Interdisciplinary Applications, 539–47. Cham: Springer Nature Switzerland, 2023. http://dx.doi.org/10.1007/978-3-031-28086-3_49.
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Crowell, Claudia S., i Kathleen Malee. "Neurocognition in Viral Suppressed HIV-Infected Children". W Global Virology II - HIV and NeuroAIDS, 257–82. New York, NY: Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-7290-6_11.
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Montana, Ismael M. "Slavery in the Middle East and North Africa". W The Palgrave Handbook of Global Slavery throughout History, 459–77. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-13260-5_26.
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AbstractIn the early 1840s and following the abolition of the trans-Atlantic slave trade by several European nations and the United States, European humanitarians—particularly the British—embarked on an earnest campaign to outlaw the vigorous enslaving activities thriving in the Middle East and North Africa. This chapter examines the extent to which the marked increase of enslavement activities and their suppression through the pressure of European abolitionism fits into the saga of the nineteenth-century transformation processes characterized by the rise of European domination of the region. Focusing on the enslavement of Black Africans, the chapter examines the impact of state modernization schemes and the rise of European capitalism on the expansion of enslaving activities and their suppression and argues that no prior historical development has shaped the contours of African slavery in the Middle East and North Africa more than the effects of the nineteenth-century transformation process.
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van Ede, Yolanda. "Sounding Contestation, Silent Suppression: Cosmopolitics and Gender in Japanese Flamenco". W Dance Ethnography and Global Perspectives, 154–71. London: Palgrave Macmillan UK, 2014. http://dx.doi.org/10.1057/9781137009449_9.
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Löfroth, Therese, Tone Birkemoe, Ekaterina Shorohova, Mats Dynesius, Nicole J. Fenton, Pierre Drapeau i Junior A. Tremblay. "Deadwood Biodiversity". W Advances in Global Change Research, 167–89. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-15988-6_6.
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AbstractDeadwood is a key component for biodiversity and ecosystem services in boreal forests; however, the abundance of this critical element is declining worldwide. In natural forests, deadwood is produced by tree death due to physical disturbances, senescence, or pathogens. Timber harvesting, fire suppression, and salvage logging reduce deadwood abundance and diversity, and climate change is expected to bring further modifications. Although the effects of these changes are not yet fully understood, restoring a continuous supply of deadwood in boreal forest ecosystems is vital to reverse the negative trends in species richness and distribution. Increasing the availability of deadwood offers a path to building resilient forest ecosystems for the future.
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Lenihan, James M., i Dominique Bachelet. "Historical Climate and Suppression Effects on Simulated Fire and Carbon Dynamics in the Conterminous United States". W Global Vegetation Dynamics, 17–30. Hoboken, NJ: John Wiley & Sons, Inc, 2015. http://dx.doi.org/10.1002/9781119011705.ch2.
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Wagg, Stephen. "The soul of a nation, long suppressed?" W Cricket: A Political History of the Global Game, 1945–2017, 90–107. Milton Park, Abingdon, Oxon ; New York, NY : Routledge, 2018.: Routledge, 2017. http://dx.doi.org/10.4324/9781315733210-7.
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De Fabo, E. C., i F. P. Noonan. "Ultraviolet-Induced Immune Suppression and its Relationship to Statospheric Ozone Depletion". W The Role of the Stratosphere in Global Change, 541–57. Berlin, Heidelberg: Springer Berlin Heidelberg, 1993. http://dx.doi.org/10.1007/978-3-642-78306-7_27.
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Johnstone, Adrian, i Elizabeth Scott. "Suppression of Redundant Operations in Reverse Compiled Code Using Global Dataflow Analysis". W Software and Compilers for Embedded Systems, 92–106. Berlin, Heidelberg: Springer Berlin Heidelberg, 2004. http://dx.doi.org/10.1007/978-3-540-30113-4_8.
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Chapin, Vincent G., Nicolas Boulanger i Patrick Chassaing. "Improvement of the Jet-Vectoring through the Suppression of a Global Instability". W IUTAM Symposium on Flow Control and MEMS, 393–96. Dordrecht: Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6858-4_48.
Pełny tekst źródłaStreszczenia konferencji na temat "Global suppressor"
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CHIBA, NATSUKO, i LEIZHEN WEI. "ANALYSIS OF TUMOR SUPPRESSOR GENE USING MOLECULAR IMAGING FOR PERSONALIZED MEDICINE". W Proceedings of the Tohoku University Global Centre of Excellence Programme. PUBLISHED BY IMPERIAL COLLEGE PRESS AND DISTRIBUTED BY WORLD SCIENTIFIC PUBLISHING CO., 2009. http://dx.doi.org/10.1142/9781848163539_0037.
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Chondro, Peter, i Shanq-Jang Ruan. "Low order SSIM-based pixel dimming algorithm with weighted high frequency spectrum suppressor for AMOLED displays". W 2017 IEEE 6th Global Conference on Consumer Electronics (GCCE). IEEE, 2017. http://dx.doi.org/10.1109/gcce.2017.8229186.
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Bhardwaj, Anjana, Zhenlin Ju, Harpreet Singh, Matthew Embury, Jing Wang i Isabelle Bedrosian. "Abstract 773: A global increase in miRNAs and a concomitant decrease in tumor suppressor pathways define preneoplastic transition in TNBC". W Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-773.
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Bhardwaj, Anjana, Zhenlin Ju, Harpreet Singh, Matthew Embury, Jing Wang i Isabelle Bedrosian. "Abstract 773: A global increase in miRNAs and a concomitant decrease in tumor suppressor pathways define preneoplastic transition in TNBC". W Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-773.
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Nikolić, Nenad. "PROBLEM IDENTITETA NACIONALNE KNjIŽEVNOSTI U MEĐUNARODNOM KONTEKSTU". W IDENTITETSKE promene: srpski jezik i književnost u doba tranzicije. University of Kragujevac, Faculty of Edaucatin in Jagodina, 2022. http://dx.doi.org/10.46793/zip21.025n.
