Relative gene expression values are reported as mRNA ALT/mRNA beta-actin. Figure 3 Effect of AG28262, a VEGR-2 inhibitor, on ALT gene expression and enzymatic activity in the caudate liver lobe. Relative gene expression values are reported as mRNA ALT/mRNA beta-actin. AG28262-induced effect on crude liver ALT enzymatic activity Both the right medial and caudate lobes demonstrated a statistical increase in ALT enzymatic activity when compared to the control with 41% (p ≤ 0.01) and 96% (p ≤ 0.01) increase respectively (Figures 1 and 3). Enzymatic ALT activity in the left lateral lobe was elevated by 29% in comparison to the control (Figure 2), but the difference was not statistically significant.

Discussion Differences in drug effects between liver lobes should be considered in toxicology evaluation of compounds. Traditional thinking regarding drug-induced hepatotoxicity commonly correlates elevated serum ALT with direct Pitavastatin in vivo hepatocellular damage. However, instances of elevated serum ALT Ruboxistaurin in the absence of microscopic evidence of hepatocellular injury do occur with some xenobiotics. This investigation was conducted to understand the ALT elevation observed with AG28262, a VEGFR-2 inhibitor, in treated rats in the absence of morphological changes in the liver. The results of this investigation suggests that the source of increased serum

ALT in AG28262 treated rats is due to an increase in gene expression rather than leakage as a result of overt hepatocellular Alanine-glyoxylate transaminase necrosis.

This study also showed a regional specific effect on ALT mRNA and protein levels within the various lobes of the liver. In an effort to rule out drug-induced hepatocellular apoptosis as a potential cause of increases in serum ALT activity, caspase 3 immunohistochemistry and TUNEL assays were used. Both assays demonstrated equivalent positive staining in the compound-treated and control rats. This information suggests that elevation in serum ALT was not due to hepatocellular apoptosis, but to an alternative mechanism. The results obtained from caspase 3 and TUNEL assays further supported the lack of morphologic hepatic changes. AG28262 treatment resulted in increased activity of ALT, AST, and ALP suggesting that AG28262 induces hepatic injury. Clinical chemistry data demonstrated a statistically significant increase in serum ALT, ALP activities, and increased (but not statistically significant) AST activity on day 8. Serum AST activity on day 8 showed individual check details variability within the compound-treated group; however there was still a remarkable elevation when compared to control animals. ALT, AST, and ALP are all enzymes found in the liver and are commonly used in conjunction to evaluate hepatic changes [8]. Despite these elevations in liver enzyme activity there were not morphological correlates within the liver. Muscle and kidney are two other sources of ALT that may contribute to the elevation in serum ALT in this study.

A residual intimal flap could be identified in the first case, whereas the second case only showed a complete thrombosis of the lumen in the absence of any additional radiological signs. Therefore, the second case outlines that one should also consider IDSMA as a diagnosis, even though clinical and radiological signs led to the conclusion of an acute embolism as a working diagnosis. We performed a colonoscopy to exclude an ischemic lesion in both cases within the first week following operative treatment. We believe that endoscopic endoluminal control of the intestinal

mucosa provides additional patient security. We suggest considering this approach to be standardized in the postoperative therapy of patients with IDSMA, even if patients present Wnt inhibitor as asymptomatic. Both patients received effective anticoagulation during direct postoperative therapy. In due course, this was changed to antiplatelet drugs. We intend to continue this medication for at least six months, after which the patients will be seen in our outpatient department and will undergo a follow-up CT scan. This regime has been described in a retrospective analysis by Li et al. and we consider it to be reasonable [17]. Conclusion IDSMA remains a severe disease. Current therapeutic

options suggest conservative management in asymptomatic patients, despite knowing that a failure rate of over 30% has been learn more evidenced in such an approach [17, 32]. Endovascular therapy should be the first therapeutic choice, as a hospital stay is shorter and mortality rate is lower compared to open surgery. Indications for open surgery are suspected bowel infarction or a rupture of the SMA [17]. www.selleckchem.com/products/mek162.html In this paper, we presented two further cases where open surgery was performed. An anatomical variant and the suspicion of an acute embolism with bowel infarction made open surgery necessary. References 1. Sartelet H, Fedaoui-Delalou D, Capovilla M, Marmonier MJ, Pinteaux A, Lallement PY: Fatal hemorrhage due to an isolated dissection of the superior mesenteric artery. Intensive Care Med

