b) standard deviation from the average mRNA, expressed in percentage. c) *, values statistically significantly different to the cells cultivated with other carbon sources.

§, values statistically significantly different to the cells cultivated with succinate or glucose. ‡, values statistically significantly different between exponential phase and stationary phase. P ≤ 0.05 in pairwise Student’s T test. Another gene that produced relatively high signals in dot-blot hybridizations was ORF100033, which urged us to analyze its expression more conspicuously by RT-PCR. Contrary to RNA isolated in stationary phase from 3-chlorobenzoate or fructose-grown cultures, Batimastat consistently no RT-PCR product was obtained for the intergenic region between ORF100952 and ORF101284 on RNA from cells that had been cultivated with glucose (Figure 5, panels d and e). RNA isolated from all three substrate conditions did produce a smaller RT-PCR Ganetespib purchase fragment directly upstream of ORF100952 (Figure 5B panel b), suggesting that an additional promoter exists that produces a transcript covering ORF100952 only. In fact, Northern hybridizations with a probe for ORF100952 produced an additional band of 0.5 kb length (Figure 3). The promoter located in front of ORF101284 might thus be specifically repressed after growth on glucose

(and perhaps succinate), or specifically activated after growth on 3-chlorobenzoate and fructose. Figure 5 Carbon Erastin cell line substrate-dependent transcript linkage in the region at the outermost ICE clc left end. A) Gene organization, reverse-transcribed regions and PCR amplicons. Arrows to the left point to inferred promoters. B) RT-PCR results for https://www.selleckchem.com/products/Cyt387.html Amplicon (a). C) idem for amplicon (b). D) Amplicon (c). E) Amplicon (d). All RNAs sampled from cultures during stationary phase after growth on the indicated carbon source. Glc, glucose. Frc, fructose. 3-CBA, 3-chlorobenzoate. Numbers below point to independent replicate

reactions. -, PCR but without RT-step.+, PCR on B13 genomic DNA as template. Promoter analysis Results from 5′-RACE were not as conclusive as expected. Although various amplicons were produced from cDNA ends, only few matched the start region for transcripts detected by RT-PCR, Northern and micro-array. In contrast, the start site for the transcript covering inrR could be mapped in the region upstream of ORF95213 to a thymine located 25 nt upstream of the ORF95213 start codon. Interestingly, the corresponding -10 box (TGTCGATCCT) and -35 (TTGACT) are close to the proposed consensus sequence of σs and not σ70, suggesting it is controlled by RpoS [26]. This could explain a higher abundance of this transcript during stationary compared to exponential phase as seen on micro-array (Figure 4).

CrossRefPubMed 25. Christie PJ, Cascales E: Structural and dynamic properties of bacterial type IV secretion systems (review). Mol Membr Biol 2005,22(1–2):51–61.CrossRefPubMed 26. Hubber AM, Sullivan JT, Ronson CW: Symbiosis-induced cascade regulation of the Mesorhizobium loti R7A VirB/D4 type IV secretion system. Mol Plant Microbe Interact

2007,20(3):255–261.CrossRefPubMed 27. Saier MH Jr: Protein secretion and membrane insertion systems in gram-negative bacteria. J Membr Biol 2006,214(2):75–90.CrossRefPubMed Emricasan ic50 28. Jacob-Dubuisson F, Fernandez R, LY2090314 cost Coutte L: Protein secretion through autotransporter and two-partner pathways. Biochimica et Biophysica Acta 2004,1694(1–3):235–257.PubMed 29. Dautin N, Bernstein HD: Protein secretion in gram-negative bacteria via the autotransporter pathway. Annual Review of Microbiology 2007, 61:89–112.CrossRefPubMed 30. Bernstein HD: Are bacterial ‘autotransporters’ Selleck Androgen Receptor Antagonist really transporters? Trends in Microbiology 2007,15(10):441–447.CrossRefPubMed 31. Henderson IR, Navarro-Garcia F, Desvaux M, Fernandez RC, Ala’Aldeen D: Type V protein secretion pathway: the autotransporter story. Microbiol Mol Biol Rev 2004,68(4):692–744.CrossRefPubMed

