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Letteratura scientifica selezionata sul tema "Degraders"

Autore: Grafiati

Pubblicato: 25 gennaio 2025

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Articoli di riviste sul tema "Degraders"

Sitrin, Jonathan, Lisa Marshall, Hai Tran, Kenneth Ng, Kimberly Hoi, Josef Gramespacher, Zhong Huang et al. "Abstract 1866: Discovery of mutation-independent EGFR degrading bispecific antibodies that suppress tumor growth in preclinical tumor models". Cancer Research 84, n. 6_Supplement (22 marzo 2024): 1866. http://dx.doi.org/10.1158/1538-7445.am2024-1866.

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Abstract Extracellular targeted protein degradation (eTPD) has emerged as a promising new drug modality focused on targeted elimination of extracellular and transmembrane proteins. In contrast to intracellular protein degraders, such as proteolysis targeting chimeras (PROTACs) and molecular glues which require ubiquitin-proteosome cellular degradation pathways, extracellular protein degraders can additionally harness endosomal-lysosomal protein degradation. Two recently published examples of extracellular protein degraders include AbTACs (antibody-based PROTAC) which co-engage a protein of interest (POI) and transmembrane E3 ligases, and KineTACs (cytokine receptor-targeting chimeras) which utilize endogenous cytokine receptors to degrade extracellular POIs. These bispecific antibody degrader platforms not only have advantageous pharmacological and drug-like manufacturing properties, but can also be engineered for tissue-specificity and to address multiple complementary targets, with the goal of increased efficacy and decreased toxicity. To that end, we have greatly expanded the extracellular degrader repertoire beyond AbTACs and KineTACs, with a novel bispecific antibody degrader platform called TrainTACs (tissue receptor antigen internalization targeting chimeras). To demonstrate the potential of this novel extracellular degrading platform, we developed degraders for the canonical receptor tyrosine kinase epidermal growth factor receptor (EGFR). EGFR is an oncogenic driver, that has been clinically validated in lung, colorectal and head and neck cancers, but patient benefit has been limited by treatment-related acquired resistance mutations and on-target/off-tumor dose-limiting toxicities. The potential of our TrainTACs, AbTACs and KineTACs to overcome the limitations of current therapeutic modalities was assessed. Gene expression profiles from tumor and normal tissues were evaluated to identify potential degraders co-expressed with EGFR in tumors. More than 70 unique bispecific antibody constructs spanning 20 receptors were generated and screened in tumor cell-based assays to evaluate EGFR antagonism, internalization, and degradation. TrainTACs, AbTACs and KineTACs degraded EGFR in multiple tumor cell lines covering a range of EGFR mutations. Degradation of EGFR led to deep inhibition of EGFR signaling, robust inhibitory effects on tumor spheroids, and in xenograft mouse tumor models. In conclusion, eTPD represents a promising new drug modality, and TrainTACs, AbTACs and KineTACs have expanded the toolbox of extracellular targeted protein degraders that can be utilized in a target-, tissue- and disease-specific manner. Citation Format: Jonathan Sitrin, Lisa Marshall, Hai Tran, Kenneth Ng, Kimberly Hoi, Josef Gramespacher, Zhong Huang, Andy Goodrich, Filomena Housley, May Dayao, Man-Tzu Wang, Katarina Pance, Aleysha Chen, Kevin Carlin, Lichao Zhang, James Lee, Rami Hannoush, Ken Flanagan, Maia Vinogradova, Isaac Rondon, Shyra Gardai. Discovery of mutation-independent EGFR degrading bispecific antibodies that suppress tumor growth in preclinical tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1866.

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He, Tongchen, Caleb Cheng, Abhijit Parolia, Alex Hopkins, Yuanyuan Qiao, Lanbo Xiao e Arul Chinnaiyan. "Abstract 1685: Overcoming acquired resistance to PROTAC degraders". Cancer Research 83, n. 7_Supplement (4 aprile 2023): 1685. http://dx.doi.org/10.1158/1538-7445.am2023-1685.

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Abstract Background: Proteolysis-targeting chimera (PROTAC) technology has been widely investigated for cancer treatment and there have been several PROTAC degrader-based drugs used for clinical trials in the past few years. PROTAC degraders are able to target crucial proteins traditionally thought to be “undruggable”, such as transcriptional factors. Hence, there is increasing interest in these drugs due to their highly efficacy and low off-target toxicity. However, upon further investigation, it has been found that after a period of treatment with PROTAC degraders, cancer cells can acquire resistance to these compounds. Thus, it is of increasing importance to figure out the mechanisms of the resistance and to overcome the acquired resistance to these PROTAC degraders. In our study, we classified resistance mechanisms of prostate cancer cells to PROTAC degraders into two classes and identified factors that can induce them to preferentially develop specific resistance mechanisms. Methods and Results: AU-15330 is a PROTAC that specifically degrades the subunits (BRG1, PBRM1, BRM) of SWI/SNF complex. We treated 22rv1, a prostate cancer cell line, with different AU-15330 concentrations over a month to establish AU-15330-resistant cell lines. Whole exome sequencing (WES) analysis of these resistant cell lines found that the resistant cell lines that were developed through high-dose (1uM) AU-15330 treatment acquired multiple point mutations within or adjacent to the AU-15330 targeting bromodomain of BRG1. However, BRG1 point mutations were absent in the resistant cell lines that developed through lower concentration of AU-15330 treatment (100nM). Instead, RNA-seq analysis revealed that ABCB1 (also known as Multidrug Resistance Protein 1) expression was upregulated in cells that developed resistance to AU-15330 at 100nM. This was further confirmed by Western blot and qPCR. Next, we overexpressed ABCB1 in LNCaP and 22RV1, and found that overexpression of ABCB1 indeed made prostate cancer cells resistant to AU15330. In addition, we tested with several different potent PROTAC degraders (ARD616, ZBC260, etc) in ABCB1-expressing AU-15530 resistant cells, and found the ABCB1 expression drove the cells to become resistant to all tested PROATC degraders compared to the parental cells. Lastly, we demonstrated that Zosuquidar, an ABCB1 inhibitor, can overcome the ABCB1-mediated resistance to AU-15330 and other PROTAC degraders, suggesting that inhibiting ABCB1 might be a direct and effective strategy to restore PROTAC degrader’s potency when ABCB1-mediated drug resistance is developed. Conclusion: Our study found that the mechanisms of resistance of PROTAC degraders can vary and may be dependent on drug concentrations. Such concepts may inform future clinical decision-making regarding drug dosing. Citation Format: Tongchen He, Caleb Cheng, Abhijit Parolia, Alex Hopkins, Yuanyuan Qiao, Lanbo Xiao, Arul Chinnaiyan. Overcoming acquired resistance to PROTAC degraders [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1685.

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Valinciute, Gintvile, Lorenz Eing, Jeffrey Mihalic, Colleen E. Casey, Hua Tian, Bikash Adhikari, Cristiana Guiducci et al. "OTHR-02. CHIMERIC AURORA A KINASE (AURKA) DEGRADERS EFFICIENTLY TARGET N-MYC". Neuro-Oncology 25, Supplement_1 (1 giugno 2023): i73—i74. http://dx.doi.org/10.1093/neuonc/noad073.284.

