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Статті в журналах з теми "NSXA"

1

Lindenbach, Brett D., Béla M. Prágai, Roland Montserret, Rudolf K. F. Beran, Anna M. Pyle, François Penin, and Charles M. Rice. "The C Terminus of Hepatitis C Virus NS4A Encodes an Electrostatic Switch That Regulates NS5A Hyperphosphorylation and Viral Replication." Journal of Virology 81, no. 17 (June 20, 2007): 8905–18. http://dx.doi.org/10.1128/jvi.00937-07.

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ABSTRACT Hepatitis C virus (HCV) nonstructural protein 4A (NS4A) is only 54 amino acids (aa) in length, yet it is a key regulator of the essential serine protease and RNA helicase activities of the NS3-4A complex, as well as a determinant of NS5A phosphorylation. Here we examine the structure and function of the C-terminal acidic region of NS4A through site-directed mutagenesis of a Con1 subgenomic replicon and through biophysical characterization of a synthetic peptide corresponding to this region. Our genetic studies revealed that in 8 of the 15 C-terminal residues of NS4A, individual Ala substitutions or charge reversal substitutions led to severe replication phenotypes, as well as decreased NS5A hyperphosphorylation. By selecting for replication-competent mutants, several second-site changes in NS3 were identified and shown to suppress these defects in replication and NS5A hyperphosphorylation. Circular-dichroism spectroscopy and nuclear magnetic resonance spectroscopy on a peptide corresponding to the C-terminal 19 aa of NS4A revealed that this region can adopt an alpha-helical conformation, but that this folding requires neutralization of a cluster of acidic residues. Taken together, these data suggest that the C terminus of NS4A acts as a dynamic regulator of NS3-4A interaction, NS5A hyperphosphorylation, and HCV replicase activity.
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2

Neddermann, Petra, Angelica Clementi, and Raffaele De Francesco. "Hyperphosphorylation of the Hepatitis C Virus NS5A Protein Requires an Active NS3 Protease, NS4A, NS4B, and NS5A Encoded on the Same Polyprotein." Journal of Virology 73, no. 12 (December 1, 1999): 9984–91. http://dx.doi.org/10.1128/jvi.73.12.9984-9991.1999.

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ABSTRACT The nonstructural protein NS5A of hepatitis c virus (HCV) has been demonstrated to be a phosphoprotein with an apparent molecular mass of 56 kDa. In the presence of other viral proteins, p56 is converted into a slower-migrating form of NS5A (p58) by additional phosphorylation events. In this report, we show that the presence of NS3, NS4A, and NS4B together with NS5A is necessary and sufficient for the generation of the hyperphosphorylated form of NS5A (p58) and that all proteins must be encoded on the same polyprotein (in cis). Kinetic studies of NS5A synthesis and pulse-chase experiments demonstrate that fully processed NS5A is the substrate for the formation of p58 and that p56 is converted to p58. To investigate the role of NS3 in NS5A hyperphosphorylation, point and deletion mutations were introduced into NS3 in the context of a polyprotein containing the proteins from NS3 to NS5A. Mutation of the catalytic serine residue into alanine abolished protease activity of NS3 and resulted in total inhibition of NS5A hyperphosphorylation, even if polyprotein processing was allowed by addition of NS3 and NS4A in trans. The same result was obtained by deletion of the first 10 or 28 N-terminal amino acids of NS3, which are known to be important for the formation of a stable complex between NS3 and its cofactor NS4A. These data suggest that the formation of p58 is closely connected to HCV polyprotein processing events. Additional data obtained with NS3 containing the 34 C-terminal residues of NS2 provide evidence that in addition to NS3 protease activity the authentic N-terminal sequence is required for NS5A hyperphosphorylation.
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3

Oliver Koch, Jan, and Ralf Bartenschlager. "Modulation of Hepatitis C Virus NS5A Hyperphosphorylation by Nonstructural Proteins NS3, NS4A, and NS4B." Journal of Virology 73, no. 9 (September 1, 1999): 7138–46. http://dx.doi.org/10.1128/jvi.73.9.7138-7146.1999.

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ABSTRACT NS5A of the hepatitis C virus (HCV) is a highly phosphorylated protein involved in resistance against interferon and required most likely for replication of the viral genome. Phosphorylation of this protein is mediated by a cellular kinase(s) generating multiple proteins with different electrophoretic mobilities. In the case of the genotype 1b isolate HCV-J, in addition to the basal phosphorylated NS5A (designated pp56), a hyperphosphorylated form (pp58) was found on coexpression of NS4A (T. Kaneko, Y. Tanji, S. Satoh, M. Hijikata, S. Asabe, K. Kimura, and K. Shimotohno, Biochem. Biophys. Res. Commun. 205:320–326, 1994). Using a comparative analysis of two full-length genomes of genotype 1b, competent or defective for NS5A hyperphosphorylation, we investigated the requirements for this NS5A modification. We found that hyperphosphorylation occurs when NS5A is expressed as part of a continuous NS3-5A polyprotein but not when it is expressed on its own or trans complemented with one or several other viral proteins. Results obtained with chimeras of both genomes show that single amino acid substitutions within NS3 that do not affect polyprotein cleavage can enhance or reduce NS5A hyperphosphorylation. Furthermore, mutations in the central or carboxy-terminal NS4A domain as well as small deletions in NS4B can also reduce or block hyperphosphorylation without affecting polyprotein processing. These requirements most likely reflect the formation of a highly ordered NS3-5A multisubunit complex responsible for the differential phosphorylation of NS5A and probably also for modulation of its biological activities.
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4

De Francesco, Raffaele, Antonello Pessi, and Christian Steinkühler. "The Hepatitis C Virus NS3 Proteinase: Structure and Function of a Zinc-Containing Serine Proteinase." Antiviral Therapy 3, no. 3_suppl (April 1998): 99–109. http://dx.doi.org/10.1177/135965359800303s01.

