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Academic literature on the topic 'Bac7'

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Published: 11 March 2023
Last updated: 1 April 2023

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Journal articles on the topic "Bac7"

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Armas, Federica, Adriana Di Stasi, Mario Mardirossian, Antonello A. Romani, Monica Benincasa, and Marco Scocchi. "Effects of Lipidation on a Proline-Rich Antibacterial Peptide." International Journal of Molecular Sciences 22, no. 15 (July 26, 2021): 7959. http://dx.doi.org/10.3390/ijms22157959.

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The emergence of multidrug-resistant bacteria is a worldwide health problem. Antimicrobial peptides have been recognized as potential alternatives to conventional antibiotics, but still require optimization. The proline-rich antimicrobial peptide Bac7(1-16) is active against only a limited number of Gram-negative bacteria. It kills bacteria by inhibiting protein synthesis after its internalization, which is mainly supported by the bacterial transporter SbmA. In this study, we tested two different lipidated forms of Bac7(1-16) with the aim of extending its activity against those bacterial species that lack SbmA. We linked a C12-alkyl chain or an ultrashort cationic lipopeptide Lp-I to the C-terminus of Bac7(1-16). Both the lipidated Bac-C12 and Bac-Lp-I forms acquired activity at low micromolar MIC values against several Gram-positive and Gram-negative bacteria. Moreover, unlike Bac7(1-16), Bac-C12, and Bac-Lp-I did not select resistant mutants in E. coli after 14 times of exposure to sub-MIC concentrations of the respective peptide. We demonstrated that the extended spectrum of activity and absence of de novo resistance are likely related to the acquired capability of the peptides to permeabilize cell membranes. These results indicate that C-terminal lipidation of a short proline-rich peptide profoundly alters its function and mode of action and provides useful insights into the design of novel broad-spectrum antibacterial agents.
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Zanetti, M., L. Litteri, R. Gennaro, H. Horstmann, and D. Romeo. "Bactenecins, defense polypeptides of bovine neutrophils, are generated from precursor molecules stored in the large granules." Journal of Cell Biology 111, no. 4 (October 1, 1990): 1363–71. http://dx.doi.org/10.1083/jcb.111.4.1363.

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Bactenecins are highly cationic polypeptides of bovine neutrophil granules and exert in vitro a potent antimicrobial activity. We have previously purified two bactenecins, designated in an abbreviated form Bac7 and Bac5 from their approximate molecular masses of 7 and 5 kD (Gennaro, R., B. Skerlavaj, and D. Romeo. 1989. Infect. Immun. 57:3142-3146). Here we have studied the biosynthesis, processing, and localization of precursors of Bac7 and Bac5 in bovine bone marrow cells of the myeloid lineage. In vitro translation directed by mRNA isolated from these cells has shown that the primary translation products are preprobactenecins of 23.5 and 21 kD, and are processed to polypeptides of 20 and 15.8 kD, respectively. The 20-kD polypeptide is the granule storage form of Bac7, or proBac7, as also demonstrated by Western blot analysis of lysates of peripheral neutrophils. Between 15 and 50 min from the beginning of its biosynthesis the 15.8-kD polypeptide is converted into the 15-kD granule storage form of Bac5, or proBac5. As shown by immunogold EM, proBac7 and proBac5 are sorted and targeted to the matrix of the so called large granules, which are the predominant organelles in the cytoplasm of bovine neutrophils and are the exclusive store of the nonoxidative antimicrobial system of these cells. Solubilization of granules with Triton X-100 with concomitant unmasking of proteases leads to cleavage of the proforms to Bac7 and Bac5. Experiments performed with protease inhibitors suggest that the proteolytic cleavage is catalyzed in detergent-solubilized neutrophils by neutral serine protease(s), very likely derived from the azurophil granules.
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Marlow, Victoria L., Andreas F. Haag, Hajime Kobayashi, Vivien Fletcher, Marco Scocchi, Graham C. Walker, and Gail P. Ferguson. "Essential Role for the BacA Protein in the Uptake of a Truncated Eukaryotic Peptide in Sinorhizobium meliloti." Journal of Bacteriology 191, no. 5 (December 12, 2008): 1519–27. http://dx.doi.org/10.1128/jb.01661-08.

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ABSTRACT The inner membrane BacA protein is essential for the establishment of chronic intracellular infections by Sinorhizobium meliloti and Brucella abortus within plant and mammalian hosts, respectively. In their free-living state, S. meliloti and B. abortus mutants lacking BacA have reductions in their outer membrane lipid A very-long-chain fatty acid (VLCFA) contents and exhibit low-level resistance to the glycopeptide bleomycin in comparison to their respective parent strains. In this paper we investigate the hypothesis that BacA is involved in peptide uptake in S. meliloti. We determined that an S. meliloti ΔbacA mutant is completely resistant to a truncated form of the eukaryotic peptide Bac7, Bac7(1-16), and this phenotype appears to be independent of its lipid A alteration. Subsequently, we discovered that BacA and/or Escherichia coli SbmA is essential for fluorescently labeled Bac7(1-16) uptake in S. meliloti. Given that there are hundreds of root nodule-specific peptides within the legume host, our data suggest that BacA-mediated peptide uptake could play a central role in the chronic infection process of S. meliloti. However, since we determined that two symbiotically defective S. meliloti bacA site-directed mutants (with the Q193G and R389G mutations, respectively) with known reductions in their lipid A VLCFA contents are still capable of peptide uptake, these findings suggest that BacA-dependent peptide uptake cannot fully account for the essential role of BacA in the legume symbiosis. Further, they provide evidence that the BacA function that leads to the S. meliloti lipid A VLCFA modification plays a key role in the chronic infection of legumes.
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Sola, Riccardo, Mario Mardirossian, Bertrand Beckert, Laura Sanghez De Luna, Dennis Prickett, Alessandro Tossi, Daniel N. Wilson, and Marco Scocchi. "Characterization of Cetacean Proline-Rich Antimicrobial Peptides Displaying Activity against ESKAPE Pathogens." International Journal of Molecular Sciences 21, no. 19 (October 6, 2020): 7367. http://dx.doi.org/10.3390/ijms21197367.