2003, 29:505–506.PubMed 2. Bauersfeld SR: Dissecting aneurysm of the aorta; a presentation of 15 cases and a review of the recent literature. Ann Intern Med 1947, 26:873–889.PubMed 3. Carter R, O’Keeffe S, Minion DJ, Sorial ioxilan EE, Endean ED, Xenos ES: Spontaneous superior mesenteric artery dissection: report of 2 patients and review of management recommendations. Vasc Endovascular Surg 2011, 45:295–298.PubMedCrossRef 4. Subhas G, Gupta A, Nawalany M, Oppat WF: Spontaneous isolated superior mesenteric artery dissection: a case report and literature review with management algorithm. Ann Vasc Surg 2009, 23:788–798.PubMedCrossRef 5. Yasuhara H, Shigematsu H, Muto T: Self-limited spontaneous dissection of the main trunk of the superior mesenteric artery. J Vasc Surg 1998, 27:776–779.PubMedCrossRef 6. Garrett HE Jr: Options for treatment of spontaneous mesenteric artery dissection.

Thus, it might be necessary to knockout the RNAi pathway in the insect to reveal long-term effects of a buy EPZ015938 compromised, antiviral immune pathway on mosquito fitness. Conclusions We generated transgenic mosquitoes that have an impaired RNAi pathway in the midgut following ingestion of a bloodmeal.

These mosquitoes, Carb/dcr16, represent a novel tool to study arbovirus-mosquito interactions at the molecular level. Temporal impairment of the RNAi pathway in the midgut epithelium of Carb/dcr16 mosquitoes significantly increased the infection intensity of SINV-TR339EGFP, thereby allowing the virus to overcome MIB and MEB. Thus, both barriers, which are affected by the endogenous RNAi mechanism, appear to be virus dose-dependent phenomena for this SINV strain in Ae. aegypti. Furthermore, selleck compound the infection pattern of SINV in Carb/dcr16 females suggests that the RNAi pathway is modulating virus replication selleck inhibitor in the midgut to prevent the virus from reaching harmful concentrations in the insect. As a consequence, longevity of SINV-TR339EGFP infected mosquitoes was similar to that of non-infected ones. Overall, our data confirm that the mosquito midgut is the central organ that determines vector competence for arboviruses. Future

Directions Using Carb/dcr16 mosquitoes, we plan to evaluate effects of RNAi pathway impairment in the midgut on infection patterns of dengue and Chikungunya viruses, which are naturally transmitted by this mosquito species. Methods Transgene design and generation of transgenic Ae. aegypti Five hundred base-pair cDNA fragments corresponding to the ribonuclease I domain encoding region of Aa-dcr2 were inserted in sense and anti-sense orientations into pSLfa1180fa. Both fragments were separated

by the small intron of the Aa-sialonkinin I gene [42]. The resulting inverted-repeat (IR) DNA was placed downstream of the AeCPA promoter and a SV40 transcription termination signal was added at the 3′ terminus of the IR construct. This construct was then inserted into the non-autonomous Mariner Mos1 TE containing an eye tissue-specific EGFP expression cassette to allow easy identification of individual mosquitoes harboring the TE [43]. Transgenic mosquitoes were generated as described earlier [24, 44, 45] using Phosphatidylethanolamine N-methyltransferase the Higgs White Eye (HWE) strain of Ae. aegypti as recipient [46]. Mosquitoes received bloodmeals from mice following Colorado State University Institutional Animal Care and Use Committee (IACUC) regulations (IACUC protocol: 09-1365A-01). Mosquitoes were reared in a BSL2 insectary at 28°C and 80% relative humidity. Hemizygous Carb/dcr16 mosquitoes were maintained as an inbred colony. In the experiments intercrossed generations G5 to G8 were used among which 60-80% of the individuals were transgenic based on fluorescent eye marker expression.