32. Bingle LE, Bailey CM, Pallen MJ: Type VI secretion: a beginner’s guide. Curr Opin Microbiol 2008,11(1):3–8.CrossRefPubMed 33. Shrivastava S, Mande SS: Identification and functional characterization of gene components of Type VI secretion system in bacterial genomes. PLoS ONE 2008,3(8):e2955.CrossRefPubMed 34. Cascales E: The type VI secretion toolkit. EMBO reports 2008,9(8):735–741.CrossRefPubMed Bupivacaine 35. Filloux A, Hachani A, Bleves S: The bacterial type VI secretion machine: yet another player for protein transport across

membranes. Microbiology 2008,154(Pt 6):1570–1583.CrossRefPubMed 36. Liu H, Coulthurst SJ, Pritchard L, Hedley PE, Ravensdale M, Humphris S, Burr T, Takle G, Brurberg MB, Birch PR, et al.: Quorum sensing coordinates brute force and stealth modes of infection in the plant pathogen Pectobacterium atrosepticum. PLoS pathogens 2008,4(6):e1000093.CrossRefPubMed 37. Wu HY, Chung PC, Shih HW, Wen SR, Lai EM: Secretome analysis uncovers an Hcp-family protein secreted via a type VI secretion system in Agrobacterium tumefaciens. J Bacteriol 2008,190(8):2841–2850.CrossRefPubMed 38. Pukatzki S, Ma AT, Revel AT, Sturtevant D, Mekalanos JJ: Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-links actin. Proc Natl Acad Sci USA 2007,104(39):15508–15513.CrossRefPubMed 39. Abdallah AM, Gey van Pittius NC, Champion PA, Cox J, Luirink J, Vandenbroucke-Grauls CM, Appelmelk BJ, Bitter W: Type VII secretion–mycobacteria show the way. Nat Rev Microbiol 2007,5(11):883–891.CrossRefPubMed Competing interests The authors declare that they have no competing interests.

A majority check details of the strains has been characterised by one or more methods including MLST, MLEE, 16S rRNA sequencing, biotyping, and capsular type. Data on the association of strains with different diseases, dates and geographical sites of isolation were also available for many strains. 46 H. influenzae strains were selected for study that

represented the diversity within a tree created from the concatenated sequence data from the entire MLST database ( http://​haemophilus.​mlst.​net). A further 15 strains were selected based on existing MLEE and biotype data. Finally, clinical, geographical and temporal data were used to identify some further strains that were included, based on criteria other than MLST or MLEE, as well as a Selleck FHPI number of strains from closely related species and sub-species of H. influenzae including H. haemolyticus, Haemophilus parahaemolyticus, Haemophilus parainfluenzae, Haemophilus paraphrophilus, H. influenzae biotype IV strains, and putative ‘hybrid’ H. influenzae-H. parainfluenzae strains (Table  1). The latter ‘hybrid’ strains are H. influenzae isolates that do not contain a fucK MLST allele,

Mocetinostat a characteristic of H. parainfluenzae, and therefore their classification is uncertain (personal communication Abdel Elamin, University of Oxford). Most of the serotype b strains were recovered from patients with invasive disease but a number were associated with non-symptomatic carriage. Bacterial isolates were cultured from frozen on solid brain heart infusion (BHI) medium supplemented with 10% Levinthals reagent and 1% agar, and incubated at 37°C. For DNA preparation, bacteria

were cultured on BHI liquid supplemented with haemin (10 μg/ml) and NAD (2 μg/ml). Genome sequencing, assembly, and comparison of genome sequence data Strains were grown on BHI broth and chromosomal DNA was isolated from bacteria using Qiagen columns as described by the supplier. The genomic DNA from 96 strains was sequenced using multiplex (12 separately indexed DNAs per lane) Illumina sequencing as described previously [21]. The sequencing was conducted utilising 7 lanes (84 DNAs) on one flow cell and one lane (12 DNAs) on a second flow cell. The 55 bp reads from each of the 96 strains were separated using Farnesyltransferase the index tags, and then assembled using the Velvet assembly programme [14]. Genome sequences for eleven strains were rejected due to poor assembly; the result of insufficient coverage or large numbers of small contigs (lower part of Table  1). For 85 Haemophilus strains, genome sequences of between 1.27 Mbp to 1.91 Mbp in length were assembled by Velvet (Table  1). The sequence reads were mapped to a reference using MAQ [15] and default parameters, these were then tested to identify the depth of reads covering the lower %G+C regions of DNA, as an indication of when coverage was insufficient for assembly.