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Abstract MYC family proteins are primary drivers of oncogenic processes in a variety of cancer histologies. N-myc overexpression and amplification induce aggressive pediatric cancers, the most common of which are solid extracranial tumors in children (neuroblastoma, NB) and malignant pediatric CNS tumors (medulloblastoma, MB). Due to the oncogenic addiction observed in these tumor types, N-myc is considered an attractive therapeutic target. However, direct small molecule targeting of N-myc remains technically challenging. Alternative approaches to target this pathway include inhibiting proteins thought to stabilize N-myc, such as Aurora A kinase (AURKA). While inhibition of AURKA was found to be effective in preclinical tumor studies, no AURKA inhibitors have been approved for clinical use due to a lack of efficacy. Here, we aim to develop chimeric degrader molecules suitable for preclinical and clinical use that degrade AURKA and concomitantly reduce N-myc levels. We used automated solid-phase synthesis to generate a library of >1000 chimeric degraders using derivatives of six known AURKA ligands (Series 1-6). Due to the limitations of using N-myc-driven MB cells in vitro, we employed NB cells as the proof-of-concept model. While the degraders based on five of the ligands showed efficient AURKA degradation, only degraders based on series 3 and 6 could also diminish N-myc. Selected series were further characterized in pharmacokinetic and pharmacodynamic experiments using NB tumor xenografts implanted in the flank in CD1-nude mice. In summary, chimeric degraders based on two individual AURKA ligands efficiently degraded AURKA and N-myc in vitro and in vivo, providing the foundation for further development of novel therapies for patients with N-myc-driven cancers. Further studies will focus on assessing antitumor properties of lead candidates in NB and patient-derived orthotopic MB xenograft models.

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Hu, Chenlin, Yanxia Zuo, Liang Peng, Nanqin Gan e Lirong Song. "Widespread Distribution and Adaptive Degradation of Microcystin Degrader (mlr-Genotype) in Lake Taihu, China". Toxins 13, n. 12 (3 dicembre 2021): 864. http://dx.doi.org/10.3390/toxins13120864.

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Microbial degradation is an important route for removing environmental microcystins (MCs). Here, we investigated the ecological distribution of microcystin degraders (mlr-genotype), and the relationship between the substrate specificity of the microcystin degrader and the profile of microcystin congener production in the habitat. We showed that microcystin degraders were widely distributed and closely associated with Microcystis abundance in Lake Taihu, China. We characterized an indigenous degrader, Sphingopyxis N5 in the northern Lake Taihu, and it metabolized six microcystin congeners in increasing order (RR > LR > YR > LA > LF and LW). Such a substrate-specificity pattern was congruent to the order of the dominance levels of these congeners in northern Lake Taihu. Furthermore, a meta-analysis on global microcystin degraders revealed that the substrate-specificity patterns varied geographically, but generally matched the profiles of microcystin congener production in the degrader habitats, and the indigenous degrader typically metabolized well the dominant MC congeners, but not the rare congeners in the habitat. This highlighted the phenotypic congruence between microcystin production and degradation in natural environments. We theorize that such congruence resulted from the metabolic adaptation of the indigenous degrader to the local microcystin congeners. Under the nutrient microcystin selection, the degraders might have evolved to better exploit the locally dominant congeners. This study provided the novel insight into the ecological distribution and adaptive degradation of microcystin degraders.

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Abbineni, Chandrasekhar, Kiran Aithal, Leena Khare, Sandeep Dukare V, Bilash Kuila, Megha Goyal, Khaji Abdul Rawoof et al. "Abstract A046: Identification of paralog selective degraders of SMARCA2 and SMARCA4 for treatment of various cancers". Molecular Cancer Therapeutics 22, n. 12_Supplement (1 dicembre 2023): A046. http://dx.doi.org/10.1158/1535-7163.targ-23-a046.

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Abstract Background: The BAF (SWI/SNF) chromatin remodeling complex comprises of two mutually exclusive ATPases, SMARCA2 (BRM) and SMARCA4 (BRG1), that affect the mobilization and positioning of nucleosomes on DNA and thereby regulate important cellular functions including transcription, DNA recombination, DNA repair and chromosome decatenation during mitosis. SMARCA4 is frequently overexpressed in several types of cancers. Overexpression has been linked to increased proliferation and survival, as well as aggressive tumors and poor prognosis. SMARCA4 knockdown in these tumors led to inhibition of proliferation and increased sensitivity to known chemotherapeutic agents, supporting the validity of targeting SMARCA4. Further, genetic silencing studies have established that the oncogenic activity of tumors lacking SMARCA4 is primarily driven by its paralog SMARCA2 containing residual SWI/SNF complex, suggesting the importance of targeting SMARCA2. Considering this well-established biological rationale, selective inhibition/degradation of either of these proteins should be very useful in precision oncology to achieve immense therapeutic benefit. Here we report selective degraders targeting either SMARCA4 or SMARCA2 that demonstrate distinct cellular phenotype. Methods and Results: As part of the initial design plan, selective SMARCA2/4 Bromodomain inhibitors and specific ligands of several E3 ligases were chosen to arrive at different degrader designs. A choice of linkers and different exit vectors were considered to construct a variety of heterobifunctional as well as monovalent degrader molecules. Our proprietary ternary complex modeling algorithm, ALMOND (ALgorithm for MOdeling Neosubstrate Degraders) helped in prioritizing the designs. Shortlisted compounds were synthesized and profiled in multiple cellular assays to understand their degradation potential. Several compounds that potently degrade either SMARCA2 or SMARCA4 selectively were identified. These compounds have shown distinct phenotype depending on the lineage as well as SMARCA2 and SMARCA4 status of the cell lines. As expected, SMARCA2 selective degraders showed exquisite sensitivity to SMARCA4 mutant cell lines (SK-MEL-5 & RERF-LC-A1 etc), whereas SMARCA4 selective degraders showed a distinct cellular sensitivity profile. Potent and selective compounds are being optimized further for their pharmacokinetic properties. Conclusions: Highly potent and selective degraders of either SMARCA2 or SMARCA4 were identified. While selective SMARCA2 degraders have been reported in the literature, to the best of our knowledge, no SMARCA4 selective degrader has been reported so far. Distinct cellular selectivity of these paralog selective degraders supports their further optimization towards advancing them to clinical trials. Citation Format: Chandrasekhar Abbineni, Kiran Aithal, Leena Khare, Sandeep Dukare V, Bilash Kuila, Megha Goyal, Khaji Abdul Rawoof, Dhaytadak Bhagwan Mahadeo, Bhagya M S Kumar, Premkumar M, Swetangini Sahu, Suraj T Gore, Lavanya Krishna N, Charamanna KB, Gopinath CH, Samiulla D S, Subhendu Mukherjee, Thomas Antony, Sanjeev Giri, Shekar Chelur, Kavitha Nellore, Girish Daginakatte, Murali Ramachandra, Susanta Samajdar. Identification of paralog selective degraders of SMARCA2 and SMARCA4 for treatment of various cancers [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A046.