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The paper analyses the global tendency of conceptualizing transnational and regional literature in order to suppress national literatures at first, and then to completely replace them. The analysis is based on History of the Literary Cultures of East-Central Europe: Junctures and disjunctures in the 19th and 20th centuries (Eds. M. Cornis-Pope and J. Neubauer, Vol. I 2004, Vol. II 2006, Vol. III 2007, Vol. IV 2010). The tendency to replace national literatures with the transnational one is depicted within the framework of broader cultural, social, and political circumstances. Based on the ideology of “Western liberalism, global capitalism, and George Soros” – which was stated as the core idea of the History of the Literary Cultures of East-Central Europe by its editors – this tendency leads to a general weakening of traditional identities framework: from personal to national identity. Therefore, the suppression of national literature is simultaneous with the suppression of nationality in general, and with changing the notion of literature as it existed in the age of national states since that notion was correspondent with the personal identity which also undergoes through changes.
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Yang, Fan, Ramin Sedaghati i Ebrahim Esmailzadeh. "Multi-Tuned Optimum Vibration Absorbers for Curved Beams". W ASME 2009 International Mechanical Engineering Congress and Exposition. ASMEDC, 2009. http://dx.doi.org/10.1115/imece2009-12998.
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Detailed investigations on the vibration suppression of beam-type structures using Multiple Tuned Mass Damper (MTMD) technology has been carried out in this study. A general curved beam has been utilized as a case study to illustrate the developed optimum design methodology. The governing differential equations of motion for the curved beam with the attached MTMD systems have been derived, and then solved using the finite element method. A hybrid optimization methodology, which combines the global optimization method based on Genetic Algorithm (GA) and the local optimization technique based on Sequential Quadratic Programming (SQP), has been developed. This has been utilized to find the optimum design parameters (damping coefficient, spring stiffness and position coordinate) of the attached Tuned Mass Damper (TMD) systems in order to suppress the vibration levels at a particular mode or several modes, simultaneously. Finally, a design principle for vibration suppression of beam-type structures using the MTMD technology has been proposed through extensive numerical investigations.
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Allen, Don W., i Stergios Liapis. "The Effect of Coverage Length and Density on the Performance of Fairings". W ASME 2014 33rd International Conference on Ocean, Offshore and Arctic Engineering. American Society of Mechanical Engineers, 2014. http://dx.doi.org/10.1115/omae2014-23108.
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While the application of fairings can both increase a tubular’s fatigue life and decrease a tubular’s drag, it is not always possible or economical to fully cover a tubular with fairings. Aside from the desire to minimize the cost of VIV suppression by only covering the necessary portion of a tubular’s span, the presence of connectors, anodes, and other appurtenances can restrict the ability to install fairings over the entire tubular’s length. The result is that it is critical to understand how much of a tubular’s span should be covered with fairings and the effect of partial coverage on the overall suppression performance, and drag reduction, of the fairings system. This paper utilizes data from a two similar test programs to examine the effects of coverage length and density on the performance of fairings. The results show that the location of the fairings has a substantial effect on both the local and global response of the tubular. In practical terms, having fairings present in the high current region can suppress VIV in both the high current and low current regions of the tubular.
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Cho, Hyung Uk, i Jong Chang Yi. "Nonlinear gain suppression coefficient of InAlGaN blue LDs". W 2010 Photonics Global Conference. IEEE, 2010. http://dx.doi.org/10.1109/pgc.2010.5706046.
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Lai, J. S., i K. W. Wang. "Parametric Control of Structural Vibrations via Adaptable Stiffness Dynamic Absorbers". W ASME 1996 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 1996. http://dx.doi.org/10.1115/imece1996-0928.
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Abstract An energy-based algorithm is developed for dynamic absorbers with adaptable stiffness to suppress structural vibrations via real-time parametric control actions. A controller with multi-objective fuzzy logic is created to reduce the main structure energy while constraining the total system energy. An adaptive-passive supervisor is designed to provide guidelines for implementing the control law. It is proved that the system using this supervisor is globally stable in the sense that all signals involved are bounded. The performance of the controller is demonstrated on a beam example. It is shown that the structure energy level and vibration amplitude can be suppressed effectively.
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Su, Kang, i Jianjiang Zhou. "Evolutionary global attitude planning for satellite signature suppression shield". W 2010 Sixth International Conference on Natural Computation (ICNC). IEEE, 2010. http://dx.doi.org/10.1109/icnc.2010.5584531.
Pełny tekst źródłaRaporty organizacyjne na temat "Global suppressor"
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Chejanovsky, Nor, i Suzanne M. Thiem. Isolation of Baculoviruses with Expanded Spectrum of Action against Lepidopteran Pests. United States Department of Agriculture, grudzień 2002. http://dx.doi.org/10.32747/2002.7586457.bard.
