The glass slides containing the adhered bacteria and eukaryotic c

The glass slides containing the adhered bacteria and eukaryotic cells were fixed and hybridized with both PNA probes and observed in fluorescence microscopy,

as referred above. An additional 4′,6-diamidino-2-phenylindole (DAPI; Sigma, Portugal) staining step was done at the end of the hybridization procedure, covering each of the glass slides with 10 μl of DAPI for 5 min at room temperature in the dark, followed by immediate observation in the fluorescence microscope. All these assays were repeated three times, on separate days, with three fields of view assessed each time. Table 4 Efficiency of the Lactobacillus spp. and G. vaginalis detection in adhesion assays with HeLa cell line Concentration of cells (CFU/ml) Multiplex PNA-FISH assay L. crispatus G. vaginalis 5-1 Lac663 CA-4948 mw Probe efficiency Gard162 Probe efficiency 1×109 1×109 +++ +++ 1×105 1×105 +++ +++ 1×103 1×103 ++++ +++ L. iners G. vaginalis 5-1 Lac663 Probe efficiency Gard162 Probe efficiency 1×109 1×109 +++ +++ 1×105 1×105 +++ +++ 1×103 1×103 ++ +++ The PNA probe (Lac663 and Gar162) efficiencies were tested in each sample with the following hybridization PNA FISH qualitative evaluation: (++) Moderate hybridization; (+++) Good hybridization; (++++) Optimal hybridization.

The table shows the median value from the three experiments for each sample. Results In silico analysis of PNA probes The Lac663 probe showed a theoretical sensitivity and specificity of 91.5% and 99.7%, respectively, which corroborates the previously reported values [26]. Actually, this publication shows that these probes match the best values of check details the existing Lactobacillus probes. Gard162 probe presented a theoretical sensitivity of 95.0% and specificity of 100%. The theoretical specificity and sensitivity of these two probes and those developed in other studies were calculated as previously described by Almeida et al.[27] and are listed in Table 2. ProbeMatch tool, from RPDII (http://​rdp.​cme.​msu.​edu/​probematch/​; last accession, May 2012), was used with the following data set options: Strain – Both; Source – Both; Size

– > 1200 bp; Quality – Both. For Lactobacillus probes, the specificity and sensitivity values previously Uroporphyrinogen III synthase determined [26], were considered. FISH Protocol optimization and autofluorescence-related factors FISH protocols on slides and in suspension were adapted from previous protocols developed by Almeida et al. [37], due to the crucial importance of fixation and hybridization conditions for an efficient multiplex FISH with different probes. From an find more initial temperature range of 50 to 72°C and an incubation time range between 30 and 180 min, the best hybridization conditions were set as a moist chamber temperature of 60°C during 90 min of incubation (data not shown). Hybridization conditions started to reveal strong signal-to-noise ratio at 59°C to 61°C from 30 min of incubation up to 120 min, reaching its peak at 60°C during 90 min of incubation.

D Miller Seattle, WA, USA) Packaging cells were transfected with

D Miller Seattle, WA, USA). Packaging cells were transfected with plasmids pTG 5391 (FB29 LTR-lacZ-SV40-Puro-LTR, clone E17-12 -TG 5391) or pTG 9344 (FB29 LTR-PGK-TK-IRES-Neo -LTR clone E 17-21 pTG 9344) to isolate the retroviral producer clone E17-12 -TG 5391 and E 17-21 TG 9344 (Transgene S.A., Strasbourg, France). selleck chemicals The retroviral producer clone were cultured in DMEM supplemented with 4.5 g/L of glucose, 1% non-essential amino acids, 40 μg/ml gentamycin (Sigma) and 10% calf serum. Culture supernatant was harvested, filtered through a 0.45 μm nitrocellulose filter (Sartorius, Goettingen, Germany) and used in the presence of polybrene (Sigma) at 8 μg/ml final concentration.