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Uitdehaag, Joost C., Jos e Man, Michelle Muller, Freek an Cauter, Sander an Gemert, Milan Hoffmann, Yvonne G. an Mil et al. "Abstract 5814: EPriL macrocycles as a platform for the rapid generation of effective kinase degrader antibody conjugates (DACs)". Cancer Research 84, n. 6_Supplement (22 marzo 2024): 5814. http://dx.doi.org/10.1158/1538-7445.am2024-5814.

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Abstract The therapeutic success of antibody drug conjugates (ADCs) drives a continuous search for novel payloads that can increase therapeutic window and thereby widen the applications for ADCs. Recently, heterobifunctional degraders have gained great interest as payloads, and degrader antibody conjugates (DACs) are seen as a novel therapeutic modality. Heterobifunctional degraders consist of a small molecule ligand that binds a target (protein of interest or POI), a spacer and an E3 ligase ligand, which can catalyze target degradation. Owing to their catalytic activity, degraders can have better potency than the equivalent inhibitors, making them suitable as ADC payload [1]. Degrader payloads can target a wider variety of mechanisms than classic payloads, which use the same antitumor strategies as chemotherapy, such as tubulin binding or topoisomerase inhibition. Since many FDA-approved targeted therapies are based on the inhibition of protein kinases, we investigated degraders of these kinases as DAC payloads. Kinase DACs could bring enhanced targeting and therefore better therapeutic window to a field where classic ADC payloads have often shown substantial toxicities. As many heterobifunctional degraders show poor cell membrane penetration, their inhibitory potential could be increased as part of a DAC, where endocytic uptake is followed by intracellular release of the degrader payload. To identify kinase degrader payloads, we present a workflow based on a platform called Energetically Privileged Ligands (EPriLs). EPriLs are macrocycle scaffolds that bind non-covalently in the kinase ATP pocket. Their unique binding mode avoids contacts with amino acid positions where resistance to kinase inhibitors frequently occurs. EPriL macrocycles can be decorated appropriately to rationally design specific inhibitors for many therapeutically relevant kinases, and provide synthetic handles to couple them to VHL or CRBN ligands to generate effective kinase degraders. Here we describe how EPriL kinase degraders can be developed into effective DACs, using consecutive libraries of EPriL ligands, spacers, E3 ligase ligands and linkers. First, suitable degraders are identified, based on rapid and deep target degradation and potent antiproliferative activity on target cell lines. Degraders are then transformed into maleimide-linked degraders using convenient attachment of enzymatically cleavable linkers. In a medium throughput fashion, these maleimides are coupled to antibodies to generate DACs, which are tested for stability and biological potency. Applying this workflow to various well-validated kinase targets in oncology resulted in a promising kinase targeting DAC with favorable ADME properties, clear potentiation compared to the parent degrader, and increased selectivity for tumor cell lines. 1] Dragovich et al., Chem. Soc. Rev. (2022) 51, 3886-3897. Citation Format: Joost C. Uitdehaag, Jos e Man, Michelle Muller, Freek an Cauter, Sander an Gemert, Milan Hoffmann, Yvonne G. an Mil, Winfried R. Mulder, Martine B. Prinsen, Jan Gerard Sterrenburg, Diep Vu, Joeri e Wit, Erik Ensing, Rogier C. Buijsman. EPriL macrocycles as a platform for the rapid generation of effective kinase degrader antibody conjugates (DACs) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5814.

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Gao, Yang, Baishan Jiang, Hellen Kim, Jianwei Che, Katherine Donovan, John Hatcher, Fidel Huerta et al. "Abstract 3426: Catalytic degraders effectively address kinase site mutations in EML-ALK oncogenic fusions". Cancer Research 83, n. 7_Supplement (4 aprile 2023): 3426. http://dx.doi.org/10.1158/1538-7445.am2023-3426.

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Abstract Heterobifunctional degraders, known as proteolysis targeting chimeras (PROTACs), is an emerging modality for drug discovery, and theoretically possess catalytic mode-of-action, yet few studies have either confirmed or exploited this potential advantage of event-driven pharmacology. Degraders of oncogenic EML4-ALK fusions were developed by conjugating ALK inhibitors to cereblon ligands guided by computational models. To study the sub-stoichiometric capacity of the degrader molecules, simultaneous optimization of pharmacology and compound properties using ternary complex modeling and physicochemical considerations yielded multiple catalytic degraders that were more resilient to clinically relevant ATP-binding site mutations than parental kinase inhibitor drugs. Using HiBiT assay to assess the target degradation and NanoBRET for target occupancy, we illustrated the concept of catalytic degradation of EML4-ALK. Our strategy culminated in the design of the orally bioavailable derivative CPD-1224 that avoided hemolysis (a feature of detergent-like PROTACs), degraded the otherwise recalcitrant compounded mutant L1196M/G1202R in vivo, and commensurately slowed tumor growth, while the third generation ALK inhibitor drug lorlatinib had no effect. These results validate our original therapeutic hypothesis by exemplifying opportunities for catalytic degraders to proactively address binding site resistant mutations in cancer. Citation Format: Yang Gao, Baishan Jiang, Hellen Kim, Jianwei Che, Katherine Donovan, John Hatcher, Fidel Huerta, Nicholas Kwiatkowski, Yingpeng Liu, Peter Liuni, Rebecca J. Metivier, Vineeth Murali, Radosław Nowak, Tinghu Zhang, Eric Fischer, Nathanael Gray, Lyn Jones. Catalytic degraders effectively address kinase site mutations in EML-ALK oncogenic fusions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3426.

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Bouvier, Corentin, Rachel Lawrence, Francesca Cavallo, Wendy Xolalpa, Allan Jordan, Roland Hjerpe e Manuel S. Rodriguez. "Breaking Bad Proteins—Discovery Approaches and the Road to Clinic for Degraders". Cells 13, n. 7 (26 marzo 2024): 578. http://dx.doi.org/10.3390/cells13070578.

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Proteolysis-targeting chimeras (PROTACs) describe compounds that bind to and induce degradation of a target by simultaneously binding to a ubiquitin ligase. More generally referred to as bifunctional degraders, PROTACs have led the way in the field of targeted protein degradation (TPD), with several compounds currently undergoing clinical testing. Alongside bifunctional degraders, single-moiety compounds, or molecular glue degraders (MGDs), are increasingly being considered as a viable approach for development of therapeutics, driven by advances in rational discovery approaches. This review focuses on drug discovery with respect to bifunctional and molecular glue degraders within the ubiquitin proteasome system, including analysis of mechanistic concepts and discovery approaches, with an overview of current clinical and pre-clinical degrader status in oncology, neurodegenerative and inflammatory disease.

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Baig, Mohammad Hassan, Juhan Bok, Dongmin Kim, Sagar Dattatraya Nale, Yun Sung Jo, Changjoong Kim, Taehhwan Park, Jaejune Dong e Byoung Gon Moon. "Abstract 4502: Design, synthesis, and evaluation of next-generation EGFR degraders to overcome osimertinib-resistance". Cancer Research 84, n. 6_Supplement (22 marzo 2024): 4502. http://dx.doi.org/10.1158/1538-7445.am2024-4502.