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Our long-term goal is to learn to control (expand and restrict) the host range of baculoviruses. In this project our aim was to expand the host range of the prototype baculovirus Autographa cali/arnica nuclear polyhedrosis virus (AcMNPV) towards American and Israeli pests. To achieve this objective we studied AcMNPV infection in the non-permissive hosts L. dispar and s. littoralis (Ld652Y and SL2 cells, respectively) as a model system and the major barriers to viral replication. We isolated recombinant baculoviruses with expanded infectivity towards L. dispar and S. littoralis and tested their infectivity towards other Lepidopteran pests. The restricted host range displayed by baculoviruses constitutes an obstacle to their further implementation in the control of diverse Lepidopteran pests, increasing the development costs. Our work points out that cellular defenses are major role blocks to AcMNPV replication in non- and semi-permissive hosts. Therefore a major determinant ofbaculovirus host range is the ability of the virus to effectively counter cellular defenses of host cells. This is exemplified by our findings showing tliat expressing the viral gene Ldhrf-l overcomes global translation arrest in AcMNPV -infected Ld652Y cells. Our data suggests that Ld652Y cells have two anti-viral defense pathways, because they are subject to global translation arrest when infected with AcMNPV carrying a baculovirus apoptotic suppressor (e.g., wild type AcMNPV carryingp35, or recombinant AcMNPV carrying Opiap, Cpiap. or p49 genes) but apoptose when infected with AcMNPV-Iacking a functional apoptotic suppressor. We have yet to elucidate how hrf-l precludes the translation arrest mechanism(s) in AcMNPV-infected Ld652Y cells. Ribosomal profiles of AcMNPV infected Ld652Y cells suggested that translation initiation is a major control point, but we were unable to rule-out a contribution from a block in translation elongation. Phosphorylation of eIF-2a did not appear to playa role in AcMNPV -induced translation arrest. Mutagenesis studies ofhrf-l suggest that a highly acidic domain plays a role in precluding translation arrest. Our findings indicate that translation arrest may be linked to apoptosis either through common sensors of virus infection or as a consequence of late events in the virus life-cycle that occur only if apoptosis is suppressed. ~ AcMNPV replicates poorly in SL2 cells and induces apoptosis. Our studies in AcMNPV - infected SL2ceils led us to conclude that the steady-state levels of lEI (product of the iel gene, major AcMNPV -transactivator and multifunctional protein) relative to those of the immediate early viral protein lEO, playa critical role in regulating the viral infection. By increasing the IEl\IEO ratio we achieved AcMNPV replication in S. littoralis and we were able to isolate recombinant AcMNPV s that replicated efficiently in S. lifforalis cells and larvae. Our data that indicated that AcMNPV - infection may be regulated by an interaction between IE 1 and lED (of previously unknown function). Indeed, we showed that IE 1 associates with lED by using protein "pull down" and immunoprecipitation approaches High steady state levels of "functional" IE 1 resulted in increased expression of the apoptosis suppressor p35 facilitating AcMNPV -replication in SL2 cells. Finally, we determined that lED accelerates the viral infection in AcMNPV -permissive cells. Our results show that expressing viral genes that are able to overcome the insect-pest defense system enable to expand baculovirus host range. Scientifically, this project highlights the need to further study the anti-viral defenses of invertebrates not only to maximi~e the possibilities for manipulating baculovirus genomes, but to better understand the evolutionary underpinnings of the immune systems of vertebrates towards virus infection.
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Sionov, Edward, Nancy Keller i Shiri Barad-Kotler. Mechanisms governing the global regulation of mycotoxin production and pathogenicity by Penicillium expansum in postharvest fruits. United States Department of Agriculture, styczeń 2017. http://dx.doi.org/10.32747/2017.7604292.bard.
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The original objectives of the study, as defined in the approved proposal, are: To characterize the relationship of CreA and LaeA in regulation of P T production To understand how PacC modulates P. expansumpathogenicity on apples To examine if other secondary metabolites are involved in virulence or P. expansumfitness To identify the signaling pathways leading to PAT synthesis Penicilliumexpansum, the causal agent of blue mould rot, is a critical health concern because of the production of the mycotoxinpatulin (PAT) in colonized apple fruit tissue. Although PAT is produced by many Penicilliumspecies, the factors activating its biosynthesis were not clear. This research focused on host and fungal mechanisms of activation of LaeA (the global regulator of secondary metabolism), PacC (the global pH modulator) and CreA (the global carbon catabolite regulator) on PAT synthesis with intention to establish P. expansumas the model system for understanding mycotoxin synthesis in fruits. The overall goal of this proposal is to identify critical host and pathogen factors that mechanistically modulate P. expansumgenes and pathways to control activation of PAT production and virulence in host. Several fungal factors have been correlated with disease development in apples, including the production of PAT, acidification of apple tissue by the fungus, sugar content and the global regulator of secondary metabolism and development, LaeA. An increase in sucrose molarity in the culture medium from 15 to 175 mM negatively regulated laeAexpression and PAT accumulation, but, conversely, increased creAexpression, leading to the hypothesis that CreA could be involved in P. expansumPAT biosynthesis and virulence, possibly through the negative regulation of LaeA. We found evidence for CreAtranscriptional regulation of laeA, but this was not correlated with PAT production either in vitro or in vivo, thus suggesting that CreA regulation of PAT is independent of LaeA. Our finding that sucrose, a key ingredient of apple fruit, regulates PAT synthesis, probably through suppression of laeAexpression, suggests a potential interaction between CreA and LaeA, which may offer control therapies for future study. We have also identified that in addition to PAT gene cluster, CreA regulates other secondary metabolite clusters, including citrinin, andrastin, roquefortine and communesins, during pathogenesis or during normal fungal growth. Following creation of P. expansumpacCknockout strain, we investigated the involvement of the global pH regulator PacC in fungal pathogenicity. We demonstrated that disruption of the pH signaling transcription factor PacC significantly decreased the virulence of P. expansumon deciduous fruits. This phenotype is associated with an impairment in fungal growth, decreased accumulation of gluconic acid and reduced synthesis of pectolytic enzymes. We showed that glucose oxidase- encoding gene, which is essential for gluconic acid production and acidification during fruit colonization, was significantly down regulated in the ΔPepacCmutant, suggesting that gox is PacC- responsive gene. We have provided evidence that deletion of goxgene in P. expansumled to a reduction in virulence toward apple fruits, further indicating that GOX is a virulence factor of P. expansum, and its expression is regulated by PacC. It is also clear from the present data that PacC in P. expansumis a key factor for the biosynthesis of secondary metabolites, such as PAT. On the basis of RNA-sequencing (RNA-seq) analysis and physiological experimentation, the P. expansumΔlaeA, ΔcreAand ΔpacCmutants were unable to successfully colonize apples for a multitude of potential mechanisms including, on the pathogen side, a decreased ability to produce proteolytic enzymes and to acidify the environment and impaired carbon/nitrogen metabolism and, on the host side, an increase in the oxidative defence pathways. Our study defines these global regulatory factors and their downstream signalling pathways as promising targets for the development of strategies to fight against this post-harvest pathogen.
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Doo, Johnny. Unsettled Issues Concerning eVTOL for Rapid-response, On-demand Firefighting. SAE International, sierpień 2021. http://dx.doi.org/10.4271/epr2021017.