Figure 1 The changes in plasma NT-proBNP level during HSCT. The changes in plasma NT-proBNP level over the 30 days following www.selleckchem.com/products/bb-94.html the HSCT were statistically significant (P < 0,01). The highest values were detected on day 1 after HSCT in 26 (70,3%) patients with a gradual decline, but without normalization to baseline. Thirty days after HSCT,

NT-proBNP remained elevated in 11 of 37 (29,7%) patients. The differences in plasma hs-cTnT level during the 30 days following HSCT were also statistically significant (Figure 2, P < 0,01). We found persistent elevations in hs-cTnT levels 1 day, 14 days and also 30 days after HSCT (27% vs 29,7% vs 29,7% patients). The concentrations of hs-cTnT in all measurements selleck chemicals llc were significantly higher in patients previously treated with ANT (P < 0,01), but not in patients receiving TBI as a part of the conditioning regimen (P = 0,14). Levels of hs-cTnT

Selleckchem SBI-0206965 showed no correlation with fever in the last week (ρ = 0,02; P = 0,75), with plasma creatinine level (ρ = -0,02; P = 0,74) and arterial hypertension (ρ = -0,02; P = 0,78). Levels of NT-proBNP showed positive correlation with hs-cTnT (ρ = 0,35; P < 0,01). Figure 2 The changes in plasma hs-cTnT level during HSCT. The differences in plasma hs-cTnT level over the 30 days following HSCT were statistically significant (P < 0,01). Persistent elevations in hs-cTnT levels 1 day and also 30 days after HSCT were found in 27% vs 29,7% patients. In the early period after HSCT, we found a statistically significant decrease in systolic LV function

(65 ± 5,7% at baseline, 61 ± 4,8% at 1 month; P < 0,01). The mean E/A ratio decreased significantly over time, whereas DT and IVRT remained unchanged (Table 2). Newly developed systolic dysfunction appeared in 5 (13,5%) patients and diastolic dysfunction in 2 (5,4%) patients. There were no differences in systolic echocardiographic parametres in patients previously treated with or without ANT and with or without TBI as a part of the conditioning regimen (P = 0,78 vs 0,27). Levels of NT-proBNP showed negative correlation with LV EF (ρ = -0,35, P = 0,03). Table 2 Echocardiographic parameters before and after HSCT   Before HSCT After HSCT P-value Systolic parameters       LVEF (%) 65 ± 5,7 61 ± before 4,8 < 0,01 Diastolic parameters       E/A 1,37 ± 0,22 1,07 ± 0,3 < 0,01 DT (ms) 174 ± 20,9 182 ± 24,5 0,3 IVRT (ms) 75,06 ± 7,5 79,11 ± 6,8 0,1 LVEF left ventricular ejection fraction, A peak flow velocity of late filling, DT E-wave deceleration time, E peak flow velocity of early filling, IVRT isovolumetric relaxation time Of 37 patients, 5 (13,5%) developed a cardiac event. All of these patients exhibited elevated plasma NT-proBNP and hs-cTnT levels prior to clinical signs occuring and these elevations persisted at least 30 days after HSCT. Characteristics of patients are described in Table 3.