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Proline-rich antimicrobial peptides (PrAMPs) may be a valuable weapon against multi-drug resistant pathogens, combining potent antimicrobial activity with low cytotoxicity. We have identified novel PrAMPs from five cetacean species (cePrAMPs), and characterized their potency, mechanism of action and in vitro cytotoxicity. Despite the homology between the N-terminal of cePrAMPs and the bovine PrAMP Bac7, some differences emerged in their sequence, activity spectrum and mode of action. CePrAMPs with the highest similarity with the Bac7(1-35) fragment inhibited bacterial protein synthesis without membrane permeabilization, while a second subgroup of cePrAMPs was more membrane-active but less efficient at inhibiting bacterial translation. Such differences may be ascribable to differences in presence and positioning of Trp residues and of a conserved motif seemingly required for translation inhibition. Unlike Bac7(1-35), which requires the peptide transporter SbmA for its uptake, the activity of cePrAMPs was mostly independent of SbmA, regardless of their mechanism of action. Two peptides displayed a promisingly broad spectrum of activity, with minimal inhibiting concentration MIC ≤ 4 µM against several bacteria of the ESKAPE group, including Pseudomonas aeruginosa and Enterococcus faecium. Our approach has led us to discover several new peptides; correlating their sequences and mechanism of action will provide useful insights for designing optimized future peptide-based antibiotics.
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Tomasinsig, Linda, Marco Scocchi, Romina Mettulio, and Margherita Zanetti. "Genome-Wide Transcriptional Profiling of the Escherichia coli Response to a Proline-Rich Antimicrobial Peptide." Antimicrobial Agents and Chemotherapy 48, no. 9 (September 2004): 3260–67. http://dx.doi.org/10.1128/aac.48.9.3260-3267.2004.

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ABSTRACT Most antimicrobial peptides (AMPs) impair the viability of target bacteria by permeabilizing bacterial membranes. However, the proline-rich AMPs have been shown to kill susceptible organisms without causing significant membrane perturbation and may act by inhibiting the activity of bacterial targets. To gain initial insight into the events that follow interaction of a proline-rich peptide with bacterial cells, we used DNA macroarray technology to monitor transcriptional alterations of Escherichia coli in response to challenge with a subinhibitory concentration of the proline-rich Bac7(1-35). Substantial changes in the expression levels of 70 bacterial genes from various functional categories were detected. Among these, 26 genes showed decreased expression, while 44 genes, including genes that are potentially involved in bacterial resistance to antimicrobials, showed increased expression. The generation of a transcriptional response under the experimental conditions used is consistent with the ability of Bac7(1-35) to interact with bacterial components and affect biological processes in this organism.
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Benincasa, Monica, Marco Scocchi, Elena Podda, Barbara Skerlavaj, Lucilla Dolzani, and Renato Gennaro. "Antimicrobial activity of Bac7 fragments against drug-resistant clinical isolates." Peptides 25, no. 12 (December 2004): 2055–61. http://dx.doi.org/10.1016/j.peptides.2004.08.004.

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Podda, Elena, Monica Benincasa, Sabrina Pacor, Fulvio Micali, Maura Mattiuzzo, Renato Gennaro, and Marco Scocchi. "Dual mode of action of Bac7, a proline-rich antibacterial peptide." Biochimica et Biophysica Acta (BBA) - General Subjects 1760, no. 11 (November 2006): 1732–40. http://dx.doi.org/10.1016/j.bbagen.2006.09.006.

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Krizsan, Andor, Daniel Knappe, and Ralf Hoffmann. "Influence of theyjiL-mdtMGene Cluster on the Antibacterial Activity of Proline-Rich Antimicrobial Peptides Overcoming Escherichia coli Resistance Induced by the Missing SbmA Transporter System." Antimicrobial Agents and Chemotherapy 59, no. 10 (July 13, 2015): 5992–98. http://dx.doi.org/10.1128/aac.01307-15.

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ABSTRACTIn view of increasing health threats from multiresistant pathogens, antimicrobial peptides (AMPs) and, specifically, proline-rich AMPs (PrAMPs) have been investigated in animal models. PrAMPs enter bacteria via the ABC transporter SbmA and inhibit intracellular targets. We used phage transduction (Tn10insertion) to screen by random mutagenesis for alternative uptake mechanisms for analogs of apidaecin 1b, a honeybee-derived PrAMP. All 24 apidaecin-resistant mutants had the Tn10insertion in thesbmAgene. ThesesbmA::Tn10insertion mutants and theEscherichia coliBW25113 ΔsbmA(JW0368) strain were still susceptible to the bactenecin PrAMP Bac7(1-35) and oncocin PrAMPs Onc18 and Onc112, as well as to Chex1-Arg20, despite significantly reduced internalizations. In a second round of random mutagenesis, the remaining susceptibility was linked to theyjiL-mdtMgene cluster.E. coliBW25113 and its ΔyjiLnull mutant (JW5785) were equally susceptible to all PrAMPs tested, whereas the BW25113 ΔmdtMmutant was less susceptible to oncocins. The JW0368yjiL::Tn10transposon mutant (BS2) was resistant to all short PrAMPs and susceptible only to full-length Bac7 and A3-APO. Interestingly, PrAMPs appear to enter bacteria via MdtM, a multidrug resistance transporter (drug/H+antiporter) of the major facilitator superfamily (MFS) that can efflux antibiotics, biocides, and bile salts. In conclusion, PrAMPs enter bacteria via ABC and MFS transporters that efflux antibiotics and cytotoxic compounds from the cytoplasm to the periplasm.
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Donati, Manuela, Antonietta Di Francesco, Maria Di Paolo, Natascia Fiani, Monica Benincasa, Renato Gennaro, Paola Nardini, Claudio Foschi, and Roberto Cevenini. "Activity of Cathelicidin Peptides against Simkania negevensis." International Journal of Peptides 2011 (April 5, 2011): 1–3. http://dx.doi.org/10.1155/2011/708710.