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The hepatitis C virus (HCV) NS3 protein contains a serine proteinase domain implicated in the maturation of the viral polyprotein. NS3 forms a stable heterodimer with NS4A, a viral memebrane protein that acts as an activator of the IMS3 proteinase. The three-dimensional structure of the NS3 proteinase complexed with an NS4A-derived peptide has been determined. The NS3 proteinase adopts a chymotrypsin-like fold. A β-strand contributed by NS4A is clamped between two β-strands within the N terminus of NS3. Consistent with the requirement for extraordinarily long peptide substrates (P6-P4’), the structure of the NS3 proteinase reveals a very long, solvent-exposed substrate-binding site. The primary specificity pocket of the enzyme is shallow and closed at its bottm by Phe-154, explaining the preference of the NS3 proteinase for cysteine residues in the substrate P, position. Another important feature of the NS3 proteinase is the presence of a tetrahedral zinc-binding site formed by residues Cys-97, Cys-99, Cys-145 and His-149. The zinc-binding site has a role in maintaining the structural stability and guiding the folding of the NS3 serine proteinase domain. Inhibition of the NS3 proteinase activity is regarded as a promising strategy to control the disease caused by HCV. Remarkably, the NS3 proteinase is susceptible to inhibition by the N-terminal cleavage products of substrate peptides corresponding to the NS4A/NS4B, NS4B/NS5A and NS5A/NS5B cleavage sites. The Ki values of the inhibitory products are lower than the Km values of the respective substrates and follow the order NS4A<NS5A<NS4B. Starting from the observation that the NS3 proteinase undergoes product inhibition, very potent, active site-directed inhibitors have been generated using a combinatorial peptide chemistry approach.
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5

Bukhtiyarova, Marina, Christopher J. Rizzo, Charles A. Kettner, Bruce D. Korant, Helen T. Scarnati, and Robert W. King. "Inhibition of the Bovine Viral Diarrhoea Virus NS3 Serine Protease by a Boron-Modified Peptidyl Mimetic of its Natural Substrate." Antiviral Chemistry and Chemotherapy 12, no. 6 (December 2001): 367–73. http://dx.doi.org/10.1177/095632020101200607.

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Bovine viral diarrhoea virus (BVDV) is closely related to hepatitis C virus (HCV), and has been used as a surrogate virus in drug development for HCV infection. Similar to HCV, BVDV-encoded NS3 serine proteinase is responsible for multiple cleavages in the viral polyprotein, generating mature NS4A, NS4B, NS5A and NS5B proteins. NS3-dependent cleavage sites of BVDV contain a strictly conserved leucine at P1, and either serine or alanine at P1′. The full length BVDV NS3/4A serine protease has been cloned and expressed in bacterial cells. The enzyme has been purified from the soluble portion of Escherichia coli via a two-step purification procedure employing chromatography on heparin resin and gel filtration. The protease activity was characterized using in vitro translated BVDV NS4A/B and NS5A/B polyprotein substrates. A boronic acid analogue of the BVDV NS4A/NS4B cleavage site was synthesized and shown to be an efficient inhibitor of the NS3 serine protease in vitro. The compound, designated DPC-AB9144–00, inhibited approximately 75% of the NS3/4 activity at 10 μM with the NS4A/B substrate. However, no antiviral activity was detected with DPC-AB9144–00 in BVDV-infected Madin—Darby bovine kidney cells at concentrations as great as 90 μM, suggesting permeability or that other cellular-derived limitations were present.
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Sudo, Kenji, Kayo Yamaji, Kouich Kawamura, Tomoko Nishijima, Naoko Kojima, Kazuhiko Aibe, Kunitada Shimotohno, and Yasuaki Shimizu. "High-Throughput Screening of Low Molecular Weight NS3-NS4A Protease Inhibitors Using a Fluorescence Resonance Energy Transfer Substrate." Antiviral Chemistry and Chemotherapy 16, no. 6 (December 2005): 385–92. http://dx.doi.org/10.1177/095632020501600605.

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Hepatitis C virus (HCV) NS3-NS4A protease is an attractive target for anti-HCV agents because of its important role in replication. An optimized fluorescence resonance energy transfer (FRET) substrate for NS3-NS4A protease, based on the sequence of the NS5A-5B cleavage site, was designed and synthesized. High-throughput screening of in-house compound libraries was performed using a FRET substrate FS10 (MOCAc-DKIVPC-SMSYK-Dnp) and MBP-NS3-NS4A fusion protein. Several hit compounds were found, including YZ-9577 (2-oxido-1,2,5-oxadiazole-3,4-diyl) bis (phenylmethanone) with potent inhibitory activity (IC50=1.6 μM) and good selectivity against other human serine proteases.
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7

Butkiewicz, Nancy, Nanhua Yao, Weidong Zhong, Jacquelyn Wright-Minogue, Paul Ingravallo, Rumin Zhang, James Durkin, et al. "Virus-Specific Cofactor Requirement and Chimeric Hepatitis C Virus/GB Virus B Nonstructural Protein 3." Journal of Virology 74, no. 9 (May 1, 2000): 4291–301. http://dx.doi.org/10.1128/jvi.74.9.4291-4301.2000.