Becker A, Barnett MJ, Capela D, Dondrup M, Kamp PB, Krol E, Linke B, Ruberg S, Runte K, Schroeder BK, Weidner S, Yurgel SN, Batut J, Long SR, Puhler A, Goesmann A: A portal for rhizobial genomes: RhizoGATE integrates a Sinorhizobium meliloti genome annotation update with postgenome data. J Biotechnol 2009,140(1–2):45–50.PubMedCentralPubMedCrossRef 31. Torres MJ, Hidalgo-Garcia A, Bedmar EJ, Delgado MJ: Functional analysis of the copy 1 of the fixNOQP operon of Ensifer meliloti under free-living micro-oxic and symbiotic conditions. J Appl Microbiol 2013,114(6):1772–1781.PubMedCrossRef 32. Delgado MJ, Bonnard N, Tresierra-Ayala A, Bedmar EJ, Muller P: The Bradyrhizobium japonicum napEDABC genes

encoding the periplasmic nitrate reductase are essential for nitrate respiration. Selleckchem LXH254 Microbiology 2003,149(Pt 12):3395–3403.PubMedCrossRef 33. García-Plazaola JI: Denitrification in lucerne nodules is not involved in nitrite detoxification. Plant Soil 1996, 182:149–155.CrossRef 34. Bedzyk L, Wang T, Ye RW: The periplasmic nitrate reductase in Pseudomonas sp . strain G-179 catalyzes the first step of denitrification. J Bacteriol 1999,181(9):2802–2806.PubMedCentralPubMed 35. Velasco L, Mesa S, Delgado MJ, Bedmar EJ: Characterization of the nirK gene encoding the respiratory, Cu-containing nitrite reductase of Bradyrhizobium japonicum . Biochim Biophys Acta 2001,1521(1–3):130–134.PubMedCrossRef

36. Mesa S, Velasco L, Manzanera ME, Delgado MJ, Bedmar EJ: Characterization Alisertib of the norCBQD genes, encoding nitric oxide reductase, in the nitrogen fixing bacterium Bradyrhizobium japonicum . Microbiology 2002,148(Pt 11):3553–3560.PubMed 37. Gomez-Hernandez N, Reyes-Gonzalez A, Sanchez C, Mora Y, Delgado MJ, Girard L: Regulation and symbiotic role of nirK and norC expression in Rhizobium etli . Mol Plant Microbe Interact 2011,24(2):233–245.PubMedCrossRef

38. Velasco L, Mesa S, Xu CA, Delgado MJ, Bedmar EJ: Molecular characterization of nosRZDFYLX genes coding for denitrifying Orotic acid nitrous oxide reductase of Bradyrhizobium japonicum . Antonie Van Leeuwenhoek 2004,85(3):229–235.PubMedCrossRef 39. Aida T, Hata S, Kusunoki H: Temporary low oxygen buy BKM120 conditions for the formation of nitrate reductase and nitrous oxide reductase by denitrifying Pseudomonas sp . G59. Can J Microbiol 1986,32(7):543–547.PubMedCrossRef 40. Bergaust L, Shapleigh J, Frostegard A, Bakken L: Transcription and activities of NOx reductases in Agrobacterium tumefaciens : the influence of nitrate, nitrite and oxygen availability. Environ Microbiol 2008,10(11):3070–3081.PubMedCrossRef 41. Bergaust L, Mao Y, Bakken LR, Frostegard A: Denitrification response patterns during the transition to anoxic respiration and posttranscriptional effects of suboptimal pH on nitrous oxide reductase in Paracoccus denitrificans . Appl Environ Microbiol 2010,76(19):6387–6396.PubMedCentralPubMedCrossRef 42.

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Applied Environmental Microbiology 1988, 54:2908–2915. 41. Armann R, Springer W, Ludwig W, Gortz HD: Identification in situ and phylogeny of uncultured bacterial endosymbionts. Nature 1991, 351:92–96. 42. Krishnan BH, Pueppke SG: A nodC-lacZ gene fusion in Rhizobium fredii facilitates direct assessment of competition for nodulation of soybean. Canadian Journal of Microbiology 1992, 38:515–519.CrossRef 43. Bjourson AJ, Stone CE, Cooper JE: Combined subtraction hybridization and polymerase chain reaction amplification procedure for isolation of strain specific Rhizobium DNA sequences. Applied and Environmental Microbiology 1992,