NIH 3T3 fibroblasts were cultured in DMEM supplemented with 40 μg/ml gentamycin and 10% heat inactivated NBBS (GIBCO/BRL). Retroviral titration was selleck screening library determined by infecting NIH 3T3 fibroblasts with serial dilutions of the culture medium and staining respectively for β-galactosidase activity with X-gal protocol [26] or for HSV-TK expression using monoclonal antibody anti-HSV-TK as described below. All point titrations were performed four times. The titer of viral preparation was 4.9 (± 1.2) × 106 focus-forming units (FFU/ml) for TG 9344 and 1.7 (± 0.9) × 107 FFU/ml for TG 5391. The absence of competent replication helper retrovirus was checked by NIH 3T3 mobilization assay Treatment of cells with MTX, ara-c or aphidicolin

DHDK12 and HT29 cells were plated into 12 well plates at

5.105 cells/well and treated with GSK1210151A mw 0.08 μM methotrexate the (Wyeth-Lederle, Puteaux, France) or 0.075 μM 1-β-D-arabinofuranosyl (Cytarabin-Pharmacia-Upjohn) or 25 μM aphidicolin (Sigma) for 24 hr. The concentrations of the drugs used in our study were chosen according to previously published studies [19, 21, 22]. Furthermore, we determined the IC50 of these drugs by a growth curve analysis. All concentrations used in our study were lower than the calculated IC50 (Table 1). After treatment, the drug-containing medium was removed; the cells were washed twice with phosphate-buffered saline (PBS) and fresh medium was provided. Every 2 to 6 hr during 72 hr, cell cycle distribution were obtained by flow cytometric determination of the DNA content of propidium-iodide (PI)-stained cells as described previously [27]. The cells were analyzed on a cytofluorometer EPICS XL-MCL (Coulter Beckman, Miami, USA) with an argon laser emitting at a wavelength of 488 nm. The analysis of fluorescence was carried out starting from an acquisition window determined by a two dimensional histogram representing the structure of the cells scaled to their size. This acquisition window was then used to produce a histogram representing the number of PI positive cells sorted by intensity of fluorescence, expressed in logarithmic curve mode. Table 1 IC50 of Methotrexate, Ara-C and Aphidicolin in DHDK12 and HT29 cell lines IC 50 Methotrexate Ara-C Aphidicolin DHDK12 cells 0.16 μM 40 μM 30 μM HT29 cells 0.

Chlamydial organisms are strict intracellular parasites, whose re

Chlamydial organisms are strict intracellular parasites, whose requirements in the metabolites are covered

by the host cells. Enhanced uptake of the substrates and metabolites by the infected host cells is a well known “”signature”" strategy of chlamydial infection mandatory for successful accomplishment of its infectious cycle [25]. However, in the case of the chlamydial growth in HepG2 cells we have seen significant decline in LDL-receptor mRNA, which may potentially result in the reduction of lipid uptake. The biological significance of this finding remains unclear. However it is possible to assume, that decline in the LDL-receptor mRNA might represent a mechanism of metabolic adaption of the host cell to chlamydial

infection targeted on limitation of lipid supply and chlamydial growth in the cells. Unfortunately we VX-689 purchase were not able to document corresponding changes in LDL-receptor protein level due to decline in number of viable HepG2 cells that occurs at 72 hour time point of post-infection period. Models of persistent chlamydial infection might CA-4948 purchase be required for evaluating hepatic LDL-receptor turnover in the infected liver cells. Secondly, we have clearly shown that mevastatin, an inhibitor of cholesterol biosynthesis, restores LDL-receptor mRNA and has a significant anti-chlamydial activity reducing chlamydial growth in infected hepatocytes. Genome of C. trachomatis does not contain genes responsible for lipid biosynthesis. Chlamydial species are known to acquire cholesterol, fatty acids and triglycerides from the host cells [26]. Therefore, it was reasonable to