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ABSTRACT GB virus B (GBV-B) is closely related to hepatitis C virus (HCV) and causes acute hepatitis in tamarins (Saguinus species), making it an attractive surrogate virus for in vivo testing of anti-HCV inhibitors in a small monkey model. It has been reported that the nonstructural protein 3 (NS3) serine protease of GBV-B shares similar substrate specificity with its counterpart in HCV. Authentic proteolytic processing of the HCV polyprotein junctions (NS4A/4B, NS4B/5A, and NS5A/5B) can be accomplished by the GBV-B NS3 protease in an HCV NS4A cofactor-independent fashion. We further characterized the protease activity of a full-length GBV-B NS3 protein and its cofactor requirement using in vitro-translated GBV-B substrates. Cleavages at the NS4A/4B and NS5A/5B junctions were readily detectable only in the presence of a cofactor peptide derived from the central region of GBV-B NS4A. Interestingly, the GBV-B substrates could also be cleaved by the HCV NS3 protease in an HCV NS4A cofactor-dependent manner, supporting the notion that HCV and GBV-B share similar NS3 protease specificity while retaining a virus-specific cofactor requirement. This finding of a strict virus-specific cofactor requirement is consistent with the lack of sequence homology in the NS4A cofactor regions of HCV and GBV-B. The minimum cofactor region that supported GBV-B protease activity was mapped to a central region of GBV-B NS4A (between amino acids Phe22 and Val36) which overlapped with the cofactor region of HCV. Alanine substitution analysis demonstrated that two amino acids, Val27 and Trp31, were essential for the cofactor activity, a finding reminiscent of the two critical residues in the HCV NS4A cofactor, Ile25 and Ile29. A model for the GBV-B NS3 protease domain and NS4A cofactor complex revealed that GBV-B might have developed a similar structural strategy in the activation and regulation of its NS3 protease activity. Finally, a chimeric HCV/GBV-B bifunctional NS3, consisting of an N-terminal HCV protease domain and a C-terminal GBV-B RNA helicase domain, was engineered. Both enzymatic activities were retained by the chimeric protein, which could lead to the development of a chimeric GBV-B virus that depends on HCV protease function.
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8

Wölk, Benno, Domenico Sansonno, Hans-Georg Kräusslich, Franco Dammacco, Charles M. Rice, Hubert E. Blum, and Darius Moradpour. "Subcellular Localization, Stability, andtrans-Cleavage Competence of the Hepatitis C Virus NS3-NS4A Complex Expressed in Tetracycline-Regulated Cell Lines." Journal of Virology 74, no. 5 (March 1, 2000): 2293–304. http://dx.doi.org/10.1128/jvi.74.5.2293-2304.2000.

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ABSTRACT A tetracycline-regulated gene expression system and a panel of novel monoclonal antibodies were used to examine the subcellular localization, stability, and trans-cleavage competence of the hepatitis C virus (HCV) NS3-NS4A complex in inducible cell lines. The NS3 serine protease domain and the full-length NS3 protein expressed in the absence of the NS4A cofactor were diffusely distributed in the cytoplasm and nucleus. Coexpression of NS4A, however, directed NS3 to the endoplasmic reticulum (ER) or an ER-like modified compartment, as demonstrated by colocalization with 3,3′-dihexyloxacarbocyanine iodide, protein disulfide isomerase, and calnexin, as well as subcellular fractionation analyses. In addition, coexpression with NS4A dramatically increased the intracellular stability of NS3 (mean protein half-life of 26 versus 3 h) and allowed for NS4A-dependent trans-cleavage at the NS4B-NS5A junction. Deletion analyses revealed that the hydrophobic amino-terminal domain of NS4A was required for ER targeting of NS3. These results demonstrate the importance of studying HCV proteins in their biological context and define a well-characterized cell culture system for further analyses of the NS3-NS4A complex and the evaluation of novel antiviral strategies against hepatitis C.
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Selimović, Denis, and Mohamed Hassan. "Inhibition of Hepatitis C virus (HCV) Core protein- induced Cell Growth by Non-structural Protein 4A (NS4A) is Mediated by Mitochondrial Dysregulation." Bosnian Journal of Basic Medical Sciences 8, no. 1 (February 20, 2008): 4–11. http://dx.doi.org/10.17305/bjbms.2008.2988.

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Hepatitis C virus (HCV) is a significant health problem facing the world. More than 170 million people are infected with HCV worldwide. HCV encodes a large polyprotein precursor that is processed into at least 10 distinct products including structural (core, E1 and E2) and non-structural (NS2, NS3, NS4A, NS4B, NS5A and NS5B). Besides its importance in virus replication, NS4A functions as a cofactor for NS3 and contributes to viral pathogenesis by influencing cellular functions. Here, we investigated the effect of NS4A protein on the growth rate induced by core protein in liver cells. Using our established tetracycline inducible system, we demonstrated the ability of NS4A protein to inhibit core protein-induced cell growth in Hepatoma cell line, HepG2. Induction of both core and NS4A proteins in HepG2- core/NS4A transfectants inhibited core-induced growth advantage in HepG2-core transfectants and blocked NS4A protein-induced cell growth inhibition in HepG2-NS4A transfectants. Using both immune fluorescence staining and Western blot analysis, we confirmed the localization of NS4A protein to the mitochondria in HepG2-NS4A transfectants expressing NS4A protein. Data obtained from flow cytometry analysis, using JC-1 demonstrated the loss of mitochondrial membrane potential (ΔΨ^ by the expression of NS4A protein in HepG2-NS4A transfectants, but not by the expression of core protein in HepG2-core transfectants. Whereas, the induction of the expression of both core and NS4A proteins in HepG2-core/NS4A transfectants blocked NS4A-induced loss of ΔΨm in HepG2 cells. Taken together, our data suggest an important role for mitochondria in the modulation HCV NS4A-induced inhibition of HCV core-mediated cell growth.
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Martin, Morgan M., Stephanie A. Condotta, Jeremy Fenn, Andrea D. Olmstead, and François Jean. "In-cell selectivity profiling of membrane-anchored and replicase-associated hepatitis C virus NS3-4A protease reveals a common, stringent substrate recognition profile." Biological Chemistry 392, no. 10 (October 1, 2011): 927–35. http://dx.doi.org/10.1515/bc.2011.076.