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Abstract The occurrence of C797S mutation in epidermal growth factor receptor (EGFR) is a leading mechanism of clinically acquired resistance to third-generation EGFR inhibitors, including Osimertinib. L858R/T790M/C797S and del19/T790M/C797S are commonly observed tertiary EGFR mutants identified in Osimertinib-resistant tumors. As of now, no clinically approved treatment exists that specifically targets these mutants. Here, we report the design and synthesis of a series of highly effective next-generation EGFR degraders effectively degrading EGFR C797S-containing triple mutants. Most compounds demonstrated antiproliferation activity in the subnanomolar range when tested on Ba/F3L858R/T790M/C797S and del19/T790M/C797S cells. Not only C797S but our designed degraders also degraded a wide range of EGFR mutants, including Exon19Del and L858R/T790M (DC50 <100nM). One representative Compound, HDBNJ2812, strongly degrades L858R/T790M/C797S and del19/T790M/C797S with DC50 of 34 nM (Dmax 88.5%) and 14 nM (Dmax 99.7%), respectively. This compound potently inhibits the proliferation of Ba/F3L858R/T790M/C797S (GI50 64 nM) and del19/T790M/C797S (GI50 40 nM). HDBNJ2812 demonstrated high inhibitory potential on HCC827 (del19) and H1975 (L858R/T790M) cell lines (GI50 18.9 and 85 nM, respectively). Furthermore, this degrader demonstrates weak cytotoxicity on non-mutant EGFR-expressing cells, such as A431, WI-26 (human lung fibroblast cells), and CHO-K1 (Chinese hamster ovary cells). Additionally, the in vivo PK/PD findings complement this compound's potential to be considered further. HDBNJ2812 may serve as a lead compound to render the greater therapeutic window for treating resistant non-small cell lung cancer patients with EGFR C797S mutants. Citation Format: Mohammad Hassan Baig, Juhan Bok, Dongmin Kim, Sagar Dattatraya Nale, Yun Sung Jo, Changjoong Kim, Taehhwan Park, Jaejune Dong, Byoung Gon Moon. Design, synthesis, and evaluation of next-generation EGFR degraders to overcome osimertinib-resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4502.

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Vrchotová, Blanka, Petra Lovecká, Milena Dražková, Martina Macková e Tomas Macek. "Influence of Root Exudates on the Bacterial Degradation of Chlorobenzoic Acids". Scientific World Journal 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/872026.

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Degradation of chlorobenzoic acids (e.g., products of microbial degradation of PCB) by strains of microorganisms isolated from PCB contaminated soils was assessed. From seven bulk-soil isolates two strains unique in ability to degrade a wider range of chlorobenzoic acids than others were selected, individually and even in a complex mixture of 11 different chlorobenzoic acids. Such a feature is lacking in most tested degraders. To investigate the influence of vegetation on chlorobenzoic acids degraders, root exudates of two plant species known for supporting PCB degradation in soil were tested. While with individual chlorobenzoic acids the presence of plant exudates leads to a decrease of degradation yield, in case of a mixture of chlorobenzoic acids either a change in bacterial degradation specificity, associated with 3- and 4-chlorobenzoic acid, or an extension of the spectrum of degraded chlorobenzoic acids was observed.

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Più fonti

Tesi sul tema "Degraders"

Gentry, Terry Joe. "Molecular ecology of chlorobenzoate degraders in soil". Diss., The University of Arizona, 2003. http://hdl.handle.net/10150/289936.

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A series of three experiments were conducted to determine the diversity of indigenous chlorobenzoate (CB) degraders in soil and to investigate the use of different methods of bioaugmentation for remediation of contaminated soil. In the first study, soil was amended with either 500 or 1000 μg of 3-CB g⁻¹ and was either uninoculated or inoculated with the 3-CB degrader Comamonas testosteroni BR60. Bioaugmentation with C. testosteroni BR60 increased 3-CB degradation at both contaminant levels, and the increase was more pronounced at the higher level due to contaminant inhibition of indigenous 3-CB degraders. Bioaugmentation also appeared to reduce the deleterious effects that 3-CB contamination had on indigenous soil microbial populations as evidenced by changes in culturable heterotrophic bacterial populations. In the second study, two similar pristine soils were contaminated with 500 μg of 2-, 3-, or 4-CB g⁻¹ . The two soils differed in their ability to degrade the compounds with one degrading 2- and 4-CB and the other degrading 3- and 4-CB. Several hundred degraders were isolated, grouped according to DNA fingerprints, and selected degraders were identified by 16S rDNA sequences. The identity of the CB degraders differed between the two soils. The results indicated that the development of 2-, 3-, and 4-CB degrader populations was site-specific even for the soils that developed under similar soil-forming conditions. The third study also used the two soils from the second study. This project investigated the potential for use of activated soil, which contained an indigenous degrader population, as a bioaugmentation inoculant. An aliquot of a given soil that contained an indigenous 2-, 3-, or 4-CB degrader population was added to a soil that did not have an indigenous degrader population for the same contaminant. The study found that bioaugmentation with activated soil increased degradation of each 2-, 3-, and 4-CB but only if the activated soil was pre-exposed to the contaminant prior to use for bioaugmentation. The results from these three studies indicate that CB degrader populations are diverse and variable in pristine soils and, if not present in contaminated soils, appropriate degrader populations may be established via different bioaugmentation strategies.

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Larke-Meji, Nasmille Liceth. "Molecular ecology of isoprene degraders in the terrestrial environment". Thesis, University of East Anglia, 2018. https://ueaeprints.uea.ac.uk/69551/.

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Isoprene (2-methyl 1, 3-butadiene) is the most abundant non-methane BVOC (biogenic volatile organic compound) released into the atmosphere. Terrestrial plants are the primary producers of isoprene and release 500-750 million tonnes of isoprene per year, to protect themselves from abiotic environmental stresses such as heat and reactive oxygen species. Many studies have explored isoprene production but very little is known about consumption of isoprene by microbes. Cleveland and Yavitt in 1998 (Cleveland and Yavitt 1998), and more recently Khawand et al. 2016 (Khawand et al. 2016), demonstrated that microbes isolated from terrestrial environments are capable of using isoprene as sole carbon and energy source. By applying cultivation-dependent and cultivation-independent techniques, such as DNA Stable Isotope Probing (Dumont and Murrell 2005), my objective was to determine the distribution, diversity and activity of isoprene-degrading bacteria in the terrestrial environment. Isoprene-degrading microbes were enriched by adding 13 to 50 ppm isoprene to microcosms using topsoil from a willow tree and topsoil/leaves from an oil palm tree. DNA stable isotope probing, using 13C-labelled isoprene, assisted in revealing the diversity of active isoprene degraders by labelling organisms that incorporated the isoprene, directly or indirectly. PCR retrieval of partial 16S rRNA genes from this DNA revealed labelled members of the genera Ramlibacter, Variovorax, Rhodococcus and Methylibium, for willow soil, and Rhodococcus, Gordonia, Aquabacterium, Aquincola, Methylobacterium and members from the Sphingomonadaceae family, for the oil palm tree. Using cultivation-dependent methods I isolated seven phylogenetically different isoprene-utilizing bacteria of the genera Rhodococcus, Nocardioides and Variovorax from willow soil environment; another four phylogenetically different bacteria belonging to the genera Gordonia, Sphingopyxis and Sphingobacterium from the oil palm tree. Results suggest Rhodococcus is a cosmopolitan isoprene-degrader, present in a variety of environments, and different isoprene-degrading bacteria were found associated to willow and oil palm trees.