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Recent advancements of electric vertical take-off and landing (eVTOL) aircraft have generated significant interest within and beyond the traditional aviation industry, and many novel applications have been identified and are in development. One promising application for these innovative systems is in firefighting, with eVTOL aircraft complementing current firefighting capabilities to help save lives and reduce fire-induced damages. With increased global occurrences and scales of wildfires—not to mention the issues firefighters face during urban and rural firefighting operations daily—eVTOL technology could offer timely, on-demand, and potentially cost-effective aerial mobility capabilities to counter these challenges. Early detection and suppression of wildfires could prevent many fires from becoming large-scale disasters. eVTOL aircraft may not have the capacity of larger aerial assets for firefighting, but targeted suppression, potentially in swarm operations, could be valuable. Most importantly, on-demand aerial extraction of firefighters can be a crucial benefit during wildfire control operations. Aerial firefighter dispatch from local fire stations or vertiports can result in more effective operations, and targeted aerial fire suppression and civilian extraction from high-rise buildings could enhance capabilities significantly. There are some challenges that need to be addressed before the identified capabilities and benefits are realized at scale, including the development of firefighting-specific eVTOL vehicles; sense and avoid capabilities in complex, smoke-inhibited environments; autonomous and remote operating capabilities; charging system compatibility and availability; operator and controller training; dynamic airspace management; and vehicle/fleet logistics and support. Acceptance from both the first-responder community and the general public is also critical for the successful implementation of these new capabilities. The purpose of this report is to identify the benefits and challenges of implementation, as well as some of the potential solutions. Based on the rapid development progress of eVTOL aircraft and infrastructures with proactive community engagement, it is envisioned that these challenges can be addressed soon. NOTE: SAE EDGE™ Research Reports are intended to identify and illuminate key issues in emerging, but still unsettled, technologies of interest to the mobility industry. The goal of SAE EDGE™ Research Reports is to stimulate discussion and work in the hope of promoting and speeding resolution of identified issues. These reports are not intended to resolve the challenges they identify or close any topic to further scrutiny.
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Manulis-Sasson, Shulamit, Christine D. Smart, Isaac Barash, Laura Chalupowicz, Guido Sessa i Thomas J. Burr. Clavibacter michiganensis subsp. michiganensis-tomato interactions: expression and function of virulence factors, plant defense responses and pathogen movement. United States Department of Agriculture, luty 2015. http://dx.doi.org/10.32747/2015.7594405.bard.
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Clavibactermichiganensissubsp. michiganensis(Cmm), the causal agent of bacterial wilt and canker of tomato, is the most destructive bacterial disease of tomato causing substantial economic losses in Israel, the U.S.A. and worldwide. The goal of the project was to unravel the molecular strategies that allow Cmm, a Gram-positive bacterium, to develop a successful infection in tomato. The genome of Cmm contains numerous genes encoding for extracellular serine proteases and cell wall degrading enzymes. The first objective was to elucidate the role of secreted serine proteases in Cmm virulence. Mutants of nine genes encoding serine proteases of 3 different families were tested for their ability to induce wilting, when tomato stems were puncture-inoculated, as compared to blisters formation on leaves, when plants were spray-inoculated. All the mutants showed reduction in wilting and blister formation as compared to the wild type. The chpCmutant displayed the highest reduction, implicating its major role in symptom development. Five mutants of cell wall degrading enzymes and additional genes (i.e. perforin and sortase) caused wilting but were impaired in their ability to form blisters on leaves. These results suggest that Cmm differentially expressed virulence genes according to the site of penetration. Furthermore, we isolated and characterized two Cmmtranscriptional activators, Vatr1 and Vatr2 that regulate the expression of virulence factors, membrane and secreted proteins. The second objective was to determine the effect of bacterial virulence genes on movement of Cmm in tomato plants and identify the routes by which the pathogen contaminates seeds. Using a GFP-labeledCmm we could demonstrate that Cmm extensively colonizes the lumen of xylem vessels and preferentially attaches to spiral secondary wall thickening of the protoxylem and formed biofilm-like structures composed of large bacterial aggregates. Our findings suggest that virulence factors located on the chp/tomAPAI or the plasmids are required for effective movement of the pathogen in tomato and for the formation of cellular aggregates. We constructed a transposon plasmid that can be stably integrated into Cmm chromosome and express GFP, in order to follow movement to the seeds. Field strains from New York that were stably transformed with this construct, could not only access seeds systemically through the xylem, but also externally through tomato fruit lesions, which harbored high intra-and intercellular populations. Active movement and expansion of bacteria into the fruit mesocarp and nearby xylem vessels followed, once the fruit began to ripen. These results highlight the ability of Cmm to invade tomato fruit and seed through multiple entry routes. The third objective was to assess correlation between disease severity and expression levels of Cmm virulence genes and tomato defense genes. The effect of plant age on expression of tomato defense related proteins during Cmm infection was analyzed by qRT-PCR. Five genes out of eleven showed high induction at early stages of infection of plants with 19/20 leaves compared to young plants bearing 7/8 leaves. Previous results showed that Cmm virulence genes were expressed at early stages of infection in young plants compared to older plants. Results of this study suggest that Cmm virulence genes may suppress expression of tomato defense-related genes in young plants allowing effective disease development. The possibility that chpCis involved in suppression of tomato defense genes is currently under investigation by measuring the transcript level of several PR proteins, detected previously in our proteomics study. The fourth objective was to define genome location and stability of virulence genes in Cmm strains. New York isolates were compared to Israeli, Serbian, and NCPPB382 strains. The plasmid profiles of New York isolates were diverse and differed from both Israeli and Serbian strains. PCR analysis indicated that the presence of putative pathogenicity genes varied between isolates and highlighted the ephemeral nature of pathogenicity genes in field populations of Cmm. Results of this project significantly contributed to the understanding of Cmm virulence, its movement within tomato xylem or externally into the seeds, the role of serine proteases in disease development and initiated research on global regulation of Cmm virulence. These results form a basis for developing new strategies to combat wilt and canker disease of tomato.