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The in vitro activity of six cathelicidin peptides against the reference strain Z of Simkania negevensis was investigated. Five peptides—PG-1, Bac7, SMAP-29, BMAP-27, and BMAP-28—proved to be active at very low concentrations (1 to 0.1 μg/mL), while LL-37 cathelicidin was ineffective even at a concentration of 100 μg/mL. In comparison to chlamydiae, S. negevensis proved to be more susceptible to the antimicrobial peptides tested.
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Zahn, Michael, Bjorn Kieslich, Nicole Berthold, Daniel Knappe, Ralf Hoffmann, and Norbert Strater. "Structural Identification of DnaK Binding Sites within Bovine and Sheep Bactenecin Bac7." Protein & Peptide Letters 21, no. 4 (February 2014): 407–12. http://dx.doi.org/10.2174/09298665113206660111.

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Dissertations / Theses on the topic "Bac7"

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Mardirossian, Mario. "Internal targets and killing mechanism of the cathelicidin Bac7 in Gram-negative bacteria." Doctoral thesis, Università degli studi di Trieste, 2013. http://hdl.handle.net/10077/8640.

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2011/2012
Bac7(1-35) is the smallest fragment of the proline-rich cathelicidin Bac7 that shows the same antibacterial activity as the whole natural peptide of 60 residues. In this work, we remarked that the unique gene whose deletion can confer resistance to E. coli against Bac7(1-35) is sbmA, coding for an inner membrane protein involved in the penetration of this peptide into bacterial cells. Moreover, we provided evidence that SbmA is also involved in the transmembrane transport of a fragment of another proline-rich antimicrobial peptide, arasin1(1-23), isolated from the spider crab. These findings suggest a general role of this membrane protein in the uptake of proline-rich antimicrobial peptides (PR-AMPs) into Gram-negative bacteria. We then measured the intrabacterial concentration reached by Bac7(1-35) in E. coli, and observed that this increases from micromolar in the medium to millimolar within the bacterial cell, suggesting that it may bind to cytosolic structures. For this reason, we looked for possible interactions between Bac7(1-35) and macromolecules involved in viable processes of bacteria. These studies showed that Bac7(1-35) completely inhibits in vitro the transcription/translation process starting from a concentration of 50 μM. Then we demonstrated that inhibition is: i) specific for Bac7(1-35), since it is not exerted by other cathelicidin-derived AMPs not belonging to the Prorich group, and ii) not stereo-specific, since it is exerted at the same level by the all-D isomer of Bac7(1-35). We also demonstrated the ability of Bac7(1-35) to bind DNA in vitro, but we excluded that this binding may represent the primary mechanism of bactericidal action. We also showed that the peptide does not significantly affect in vitro the transcription process, deducing that the inhibition of the transcription/translation targets primarily the translation process. We verified these data in vivo on E. coli cells measuring the incorporation of radioactive precursors of bacterial macromolecules. We observed that the exposure of bacteria to Bac7(1-35) inhibited the incorporation of radioactive leucine, but not of radioactive thymidine and uridine, indicating a specific block at the protein synthesis level and not of DNA and RNA synthesis. In the near future, a clearer definition of the intrabacterial target(s) of Bac7(1-35) would hopefully lead to the experimentation of this molecule or of its derivatives as a new generation antibiotic drug.
Bac7(1-35) è il più breve frammento del peptide Bac7, una catelicidina ricca in prolina di 60 residui, dotato della stessa attività battericida del peptide intero. In questo lavoro di tesi, abbiamo rimarcato che sbmA è l’unico gene la cui delezione conferisce ad E. coli una resistenza a Bac7(1- 35). Tale gene codifica per una proteina della membrana interna coinvolta nell’ingresso del peptide nel citoplasma della cellula batterica. Inoltre, abbiamo dimostrato che SbmA è coinvolta anche nel trasporto transmembrana di un frammento di un altro peptide antimicrobico, l’arasina1(1-23). Tali risultati suggeriscono che questa proteina giochi un ruolo generale nell’internalizzazione di peptidi antimicrobici ricchi in prolina nei batteri Gram-negativi. Abbiamo quindi misurato la concentrazione intrabatterica raggiunta da Bac7(1-35) in E. coli e abbiamo osservato che questa aumenta da valori micromolari nel terreno di coltura a millimolari nel citosol batterico, suggerendo un suo legame a strutture interne della cellula. Per questo abbiamo cercato possibili interazioni tra il peptide e macromolecole coinvolte in processi vitali del batterio. Con questi studi abbiamo appurato che Bac7(1-35) in vitro inibisce completamente il processo di trascrizione/traduzione a partire da una concentrazione di 50 μM. Successivamente abbiamo dimostrato che questa inibizione è una peculiarità di Bac7(1-35), in quanto altri AMP derivati da catelicidine ma non ricchi in prolina non hanno dimostrato un’attività comparabile. Inoltre, questa inibizione non è stereo-specifica, in quanto anche l’isomero D di Bac7(1-35) blocca tale processo esattamente come il suo isomero L. Abbiamo inoltre dimostrato la capacità di Bac7(1-35) di legare in vitro il DNA, ma abbiamo escluso che tale legame rappresenti il meccanismo primario della sua attività battericida. Abbiamo anche dimostrato che il peptide non interferisce in vitro in maniera significativa con il processo di trascrizione, deducendo che l’effetto osservato sul processo di trascrizione/traduzione fosse da attribuirsi prevalentemente all’inibizione della traduzione. Abbiamo verificato tali dati in vivo su cellule di E. coli misurando l’incorporazione di precursori radioattivi delle macromolecole batteriche. Abbiamo osservato che l’esposizione di batteri a Bac7(1-35) bloccava l’incorporazione di leucina radioattiva ma non di timidina ed uridina, indicando un blocco specifico della sintesi proteica ma non di quelle di DNA e RNA. In futuro, una definizione ancora più chiara del target intrabatterico di Bac7(1-35) potrebbe portare alla sperimentazione di tale molecola o di suoi analoghi come farmaci antibiotici di nuova generazione.
XXV Ciclo
1985
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2