58:2296–2301.PubMed 44. McCormick D: Detection technology: the key to environmental Venetoclax biotechnology. Biotechnology 1986, 4:419–422.CrossRef 45. Pankhurst CE, MacDonald PE, Reeves JM: Enhanced nitrogen fixation and competitiveness for nodulation of Lotus pedunculatus by a plasmid-cured derivative of Rhizobium loti. Journal of General Microbiology 1986, 132:2321–2328. 46. Law IJ, Strijdom BW: Negative effects of agrocin 84-encoding Agrobacterium plasmids on symbiotic properties of Rhizobium meliloti. Archives of Microbiology 1989, 152:463–467.CrossRef 47. Liu R, Tran VM, Schmidt EL: Nodulating competitiveness of a non-motile Tn7 mutant of Bradyrhizobium japonicum in non-sterile soil. Applied Environmental Microbiology 1989, 55:1895–1900. 48. Veal DA, Stokes HW, Grant D: Genetic exchange in natural communities. Advanced Microbiology Ecology 1992, 12:383–430. 49.

g., [11, 18–24]), which have revealed the diversity and complexity of the genus [23, HSP inhibitor drugs 24], while showing the limitations of single locus analyses [25]. However,

during the last decade the taxonomy of this genus has still been subject to considerable debate. Genus-wide reclassifications have been proposed [26, 27], and frequent sub-specific reclassifications and proposals for new species have been published [19–21, 28–30]. A remarkable example of these conflicts is the classification of X. fuscans aurantifolii [26, 27], also known as X. axonopodis pv. “”aurantifolii”" [2, 6, 18, 31]. This taxon was originally identified as part of the DNA hybridization homology group “”X. axonopodis”" [6], but after its differentiation from other xanthomonads by DNA sequence-based molecular techniques, production of water-soluble brown pigment and host range, it was designated as X. fuscans [26]. However, when these traits/methods were examined, none of them could individually differentiate X. fuscans from other pathovars within X. axonopodis [18, 31]. DNA-DNA reassociation assays, in turn, have differentiated X. fuscans from X. axonopodis, X. campestris and X. citri [2, 26, 27]. Additional host-range evidence has also been used to support the designation X. fuscans, separated from X. axonopodis and X. citri. Phaseolus vulgaris ASK inhibitor and Citrus spp. are infected by X. fuscans pvs. fuscans and aurantifolii,

respectively, but are not infected by either X. axonopodis or X. campestris. Citrus spp., on the other hand, is also infected by X. citri [1]. However, host range is usually a criterion to separate pathovars and not

species. This example underscores the importance of a solid taxonomic classification with a phylogenetic basis. Molecular phylogenetics has this website played an important role in the classification of the genus. Single locus Cyclin-dependent kinase 3 analyses, including the use of 16S-23S rDNA spacers, the 16S rRNA gene and the DNA gyrase gyrB [32–35], generally agree with standing nomenclature but with low resolution below the species level. MLSA including sequences of protein-coding genes dnaK, fyuA and rpoD [31], has significantly extended previous results. In general, MLSA results suggest that X. citri and X. fuscans are closely related species and should be considered as a single species based on their 98.34% similarity in the proteins encoded by dnaK, fyuA, gyrB and rpoD [31]. Recently, a phylogenomic approach was applied to resolve the phylogenetic relationships within the genus [11], although this work did not explore the phylogenetic distances between strains, and did not include sequences from X. axonopodis species. The general structure of the genus agreed with the standing nomenclature. The use of genomic sequences as the basis for species delimitation has been explored as a new standard in bacteria in replacement of DNA-DNA hybridization [36, 37], particularly based on metrics such as the ANI (Average Nucleotide Identity) [38].

Virus Genes 2012, 44:408–414.PubMedCrossRef 17. Tang Y, Rodpradit P, Chinnawirotpisan P, Mammen MP Jr, Li T, Lynch JA, Putnak R, Zhang C: Comparative analysis of full-length genomic sequences of 10 dengue serotype 1 viruses associated with different genotypes, epidemics, and disease severity isolated in Thailand over 22