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Kelly, Luke. Direct and Indirect Impacts of the COVID-19 Pandemic on Women and Girls. Institute of Development Studies (IDS), sierpień 2021. http://dx.doi.org/10.19088/k4d.2021.141.
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This rapid literature review finds that women have been disproportionately affected by Covid-19 in several ways. As the Covid-19 pandemic began, it was widely predicted that women would face worse outcomes than men in many spheres. This was based on evidence of pre-existing inequalities (e.g. the high share of women in informal work) and evidence from earlier disease outbreaks such as Ebola. Evidence from the past year and a half supports the idea that women have been disproportionately affected by Covid-19 in many of the issues investigated for this report. A wide-ranging World Bank review of evidence from April 2020 to April 2021 states that “women often appear to have lost out more than men economically and socially” (Nieves et al., 2021, p. 4). It was not possible to find evidence on the effect of Covid-19 on women’s role in the green economy and the effects of climate change (beyond calls for inclusive green growth), or on gender stereotyping in the media (although there is a small amount of literature on perceptions of women leaders during the pandemic). In all cases, the effect of Covid-19 and measures to suppress it have directly or indirectly continued or worsened pre-existing inequalities. In some instances, Covid-19 has created distinct difficulties for women (e.g. lockdowns and increased domestic violence). This report has found no evidence of Covid-19 improving the position of women in the areas of interest surveyed, beyond possible benefits from working from home for some women in high-income countries; and some suggestions that female leadership during the pandemic may lead to better perceptions of women (Piazza & Diaz, 2020). Studies also point to the intersection of gender with other factors, such as caste and ethnicity, leading to worse outcomes (Chen et al., 2021; Kabeer et al., 2021). In many cases, migrant women and women with disabilities are at an increased disadvantage. The report focuses on evidence from low- and middle-income countries (LMICs) and G7 members. It is not comprehensive but surveys the available evidence focusing on global, regional or synthesis evidence to provide a more representative coverage. It, therefore, does not cover every context or provide any country case studies and overlooks variations in some countries in favour of broader trends.
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Aalto, Juha, i Ari Venäläinen, red. Climate change and forest management affect forest fire risk in Fennoscandia. Finnish Meteorological Institute, czerwiec 2021. http://dx.doi.org/10.35614/isbn.9789523361355.
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Forest and wildland fires are a natural part of ecosystems worldwide, but large fires in particular can cause societal, economic and ecological disruption. Fires are an important source of greenhouse gases and black carbon that can further amplify and accelerate climate change. In recent years, large forest fires in Sweden demonstrate that the issue should also be considered in other parts of Fennoscandia. This final report of the project “Forest fires in Fennoscandia under changing climate and forest cover (IBA ForestFires)” funded by the Ministry for Foreign Affairs of Finland, synthesises current knowledge of the occurrence, monitoring, modelling and suppression of forest fires in Fennoscandia. The report also focuses on elaborating the role of forest fires as a source of black carbon (BC) emissions over the Arctic and discussing the importance of international collaboration in tackling forest fires. The report explains the factors regulating fire ignition, spread and intensity in Fennoscandian conditions. It highlights that the climate in Fennoscandia is characterised by large inter-annual variability, which is reflected in forest fire risk. Here, the majority of forest fires are caused by human activities such as careless handling of fire and ignitions related to forest harvesting. In addition to weather and climate, fuel characteristics in forests influence fire ignition, intensity and spread. In the report, long-term fire statistics are presented for Finland, Sweden and the Republic of Karelia. The statistics indicate that the amount of annually burnt forest has decreased in Fennoscandia. However, with the exception of recent large fires in Sweden, during the past 25 years the annually burnt area and number of fires have been fairly stable, which is mainly due to effective fire mitigation. Land surface models were used to investigate how climate change and forest management can influence forest fires in the future. The simulations were conducted using different regional climate models and greenhouse gas emission scenarios. Simulations, extending to 2100, indicate that forest fire risk is likely to increase over the coming decades. The report also highlights that globally, forest fires are a significant source of BC in the Arctic, having adverse health effects and further amplifying climate warming. However, simulations made using an atmospheric dispersion model indicate that the impact of forest fires in Fennoscandia on the environment and air quality is relatively minor and highly seasonal. Efficient forest fire mitigation requires the development of forest fire detection tools including satellites and drones, high spatial resolution modelling of fire risk and fire spreading that account for detailed terrain and weather information. Moreover, increasing the general preparedness and operational efficiency of firefighting is highly important. Forest fires are a large challenge requiring multidisciplinary research and close cooperation between the various administrative operators, e.g. rescue services, weather services, forest organisations and forest owners is required at both the national and international level.
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Chen, Junping, Zach Adam i Arie Admon. The Role of FtsH11 Protease in Chloroplast Biogenesis and Maintenance at Elevated Temperatures in Model and Crop Plants. United States Department of Agriculture, maj 2013. http://dx.doi.org/10.32747/2013.7699845.bard.