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AbstractThe need to identify anti-Flaviviridaeagents has resulted in intensive biochemical study of recombinant nonstructural (NS) viral proteases; however, experimentation on viral protease-associated replication complexes in host cells is extremely challenging and therefore limited. It remains to be determined if membrane anchoring and/or association to replicase-membrane complexes of proteases, such as hepatitis C virus (HCV) NS3-4A, plays a regulatory role in the substrate selectivity of the protease. In this study, we examined trans-endoproteolytic cleavage activities of membrane-anchored and replicase-associated NS3-4A using an internally consistent set of membrane-anchored protein substrates mimicking all known HCV NS3-4A polyprotein cleavage sequences. Interestingly, we detected cleavage of substrates encoding for the NS4B/NS5A and NS5A/NS5B junctions, but not for the NS3/NS4A and NS4A/NS4B substrates. This stringent substrate recognition profile was also observed for the replicase-associated NS3-4A and is not genotype-specific. Our study also reveals that ER-anchoring of the substrate is critical for its cleavage by NS3-4A. Importantly, we demonstrate that in HCV-infected cells, the NS4B/NS5A substrate was cleaved efficiently. The unique ability of our membrane-anchored substrates to detect NS3-4A activity alone, in replication complexes, or within the course of infection, shows them to be powerful tools for drug discovery and for the study of HCV biology.
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Більше джерел

Дисертації з теми "NSXA"

1

Stone, Michael H. "North Carolina State NSCA Meeting." Digital Commons @ East Tennessee State University, 2005. https://dc.etsu.edu/etsu-works/4488.

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2

Snell, Jay. "Deep freeze and the NSSA labs /." Online version of thesis, 2009. http://hdl.handle.net/1850/9589.

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3

Kashfi, S. Ruhollah. "Towards Evaluation of the Adaptive-Epsilon-R-NSGA-II algorithm (AE-R-NSGA-II) on industrial optimization problems." Thesis, Högskolan i Skövde, Institutionen för ingenjörsvetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-10841.

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Simulation-based optimization methodologies are widely applied in real world optimization problems. In developing these methodologies, beside simulation models, algorithms play a critical role. One example is an evolutionary multi objective optimization algorithm known as Reference point-based Non-dominated Sorting Genetic Algorithm-II (R-NSGA-II), which has shown to have some promising results in this regard. Its successor, R-NSGA-II-adaptive diversity control (hereafter Adaptive Epsilon-R-NSGA-II (AE-R-NSGA-II) algorithm) is one of the latest proposed extensions of the R-NSGA-II algorithm and in the early stages of its development. So far, little research exists on its applicability and usefulness, especially in real world optimization problems. This thesis evaluates behavior and performance of AE-R-NSGA-II, and to the best of our knowledge is one of its kind. To this aim, we have investigated the algorithm in two experiments, using two benchmark functions, 10 performance measures, and a behavioral characteristics analysis method. The experiments are designed to (i) assess behavior and performance of AE-R-NSGA-II, (ii) and facilitate efficient use of the algorithm in real world optimization problems. This is achieved through the algorithm parameter configuration (parametric study) according to the problem characteristics. The behavior and performance of the algorithm in terms of diversity of the solutions obtained, and their convergence to the optimal Pareto front is studied in the first experiment through manipulating a parameter of the algorithm referred to as Adaptive epsilon coefficient value (C), and in the second experiment through manipulating the Reference point (R) according to the distance between the reference point and the global Pareto front. Therefore, as one contribution of this study two new diversity performance measures (called Modified spread, and Population diversity), and the behavioral characteristics analysis method called R-NSGA-II adaptive epsilon value have been introduced and applied. They can be modified and applied for the evaluation of any reference point based algorithm such as the AE-R-NSGA-II. Additionally, this project contributed to improving the Benchmark software, for instance by identifying new features that can facilitate future research in this area. Some of the findings of the study are as follows: (i) systematic changes of C and R parameters influence the diversity and convergence of the obtained solutions (to the optimal Pareto front and to the reference point), (ii) there is a tradeoff between the diversity and convergence speed, according to the systematic changes in the settings, (iii) the proposed diversity measures and the method are applicable and useful in combination with other performance measures. Moreover, we realized that because of the unexpected abnormal behaviors of the algorithm, in some cases the results are conflicting, therefore, impossible to interpret. This shows that still further research is required to verify the applicability and usefulness of AE-R-NSGA-II in practice. The knowledge gained in this study helps improving the algorithm.
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4

Gran, Mikael, and Claes Karlsson. "Survey of VMware NSX Virtualized Network Platform : Utvärdering av VMware NSX Virtualized Network Platform." Thesis, Mälardalens högskola, Akademin för innovation, design och teknik, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-35596.