Each promoter has a control lane (-) that contains no protein, a binding reaction that contains either Ma or Mth MsvR (200 nM) in the absence of DTT (non-reduced, +), and a binding reaction that contains either Ma or Mth MsvR (200 nM) in the presence of 5 mM DTT (reduced, R). (c) EMSA assay (10 nM Ma P msvR DNA) with decreasing concentrations of reduced MaMsvR (5 mM DTT) [monomer] 1 μM, 500 nM, 250 nM, 125 nM, 62.5 nM, 31.3 nM, 15.6

nM, 7.8 nM, and 3.9 nM. (d) EMSA assay (10 nM Mth P msvR/fpaA DNA) with decreasing concentrations of reduced MaMsvR (5 mM DTT) [monomer] 1 μM, 500 nM, 250 nM, 125 nM, 62.5 nM, 31.3 nM, 15.6 nM, 7.8 nM, and 3.9 nM. (e) EMSA assay (10 nM VS-4718 Mth P msvR/fpaA DNA) with decreasing concentrations of reduced MthMsvR (5 mM DTT) [monomer] 1 μM, 500 nM, 250 nM, 125 nM, 62.5 nM, 31.3 nM, 15.6 nM, 7.8 nM, and 3.9 nM. The observed promoter binding behavior of MaMsvR is consistent with the hypothesis that MaMsvR acts as a transcription repressor of Ma P msvR under reducing conditions. An oxidizing environment inhibits Ma P msvR binding, likely leading to derepression. A mechanism for MthMsvR is less clear. Under reducing conditions, GDC-0994 concentration MthMsvR functions

as a transcription repressor in vitro, yet MthMsvR binds the promoter under both reducing and non-reducing conditions. To reconcile this apparent discrepancy, it has been proposed that MthMsvR follows a mechanism reminiscent of the well-characterized redox regulator, OxyR, which binds DNA irrespective 17-DMAG (Alvespimycin) HCl of redox status but has different effects on transcription under varying redox conditions [9, 26]. These effects would likely be regulated by conformational changes in MthMsvR between the oxidized and reduced states. However, addressing this experimentally has been problematic because of

both the limitations of the M. thermautotrophicus in vitro transcription system, which requires reducing conditions, and the complexity of the divergent promoter structure within Mth P msvR/fpaA . MaMsvR exhibits different DNA binding patterns than MthMsvR MaMsvR appears to produce higher molecular weight complexes on Mth P msvR/fpaA as movement of the DNA is further retarded in the gel compared to the shifted complex seen on Ma P msvR (Dinaciclib supplier Figure 2a, c, and d). Consistent with previously published data, MthMsvR binding to Mth P msvR/fpaA produced two distinct multiple shifted complexes, suggesting that varying stoichiometries of MthMsvR bound to Mth P msvR/fpaA (Figure 2b) [9]. In contrast, only one shifted complex was seen with MaMsvR (Figure 2a, c, and d). To determine if MaMsvR was capable of producing complexes of varying stoichiometry, increasing concentrations of MaMsvR were incubated with Ma P msvR (Figure 2c) or Mth P msvR/fpaA (Figure 2d). Even at concentrations of one hundred-fold excess MaMsvR over DNA, only a single shifted complex was observed for either promoter.

Furthermore, to quantitatively access the influence of probe radius on the frictional property of the substrate, the average friction Eltanexor cost coefficient is obtained by averaging more than 1,000 instantaneous points of friction coefficient in the range between 3 and 12.2 nm. Table 1 summarizes

the mechanical responses of the substrate extracted during friction with the four probe radiuses. Figure 5a shows that the slope of the contact pressure-penetration depth curve in the elastic deformation regime decreases with increasing probe radius, indicating that the elastic deformation of Bafilomycin A1 supplier the substrate is more compliant with the larger probe. However, the contact pressure reflecting the critical stress for initial dislocation nucleation from penetrated surface is approximately independent on the probe radius. It is seen from Table 1 that with the increase of the probe radius, both the critical