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specific objectives of this proposal were to: 1) determine the location, topology, and oligomerization of FtsH11 protease; 2) identify the substrate/s of FtsH11 and the downstream components involved in maintaining thermostability of chloroplasts; 3) identify new elements involved in FtsH11 protease regulatory network related to HT adaptation processes in chloroplast; 4) Study the role of FtsH11 homologs from crop species in HT tolerance. Background to the topic: HT-tolerant varieties that maintain high photosynthetic efficiency at HT, and cope better with daily and seasonal temperature fluctuations are in great need to alleviate the effect of global warming on food production. Photosynthesis is a very complex process requiring accurate coordination of many complex systems and constant adjustments to the changing environments. Proteolytic activities mediated by various proteases in chloroplast are essential part of this process and critical for maintaining normal chloroplast functions under HT. However, little is known about mechanisms that contribute to adaptation of photosynthetic processes to HT. Our study has shown that a chloroplast-targeted Arabidopsis FtsH11 protease plays an essential and specific role in maintaining thermostability of thylakoids and normal photosynthesis at moderate HT. We hypothesized that FtsH11 homologs recently identified in other plant species might have roles similarly to that of AtFtsH1. Thus, dissecting the underlying mechanisms of FtsH11 in the adaptation mechanisms in chloroplasts to HT stress and other elements involved will aid our effort to produce more agricultural products in less favorable environments. Major conclusions, solutions, achievements - Identified the chloroplast inner envelope membrane localization of FtsH11. - Revealed a specific association of FtsH11 with the a and b subunits of CPN60. - Identified the involvement of ARC6, a protein coordinates chloroplast division machineries in plants, in FtsH11 mediated HT adaptation process in chloroplast. -Reveal possible association of a polyribonucleotide nucleotidyltransferase (cpPNPase), coded by At3G03710, with FtsH11 mediated HT adaptation process in chloroplast. - Mapped 4 additional loci in FtsH11 mediated HT adaptation network in chloroplast. - Demonstrated importance of the proteolytic activity of FtsH11 for thermotolerance, in addition to the ATPase activity. - Demonstrated a conserved role of plant FtsH11 proteases in chloroplast biogenesis and in maintaining structural and functional thermostability of chloroplast at elevated temperatures. Implications, both scientific and agricultural:Three different components interacting with FtsH11 were identified during the course of this study. At present, it is not known whether these proteins are directly involved in FtsH11mediated thermotolerance network in chloroplast and/or how these elements are interrelated. Studies aiming to connect the dot among biological functions of these networks are underway in both labs. Nevertheless, in bacteria where it was first studied, FtsH functions in heat shock response by regulating transcription level of σ32, a heat chock factor regulates HSPsexpression. FtsH also involves in control of biosynthesis of membrane components and quality control of membrane proteins etc. In plants, both Arc 6 and CPN60 identified in this study are essential in chloroplast division and developments as mutation of either one impairs chloroplast division in Arabidopsis. The facts that we have found the specific association of both α and β CPN60 with FtsH11 protein biochemically, the suppression/ enhancement of ftsh11 thermosensitive phenotype by arc6 /pnp allele genetically, implicate inter-connection of these networks via FtsH11 mediated network(s) in regulating the dynamic adaptation processes of chloroplast to temperature increases at transcriptional, translational and post-translational levels. The conserved role of FtsH11 proteases in maintaining thermostability of chloroplast at HT demonstrated here provides a foundation for improving crop photosynthetic performance at high temperatures.
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Lewis, Dustin, i Naz Modirzadeh. Taking into Account the Potential Effects of Counterterrorism Measures on Humanitarian and Medical Activities: Elements of an Analytical Framework for States Grounded in Respect for International Law. Harvard Law School Program on International Law and Armed Conflict, maj 2021. http://dx.doi.org/10.54813/qbot8406.
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For at least a decade, States, humanitarian bodies, and civil-society actors have raised concerns about how certain counterterrorism measures can prevent or impede humanitarian and medical activities in armed conflicts. In 2019, the issue drew the attention of the world’s preeminent body charged with maintaining or restoring international peace and security: the United Nations Security Council. In two resolutions — Resolution 2462 (2019) and Resolution 2482 (2019) — adopted that year, the Security Council urged States to take into account the potential effects of certain counterterrorism measures on exclusively humanitarian activities, including medical activities, that are carried out by impartial humanitarian actors in a manner consistent with international humanitarian law (IHL). By implicitly recognizing that measures adopted to achieve one policy objective (countering terrorism) can impair or prevent another policy objective (safeguarding humanitarian and medical activities), the Security Council elevated taking into account the potential effects of certain counterterrorism measures on exclusively humanitarian activities to an issue implicating international peace and security. In this legal briefing, we aim to support the development of an analytical framework through which a State may seek to devise and administer a system to take into account the potential effects of counterterrorism measures on humanitarian and medical activities. Our primary intended audience includes the people involved in creating or administering a “take into account” system and in developing relevant laws and policies. Our analysis zooms in on Resolution 2462 (2019) and Resolution 2482 (2019) and focuses on grounding the framework in respect for international law, notably the U.N. Charter and IHL. In section 1, we introduce the impetus, objectives, and structure of the briefing. In our view, a thorough legal analysis of the relevant resolutions in their wider context is a crucial element to laying the conditions conducive to the development and administration of an effective “take into account” system. Further, the stakes and timeliness of the issue, the Security Council’s implicit recognition of a potential tension between measures adopted to achieve different policy objectives, and the relatively scant salient direct practice and scholarship on elements pertinent to “take into account” systems also compelled us to engage in original legal analysis, with a focus on public international law and IHL. In section 2, as a primer for readers unfamiliar with the core issues, we briefly outline humanitarian and medical activities and counterterrorism measures. Then we highlight a range of possible effects of the latter on the former. Concerning armed conflict, humanitarian activities aim primarily to provide relief to and protection for people affected by the conflict whose needs are unmet, whereas medical activities aim primarily to provide care for wounded and sick persons, including the enemy. Meanwhile, for at least several decades, States have sought to prevent and suppress acts of terrorism and punish those who commit, attempt to commit, or otherwise support acts of terrorism. Under the rubric of countering terrorism, States have taken an increasingly