Chettaf, Aïssa. "Contribution à l'étude du séchage par rayonnement infrarouge : Application au séchage en couche mince d'une enduction." Valenciennes, 1994. https://ged.uphf.fr/nuxeo/site/esupversions/9a259158-201e-4807-bac7-56fdaf6a482b.

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Dans cette étude, nous nous intéressons particulièrement au séchage d'une enduction (colle à eau) soumise à des contraintes radiatives et convectives. L'apport d'énergie nécessaire à la vaporisation du solvant provient essentiellement d'un émetteur de rayonnement infrarouge. Dans un premier temps, nous avons procédé à la caractérisation physico-chimique du produit, en l'occurrence une colle à papier. Quelques propriétés intrinsèques ont été déterminées au laboratoire pour être utilisées dans une modélisation des transferts de matière et de chaleur et enfin le choix de l'émetteur infrarouge utilisé dans toutes nos opérations de séchage. Dans une deuxième partie, l'émetteur infrarouge a fait l'objet d'une caractérisation thermique. La technique utilisée est la thermographie infrarouge pour déterminer le champ de température de la plaque. A partir du champ de température, nous avons résolu numériquement l'équation inverse du bilan énergétique pour déterminer les densités de flux. L'analyse des résultats expérimentaux de séchage nous a permis de vérifier la validité du modèle, purement diffusif, décrivant d'une manière satisfaisante le comportement de la colle. Les résultats de caractérisation de l'émetteur nous ont permis de déterminer la disposition géométrique de plusieurs émetteurs afin d'avoir un séchage relativement homogène sur tout le produit. L'ensemble des résultats est utilisé pour concevoir une installation de séchage par rayonnement infrarouge qui sera expérimentée sur site industriel.
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Pelillo, Chiara. "Therapeutic potential of BAC7(I-35), a Proline-rich Antimicrobial Peptide: in vitro and in vivo studies and Pegylation strategy to improve its bioavailability." Doctoral thesis, Università degli studi di Trieste, 2011. http://hdl.handle.net/10077/5978.

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2009/2010
The antimicrobial peptides (AMPs) are an important component of the innate defense against invading microorganisms, are widespread in nature and may have multiple and diversified mechanisms of bactericidal action. In addition to their direct antimicrobial activity the are also involved in other biological processes. The aim of this project was to investigate the in vivo activity of Bac7(1-35), a bovine proline-rich antimicrobial peptide, having in mind its possible use as a lead compound for the development of novel anti-infective agents. Before moving to animal models of infection, the in vitro stability of the peptide in the presence of murine and human serum or plasma as well as its biodistribution in mouse were investigated. Antibacterial activity assays against Salmonella enterica showed that the presence of murine blood components largely inhibits the antibacterial activity of the peptide. On the contrary, in human serum and plasma Bac7(1-35) maintains its efficacy. This is due to the more rapid degradation by proteases of murine blood. The in vivo biodistribution of Bac7(1-35) was investigated by using a time-domain optical imaging apparatus and a fluorescently-labeled Bac7(1-35) derivative. The compound reaches the kidney and the bladder respectively 1 and 3 hours after i.p. injection. The in vivo and ex vivo analyses performed after 24 h confirm that the compound has been totally excreted. A mouse model of S. typhimurium infection was set up and used to test the therapeutic efficacy of Bac7(1-35). Treatment of infected mice with the peptide injected i.p. immediately after a lethal, intraperithoneal bacterial challenge, increased the mean survival time and reduced significantly the number of viable bacterial cells in liver and spleen of treated mice at 3 days post-inoculum. In 1/3 of the organ homogenates, the bacterial presence was undetectable and this result matches the percentage of cured animals (35%). In an attempt to improve its pharmacokinetic profile, the peptide was conjugated with polyethylene glycol (PEG), a non-toxic, non-immunogenic and FDA-approved polymer. Different strategies of pegylation have been considered to find the best method in terms of chemical yield and of maintenance of biological activity. Pegylation via a thioether ligation resulted the best strategy to obtain a slow active peptide release in human blood components with a reduced renal clearance and an increased bioavailability of Bac7(1-35), as biodistribution analyses demonstrated. Several important pathogens, such as S. enterica, cause disease by surviving and replicating within host cells. Since many AMPs have also immunomodulatory activities, we investigated the effect of Bac7(1-35) on the interaction between macrophages and Salmonella. We carried out phagocytosis assays with macrophages and the results suggest that Bac7(1-35) plays a positive modulatory effect on this function. Phagocytosis assays were also performed to determine if Bac7(1-35) could inhibit survival and replication of intracellular Salmonella. The results show that the peptide inhibits the replication of intracellular Salmonella, suggesting that it can exert its antibacterial activity within eukaryotic cells. Further studies are required to fully understand the details of the Bac7(1-35) biological activities. The results obtained provide encouraging evidence for future investigations on Bac7(1-35) and on the pegylated form Bac7(1-35)CAM-PEG20k also in other models of infection and with different intracellular pathogens.
XXIII Ciclo
1981
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4