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Donoghue, Craig. "Syntheses of Protein Degraders and Compounds for Targeted Drug Release". Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/667875.

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The thesis consists of two main projects: a) the development of a novel strategy to gain genetic control with spatiotemporal precision, and b) the optimisation of inhibitors of the protein kinase p38α, which has a major role in the homeostasis of tumours and in the regulation of metastasis, invasion and proliferation, amongst other processes in cancer. a) Guaymoxifen is a molecule that is inactive with respect to the Cre method for genetic modification, but can be cleaved by a xeno-enzyme (LigF, artificially expressed in the metastatic cells of our mouse model, but not in the innate cells of the model) to liberate the active compound hydroxytamoxifen (4OHT). When guaymoxifen is administered to a CreER-GFP mouse (which has the potential to express green fluorescent protein upon exposure to 4OHT) that possesses LigF metastatic tumours, 4OHT will only be released around these metastatic tumour cells. Therefore, genetic modification (expression of GFP in this case) will only occur in the cells surrounding the tumour sites (stroma), allowing visualisation and isolation of key stromal cells during tumour development. A drawback was that the liver of the mouse was also capable of cleaving guaymoxifen and releasing 4OHT, which caused genetic recombination to occur away from the stroma and thus generated background noise, which limited the use of this technique in vivo. In order to address this problem, we developed a family of compounds based on guaymoxifen that would be more resistant to oxidative metabolism in the liver, by substitution of the beta- ether bond. Initial biological testing of these compounds identified 2 analogues that were more resistant to liver cleavage, yet could still be effectively cleaved by LigF in vitro. Ongoing work will complete the data needed for proof of concept of this strategy. 4OHT, (the active part), possesses a double bond with four distinct substituents, which leads to the existence of 2 stereoisomers. Only the Z stereoisomer is active against CreER, and furthermore, the proZ isomer of guaymoxifen is preferentially cleaved by LigF over the proE isomer. We therefore synthesised a modified analogue of 4OHT: 2Me-4OHT which favours the formation of the active isomer due to steric repulsion from the additional methyl group. This analogue was demonstrated to have comparable activity to 4OHT in CreER assays and in vivo. We therefore prepared the corresponding compound including the guaiacol moiety and observed that it could be cleaved by LigF to liberate active 2Me-4OHT in vitro. The liberated compound possessed a Z:E isomer ratio that was approximately 8x higher than that of 4OHT. In vivo examination is ongoing to determine the performance of these compounds in the complete mouse models. b) Our objective was to design and synthesise a new family of compounds based on the existing p38α inhibitor PH-797804 (PH), developed by Pfizer. We incorporated a variety of functional groups at different lengths distant from a crucial amide moiety of the molecule, which could be modified without adversely affecting the affinity for the target protein. The added functionalities were amenable to conjugation to moieties for the accumulation in tumour cells, such as peptide sequences or gold nanoparticles. The selective accumulation of these drug conjugates in the tumour cells would avoid the side effects associated with p38α inhibitors, such as skin rash and liver toxicity, identified in a number of phase II clinical trials. Our free analogues, before incorporation of the directing groups, were tested in a number of biological assays and in vivo. They maintained the activity of PH, and in the case of 4-13a even displayed superior activity. A new series of conjugates bound to RGD (an integrin recognition fragment) and analogues of somatostatin (a ligand for somatostatin receptor) were synthesised and shown to possess activity in vitro and preliminary in vivo tests. The conjugates were predicted to have an affinity for the corresponding receptors, which are overexpressed on the surface of many types of tumour cells and would thereby cause the accumulation of the conjugates in tumours. Endosomic assisted internalisation and cleavage would then release the active analogues within the tumour cells. Ongoing testing aims to establish the therapeutic benefit of these conjugates. We also designed a PROTAC (“Proteolysis Targeting Chimera”) using PH as the warhead. After screening of appropriate ligands for E3 ubiquitin ligase and optimisation of the linker, we obtained a family of compounds that induced the ubiquitination and degradation of p38α and p38 in cellular assays at nanomolar concentrations. The degradation took less than 8 hours and was maintained for over 48 hours, in a range of cell lines. These PROTACs were also effective in vivo, whereby p38α was degraded in lung tissue after 16 h when administered intratracheally, but not in nearby tissues such as heart or lung. Ongoing optimisation to improve the solubility and bioavailability of this PROTAC hopes to achieve a novel therapy for use against cancer.
La tesis consiste en dos proyectos principales: a) desarrollo de una estrategia novedosa para la modificación genética con control espaciotemporal, y b) mejora de inhibidores de la proteína p38α, que tiene un papel muy importante en la homeostasis de tumores y en la regulación de la metástasis, invasión y proliferación, etc. a) Una molécula (que denominamos Guaymoxifen) inactiva respeto al método “Cre” de modificar genes, que mediante la acción de una xeno-enzima (LigF, sólo expresada en bacterias, no en las células humanas), se parte y libera hydroxytamoxifen (4OHT, la parte activa). Cuando se administra guaymoxifen a un ratón con tumores que expresan LigF, libera 4OHT sólo alrededor de las células tumorales, y entonces solo se modifica la genética de dichas células. El problema es que en el hígado también se libera 4OHT y causa ruido de fondo en los datos. Para afrontar ésta problema del metabolismo en el hígado, desarrollamos una familia de nuevos análogos de guaymoxifen que fueron más resistentes. Las pruebas biológicas identificaron dos análogos más resistentes, pero 4OHTam todavía fue liberado por la enzima LigF. También sintetizamos un nuevo análogo de 4OHT (la parte activa): 2Me-4OHT, que favorece la formación del estereoisómero activo debido a la repulsión estérica del grupo metilo añadido. Esté análogo tenía una actividad en los ensayos Cre-ER parecido a 4OHT. Preparamos el compuesto correspondiente incluyendo la parte “guay” y vimos en los ensayos de escisión que LigF rompe la molécula, liberando 2Me-4OHT. Así pues, cuando tenga lugar la isomerización se generará una mezcla enriquecida en el isómero activo. b) Nuestro objetivo es diseñar y sintetizar una nueva familia de compuestos basada en un inhibidor ya existente, PH-797804 (PH), desarrollado por Pfizer. Hemos incorporado una variedad de grupos funcionales en estos análogos para que pudiéramos unir grupos directores, como por ejemplo nanopartículas de oro, o secuencias peptídicas, para direccionar el inhibidor al tumor con más especificidad. Así ganaríamos más eficacia y superaríamos los efectos secundarios asociados con los inhibidores de p38α ya descritos. Nuestros análogos, antes de incorporar los grupos directores, fueron probados en ensayos celulares y también in vivo en tumores implantados en ratones y mantuvieron la actividad de la inhibición de p38α, o incluso más alta que la del PH. Una nueva serie de análogos fue sintetizada con nuestros análogos enlazado covalentemente a RGD, y a análogos de somatostatina. El mismo análogo de la serie también fue modificado para incluir un iniciador de “E3 ubiquitin ligase”, para obtener un PROTAC (“Proteolysis Targeting Chimera”) con capacidad de degradar p38α. Después de un programa de optimización de los iniciadores de E3 ubiquitin ligase y optimización del “linker,” conseguimos una familia de compuestos “PROTAC” que degradaban eficazmente la proteína. Estas son las primeras moléculas pequeñas con capacidad para degradar únicamente p38α y p38beta descritas hasta el momento. La degradación fue probada en una variedad de líneas células y también in vivo.