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Atea Eskilstuna hade behovet av en plattform som kan förenkla och minska antalet konfigurationer vid implementation av kunder. Arbetet gick ut på att utvärdera plattformen VMware NSX och jämföra det mot traditionella nätverkslösningar. I dagens datacenter är virtualisering en viktig del av dess verksamhet. Användandet av virtualisering optimerar hanteringen av hårdvaru-resurser och kostnader. Virtualisering har hittills främst fokuserat på hantering av servrar och klienter, vilket har passerat nätverksutvecklingen, och därför har det uppstått vissa problem med traditionella datacenter gällande trafikflöden, säkerhet och implementering. Datacenter har tidigare varit optimerade för trafik som ska in eller ut ur datacentret. Detta har lett till att brandväggar och säkerhetspolicies ofta placerats vid datacentrets kant. I dagens datacenter har det däremot blivit en ökning på trafik mellan enheter inom datacentret som behöver skyddas. Denna typ av interna säkerhet kan uppnås av interna policies på samtliga nätverksenheter, dock blir det ohållbart vid implementation då antalet konfigurationspunkter i nätverket ökar. Dessa problem kan hanteras med hjälp av VMware NSX som virtualiserar nätverksenheter och centraliserar administration. NSX har en distribuerad brandväggs-funktion vilket medför att policies kan appliceras direkt på virtuella maskiner och virtuella routrar, från en central konfigurationspunkt. Detta ökar säkerheten och minskar implementationstiden jämfört med traditionella datacenter. Arbetet fokuserar på hur NSX arbetar till skillnad från fysiska nätverksenheter samt hur NSX hanterar frågor som trafikflöden, säkerhet och automation. För dessa ändamål byggdes en laborationsmiljö i Ravellos molntjänst med flertalet virtuella maskiner och en litteraturstudie utfördes. Laborationsmiljön användes för att sätta upp kunder med hjälp av virtuella nätverksenheter och virtuella maskiner. Laborationsmiljön användes som referens för hur implementation av NSX och dess funktioner går till. Litteraturstudien fokuserar på vad som är möjligt i NSX och vilka för- och nackdelar som finns med NSX jämfört med traditionella datacenter. Resultaten visade på att den enda nackdelen med NSX var dess licenskostnader.
Atea Eskilstuna had the need of a platform that simplify and reduce the number of configurations while implementing customer environments. The purpose of this thesis was to do a survey of VMware NSX networking platform and compare it to traditional networking solutions. The virtualization is an important part in data centers and its operations today. With the use of virtualization both hardware resources and costs optimizes. Virtualization has primary been focusing on servers and clients and the network evolution has been overlooked. Therefore, some problems have occurred within traditional data centers regarding traffic flows, security and management. Traditional datacenters have previously been optimized for traffic flows inbound or outbound of the datacenter. This optimization has led to implementation of firewalls and security policies at the datacenter edge. However, in the modern datacenters there’s been an increase of traffic flows between devices inside the datacenter, which needs to be secured. Securing these internal traffic flows can be accomplished through internal policies on the network devices. Implementing these policies however is not a scalable solution as the number of configuration points increases. These problems can be handled through VMware NSX which virtualize network units and centralizes administration. NSX provides a distributed firewall function that through a central management platform can be applied directly on groups of virtual machines and virtual routers. This approach increases security inside the datacenter as well as decreasing the implementation time compared to traditional datacenters. This thesis focus how NSX work unlike physical network units and how it handles issues like hairpinning, security and automation. A lab environment was built up in Ravellos cloud service with virtual machines and a literature study was made for this purpose. The lab environment was used to implement different customers with the help of virtual network components and virtual machines. This lab environment served as a reference point how implementation of NSX, its functions and components was made. The literature study focus on what is possible in NSX and which pros and cons that comes with NSX compared to traditional solutions in data centers. Results shows that the only cons with NSX is license costs.
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5

Grimm, Christian [Verfasser], Robert [Gutachter] Tampé, and Christoph [Gutachter] Welsch. "Charakterisierung des Lipidbindungsverhaltens und der Proteinfaltung von HCV NS5A unter Einfluss des NS5A-Inhibitors Daclatasvir / Christian Grimm ; Gutachter: Robert Tampé, Christoph Welsch." Frankfurt am Main : Universitätsbibliothek Johann Christian Senckenberg, 2021. http://d-nb.info/1239730276/34.

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6

Dias, Tiago Fouchy. "Otimização multiobjetivo de uma máquina pentafásica utilizando NSGA-II." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/156471.

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Neste trabalho é desenvolvida uma metodologia de otimização multiobjetivo baseada no NSGA-II (Nondominated Sorting Genetic Algorithm), a qual visa a otimização do projeto de máquinas de indução pentafásicas. A escolha deste tipo de máquina se justifica pelo fato de que elas apresentam vantagens importantes quando comparadas com as trifásicas convencionais, tais como maior potência e maior torque para um mesmo volume de material ativo, além da possibilidade de operar na ocorrência de falhas (perda de uma ou duas fases). Na otimização de máquinas de indução vários objetivos podem ser definidos, sendo estes muitas vezes conflitantes. Neste contexto, este trabalho visa obter soluções que representam um compromisso entre dois objetivos: rendimento e custo do material ativo (ferro e material condutor). O algoritmo de otimização desenvolvido e implementado utiliza dois controles de diversidade da população, um baseado no fenótipo dos indivíduos, que é característico do NSGA-II, e outro adicional que é baseado no genótipo. A geometria do estator e do rotor da máquina e o seu modo de acionamento são parametrizados por 14 variáveis inteiras. O método desenvolvido foi implementado no Matlab R e aplicado a um caso prático de otimização de uma máquina de indução pentafásica considerando os dois objetivos citados. Os resultados práticos mostram que o método é capaz de obter projetos otimizados com maior rendimento e menor custo aproveitando as características particulares deste tipo de máquina.
In this work, it is developed a method of multiobjective optimization based on NSGAII (Nondominated Sorting Genetic Algorithm), which aims at optimizing the design of five-phase induction machines. The choice of this particular type of machine is justified by the fact that they have important advantages over conventional three-phase machines, such as higher power and higher torque for the same volume of material; in addition, they can operate under fault (loss of one or even two phases). When optimizing induction machines, several objectives can be defined, which are often conflicting. In this context, this work aims to obtain solutions that represent a trade-off between two objectives: efficiency and cost of active material (iron and conductor materials). The optimization algorithm that was developed and implemented uses two types of control for the diversity of the population, one based on the phenotype of the individuals, characteristic of the NSGA-II, and another one based on the genotype. The geometrical dimensions of the stator and rotor, together with the driving strategy, are parameterized by 14 integer variables. The developed method was implemented using Matlab R and applied to a practical case of a five-phase induction machine considering the aforementioned objectives. The practical results show that the method can lead to an optimized design with higher efficiency and at a lower cost, accounting for the special characteristics of this type of machine.
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Gerdhem, Lovisa. "Cloning and Expression of TBEV NS4A in A549 cells." Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-78018.