Runti, Giulia. "New insights into the architecture and function of SbmA, an unusual transporter of the inner membrane of E. coli." Doctoral thesis, Università degli studi di Trieste, 2012. http://hdl.handle.net/10077/7409.

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2010/2011
SbmA/BacA è una proteina della membrana interna presente nei batteri Gram negativi e caratterizzata da omologia di sequenza con i domini transmembrana (TMDs) dei sistemi di trasporto di tipo ABC. Ceppi di E. coli con una delezione completa del gene sbmA mostrano un’aumentata resistenza al peptide antimicrobico Bac7 e ad altri peptidi ricchi in prolina a seguito di una loro ridotta internalizzazione. Gli omologhi di SbmA in altre specie sono essenziali per instaurare un’infezione cronica sia in ospiti di origine vegetale che animale. Lo scopo del presente lavoro è stato caratterizzare l’organizzazione e la funzione del sistema di trasporto rappresentato da SbmA in E. coli. Mediante saggi di cromatografia di affinità e di anisotropia a fluorescenza, è stato mostrato come SbmA sia in grado di legare Bac7 senza la necessità di una proteina di legame del substrato (SBP). Inoltre, mediante la tecnica del doppio ibrido in batterio e saggi di crosslinking in vitro, è stato mostrato come SbmA formi dimeri sia in vivo sia in vitro. Saggi di citofluorimetria in presenza di diversi inibitori metabolici indicano come la presenza di un gradiente protonico sia essenziale per garantire il trasporto del peptide attraverso la membrana batterica, trasporto che sembra essere indipendente dall’energia derivata dall’idrolisi dell’ATP. Allo scopo di identificare possibili interattori di SbmA, è stato analizzato il locus genomico di sbmA ed è stato dimostrato che il gene yaiW, localizzato a valle di sbmA, forma con quest’ultimo un’unica unità trascrizionale. Sebbene i due geni siano cotrascritti, le corrispondenti proteine non sembrano interagire né a livello citoplasmatico né di membrana interna. Tuttavia, l’interazione tra queste due proteine a livello periplasmico non può essere esclusa ed il coinvolgimento di YaiW nell’internalizzazione di Bac7 mediata da SbmA può essere ipotizzato sulla base dell’aumentata resistenza al peptide mostrata dal ceppo con una delezione completa del gene yaiW. Dal vaglio in vivo dell’intero proteoma di E. coli versus SbmA mediante il sistema BACTH non è stato identificato alcun dominio di legame dell’ATP, rafforzando quindi l’ipotesi che il sistema di trasporto rappresentato da SbmA non richieda l’idrolisi dell’ATP come fonte di energia. Questo studio ha permesso di identificare 9 possibili interattori di SbmA, tra i quali la proteina della membrana interna FieF, coinvolta nell’efflusso di ioni Zn(II) dalla cellula batterica. E’ stato mostrato come FieF sia coinvolta nell’internalizzazione di Bac7 mediata da SbmA e come l’espressione di sbmA sia modulata dagli ioni Zn(II) in maniera complessa, suggerendo un possibile ruolo per questa proteina nella risposta allo stress da parte del batterio. Questi risultati suggeriscono come SbmA sia un insolito trasportatore di peptidi derivato dalla famiglia dei trasportatori ABC, che ha successivamente perso e/o cambiato nel corso dell’evoluzione alcune caratteristiche, come ad esempio la necessità di una proteina di legame del substrato o la fonte di energia richiesta per il trasporto dei substrati. Inoltre, l’interazione osservata tra le due proteine SbmA e FieF potrebbe suggerire un possibile ruolo della prima nel processo di detossificazione dello zinco, attività che potrebbe essere modulata dal legame di un substrato di natura peptidica a SbmA. Infine, la regolazione dell’espressione di sbmA mediata dagli ioni Zn(II) potrebbe avere un ruolo fisiologico nell’ospite in quanto promuove una maggiore suscettibilità dei batteri ai peptidi antimicrobici ed è in grado di attivare effettori cellulari come i neutrofili.
SbmA/BacA is a protein of the inner membrane of many Gram negative bacteria, predicted to be the transmembrane domain of an ABC transport system. sbmA-deleted E. coli strain shows an increased resistance to the antimicrobial peptide Bac7 and other proline-rich peptides due to their reduced uptake. In addition, BacA of some Gram negative species is essential to establish chronic infection in animal and plant hosts. The aim of this study was to characterize the architecture and function of the SbmA transport system in E. coli. By affinity chromatography and fluorescence anisotropy assays we showed that SbmA is able to bind Bac7 also without the requirement of a substrate-binding protein. By using a bacterial two-hybrid BACTH system and in vitro crosslinking assay we showed that SbmA forms dimers both in vivo and in vitro. Flow cytometry analysis using different metabolic inhibitors indicate that the proton motive force rather than ATP hydrolysis may represent the driving force for the translocation of peptide substrates. Searching for possible interactors of SbmA, we showed that the yaiW gene, located downstream of sbmA, is part of the same operon. Even if the two genes are cotranscribed, the corresponding proteins do not seem to interact neither at the cytoplasmic nor at the inner membrane level. However, ΔyaiW strain showed an increased resistance to Bac7 suggesting the involvement of this protein in the SbmA-mediated uptake of the peptide. An in vivo screening of the whole proteome of E. coli against SbmA by the BACTH system did not identify any nucleotide-binding domain of the transporter, strengthening the hypothesis that the transport system is energized by a mechanism different from ATP hydrolysis. Two-hybrid analysis allowed us to fish out 9 potential interactors and among those our attention was focused on FieF, an inner membrane protein involved in zinc efflux from the bacterial cell. We demonstrated that FieF is involved in the SbmA-mediated uptake of Bac7 and that the expression of sbmA is modulated by zinc ions in a complex manner, suggesting a stress role for this protein in bacteria. Overall, these findings suggest that SbmA is an unusual peptide transporter likely derived from the widespread ABC transporters, which has evolutionary lost/changed some typical features of this transport systems, such as the request of a substrate-binding protein and the ATP binding domain. The interaction between SbmA and FieF points to a possible involvement of the former in zinc detoxification, a function which may be modulated by the binding of an unidentified peptide substrate. The regulation of the expression of SbmA by zinc ions might have a physiological relevance in the host because it makes the target bacteria more susceptible to the AMPs and activates cellular effectors such as the neutrophils.
XXIV Ciclo
1984
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Mawson, Mark. "Interactive fluid-structure interaction with many-core accelerators." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/interactive-fluidstructure-interaction-with-manycore-accelerators(a4fc2068-bac7-4511-960d-41d2560a0ea1).html.