broad and diverse array of actions at the global, regional, and national levels. A growing body of qualitative and quantitative evidence documents how certain measures designed and applied to counter terrorism can impede or prevent humanitarian and medical activities in armed conflicts. In a nutshell, counterterrorism measures may lead to diminished or complete lack of access by humanitarian and medical actors to the persons affected by an armed conflict that is also characterized as a counterterrorism context, or those measures may adversely affect the scope, amount, or quality of humanitarian and medical services provided to such persons. The diverse array of detrimental effects of certain counterterrorism measures on humanitarian and medical activities may be grouped into several cross-cutting categories, including operational, financial, security, legal, and reputational effects. In section 3, we explain some of the key legal aspects of humanitarian and medical activities and counterterrorism measures. States have developed IHL as the primary body of international law applicable to acts and omissions connected with an armed conflict. IHL lays down several rights and obligations relating to a broad spectrum of humanitarian and medical activities pertaining to armed conflicts. A violation of an applicable IHL provision related to humanitarian or medical activities may engage the international legal responsibility of a State or an individual. Meanwhile, at the international level, there is no single, comprehensive body of counterterrorism laws. However, States have developed a collection of treaties to pursue specific anti-terrorism objectives. Further, for its part, the Security Council has assumed an increasingly prominent role in countering terrorism, including by adopting decisions that U.N. Member States must accept and carry out under the U.N. Charter. Some counterterrorism measures are designed and applied in a manner that implicitly or expressly “carves out” particular safeguards — typically in the form of limited exceptions or exemptions — for certain humanitarian or medical activities or actors. Yet most counterterrorism measures do not include such safeguards. In section 4, which constitutes the bulk of our original legal analysis, we closely evaluate the two resolutions in which the Security Council urged States to take into account the effects of (certain) counterterrorism measures on humanitarian and medical activities. We set the stage by summarizing some aspects of the legal relations between Security Council acts and IHL provisions pertaining to humanitarian and medical activities. We then analyze the status, consequences, and content of several substantive elements of the resolutions and what they may entail for States seeking to counter terrorism and safeguard humanitarian and medical activities. Among the elements that we evaluate are: the Security Council’s new notion of a prohibited financial “benefit” for terrorists as it may relate to humanitarian and medical activities; the Council’s demand that States comply with IHL obligations while countering terrorism; and the constituent parts of the Council’s notion of a “take into account” system. In section 5, we set out some potential elements of an analytical framework through which a State may seek to develop and administer its “take into account” system in line with Resolution 2462 (2019) and Resolution 2482 (2019). In terms of its object and purpose, a “take into account” system may aim to secure respect for international law, notably the U.N. Charter and IHL pertaining to humanitarian and medical activities. In addition, the system may seek to safeguard humanitarian and medical activities in armed conflicts that also qualify as counterterrorism contexts. We also identify two sets of preconditions arguably necessary for a State to anticipate and address relevant potential effects through the development and execution of its “take into account” system. Finally, we suggest three sets of attributes that a “take into account” system may need to embody to achieve its aims: utilizing a State-wide approach, focusing on potential effects, and including default principles and rules to help guide implementation. In section 6, we briefly conclude. In our view, jointly pursuing the policy objectives of countering terrorism and safeguarding humanitarian and medical activities presents several opportunities, challenges, and complexities. International law does not necessarily provide ready-made answers to all of the difficult questions in this area. Yet devising and executing a “take into account” system provides a State significant opportunities to safeguard humanitarian and medical activities and counter terrorism while securing greater respect for international law.
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Monetary Policy Report - October 2020. Banco de la República de Colombia, luty 2021. http://dx.doi.org/10.32468/inf-pol-mont-eng.tr4.-2020.
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Recent data suggest that the technical staff’s appraisals of the condition and development of economic activity, inflation and the labor market have been in line with current trends, marked by a decline in demand and the persistence of ample excess productive capacity. A significant projected fall in output materialized in the second quarter, contributing to a decline in inflation below the 3% target and reflected in a significant deterioration of the labor market. A slow recovery in output and employment is expected to continue for the remainder of 2020 and into next year, alongside growing inflation that should remain below the target. The Colombian economy is likely to undergo a significant recession in 2020 (GDP contraction of 7.6%), though this may be less severe than projected in the previous report (-8.5%). Output is expected to have begun a slow recovery in the second half of this year, though it is not projected to return to pre-pandemic levels in 2021 amid significant global uncertainty. The output decline in the first half of 2020 was less severe than anticipated, thanks to an upward revision in first-quarter GDP and a smaller contraction in the second quarter (-15.5%) than had been projected (-16.5%). Available economic indicators suggest an annual decline in GDP in the third quarter of around 9%. No significant acceleration of COVID-19 cases that would imply a tightening of social distancing measures is presumed for the remainder of this year or in 2021. In that context, a gradual opening of the economy would be expected to continue, with supply in sectors that have been most affected by the pandemic recovering slowly as restrictions on economic activity continue to be relaxed. On the spending side, an improvement in consumer confidence, suppressed demand for goods and services, low interest rates, and higher expected levels of foreign demand should contribute to a recovery in output. A low base of comparison would also help explain the expected increase in GDP in 2021. Based on the conditions laid out above, economic growth in 2020 is expected to be between -9% and -6.5%, with a central value of -7.6%. Growth in 2021 is projected to be between 3% and 7%, with a central value of 4.6% (Graph 1.1). Upward revisions compared to the July report take into account a lower-than-expected fall in first-semester growth and a somewhat faster recovery in the third quarter in some sectors. The forecast intervals for 2020 and 2021 growth tightened somewhat but continue to reflect a high degree of uncertainty over theevolution of the pandemic, the easures required to deal with it, and their effects on global and domestic economic activity.
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Monetary Policy Report - April 2022. Banco de la República, czerwiec 2022. http://dx.doi.org/10.32468/inf-pol-mont-eng.tr2-2022.