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Background: Tick borne Encephalitis Virus (TBEV), the cause of the fatal Central Nervous System (CNS) infection Tick Borne Encephalitis (TBE), belongs to the family of Flaviviridae and the genusFlavivirus. In order to replicate themselves, they cause the formation of a replication complex, which is nestled inside vesicles of the Endoplasmic Reticulum (ER) membrane to protect the RNA from host defense mechanisms. These membrane vesicles are created by the interaction of viral nonstructural proteins and host proteins. The nonstructural protein, NS4A, is believed to play an important part in the formation of ER membrane vesicles, but it is not precisely known how. Earlier studies have shown that the cleavage of the NS4A protein from its C-terminal fragment,called 2k,is an important process in the formation of membrane vesicles. Aim: To express NS4Ain human A549 cells, and analyzeit with Western Blot in order to later purify said proteins and study their interactions with host proteins.This is important information in the study of mechanisms in membrane bending, which is crucial for the replication of TBEV as well as other flaviviruses. Methods: The DNA fragments were amplifiedusing PCR and tagged with a HIS-tag sequence. The fragments were then cloned into plasmids and transfected into A549 cells. SDS page and Western Blot were used to express the proteins. Results: The results showeda successfulexpression of the proteinsNS4A and NS4A-2k. The expression was stronger for the NS4A proteins lacking the 2k-fragment. The expression also seemed to be strongerin the cell cultures harvested on the second day of culturing. Conclusion: The results imply that the expression of NS4A is affected by whether or not it is cleaved from its 2k fragment. However,the experiment was only done once, and so,no absolute conclusions can be drawn.
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Zamani, Iman. "Optimal distributed generation planning based on NSGA-II and MATPOWER." Thesis, Brunel University, 2015. http://bura.brunel.ac.uk/handle/2438/11483.

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The UK and the world are moving away from central energy resource to distributed generation (DG) in order to lower carbon emissions. Renewable energy resources comprise a big percentage of DGs and their optimal integration to the grid is the main attempt of planning/developing projects with in electricity network. Feasibility and thorough conceptual design studies are required in the planning/development process as most of the electricity networks are designed in a few decades ago, not considering the challenges imposed by DGs. As an example, the issue of voltage rise during steady state condition becomes problematic when large amount of dispersed generation is connected to a distribution network. The efficient transfer of power out or toward the network is not currently an efficient solution due to phase angle difference of each network supplied by DGs. Therefore optimisation algorithms have been developed over the last decade in order to do the planning purpose optimally to alleviate the unwanted effects of DGs. Robustness of proposed algorithms in the literature has been only partially addressed due to challenges of power system problems such multi-objective nature of them. In this work, the contribution provides a novel platform for optimum integration of distributed generations in power grid in terms of their site and size. The work provides a modified non-sorting genetic algorithm (NSGA) based on MATPOWER (for power flow calculation) in order to find a fast and reliable solution to optimum planning. The proposed multi-objective planning tool, presents a fast convergence method for the case studies, incorporating the economic and technical aspects of DG planning from the planner‟s perspective. The proposed method is novel in terms of power flow constraints handling and can be applied to other energy planning problems.
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Baltz, Andre. "Merkel med NSA på andra sidan luren." Thesis, Umeå universitet, Institutionen för kultur- och medievetenskaper, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-84848.

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Title: Merkel with NSA on the telephone The aim of this essay is to study how Angela Merkel is being portrayed in context of NSAs surveillance in the Swedish newspapers Dagens Nyheter and Aftonbladet. The time period for the study is from the 24th of October to the 7th of November in the autumn of 2013. To concretize the aim three questions was formulated, how Angela Merkel was being portrayed in the material, how NSAs surveillance of Angela Merkel was being portrayed in the material and how different statements for various individuals in the material could affect the truth about the surveillance. The method chosen to study these questions was a discourse analysis, which also would contain parts of a linguistic analysis. The theories to support the method were Laclau & Mouffes discourse theory and Michel Foucault’s genealogical discourse analysis. The results of the analysis points to that Angela Merkel are being portrayed with titles, which represent her position in a democratic society. Words such as “head of government” “Bundeskansler” and “Kansler” are all frequently used to describe Angela Merkel’s position. Other findings points to that Angela Merkel’s position in the material is defined trough relationships with other political actors and leaders. The surveillance itself had in the material mostly negative effects on the relationships between the USA/Obama and EU/Germany/Merkel and was also pointed out as a problem for the on going talks of the FTA. More findings include the battle of the truth surrounding the surveillance, where at one side the USA with representative leaders from agencies like NSA and resides and on the other side journalists and leaders from EU resides. Both parties produce new knowledge with which they attempt to make a claim at the truth. Many conclusions that can be drawn from this essay the first is the way journalists use elites to verify and strengthen its articles. The second is the synoptic power that the media posses with which the members of societies can watch its leaders. And third, the way, in these case, the politicians gets there power and position verified due to different relationships with other political leaders of powerful individuals.
Titel: Merkel med NSA på andra sidan luren Syftet med den undersökning var att studera hur Angela Merkel blir framställd i en kontext av NSAs övervakning i de svenska tidningarna Dagens Nyheter och Aftonbladet. Tidsperioden som studeras är mellan den 24 oktober till och med den 7:e november 2013. Syftet konkretiserades genom tre frågor, hur Angela Merkel framställdes i materialet, hur NSAs övervakning av Angela Merkel framställdes samt hur olika uttalanden från olika personer i materialet kunde påverka sanningen om övervakningen. Metoden som användes för undersökningen var en diskursanalys, vilken även innehöll delar av en lingvistiskanalys. De teorier som valdes för att stötta metoden var Laclau & Mouffes diskursteori samt Michel Foucaults genealogiska diskursanalys. Undersökningens resultat pekar på att Angela Merkel blev framställd genom titlar, vilka representerar hennes position i ett demokratiskt samhälle. Ord som ”regeringschef, ”Bundeskansler” och Kansler var frekvent använda för att beskriva Angela Merkels position. Andra analysresultat pekar på att Angela Merkels position ofta blir definierad genom relationer med andra politiska aktörer och ledare. Själva övervakningen hade för det mesta negativa effekter på relationerna mellan USA/Obama och Eu/Tyskland/Merkel. Övervakningen pekades också ut som ett problem i de pågående förhandlingarna om frihandelsavtalet mellan EU och USA. Vidare framkom det en kamp om sanningen mellan aktörerna i materialet. På ena sidan fanns USA med representativa ledare från institutioner som NSA. På andra sidan fanns journalister och ledare från EU. Båda sidorna producerade ny kunskap om vad som hade skett, med vilken kunskap de försökte göra anspråk på sanningen. Många slutsatser går att dra från denna undersökning, den första är hur journalister använder ”eliter” för att verifiera och stärka sina artiklar. Den handlar om den synoptiska makten som medier innehar, genom vilken medlemmar av samhället kan övervaka sina ledare. Den tredje är på vilket sätt politiker kan få sina positioner och makt bekräftade genom olika relationer de har till andra politiskaledare eller mäktiga individer.
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Magsombol, Anacleto M. "Navy Stock Account (NSA) material expenditure errors." Thesis, Monterey, California. Naval Postgraduate School, 1990. http://hdl.handle.net/10945/37518.