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Mao, Tianqi [Verfasser], Felix [Akademischer Betreuer] Hausch e Boris [Akademischer Betreuer] Schmidt. "Development of Novel Small-Molecule Degraders of FK506-Binding Protein 51 / Tianqi Mao ; Felix Hausch, Boris Schmidt". Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2020. http://d-nb.info/1216243409/34.

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Kiesel, Carola Angelika [Verfasser], Jean Charles [Akademischer Betreuer] Munch e Jens [Akademischer Betreuer] Aamand. "Enhanced degradation of isoproturon in soils: sustainability of inoculated, microbial herbicide degraders, and adaptation of native microbes / Carola Angelika Kiesel. Gutachter: Jean Charles Munch ; Jens Aamand. Betreuer: Jean Charles Munch". München : Universitätsbibliothek der TU München, 2014. http://d-nb.info/1064523145/34.

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Douglass, James F. "Biomineralization of atrazine and analysis of 16S rRNA and catabolic genes of atrazine-degraders in a former pesticide mixing and machinery washing area at a farm site and in a constructed wetland". The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1440373757.

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Louvel, Brice. "Etude en microcosmes de l'effet du ray-grass et de ses exsudats racinaires sur la dissipation des HAP et les communautés bactériennes dégradantes". Thesis, Nancy 1, 2010. http://www.theses.fr/2010NAN10113/document.

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Les hydrocarbures aromatiques polycycliques (HAP) sont des polluants organiques, ubiquistes, potentiellement toxiques et cancérigènes. Dans les sols, la dégradation des HAP est principalement due à l'activité microbienne. Certaines études ont montré que la biodégradation des HAP pouvait être augmentée dans la rhizosphère des plantes où le nombre et l'activité microbienne sont stimulés, grâce aux exsudats racinaires. Cependant les bénéfices des plantes ne sont pas toujours observés, et les exsudats pourraient aussi modifier la biodisponibilité des HAP. Les objectifs de ce travail ont été de mieux comprendre ces interactions sol-plante-microorganismes qui conditionnent le devenir des HAP dans la rhizosphère en suivant notamment (i) les bactéries possédant les gènes codant une HAP-dioxygènase, (ii) les espèces bactériennes impliquées dans la dégradation du phénanthrène, et (iii) la disponibilité et la biodégradation des HAP dans des terres industrielles historiquement contaminées.Les expériences ont été conduites dans des dispositifs à compartiments, lesquels permettent une diffusion des exsudats racinaires dans le sol tout en retenant physiquement les racines, puis en microcosmes avec un ajout d'exsudats racinaires naturels produits à partir d'une culture hydroponique de ray-grass (Lolium perenne, L). Les expériences ont été réalisées dans un premier temps avec du sable en ajoutant du phénanthrène (PHE) et un inoculum bactérien issu d'un sol d'une ancienne cokerie puis directement avec des sols historiquement contaminés en HAP. Les nombres de copies de gènes codant pour l'ADNr 16S et pour des HAP-dioxygènases ont été quantifiés par PCR en temps réel pour estimer la proportion de bactéries dégradantes. Les structures des communautés ont été comparées par électrophorèses (TTGE). En plus de l'analyse des 16 HAP totaux, une extraction non exhaustive des HAP a été réalisée à la cyclodextrine pour en estimer la disponibilité. L'utilisation de la méthode SIP (stable isotope probing) avec du 13C-phénanthrène a permis d'identifier les bactéries directement impliqués sa dégradation dans un sol historiquement contaminé. Les expériences en dispositifs à compartiments ont confirmé que la dissipation du phénanthrène est plus importante lorsque la distance aux racines est plus faible, et montrent que le nombre de copies de gène 16S et de gène de HAP-dioxygénase varie avec l'âge des plantes et du temps de contact des compartiments latéraux avec le tapis racinaire. Mais elles montrent aussi que la dissipation du phénanthrène n'est pas plus importante dans les pots plantés, tandis que dans les expériences en microcosmes une inhibition de la dissipation du PHE a même été observée en présence d'exsudats. La présence d'exsudats racinaires a profondément modifié la structure des communautés dégradant les HAP, et l'expérience SIP a permis d'identifier les bactéries directement impliquées dans la dégradation du 13C-phénanthrène et de montrer qu'elles étaient différentes en présence ou non d'exsudats. En présence d'exsudats, la proportion des bactéries dégradantes dans la population totale est passée de 1 % dans la terre d'origine et dans les traitements sans exsudats à plus de 10 %. Même si les exsudats racinaires ralentissent la dissipation du phénanthrène, en fournissant une source de carbone plus facilement métabolisable, ils ont augmenté la quantité de HAP extractibles à la cyclodextrine dans deux des trois sols historiquement contaminés, suggérant un effet de ceux-ci sur la biodisponibilité des HAP
Polycyclic Aromatic Hydrocarbons (PAH) are organics pollutants, ubiquitous, toxics and potentially carcinogenic. In soil, PAH degradation is mainly attributed to microbial organism. Several studies have thus reported enhanced PAH degradation in soil in the presence of plants. Rhizospheric soil increase the number et the activity of microorganisms in soil by the release of roots exudates. However, bene?cial effects of plants in the remediation are not always observed and roots exudates could be limited PAH biodegradation. The object of this study was to investigate the fate of PAHs in rhizosphere, following (i) the PAH-dioxygenase genes DNA to quantify the PAH-degrading bacteria, (ii) species implicated in phenanthrene biodegradation, and (iii) PAH availability and biodegradation from industrial soils.Different experimental devices have been designed to study detailed processes in the rhizosphere. First is a compartments devices were a nylon mesh permits diffusion of plant soluble substances towards the adjacent root free compartment as a rhizosphere. Secondly microcosms were enriched with natural roots exudates from hydroponic culture of ray-grass (Lolium perenne L.). In first time, experiments were conducted using sand and bacterial inoculum from an industrially PAH-contaminated soil and then directly with a soil historically contaminated by PAH. The Real-Time PCR quantification of 16S rRNA gene copy and of functional PAH-RHD? genes permitted to assess the proportion of a degrading bacteria. Bacterial community structure was approached from Temporal Thermal Gradient gel Electrophoresis (TTGE) fingerprinting, and bands sequencing. Nonexhaustive cyclodextrin-based extraction technique provided a estimate of the ?labile? or available pool of PAH in soil. Use of stable isotope probing (SIP) technique with [13C]phenanthrene allowed a bacterial identification of directly implicated in industrial soil.The presence of exudates modified microbial community of PAH-degrading bacteria. SIP experiment showed that 13C-labelled PHE-degrading bacteria was different depending on the exudates input. Many species having to degrade phenanthrene were able to use exudates. Presence of root exudates increased the proportion of PAH-RHD? genes compared to the bulk soil at the beginning and in microcosms without exudates (respectively 10% and 1 %). However, phenanthene dissipation in sand or soil were weaker with root exudates and aged PAH concentrations has not shifted during incubation time. Nevertheless, the root exudates increased the PAH labile fraction extract with cyclodextrin solution into two in three soils historically contaminated

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Sohoglu, Ediz. "Perception of degraded speech". Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608225.