force and the critical penetration depth associated with the initiation of plasticity increases, but the average friction coefficient decreases. Figure 5 Influence of probe radius on mechanical and frictional properties of the substrate under friction. (a) Contact pressure-penetration depth curves. (b) Friction coefficient-scratching length curves. Table 1 Mechanical responses of the substrate under friction with different probe radiuses Probe radius 6 nm 8 CDK assay nm 10 nm 12 nm Critical penetration force (nN) 387.1 565.9 814.4 1,081.1 Critical penetration depth (nm) 0.65 0.72 0.80 0.87 Critical contact pressure (GPa) 28.3 25.1 25.2 25.2 Average friction coefficient 0.126 0.118 0.103 0.098 Figure 6a,b,c,d presents the surface morphologies Axenfeld syndrome of the substrate after the completion of scratching with probe radiuses of 6, 8, 10, and 12 nm, respectively. A larger probe results in a larger volume and also wider extent of the wear debris, indicating that more atoms within the substrate are involved in the scratching action. To quantitatively characterize the scratching-induced motion of atoms, the shear strain of each atom is calculated by comparing the current atomic configuration

of the substrate with the reference configuration obtained after relaxation. Figure 6e,f presents the cross-sectional views of the substrate after scratching with the four probe radiuses, respectively, in which atoms are colored according to their shear strains ranging from 0 to 1. It is seen from Figure 6 that the distributions of wear debris and shear strain are closely correlated for each probe radius. When probe radius is small, Figure 6e shows that the distribution of shear strain is compact and shallow. Furthermore, the atoms in the wear debris have significantly larger mobility than that within the material. In contrast, a lager probe leads to larger and more compliant distribution of shear strain. Figure 6 Influence of probe radius on the friction of the substrate.

, Sparks, MD) Middlebrook 7H11 selective agar supplemented with Polymyxin B (200,000 units), Carbenicillin (50.0 mg), Amphotericin B (10.0 mg), Trimethoprim Lactate (20.0 mg) to hinder bacterial and fungal overgrowth. CFU counts

were enumerated on day 14, 21 and day 28. Scoring of gross pathology A gross pathology scoring sheet was developed to enumerate the gross pathology seen at necropsy (Additional File 1). The sheet was based upon an earlier published scoring sheet in the cynomolgus maqaque model by Lin and colleagues [13]. Grossly visible lesions from all lung lobes and extrapulmonary sites were described and enumerated. The total score was determined by adding all subtotal numbers assigned to each evaluable anatomic site. Standard descriptive strategies were also employed to document disease burden at necropsy and compared to the developed OSI-027 molecular weight scoring system. Statistical analysis Data are reported as mean values unless otherwise stated. Mean quantitative

scores based on gross pathology were compared via non-parametric analyses by Mann-Whitney U test. Mean paired values of thoracic/extrapulmonary CFUs were summed and compared by paired t-test analyses. Tissue CFUs in each rabbit population were paired, regardless of sensitization status, during comparative tissue analyses. The level of significance was set at P < 0.10. Acknowledgements and Funding We gratefully acknowledge the support of NIH

grants/contracts Torin 2 AI36973, AI37856, AI079590, and AI30036. We thank Nicole C. Ammerman for her generous assistance in the acquisition of experimental data. Electronic supplementary material Additional file 1: Gross Scoring System Employed for the Rabbit of Tuberculosis. A scoring sheet was developed to enumerate the gross pathology seen at necropsy. Visible lesions from all lung lobes and extrapulmonary sites were described and enumerated (maximum possible score of 50). The total score was determined by adding Digestive enzyme all subtotal numbers assigned to each evaluable anatomic site. (DOCX 30 KB) References 1. World Health Organization: Global Eltanexor in vitro tuberculosis Control. Surveillance, Planning, Financing 2007. 2. Nardell EA, Piessens WF: Transmission of tuberculosis. In Tuberculosis: A comprehensive international approach. Edited by: LB Reichman, Hershfield ES. Marcel Dekker, New York (NY); 2000:215–240. 3. Iseman MD: A clinician’s guide to tuberculosis, Lippincott Williams & Wilkins, Philadelphia, PA. 2000, 51–62. 4. Kramnik I, Dietrich WF, Demant P, Bloom BR: Genetic control of resistance to experimental infection with virulent Mycobacterium tuberculosis. Proc Natl Acad Sci USA 2000, 97:8560–8565.PubMedCrossRef 5. Smith DW, Harding GE: Animal model: Experimenal airborne tuberculosis in the guinea pig. Am J Pathol 1977, 89:273–276.PubMed 6.