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The use of accelerator technology, particularly Graphics Processing Units (GPUs), for scientific computing has increased greatly over the last decade. While this technology allows larger and more complicated problems to be solved faster than before it also presents another opportunity: the real-time and interactive solution of problems. This work aims to investigate the progress that GPU technology has made towards allowing fluid-structure interaction (FSI) problems to be solved in real-time, and to facilitate user interaction with such a solver. A mesoscopic scale fluid flow solver is implemented on third generation nVidia ‘Kepler’ GPUs in two and three dimensions, and its performance studied and compared with existing literature. Following careful optimisation the solvers are found to be at least as efficient as existing work, reaching peak efficiencies of 93% compared with theoretical values. These solvers are then coupled with a novel immersed boundary method, allowing boundaries defined at arbitrary coordinates to interact with the structured fluid domain through a set of singular forces. The limiting factor of the performance of this method is found to be the integration of forces and velocities over the fluid and boundaries; the arbitrary location of boundary markers makes the memory accesses during these integrations largely random, leading to poor utilisation of the available memory bandwidth. In sample cases, the efficiency of the method is found to be as low as 2.7%, although in most scenarios this inefficiency is masked by the fact that the time taken to evolve the fluid flow dominates the overall execution time of the solver. Finally, techniques to visualise the fluid flow in-situ are implemented, and used to allow user interaction with the solvers. Initially this is achieved via keyboard and mouse to control the fluid properties and create boundaries within the fluid, and later by using an image based depth sensor to import real world geometry into the fluid. The work concludes that, for 2D problems, real-time interactive FSI solvers can be implemented on a single laptop-based GPU. In 3D the memory (both size and bandwidth) of the GPU limits the solver to relatively simple cases. Recommendations for future work to allow larger and more complicated test cases to be solved in real-time are then made to complete the work.
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Saunders, Catherine. "Asymptotic methods applied to problems of steady-streaming flows and acoustic radiation forces." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/asymptotic-methods-applied-to-problems-of-steadystreaming-flows-and-acoustic-radiation-forces(7c4856bd-5d9d-44b5-bac7-d2aed745f258).html.

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Small-amplitude, high-frequency (ultrasound) forcing of fluid/particle systems is being used in a number of applications associated with non-destructive fluid mixing and the movement/manipulation of particles in suspension. Of most importance in this context are the second-order, steady, effects arising from the nonlinear interaction of a leading-order oscillatory field with itself. In this thesis we consider some of these steady effects in both incompressible and compressible fluids. We first consider the axisymmetric steady streaming generated in an incompressible, viscous fluid contained between two (radially) infinite parallel plates, each oscillating in a direction normal to its own plane. In the limit of small-amplitude, high-frequency oscillations, we show that the steady-streaming flow in the fluid bulk is driven by thin streaming sublayers at the plates, at which the normal velocity is zero and the radial velocity varies linearly with distance from the axis of rotational symmetry. Effectively, in the bulk flow, the bounding plates appear as (no-slip) impermeable walls that stretch radially. This bulk-flow problem is extended to allow for the analogous steady flow of two immiscible, incompressible, viscous fluids, each undergoing a radial-stretching motion appropriate to high-frequency steady streaming. For a flat interface between the fluids, a self-similar solution reduces the Navier--Stokes equations to a nonlinear boundary-value problem, the solution of which exhibits an interesting structure in the limit of large Reynolds number. In this limit, solutions can be found using matched asymptotic expansions, but the location of the interface between the fluids can only be determined if terms that are exponentially small in the Reynolds number are included. It is shown that for fluids of almost-equal densities, exponentially-small differences can have a leading-order effect on the observed flow. The second part of the thesis is concerned with the (steady) acoustic radiation force on a rigid sphere submerged in a compressible, inviscid fluid, when the wavelength of the incident acoustic field is large compared to the radius of the sphere. In this limit, a matched asymptotic expansion method is used to derive an expression for the acoustic radiation force, on both fixed and free rigid spheres, due to a range of incident fields. For incident acoustic fields that are appropriate to planar and circular waveguides/channels, expressions are derived for the scattered field and the radiation force on a rigid sphere in the long-wavelength limit. Fixed and free spheres located both on and off the axis of symmetry of these incident fields are considered. This is an extension to the current literature, in which numerical methods are used to examine the scattering from spheres in an off-axis position, and problems are restricted to the consideration of fixed spheres only. It is shown that there are stable and unstable positions within the waveguide where any off-axis acoustic radiation force vanishes, leaving only an along-channel component. For free spheres, these positions are shown to be dependent on the relative particle density and it is suggested that this may allow for a mechanism to sort such small particles radially in a circular waveguide, if secondary scattering effects are neglected.
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Gray, Imara. "Self-esteem and self-concept in individuals with 'poor me' and 'bad me' persecutory beliefs." Thesis, Bangor University, 2009. https://research.bangor.ac.uk/portal/en/theses/selfesteem-and-selfconcept-in-individuals-with-poor-me-and-bad-me-persecutory-beliefs(60be59cb-0d54-4275-bac7-823bea6cf811).html.