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Torres, Josette Annmarie. "Bodies Degraded by Friction". Thesis, Virginia Tech, 2010. http://hdl.handle.net/10919/77491.

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Bodies Degraded by Friction is a collection of poetry existing in finite spaces. The first section, “A Moment and a Moment and a Moment," attempts to capture in words small passages of time as simple as clicking through a Facebook photo album and as destructive as new love. The second section, “It’s Complicated," is a manuscript in progress detailing a year in the life of an “other woman" negotiating an interpersonal relationship role underrepresented in self-help books and mass media. Several themes run throughout the book: the consequences of the use of technology-mediated communication as digital isolationist mechanisms, the collisions of real/virtual identity and real/virtual place, disruption as a poetic device, and the idea that love is a fleeting and ultimately impermanent state.
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BEHEIM, LARBI. "Cooperation entre segmentation et reconnaissance des caracteres imprimes degrades". Paris 6, 2001. http://www.theses.fr/2001PA066015.

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La segmentation des caracteres degrades est un probleme tres complique. Les caracteres coupes et les caracteres colles sont deux types de degradation que nous rencontrons frequemment dans les vieux documents. Beaucoup de systemes de reconnaissance de caracteres restent obsoletes devant ce probleme. Ces systemes peuvent actuellement, reconnaitre des documents complexes : texte et images en nivaux de gris, disposition complique du texte, colonnes, etc. Mais, ces systemes sont incapables de reconnaitre les documents tres degrades. Des milliards de pages sont a scanner et reconnaitre une fois le probleme des caracteres coupes, colles et sous-echantillonnes sera resolu. Nous proposons donc dans cette these des techniques tres efficaces pour resoudre le probleme de segmentation et reconnaissance des caracteres coupes et ceux qui sont colles basees sur la cooperation segmentation/reconnaissance. Ces techniques utilisent plusieurs outils mathematiques comme la logique floue ou les statistiques. Un algorithme regroupant toutes ces techniques est ensuite expose. Il reussit a traiter les chaines de caracteres constituees d'un certain nombre de caracteres coupes ou colles sans une connaissance a priori de la largeur des caracteres ni de leur nombre. Le taux de reconnaissance est de 75% pour les caracteres colles, et de 87% pour les caracteres coupes. Un post-traitement base sur des contraintes lexicales permet facilement de ramener ces taux a 94% pour les caracteres colles et 98% pour les caracteres coupes.

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Libri sul tema "Degraders"

Watson, J. T. Raped degraded mother. San Diego, Calif: Greenleaf Classics, 1985.

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Petrovici, Radu, e Anamaria Mortu. Degradări ale anvelopei clădirilor. București: Editura Universitară "Ion Mincu", 2010.

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Dagar, Jagdish Chander, Sharda Rani Gupta e Demel Teketay, a cura di. Agroforestry for Degraded Landscapes. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-6807-7.

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Dagar, Jagdish Chander, Sharda Rani Gupta e Demel Teketay, a cura di. Agroforestry for Degraded Landscapes. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-4136-0.

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Domhardt, Yvonne. Alfred Dreyfus: Degradiert, deportiert, rehabilitiert. Teetz: Hentrich & Hentrich, 2005.

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Manske, Llewellyn L. Restoration of degraded prairie ecosystems. Dickinson, N.D: North Dakota State University, Dickinson Research Extension Center, 2007.

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Prabhakar, R. How degraded are Himalayan forests? Anand: Foundation for Ecological Security, 2005.

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Manske, Llewellyn L. Restoration of degraded prairie ecosystems. Dickinson, N.D: North Dakota State University, Dickinson Research Extension Center, 2007.

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Logan, Terry J. Reclamation of chemically degraded soils. S.l: s.n, 1992.

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Bonds, Jason. Wife degraded by a dog. Los Angeles: Oakmore Enterprise, 1985.

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Prince, Roger C., Tivkaa J. Amande e Terry J. McGenity. "Prokaryotic Hydrocarbon Degraders". In Taxonomy, Genomics and Ecophysiology of Hydrocarbon-Degrading Microbes, 1–39. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-14796-9_15.

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Prince, Roger C. "Eukaryotic Hydrocarbon Degraders". In Taxonomy, Genomics and Ecophysiology of Hydrocarbon-Degrading Microbes, 53–72. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-14796-9_16.

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Prince, Roger C., Tivkaa J. Amande e Terry J. McGenity. "Prokaryotic Hydrocarbon Degraders". In Taxonomy, Genomics and Ecophysiology of Hydrocarbon-Degrading Microbes, 1–41. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-60053-6_15-1.

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Prince, R. C. "Eukaryotic Hydrocarbon Degraders". In Taxonomy, Genomics and Ecophysiology of Hydrocarbon-Degrading Microbes, 1–20. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-60053-6_16-1.

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Prince, R. C., A. Gramain e T. J. McGenity. "Prokaryotic Hydrocarbon Degraders". In Handbook of Hydrocarbon and Lipid Microbiology, 1669–92. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-77587-4_118.

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McGenity, T. J., C. Whitby e A. Fahy. "Alkaliphilic Hydrocarbon Degraders". In Handbook of Hydrocarbon and Lipid Microbiology, 1931–37. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-77587-4_141.

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McGenity, T. J. "Halophilic Hydrocarbon Degraders". In Handbook of Hydrocarbon and Lipid Microbiology, 1939–51. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-77587-4_142.

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Prince, R. C. "Eukaryotic Hydrocarbon Degraders". In Handbook of Hydrocarbon and Lipid Microbiology, 2065–78. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-77587-4_150.

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Rojo, Fernando, e José Luis Martínez. "Hydrocarbon Degraders as Pathogens". In Health Consequences of Microbial Interactions with Hydrocarbons, Oils, and Lipids, 267–81. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-15147-8_22.

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Rojo, Fernando, e José Luis Martínez. "Hydrocarbon Degraders as Pathogens". In Health Consequences of Microbial Interactions with Hydrocarbons, Oils, and Lipids, 1–15. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-72473-7_22-1.

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Atti di convegni sul tema "Degraders"

Ciulli, Alessio. "Abstract IACICR01: Perspective on bivalent degraders". In Abstracts: AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; October 7-10, 2021. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1535-7163.targ-21-iacicr01.

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Engle, J. W., K. Gagnon, G. W. Severin, H. F. Valdovinos, R. J. Nickles e T. E. Barnhart. "Flexible, durable proton energy degraders for the GE PETtrace". In 14TH INTERNATIONAL WORKSHOP ON TARGETRY AND TARGET CHEMISTRY. AIP, 2012. http://dx.doi.org/10.1063/1.4773933.

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Abbineni, Chandrasekhar, Mahaboobi Jaleel, Subhendu Mukherjee, Sivapriya Marappan, Nirbhay Kumar Tiwari, DS Samiulla, AB Aravind et al. "Abstract 1754: First in class orally bioavailable BETBRD degraders". In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-1754.