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Approved for public release; distribution is unlimited
This thesis was an investigation of the causes that prevented large numbers of Pacific Fleet units' NSA expenditures from processing through the Fleet Resource Accounting Module (FRAM) at the Fleet Accounting and Disbursing Center Pacific (FAADCPAC), San Diego, CA. Six consecutive months' NSA expenditure errors from December 1989 to May 1990 were used in the analysis. The researcher concluded that the major cause of the problem was the use of wrong fund codes by the fleet units when they requisitioned their materials from the shore supply activities. The researcher identified inadequate training of shipboard supply personnel and the lack of an edit/validation process at the shore supply activities, as the major deficiencies. Recommendations designed to prevent large numbers of NSA expenditure errors and to improve the current accounting system were provided.
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Книги з теми "NSXA"

1

National Society for Clean Air. Conference. NSCA 57th conference: Proceedings. Brighton: National Societyfor Clean Air, 1990.

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Miller, Judith C., and Alice M. Stein. NSNA, NCLEX-RN review. 2nd ed. Albany, NY: Delmar Publishers, 1994.

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National Society for Clean Air and Environmental Protection. NSCA national noise survey. Brighton: National Society for Clean Air and Environmental Protection, 1999.

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NATIONAL SOCIETY FOR CLEAN AIR. NSCA Conference Proceedings of 64th NSCA environmental protection conference and exhibition 1997. Brighton: NSCA, 1998.

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NATIONAL SOCIETY FOR CLEAN AIR. 1984-85 NSCA members handbook. Brighton: NSCA, 1985.

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6

k, Pavel Nova. Zli nska architektura 1900-1950. [Czechoslovakia]: C as, 1993.

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L, Motz LaMoine, West Sandra S, and National Science Teachers Association, eds. NSTA guide to school science facilities. Arlington, VA: National Science Teachers Association, 1999.

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Association, National Science Teachers, ed. NSTA tool kit for teaching evolution. Arlington, VA: NSTA Press, 2008.

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9

Mohan, Shashank. NSX-T Logical Routing. Berkeley, CA: Apress, 2022. http://dx.doi.org/10.1007/978-1-4842-7458-3.

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Lowell, Barbara. NSA. Black Rabbit Books, 2023.

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Частини книг з теми "NSXA"

1

Lembke, Gerald, and Ingo Leipner. "Virtuelles NSA-Gefängnis." In Zum Frühstück gibt's Apps, 101–17. Berlin, Heidelberg: Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-662-45895-2_8.

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Gooch, Jan W. "Nsa-Sana Oil." In Encyclopedic Dictionary of Polymers, 491. New York, NY: Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4419-6247-8_8011.

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Hankerson, Darrel, and Alfred Menezes. "NSA Suite B." In Encyclopedia of Cryptography and Security, 857. Boston, MA: Springer US, 2011. http://dx.doi.org/10.1007/978-1-4419-5906-5_648.

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Hoogendoorn, Iwan. "NSX-T Federation." In Multi-Site Network and Security Services with NSX-T, 247–301. Berkeley, CA: Apress, 2021. http://dx.doi.org/10.1007/978-1-4842-7083-7_9.

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Hoogendoorn, Iwan. "NSX-T VPN." In Multi-Site Network and Security Services with NSX-T, 157–94. Berkeley, CA: Apress, 2021. http://dx.doi.org/10.1007/978-1-4842-7083-7_6.

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Mohan, Shashank. "Data Plane Availability." In NSX-T Logical Routing, 161–226. Berkeley, CA: Apress, 2021. http://dx.doi.org/10.1007/978-1-4842-7458-3_5.

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Mohan, Shashank. "Logical Routing." In NSX-T Logical Routing, 69–159. Berkeley, CA: Apress, 2021. http://dx.doi.org/10.1007/978-1-4842-7458-3_4.