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Background: Persecutory delusions are a common psychiatric symptom, affecting between 50 and 90% of those with psychosis. They are associated with high levels of distress, social isolation and hospitalisation. Psychological theories of persecutory delusions have been developed in order to inform the care of this distressing symptom. Objectives: The current thesis has two aims. The literature review aims to evaluate two current psychological models of persecutory delusions, namely Daniel Freeman's model, which suggests that anxiety plays a direct causal role in persecutory beliefs, and Richard Bentall's model, which suggests that persecutory delusions are a defence against low self-esteem and depression. The research project aimed to further investigate Richard Bentall's model by looking at patterns of self-esteem in two different types of persecutory delusion: 'poor me' delusions, in which the individual feels that their persecution is not deserved; and 'bad me' delusions, in which the individual feels that their persecution is deserved. Methods: The literature review comprises a comprehensive review of the literature looking at anxiety, self-esteem and depression in those with persecutory delusions. The research project used a combination of self-report questionnaires and a computer task to measure self-esteem in those with persecutory delusions. Findings: The literature review outlines high levels of anxiety, depression and low self-esteem in those with persecutory delusions. Little evidence is found to support Freeman's model of persecutory delusions. Some initial evidence however is found in support of a revised version of Bentall's model. The research project meanwhile found patterns of self-esteem in 'poor me' and 'bad me' delusions that were consistent with Bentall's revised model. Conclusions: The current thesis outlines support for Bentall's revised model of persecutory delusions. The thesis also outlines the need for further research in a number of areas.
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Lindberg, Erik, and Lukas Magnusson. "WEC Back-to-back Topology." Thesis, Uppsala universitet, Institutionen för teknikvetenskaper, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-351912.

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Johnson, Lisa Marie. "Back to back they faced each other." Thesis, University of Iowa, 2011. https://ir.uiowa.edu/etd/993.

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Fluhrer, Regina. "Zwei neuartige Aspartylproteasen BACE-1 und BACE-2." Diss., lmu, 2003. http://nbn-resolving.de/urn:nbn:de:bvb:19-14423.

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Books on the topic "Bac7"

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1906-, Back Custer, and Back/Bach Genealogy Society, eds. A Back family history: The story of a major branch of the Bach/Back family. [United States]: Back/Bach Genealogy Society, 1994.

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Moses, Itamar. Back back back. New York: Samuel French, 2009.

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Brebrayer, David. Evidence based management of low back pain. Sudbury,ON: NEORCC, 2004.

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Commission royale sur le transport des voyageurs au Canada. Étude de l'industrie des traversiers au Canada. Ottawa, Ont: Division de la recherche, Commission royale sur le transport des voyageurs au Canada, 1991.

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Katrin, Kintzel, and Schrastetter Lydia, eds. Strong and healthy back: Stay flexible - live without pain. New York: Barnes & Noble, 2006.

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Applied anatomy of the back. Berlin: Springer-Verlag, 1985.

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Back strengthening for health & fitness. New York: Sterling Innovation, 2008.

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Kennedy, Robert. Herculean back! New York: Sterling Pub. Co., 1988.

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Irv, Rubenstein, ed. Exercise ideas for core strengthening. Tacoma, Wash: Visual Health Information, 2005.

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Innere Harmonie durch Bach-Blüten: Natürlich und wirksam ; bei seelischer Belastung, bei Krankheiten, in Notfällen. 2nd ed. München: Gräfe und Unzer, 1995.

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Book chapters on the topic "Bac7"

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Fretheim, B. Solveig. "Back to Bach." In Narratives and Reflections in Music Education, 237–54. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-28707-8_18.

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"8 Literatur." In Familie - nein danke?!, 225–35. Göttingen: Vandenhoeck & Ruprecht GmbH & Co. KG, 2012. http://dx.doi.org/10.13109/9783666401824.back.

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"Quellen." In Meine andere Welt, 153–56. Göttingen: Vandenhoeck & Ruprecht GmbH & Co. KG, 2012. http://dx.doi.org/10.13109/9783666401886.back.