An observation cannot be explained was 10-6M of SMSP showed inhibitory effect, and the detail needs to be further studied. The other finding in this study was the presence of visible apoptosis after administration of SR140333. This is consistent with earlier studies, in which

the use of certain NK-1 antagonists inhibited the growth of other human breast Tideglusib cancer cell lines such as MDA-MB-231 and MDA-MB-468 [26, 27]. It was speculated that this finding was induced by a signal transduction pathway for apoptosis [7, 20, 28, 29]. In addition, the blockade of NK-1 could inhibit both DNA synthesis and cell proliferation by the mitogen-activated protein kinase (MAPK) pathway [25]. However, in the presence of CP-96345 or C-99994, which belongs to NK-1 antagonist, no apoptotic cells but only inhibitory effect was observed in human breast cancer cell line T47D [2, 3]. The authors think the reason is that the cell cycle remained in the G2 phase [2]. Probably this different power action could be related with the different affinity for the NK-1 and with the expression of the amount of NK-1 receptors in the different tumor cells [30]. Moreover, previous see more studies have demonstrated

that in the great majority of malignant tumors, NK-1 receptors were found on intra- and peritumoral blood vessels [6, 23]. This finding indicated that NK-1 may serve as a preferred target for cancer therapy, which could mediate vasodilatation and mitogenesis. In fact, our unpublished immunohistochemical study has demonstrated the expression of NK-1 on both intratumoral and peritumoral blood vessels. Therefore, targeting NK-1 using SR140333 could decrease both nutrition supply and signal transduction. It is well known that cell growth is regulated by various growth factors through their specific receptor linked various signal-transduction pathways [31]. A peptide growth ARRY-438162 chemical structure factor may act through different receptors coupled to different post-receptor signal-transduction pathways [32] or the same receptor for a given

peptide growth factor may be coupled to different post-receptor signal-transduction pathways by crosstalk [33]. T47D cells contain estrogen receptors (ER), and the ER dimer binds either directly to DNA at an estrogen response Cediranib (AZD2171) element or tethers to other bound transcription factors, thereby altering the transcription of estrogen sensitive genes [34] Although most ER is in the nucleus, a population resides in the cytoplasm and/or membrane, available for cross talk with other cytoplasmic/membrane-associated signaling molecules, such as shc. Because ER itself has no kinase activity, phosphorylation must occur through another molecule that associates with ER or is activated by the receptor. The activation of NK-1 induces releasing of G-protein βγ subunits, and the latter recruit components of the ras-dependent cascade, such as shc, grb2, and src, leading to the activation of raf-1 and MAPK [35].

Furthermore, swimmers often compete in several events within a 30–90 min time frame during any given session. Swimmers must also contend with restrictions placed on their breathing frequency during

intense exercise as a result a unique interaction between muscle physiology, technique, and ventilation. Exercise hyperpnoea is limited during high intensity swimming because turning or lifting the head to breathe may Autophagy inhibitor cost jeopardize execution of proper stroke technique [17, 18]. Indeed, swimming requires that the athlete sustain a high rate of energy expenditure and the suspension of breathing for approximately 20 – 30% of a race [19]. Given these limitations and the physiological consequences, it is likely that anaerobic metabolism is a significant contributor to metabolic power in competitive swimming, and may also be a primary determinant of fatigue and limitations in performance [7]. Another reason why competitive

swimming is an appropriate model for studying the effectiveness of alkalizing agents is that swimmers are often young when they reach elite level competition; among the swimming medalists in the 2012 Olympics (n = 78), twenty-five were under 21 and eight were under 18 years old. This creates a highly competitive environment, where 80% of elite adolescent athletes are using supplements and other non-doping strategies to improve performance [20]. It is, therefore, surprising that there is such a lack of research on the effectiveness of such ergogenic aids in this selleck kinase inhibitor population [20], especially when acid base regulation in adolescents may be significantly different than that of adults. The overall purpose of this study was to evaluate the ergogenic effect of two Na-CIT Temsirolimus clinical trial supplementation protocols, previously used in adults, in adolescent swimmers. Cytidine deaminase Specifically, the types of Na-CIT supplementation protocols that have been previously applied include an acute (single) dose and a chronic (multi-day) dose prior to performance. During the acute delivery