years. Am J Trop Med Hyg 2010, 83:1156–1165.PubMedCrossRef 18. Holmes EC, Worobey M, Rambaut A: Phylogenetic evidence for recombination in dengue virus. Mol Biol Evol 1999, 16:405–409.PubMedCrossRef 19. Arenas M, Posada D: Recodon: coalescent simulation of coding DNA sequences with recombination, migration and demography. BMC Bioinformatics 2007, 8:458.PubMedCrossRef 20. Arenas M, Posada D: Coalescent selleck inhibitor simulation of intracodon recombination. Genetics 2010, 184:429–437.PubMedCrossRef 21. Thompson JD, Higgins DG, Gibson TJ: CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position specific gap penalties and weight matrix choice. Nucleic Acids Res 1994, 22:4673–4680.PubMedCrossRef 22. Tamura K, Dudley J, Nei M, Kumar S: MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 2007, 24:1596–1599.PubMedCrossRef 23. Rozas J, Sánchez-DelBarrio JC, Messeguer X, Rozas R: DnaSP, DNA polymorphism analyses by the coalescent and other methods. check details Bioinformatics

2003, 19:2496–2497.PubMedCrossRef 24. Kosakovsky Pond SL, Frost SD: Not so different after all: a comparison of find more methods for detecting amino acid sites under selection. Mol Biol Evol 2005, 22:1208–1222.PubMedCrossRef 25. Moura G, Pinheiro M, Arrais J, Gomes AC, Carreto L, Freitas A, Oliveira JL, Santos MA: Large scale comparative codon-pair context analysis unveils general rules that

fine-tune evolution of mRNA primary structure. PLoS One 2007, 2:e847.PubMedCrossRef 26. Moura G, Pinheiro M, Silva R, Miranda I, Afreixo V, Dias G, Freitas A, Oliveira JL, Santos MA: Comparative context analysis of codon pairs on an ORFeome scale. Genome Biol 2005, 6:R28.PubMedCrossRef 27. Hudson RR: Two-locus sampling distributions and their application. Genetics 2001, 159:1805–1817.PubMed 28. McVean G, Awadalla P, Fearnhead Epothilone B (EPO906, Patupilone) P: A coalescent-based method for detecting and estimating recombination rates from gene sequences. Genetics 2002, 160:1231–1241.PubMed 29. Hudson RR, Kaplan N: Statistical properties of the number of re-combination events in the history of a sample of DNA sequences. Genetics 1985, 111:147–164.PubMed 30. Myers SR, Griffiths RC: Bounds on the minimum number of re-combination events in a sample history. Genetics 2003, 163:375–394.PubMed 31. Hudson RR: Generating samples under a Wright-Fisher neutral model of genetic variation. Bioinformatics 2002, 18:337–338.PubMedCrossRef 32. Fury W, Batliwalla F, Gregersen PK, Li W: Overlapping probabilities of top ranking gene lists, hypergeometric distribution, and stringency of gene selection criterion.

(D) Optical section, where SCs infected by S. learn more pneumoniae for 3 h were immunolabeled for cMR (red). Bacteria were stained with DAPI (blue). Orthogonal z-sections in the horizontal and vertical planes reveal

S. pneumoniae adhered (arrow) or internalized (arrowheads) by SCs (D). The nuclei were counterstained with DAPI. These results are representative of five separate experiments. Scale bar = 18 μm in (A); 18 μm in (B – C); 12 μm in (D). To monitor the course of infection, the number of SCs containing adhered and/or internalized S. pneumoniae was quantified at different times up to 24 h. Immediately selleck kinase inhibitor after the interaction step, as well as 3 h later, the percentage of association was 56.5%, and decreased to 47.2% and 40.8% after 12 and 24 h, respectively (Figure 2). Figure 2 Kinetics of association (adhesion or internalization) of Streptococcus pneumoniae with Schwann cells (SCs). The percentage of SCs containing adhered or internalized S. pneumoniae was quantified at different times up to 24 h. The graph shows a progressive decrease in the number of S. pneumoniae associated with the SCs. These data are representative of three separate experiments, each of which was conducted in triplicate. ***P selleckchem <0.0001. For statistical analysis, we used Two-way ANOVA and Tukey’s Multiple Comparison Test. We evaluated the endocytosis of S. pneumoniae by SCs, maintained either in

medium alone or in medium containing an excess of mannan, according to a protocol previously described by us for the endocytosis of S. pneumoniae by OECs [3]. Observations were made after interaction of