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"Namen-und Sachregister, Stellenregister." In Ausonius an Paulinus von Nola, 357–76. Göttingen: Vandenhoeck & Ruprecht GmbH & Co. KG, 2012. http://dx.doi.org/10.13109/9783647252971.back.

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Omar, Haim. "Anzeigen." In Autorität durch Beziehung, 263–64. Vandenhoeck & Ruprecht, 2016. http://dx.doi.org/10.13109/9783666490774.back.

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"Back Pain." In Quick Reference Guide to Pediatric Care, 100–105. 2nd ed. American Academy of Pediatrics, 2017. http://dx.doi.org/10.1542/9781610021128-back.

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"Index." In Biodiesel Science and Technology, 822–40. Elsevier, 2010. http://dx.doi.org/10.1533/back-matter.

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"Back Pain." In Quick Reference Guide to Pediatric Care, 114–18. American Academy of Pediatrics, 2005. http://dx.doi.org/10.1542/9781581106220-part01-back.

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"Index." In Functional Assessment of Wetlands, 661–72. Elsevier, 2009. http://dx.doi.org/10.1533/9781845695163.back-matter.

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"Index." In Improving the Sensory and Nutritional Quality of Fresh Meat, 647–64. Elsevier, 2009. http://dx.doi.org/10.1533/9781845695439.back-matter.

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Conference papers on the topic "Bac7"

1

Hertanto, Anthony, Honggang Liu, Davit Yeghikyan, B. Gangadhar Rayaprol, Nazir P. Kherani, and Stefan Zukotynski. "Back Amorphous-Crystalline Silicon Heterojunction (bach) photovoltaic device." In 2009 34th IEEE Photovoltaic Specialists Conference (PVSC). IEEE, 2009. http://dx.doi.org/10.1109/pvsc.2009.5411466.

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Pfenniger, Daniel. "Fractal geometry of interstellar gas and dark matter in HI disks." In Back to the Galaxy. AIP, 1992. http://dx.doi.org/10.1063/1.43943.

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Wilson, Thomas L. "The cosmological constant and dark matter in the Galaxy." In Back to the Galaxy. AIP, 1992. http://dx.doi.org/10.1063/1.43944.

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de Geus, Eugène J. "Formation of massive stars at the edge of our Galaxy." In Back to the Galaxy. AIP, 1992. http://dx.doi.org/10.1063/1.43974.

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Dettmar, Ralf-Jürgen. "The ionization of diffuse ionized gas in galaxies: A comparison with the Reynolds-layer in the Milky Way." In Back to the Galaxy. AIP, 1992. http://dx.doi.org/10.1063/1.43989.

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Petuchowski, S. J., and C. L. Bennett. "Probes of the warm ionized medium in the disk of the Galaxy." In Back to the Galaxy. AIP, 1992. http://dx.doi.org/10.1063/1.43990.

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Weinberg, Martin D. "Distribution of stars in the disk." In Back to the Galaxy. AIP, 1992. http://dx.doi.org/10.1063/1.44000.

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Wyse, Rosemary, and Gerard Gilmore. "The dynamical evolution of the Galaxy." In Back to the Galaxy. AIP, 1992. http://dx.doi.org/10.1063/1.44001.

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Binney, James, and Ortwin Gerhard. "Dynamics of the galactic bulge-bar." In Back to the Galaxy. AIP, 1992. http://dx.doi.org/10.1063/1.43925.

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Blitz, Leo. "Photometric evidence for the bar." In Back to the Galaxy. AIP, 1992. http://dx.doi.org/10.1063/1.43926.

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Reports on the topic "Bac7"

1

Chase, Benjamin, Troy Unruh, and Joy Rempe. Initial Back-to-Back Fission Chamber Testing in ATRC. Office of Scientific and Technical Information (OSTI), June 2014. http://dx.doi.org/10.2172/1164850.

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Kim, U. J., Hiroaki Shizuya, and M. I. Simon. Development of BAC libraries and integrated physical mapping of human chromosome 22 using BACs. Annual report, July 1994--June 1995. Office of Scientific and Technical Information (OSTI), December 1995. http://dx.doi.org/10.2172/639707.

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Riewe, Krissi. Pieced Back Together. Ames (Iowa): Iowa State University. Library, January 2019. http://dx.doi.org/10.31274/itaa.8754.

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Marshak, Ronni. Winning Back Customers. Boston, MA: Patricia Seybold Group, September 2002. http://dx.doi.org/10.1571/ce9-12-02cc.

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Binnendijk, Hans, and Alan Henrikson. Back to Bipolarity? Fort Belvoir, VA: Defense Technical Information Center, May 1999. http://dx.doi.org/10.21236/ada385982.

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Ravindranath, R., T. Reddy, G. Salgueiro, V. Pascual, and P. Ravindran. DTLS-SRTP Handling in SIP Back-to-Back User Agents. RFC Editor, May 2016. http://dx.doi.org/10.17487/rfc7879.

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Morton, A. Updates for the Back-to-Back Frame Benchmark in RFC 2544. RFC Editor, May 2021. http://dx.doi.org/10.17487/rfc9004.

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DeSantis, G. N. Strong-back safety latch. Office of Scientific and Technical Information (OSTI), March 1995. http://dx.doi.org/10.2172/32765.

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Strandwitz, Nicholas, and Ben Davis. Tunneling Back-Contacted Photovoltaics. Office of Scientific and Technical Information (OSTI), July 2019. http://dx.doi.org/10.2172/1542790.

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Kaplan, H., and V. Pascual. A Taxonomy of Session Initiation Protocol (SIP) Back-to-Back User Agents. RFC Editor, December 2013. http://dx.doi.org/10.17487/rfc7092.

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