mode participants take one single dose (0.3 – 0.6 g∙ kg-1 body mass Na-CIT) 60 to 180 min before the start of competition [2–4, 11, 13] while a chronic dose (0.3 g∙ kg-1 body mass Na-CIT) is given for a number of days prior to performance [21]. Chronic dosing of alkalizing agents was first employed by McNaughton et al. [22] using sodium bicarbonate in an effort to elicit an ergogenic effect while minimizing GI upset, which often occurs with acute dosing protocols. Based on these studies, a double-blinded, placebo controlled, cross-over design was used to investigate the effects of an acute versus a chronic Na-CIT supplementation protocol on 200 m swimming performance and acid–base parameters in male, adolescent swimmers. Methods Participants Sample size was calculated using pre- and post-trial blood lactate concentrations from a published 5 km run trial in adults, an 80% power, and a 0.05 level of significance; this resulted in a minimum sample size of 8 [13].

The device size is 4 × 4 μm2. Every cycle data was captured during measurement. The P/E voltages were +2/−2.2 V. Both HRS and LRS were read out at +0.1 V, and pulse width was 500 μs. The P/E cycles are not stable as we expected. Further study is selleckchem needed to obtain stable P/E cycles. Long read pulse endurance of >106 cycles is shown in Figure 6b. In this case, stress pulse width was 500 μs and read pulse width was 10 μs. Stable LRS

is obtained at a V read of 0.1 V. Due to the strong conducting filament formation, stable LRS is observed under random read pulse. For LRS only, it took a long measurement time of approximately 3 days. On the other hand, the data retention is quite good after programming the device. The HRS was read out at two different V read’s of IWP-2 +0.1 and +0.05 V. Stable HRS is observed up to 400,000 cycles, and the HRS is decreased with pulse numbers. This may be due to defects creation during continuous see more stress on the TaO x switching layer or the migration of oxygen ions

due to heating effects. Further study is needed to improve P/E endurance and instability of read pulse endurance of HRS after long cycles. However, a resistance ratio of >10 is obtained after 106 cycles. Our memory device also performs good data retention of >104 s as shown in Figure 7. The read voltage for both HRS and LRS was −0.2 V. An acceptable resistance ratio of >10 is observed after a retention time of Astemizole 104 s. This RRAM device is very useful for nanoscale non-volatile memory application. Figure 6 Endurance characteristics. (a) P/E

endurance of >103 cycles and (b) long read pulse endurance of >106 cycles of our novel W/TaO x /TiN memory device. The device size is 4 × 4 μm2. Figure 7 Data retention characteristics. Good data retention of >104 s of our W/TaO x /TiN memory device. An acceptable resistance ratio of >10 is obtained after 104 s. Conclusions One hundred consecutive switching cycles in the W/TaO x /TiN structures under self-compliance (<200 μA) and low-voltage operation of ±2.5 V are obtained. The thicknesses of TaO x and TiO x N y layers are 7 and 3 nm, respectively, which are observed by HRTEM. The RRAM device sizes are also confirmed by TEM. Our memory device shows good switching characteristics at low self-current compliance with tight distribution of HRS/LRS, excellent device-to-device uniformity, and program/erase endurance of >1,000 cycles. The smaller size devices show better switching characteristics and uniformity as compared to the larger size devices, owing to the thinner W electrode as well as higher series resistance. Interfacial oxygen-rich TaO x layer acts as a series resistance to control the resistive switching characteristics which may also cause the self-compliance resistive switching behavior and non-linear I-V curve at LRS. Switching mechanism is based on the formation and rupture of oxygen vacancy conducting path in the TaO x switching material.