S. pneumoniae with SCs for 3, 12, and 24 h in both conditions. Inositol monophosphatase 1 Variable numbers of internalized bacteria as detected by labeling with anti-pneumococcal antiserum and counterstained with DAPI were seen throughout the cytoplasm of SCs maintained in medium alone (Figure 3, detailed in Figure 4A-E). On the other hand, the interaction assays performed in the presence of mannan impaired the bacterial binding to the cellular surfaces, thus drastically reducing the number of infected cells after 3 h of association (Figure 3). However, the number of infected cells was not significantly affected from 3 to 24 h of infection in the mannan-treated cultures (Figure 3). Figure 3 Competition assays showing the participation of mannose receptor (MR) during the association of Streptococcus pneumoniae with Schwann cells (SCs). The assays were performed by adding increasing doses of mannan (10 to 1000 μg/ml) in the interaction medium, and the results were highly statistically significant (***P <0.0001) at a dose equal to or higher than 100 μg/ml. The graph shows an inhibition of the percentage of SCs with associated bacteria immediately after 3 h of association (black bar versus white bar). However, this percentage was not significantly affected after this time up to 24 h of infection in mannan-treated cultures (black bar versus dark-gray bar).

13C NMR (DMSO-d 6, δ ppm): 17.45 (CH3), 43.56 (CH2), 46.49 (CH2), 53.96 (2CH2), 63.67 (CH2), 67.10 (CH2), arC: [105.40 (d, CH, J C–F = 40.1 Hz), 114.19 (CH), 118.62 (d, CH, J C–F = 36.6 Hz), 121.70 (2CH), 124.54 (2CH), 128.55 (d, C, J C–F = 36.4 Hz), 140.19 (d, CH, J C–F = 37.0 Hz), 150.36 (d, C, J C–F = 184.7 Hz), 157.43 (2C)], 168.24 (C=O), 172.66 (C=O), 190.04 (C=S). Ethyl 4-[4-(2-[2-(anilinocarbonothioyl)selleck inhibitor hydrazino]-2-oxoethylamino)-2-fluorophenyl] piperazine-1-carboxylate (11) The mixture of compound 9 (10 mmol) and phenylisothiocyanate

(10 mmol) click here in absolute ethanol was heated under reflux for 10 h. On cooling the reaction mixture to room temperature, a white solid appeared. This crude product was filtered off and recrystallized from ethanol. Yield: 85 %, M.p: 160–163 °C. FT-IR (KBr, ν, cm−1): 3340, 3256, 3193 (4NH),

1697 (C=O), 1633 (C=O), QNZ 1286 (C=S). Elemental analysis for C22H27FN6O3S calculated (%): C, 55.68; H, 5.73, N, 17.71. Found (%): C, 55.98; H, 5.78; N, 17.87. 1H NMR (DMSO-d 6, δ ppm): 1.19 (t, 3H, CH3, J = 7.0 Hz), 2.78 (s, 4H, 2CH2), 3.47 (s, 4H, 2CH2), 3.77 (s, 2H, CH2), 4.04 (q, 2H, CH2, J = 7.2 Hz), 6.34–6.51 (m, 2H, arH), 6.80–6.85 (m, 1H, arH), 7.17 (s, 1H, arH), 7.34–7.38 (d, 4H, arH, J = 8.2 Hz), 9.56 (s, 1H, NH), 9.69 (s, 1H, NH), 10.12 (s, 2H, 2NH). 13C NMR (DMSO-d 6, δ ppm): 15.29 (CH3), 44.25 (CH2), 45.92 (CH2), 51.83 (2CH2), 61.51 (2CH2), arC: [101.29 (d, CH, J C–F = 24.1 Hz), 108.72 (CH), 121.68 (CH), 125.92 (2CH), 126.48 (CH), 128.82 (2CH), 139.70 (C), 146.20 (d, C, J C–F = 10.0 Hz), 154.00 (d, C, J C–F = 63.3 Hz), 157.35 (d, C, J C–F = 209.8 Hz)], 168.64 (C=O), 170.64 (C=O), 181.58 (C=S). MS m/z (%): 475.41 ([M+1]+, 32), 414.53 enough (26), 413.53 (100), 149.03 (32). Ethyl 4-(4-[(5-anilino-1,3,4-thiadiazol-2-yl)methyl]amino-2-fluorophenyl)piperazine-1-carboxylate