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Cindy Tan Soo Yun e Ang Chung Huap. "Isolation of potential total petroleum hydrocarbon degraders from river sediments". In 2010 International Conference on Science and Social Research (CSSR). IEEE, 2010. http://dx.doi.org/10.1109/cssr.2010.5773884.

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Angzzas, Sari Mohd Kassim, Mohd Aripin Ashuvila e Norul Fairuz Abang Zaidel Dayang. "Potential lignin degraders isolated from the gut of rhynchophorus ferrugineus". In International Conference on Mechanics,Materials and Structural Engineering (ICMMSE 2016). Paris, France: Atlantis Press, 2016. http://dx.doi.org/10.2991/icmmse-16.2016.22.

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Bandura, L., B. Erdelyi e J. Nolen. "Optical effects of energy degraders on the performance of fragment separators". In 2007 IEEE Particle Accelerator Conference (PAC). IEEE, 2007. http://dx.doi.org/10.1109/pac.2007.4440447.

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Abbineni, Chandrasekhar, Leena Khare Satyam, Bilash Kuila, Ashok Ettam, Khaji Abdul Rawoof, Sreevidya MR, Sandeep Vitthal Dukare et al. "Abstract 1144: Orally bioavailable SMARCA2 degraders with exceptional selectivity and potency". In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-1144.

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Chong, Nyuk-Min. "Molecular Biological Method Can Indicate Evolution of Xenobiotic Degraders from Activated Sludge". In The 2nd World Congress on New Technologies. Avestia Publishing, 2016. http://dx.doi.org/10.11159/icepr16.112.

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Kregel, Steven, Chao Wang, Xin Han, Lanbo Xiao, Ester Fernandez-Salas, Pushpinder Bawa, Brooke L. McCollum et al. "Abstract 5679: Androgen receptor degraders overcome common resistance mechanisms developed during prostate cancer treatment". In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-5679.

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Lu, Jing, Yimin Qian, Martha Altieri, Hanqing Dong, Jing Wang, Kanak Raina, Jim Winkler et al. "Abstract LB-010: Hijacking the E3 ubiquitin ligase cereblon to create efficient BRD4 degraders". In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-lb-010.

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Rapporti di organizzazioni sul tema "Degraders"

Buckley, Merry. The Fungal Kingdom: diverse and essential roles in earth's ecosystem. American Society for Microbiology, 2008. http://dx.doi.org/10.1128/aamcol.2nov.2007.

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There's more to fungi than just mushrooms. Fungi are the cause of scores of life-threatening diseases, they are the earth's best degraders of organic matter, and they are proving to be more useful to science and manufacturing every year. They come in many forms, ranging from single-celled yeasts on the order of ~10 ÌM to mushrooms the size of dinner plates to thin, powdery coatings of mold. Despite the diversity that science has revealed about fungi and their myriad roles in health, ecology, and industry, much about these organisms remains a mystery. The American Academy of Microbiology convened a colloquium November 2–4, 2007, in Tucson, Arizona, to discuss fungi, the current state of research in fungal biology (mycology), and the gaps in our understanding of this important group of organisms. Experts in mycology, medicine, plant pathogens, genetics/genomics, ecology, and other areas developed specific recommendations for advancing fungal research.

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Stevens e Olsen. PR-179-12214-R01 CO Sensor Experimental Evaluation for Catalyst Health Monitoring. Chantilly, Virginia: Pipeline Research Council International, Inc. (PRCI), settembre 2014. http://dx.doi.org/10.55274/r0010827.

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Oxidation catalysts and three-way catalysts can be used to reduce the amount of CO present in engine exhaust. For 2-stroke lean-burn engines, the oxidation catalyst degrades over time be-cause of the buildup of poisons such as sulfur, zinc, phosphorous, and calcium. Three-way cata-lysts used with stoichiometric engines also degrade over time. Emissions analyzers are often used to evaluate the degradation of oxidation catalysts and three-way catalysts, but it can be very time consuming and expensive. Ideally, a simple sensor system would be beneficial for operating companies to determine if the catalyst were out of compliance according to normal operating standards. An ECM CO sensor and recording device was acquired for testing. The CO sensor system was evaluated for its ability to monitor post-catalyst CO concentration. The results show that this CO sensor system is ineffective at monitoring post-catalyst CO concentration.

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Fite, Jesse, S. Nemesure, M. Sivertz, A. Rusek e I.-H. Chiang. Beam Degrader Wheel for Gold Beams at NSRL. Office of Scientific and Technical Information (OSTI), novembre 2010. http://dx.doi.org/10.2172/1775551.

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Rimsza, Jessica. Resiliency of Degraded Built Infrastructure. Office of Scientific and Technical Information (OSTI), settembre 2020. http://dx.doi.org/10.2172/1661753.

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Ghitza, Oded. Auditory Peripheral Processing of Degraded Speech. Fort Belvoir, VA: Defense Technical Information Center, gennaio 2003. http://dx.doi.org/10.21236/ada420098.

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Renlund, A. M., J. C. Miller, W. M. Trott, K. L. Erickson, M. L. Hobbs, R. G. Schmitt, G. W. Wellman e M. R. Baer. Characterization of thermally degraded energetic materials. Office of Scientific and Technical Information (OSTI), dicembre 1997. http://dx.doi.org/10.2172/629380.

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VanGuilder, Jonathan. Does MOOTW Degrade Combat Readiness. Fort Belvoir, VA: Defense Technical Information Center, maggio 2000. http://dx.doi.org/10.21236/ada381727.

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Tsai, Francis. To Degrade or Not Degrade: Targeting the Androgen Receptor in AR-Dependent Prostate Cancer. Fort Belvoir, VA: Defense Technical Information Center, aprile 2012. http://dx.doi.org/10.21236/ada560755.

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Crocker, Fiona, Mark Fuller e Kayla Clark. Bioaugmentation for enhanced mitigation of explosives in surface soil. Engineer Research and Development Center (U.S.), aprile 2024. http://dx.doi.org/10.21079/11681/48450.

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Residual munition constituents (MCs) generated from live-fire training exercises persist in soil and can migrate to groundwater, surface waters, and off-range locations. Techniques to mitigate this potential migration are needed. Since the MC hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) can be biodegraded, soil inoculation with RDX-degrading bacteria (i.e., bioaugmentation) was investigated as a means to reduce the migration potential of RDX. Metagenomic studies using contaminated soils have suggested that a greater diversity of bacteria are capable of RDX biodegradation. However, these bacteria remain uncultivated and are potentially a source of novel enzymes and pathways for RDX biodegradation. In situ soil cultivation of a novel soil array was used to isolate the uncultivated bacteria that had been inferred to degrade RDX. Approximately 10.5% of the bacteria isolated from the soil arrays degraded RDX by the aerobic denitration pathway. Of these, 26.5% were possibly novel species of RDX-degrading bacteria, based on 16S rRNA sequence similarity. Both cell encapsulation in hydrogels and coating cells onto granules of polymeric carbon sources were investigated as carrier/delivery approaches for soil inoculation. However, neither of these approaches could confirm that the observed RDX degradation was by the inoculated bacteria.

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Zeger, Linda, e Ira Kohlberg. Survivability and Recovery of Degraded Communication Networks. Fort Belvoir, VA: Defense Technical Information Center, maggio 2011. http://dx.doi.org/10.21236/ada570718.

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