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Macroeconomic summary Annual inflation continued to rise in the first quarter (8.5%) and again outpaced both market expectations and the technical staff’s projections. Inflation in major consumer price index (CPI) baskets has accelerated year-to-date, rising in March at an annual rate above 3%. Food prices (25.4%) continued to contribute most to rising inflation, mainly affected by a deterioration in external supply and rising costs of agricultural inputs. Increases in transportation prices and in some utility rates (energy and gas) can explain the acceleration in regulated items prices (8.3%). For its part, the increase in inflation excluding food and regulated items (4.5%) would be the result of shocks in supply and external costs that have been more persistent than expected, the effects of indexation, accumulated inflationary pressures from the exchange rate, and a faster-than-anticipated tightening of excess productive capacity. Within the basket excluding food and regulated items, external inflationary pressures have meaningfully impacted on goods prices (6.4%), which have been accelerating since the last quarter of 2021. Annual growth in services prices (3.8%) above the target rate is due primarily to food away from home (14.1%), which was affected by significant increases in food and utilities prices and by a rise in the legal monthly minimum wage. Housing rentals and other services prices also increased, though at rates below 3%. Forecast and expected inflation have increased and remain above the target rate, partly due to external pressures (prices and costs) that have been more persistent than projected in the January report (Graphs 1.1 and 1.2). Russia’s invasion of Ukraine accentuated inflationary pressures, particularly on international prices for certain agricultural goods and inputs, energy, and oil. The current inflation projection assumes international food prices will increase through the middle of this year, then remain high and relatively stable for the remainder of 2022. Recovery in the perishable food supply is forecast to be less dynamic than previously anticipated due to high agricultural input prices. Oil prices should begin to recede starting in the second half of the year, but from higher levels than those presented in the previous report. Given the above, higher forecast inflation could accentuate indexation effects and increase inflation expectations. The reversion of a rebate on value-added tax (VAT) applied to cleaning and hygiene products, alongside the end of Colombia’s COVID-19 health emergency, could increase the prices of those goods. The elimination of excess productive capacity on the forecast horizon, with an output gap close to zero and somewhat higher than projected in January, is another factor to consider. As a consequence, annual inflation is expected to remain at high levels through June. Inflation should then decline, though at a slower pace than projected in the previous report. The adjustment process of the monetary policy rate wouldcontribute to pushing inflation and its expectations toward the target on the forecast horizon. Year-end inflation for 2022 is expected to be around 7.1%, declining to 4.8% in 2023. Economic activity again outperformed expectations. The technical staff’s growth forecast for 2022 has been revised upward from 4.3% to 5% (Graph 1.3). Output increased more than expected in annual terms in the fourth quarter of 2021 (10.7%), driven by domestic demand that came primarily because of private consumption above pre-pandemic levels. Investment also registered a significant recovery without returning to 2019 levels and with mixed performance by component. The trade deficit increased, with significant growth in imports similar to that for exports. The economic tracking indicator (ISE) for January and February suggested that firstquarter output would be higher than previously expected and that the positive demand shock observed at the end of 2021 could be fading slower than anticipated. Imports in consumer goods, retail sales figures, real restaurant and hotel income, and credit card purchases suggest that household spending continues to be dynamic, with levels similar to those registered at the end of 2021. Project launch and housing starts figures and capital goods import data suggest that investment also continues to recover but would remain below pre-pandemic levels. Consumption growth is expected to decelerate over the year from high levels reached over the last two quarters. This would come amid tighter domestic and external financial conditions, the exhaustion of suppressed demand, and a deterioration of available household income due to increased inflation. Investment is expected to continue to recover, while the trade deficit should tighten alongside high oil and other export commodity prices. Given all of the above, first-quarter economic growth is now expected to be 7.2% (previously 5.2%) and 5.0% for 2022 as a whole (previously 4.3%). Output growth would continue to moderate in 2023 (2.9%, previously 3.1%), converging similar to long-term rates. The technical staff’s revised projections suggest that the output gap would remain at levels close to zero on the forecast horizon but be tighter than forecast in January (Graph 1.4). These estimates continue to be affected by significant uncertainty associated with geopolitical tensions, external financial conditions, Colombia’s electoral cycle, and the COVID-19 pandemic. External demand is now projected to grow at a slower pace than previously expected amid increased global inflationary pressures, high oil prices, and tighter international financial conditions than forecast in January. The Russian invasion of Ukraine and its inflationary effects on prices for oil and certain agricultural goods and inputs accentuated existing global inflationary pressures originating in supply restrictions and increased international costs. A decline in the supply of Russian oil, low inventory levels, and continued production limits on behalf of the Organization of Petroleum Exporting Countries and its allies (OPEC+) can explain increased projected oil prices for 2022 (USD 100.8/barrel, previously USD 75.3) and 2023 (USD 86.8/barrel, previously USD 71.2). The forecast trajectory for the U.S. Federal Reserve (Fed) interest rate has increased for this and next year to reflect higher real and expected inflation and positive performance in the labormarket and economic activity. The normalization of monetary policy in various developed and emerging market economies, more persistent supply and cost shocks, and outbreaks of COVID-19 in some Asian countries contributed to a reduction in the average growth outlook for Colombia’s trade partners for 2022 (2.8%, previously 3.3%) and 2023 (2.4%, previously 2.6%). In this context, the projected path for Colombia’s risk premium increased, partly due to increased geopolitical global tensions, less expansionary monetary policy in the United States, an increase in perceived risk for emerging markets, and domestic factors such as accumulated macroeconomic imbalances and political uncertainty. Given all the above, external financial conditions are tighter than projected in January report. External forecasts and their impact on Colombia’s macroeconomic scenario continue to be affected by considerable uncertainty, given the unpredictability of both the conflict between Russia and Ukraine and the pandemic. The current macroeconomic scenario, characterized by high real inflation levels, forecast and expected inflation above 3%, and an output gap close to zero, suggests an increased risk of inflation expectations becoming unanchored. This scenario offers very limited space for expansionary monetary policy. Domestic demand has been more dynamic than projected in the January report and excess productive capacity would have tightened more quickly than anticipated. Headline and core inflation rose above expectations, reflecting more persistent and important external shocks on supply and costs. The Russian invasion of Ukraine accentuated supply restrictions and pressures on international costs. This partly explains the increase in the inflation forecast trajectory to levels above the target in the next two years. Inflation expectations increased again and are above 3%. All of this increased the risk of inflation expectations becoming unanchored and could generate indexation effects that move inflation still further from the target rate. This macroeconomic context also implies reduced space for expansionary monetary policy. 1.2 Monetary policy decision Banco de la República’s board of directors (BDBR) continues to adjust its monetary policy. In its meetings both in March and April of 2022, it decided by majority to increase the monetary policy rate by 100 basis points, bringing it to 6.0% (Graph 1.5).