(12) Concentrated sulfuric acid (64 mmol) was added to compound 11 (10 mmol) dropwise while stirring, and the reaction mixture was stirred in an ice bath for 15 min. Then, the mixture was allowed to reach room temperature and stirred for additional 2 h. The resulting solution was poured into ice cold water and made alkaline (pH 8) with ammonia. The precipitated product was filtered, washed with water, and recrystallized from dimethysulfoxide:water (1:3). Yield 74 %. M.p: 93–95 °C. FT-IR (KBr, ν, cm−1): 3257 (2NH), 1677 (C=O), 1433 (C=N). Elemental analysis for C22H25F2N6O2S calculated (%): C, 57.88; H, 5.52; N, 18.41. Found (%): C, 58.08; H, 5.75; N, 18.78. 1H NMR (DMSO-d 6, δ ppm): 1.17 (t, 3H, CH3, J = 7.0 Hz), 2.78 (s, 4H, 2CH2), 3.46 (s, 6H, 3CH2 + H2O), 4.03 (q, 2H, CH2, J = 7.2 Hz), 4.48 (s, 1H, NH), 6.37–6.51 (m, 2H, arH), 6.80–6.99 (m, 2H, arH), 7.17 (brs, 1H, NH), 7.27–7.33 (m, 3H, arH), 7.56 (d, 1H, arH, J = 7.8 Hz). 13C NMR (DMSO-d 6, δ ppm): 14.

Figure 3 shows

the AFM images of 20-nm-thick Lu2O3 film. The rms value obtained by AFM observation was 1.82 nm. The lower surface roughness may result in better uniformity and higher yield of the fabricated memory devices. Figure 1 XRD micrographs of amorphous Lu 2 O 3 thin film sputtered on flexible ITO/PET substrate. Figure 2 XPS line-shape analyses. (a) O 1 s. (b) Lu 4d spectra for Lu2O3 thin film on ITO/PET substrate. Figure 3 AFM image of Lu 2 O 3 thin film on flexible SBI-0206965 in vitro ITO/PET substrate. In order to investigate the memory performance of the flexible Ru/Lu2O3/ITO ReRAM cell, the RS characteristics were analyzed. A high bias voltage with predefined current compliance (I CC) of 100 μA was applied to the pristine memory cell to initiate the RS into the Lu2O3 thin film, as shown in Figure 4a. I CC is required to protect the device from hard breakdown. During this initial bias sweeping, a sudden abrupt decrease in oxide conductance was observed, which is known as soft breakdown or Belnacasan chemical structure electroforming

process. A nanomorphological change into the oxide layer is assumed due to the introduction of a high oxygen vacancy density of the oxide thin films [25]. After the electroforming process, the memory device switches to low-resistance state (LRS). To change the resistance state of the memory device, a sufficient positive bias of certain value (V reset) was applied and the devices transform to high-resistance oxyclozanide state (HRS), as shown in Figure 4b. In contrast, an application of negative bias results in a transition from HRS to LRS at certain set voltage (V set) and this effect is reproducible over several hundreds of voltage 10058-F4 order sweeping cycles. As can be seen that the Ru/Lu2O3/ITO ReRAM cell can be switched between two distinguished resistance state (HRS to LRS and vice versa), at a very low voltage of approximately 0.8 V (100 μA set current) and approximately 1.2 V (<1 mA reset current) for set and reset operations, respectively. The lower switching

voltage is believed due to the low power hopping conduction via oxide defects [7]. In order to realize the current conduction mechanism into the Lu2O3 thin film, both HRS and LRS current–voltage (I-V) characteristics at different temperature were analyzed. Figure 4 Analysis of the RS characteristics of Ru/Lu 2 O 3 /ITO ReRAM device. (a) The electroforming process of the Ru/Lu2O3/ITO ReRAM device with current compliance of 100 μA. Shaded area shows the typical RS behavior after electroforming process. (b) Enlarged view of the shaded region showing promising RS characteristics of the Ru/Lu2O3/ITO ReRAM device. Figure 5 shows the resistance variation of the memory device at different resistance states at different temperatures ranging from 303 to 353 K. In HRS, the resistance value decreases as the temperature increase to 353 K.