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Mohan, Shashank. "Tunnel Endpoints." In NSX-T Logical Routing, 15–55. Berkeley, CA: Apress, 2021. http://dx.doi.org/10.1007/978-1-4842-7458-3_2.

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Mohan, Shashank. "Remote Tunnel Endpoints." In NSX-T Logical Routing, 57–67. Berkeley, CA: Apress, 2021. http://dx.doi.org/10.1007/978-1-4842-7458-3_3.

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Mohan, Shashank. "Introduction." In NSX-T Logical Routing, 1–14. Berkeley, CA: Apress, 2021. http://dx.doi.org/10.1007/978-1-4842-7458-3_1.

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Тези доповідей конференцій з теми "NSXA"

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Parker, M. "Building Foundations for Mathematics and Science Success." In NSTA 1999 NATIONAL CONVENTION, Boston, Massachusetts, March 25-28, 1999. US DOE, 1999. http://dx.doi.org/10.2172/761367.

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Lu, Zhichao, Ian Whalen, Vishnu Boddeti, Yashesh Dhebar, Kalyanmoy Deb, Erik Goodman, and Wolfgang Banzhaf. "NSGA-Net." In GECCO '19: Genetic and Evolutionary Computation Conference. New York, NY, USA: ACM, 2019. http://dx.doi.org/10.1145/3321707.3321729.

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Fahl, Sascha, Sergej Dechand, Henning Perl, Felix Fischer, Jaromir Smrcek, and Matthew Smith. "Hey, NSA." In CCS'14: 2014 ACM SIGSAC Conference on Computer and Communications Security. New York, NY, USA: ACM, 2014. http://dx.doi.org/10.1145/2660267.2660311.

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Ohana, David, Bruno Wassermann, Moshik Hershcovitch, Elliot K. Kolodner, Michal Malka, Eran Raichstein, Ronen Schaffer, and Robert Shahla. "DeCorus-NSA." In SYSTOR '21: The 14th ACM International Systems and Storage Conference. New York, NY, USA: ACM, 2021. http://dx.doi.org/10.1145/3456727.3463827.

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"ASME Conference Presenter Attendance Policy and Archival Proceedings." In ASME 2013 32nd International Conference on Ocean, Offshore and Arctic Engineering. ASME, 2013. http://dx.doi.org/10.1115/omae2013-ns2a.

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"ASME Conference Presenter Attendance Policy and Archival Proceedings." In ASME 2013 32nd International Conference on Ocean, Offshore and Arctic Engineering. ASME, 2013. http://dx.doi.org/10.1115/omae2013-ns4a.

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"ASME Conference Presenter Attendance Policy and Archival Proceedings." In ASME 2016 International Mechanical Engineering Congress and Exposition. ASME, 2016. http://dx.doi.org/10.1115/imece2016-ns4a.

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"ASME Conference Presenter Attendance Policy and Archival Proceedings." In ASME 2016 International Mechanical Engineering Congress and Exposition. ASME, 2016. http://dx.doi.org/10.1115/imece2016-ns6a.

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"ASME Conference Presenter Attendance Policy and Archival Proceedings." In ASME 2017 International Mechanical Engineering Congress and Exposition. ASME, 2017. http://dx.doi.org/10.1115/imece2017-ns4a.

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"ASME Conference Presenter Attendance Policy and Archival Proceedings." In ASME 2015 International Mechanical Engineering Congress and Exposition. ASME, 2015. http://dx.doi.org/10.1115/imece2015-ns6a.

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Звіти організацій з теми "NSXA"

1

Coltun, R., and V. Fuller. The OSPF NSSA Option. RFC Editor, March 1994. http://dx.doi.org/10.17487/rfc1587.

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Sparks, Valerie, Frederick M. Helsel, Daniel A. Lucero, and Darielle Dexheimer. ARM/NSA Monthly Report. Office of Scientific and Technical Information (OSTI), November 2016. http://dx.doi.org/10.2172/1331868.

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Helsel, Frederick M., Daniel A. Lucero, and Darielle Dexheimer. NSA Monthly Report- July 2016. Office of Scientific and Technical Information (OSTI), November 2016. http://dx.doi.org/10.2172/1334935.

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Murphy, P. The OSPF Not-So-Stubby Area (NSSA) Option. RFC Editor, January 2003. http://dx.doi.org/10.17487/rfc3101.

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Turner, S. The NSA (No Secrecy Afforded) Certificate Extension. RFC Editor, April 2014. http://dx.doi.org/10.17487/rfc7169.

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Janet M. Intrieri and Matthew D. Shupe. The NSA/SHEBA Cloud & Radiation Comparison Study. Office of Scientific and Technical Information (OSTI), August 2004. http://dx.doi.org/10.2172/828460.

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Scielzo, N. D., C. Y. Wu, J. Henderson, and A. T. Gallant. The LLNL Program in Nuclear Structure and Nuclear Astrophysics (NSNA): FY19 Annual Report. Office of Scientific and Technical Information (OSTI), September 2019. http://dx.doi.org/10.2172/1562384.

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Wu, C., N. Scielzo, A. Gallant, S. Kisyov, and B. Longfellow. The LLNL Program in Nuclear Structure and Nuclear Astrophysics (NSNA) FY21 Annual Report. Office of Scientific and Technical Information (OSTI), July 2021. http://dx.doi.org/10.2172/1811236.

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9

MT Ritsche. Surface and Tower Meteorological Instrumentation at NSA Handbook - January 2006. Office of Scientific and Technical Information (OSTI), January 2006. http://dx.doi.org/10.2172/948528.

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Anderson, Katherine A. A Code Of Ethics And Professional Conduct For NSA Intelligence Professionals. Fort Belvoir, VA: Defense Technical Information Center, February 2015. http://dx.doi.org/10.21236/ada620280.

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