believe that targeting Sitaxentan the cholesterol biosynthetic pathway in the host cells might affect chlamydial infection rate. This prediction was confirmed by RT PCR analysis. It is well acknowledged, that C. trachomatis 16S rRNA gene expression is an informative criterion of chlamydial developmental cycle expressed in both early and late stages of C. trachomatis infection [27]. Detection of 16S rRNA transcript as a marker of viable and metabolically active Chlamydia allows to evaluate the effectiveness of different antibacterial agents [28]. Maximum inhibition of 16S rRNA as well as drastic reduction in the number of infected immunofluorescence-positive cell has been seen at 40 μM mevastatin level. Less pronounced decline in 16S rRNA transcript level has been observed at 20 μM mevastatin concentration. Even though addition of 20 μM mevastatin did not result in Tideglusib in vivo complete inhibition of chlamydial growth in HepG2 cells, there was formation of smaller chlamydial inclusions. Those are often observed in antibiotic- and/or cytokine-treated cells when concentration of the agent is not enough to induce complete eradication of the pathogen [23]. “”Aberrant”" chlamydial cells are known to have some metabolic activity but fail to induce new rounds of chlamydial infection [23, 28].

Mon Not R Astron Soc 374:1321–1333CrossRef Hahn JM, Ward WR (1996

Mon Not R Astron Soc 374:1321–1333CrossRef Hahn JM, Ward WR (1996) Resonance trapping due to nebula disk torques. Lunar Planet Sci 27:479–480 Hatzes AP, Guenther EW, Endl M, Cochran WD, Döllinger MP, Bedalov A (2005) A giant planet around the massive giant star HD 13189. Astron Astrophys 437:743–751CrossRef Hartmann L, Calvet N, Gullbring E, D’Alessio P (1998) Accretion and the evolution of T Tauri disks. Astrophys J 495:385–400CrossRef Holman MJ, Murray NW (2005) The use of transit timing to detect terrestrial-mass extrasolar planets. Science 307:1288–1291PubMedCrossRef Holman M, Fabrycky D, Ragozzine D et al (2010) Kepler-9:

a this website system of multiple planets transiting a Sun-like star, confirmed by timing variations. Science 330:51–54PubMedCrossRef Howard AW, Marcy GW, Johnson JA et al (2010)

The occurrence and mass distribution of close-in super-Earths, Neptunes, and Jupiters. Science 330:653–655PubMedCrossRef Haghighipour N (1999) Dynamical friction and resonance trapping in planetary systems. Mon Not R Astron Soc 304:185–194CrossRef Johnson JA, Butler RP, Marcy GW, Fischer DA, Vogt SS, Wright JT, Peek KMG (2007) A new planet around an M dwarf: revealing a crrelation between exoplanets and stellar mass. Astrophys J 670:833–840CrossRef Johnson JA, Payne M, Howard AW et al (2011) Retired a stars and their companions. VI. A pair of interacting exoplanet pairs around the subgiants 24 sextanis and HD 200964. Astron Ro 61-8048 purchase J 141:16. doi:10.​1088/​0004-6256/​141/​1/​16 CrossRef Kepler J (1596) Mysterium cosmographicum, 1st edn. Tubingen Kepler J (1609) Astronomia nova. Heidelberg Kepler J (1619) Harmonices mundi libri V. Linz Ketchum JA, Adams FC, Bloch AM (2011) Phosphoribosylglycinamide formyltransferase Effects of turbulence, eccentricity damping, and migration rate on the capture of planets into mean motion resonance. Astrophys J 726:53. doi:10.​1088/​0004-637X/​726/​1/​53 CrossRef Kley W (2000) On the migration of a system of protoplanets. Mon Not R Astron Soc 313:L47–L51CrossRef Kley W, Lee MH, Murray N, Peale SJ (2005) Modeling the resonant planetary system GJ 876. Astron

Astrophys 437:727–742CrossRef Kley W, Peitz J, Bryden G (2004) Evolution of planetary systems in resonance. Astron Astrophys 414:735–747CrossRef Konacki M, Wolszczan A (2003) Masses and orbital inclinations of planets in the PSR B1257+12 system. Astrophys J 591:L147–L150CrossRef Laskar J, Correia A (2009) HD 60532, a planetary system in a 3:1 mean motion resonance. Astron Astrophys 496:L5–L8CrossRef Latham DW, Rowe JF, Quinn SN et al (2011) A first comparison of Kepler planet candidates in single and multiple systems. Astrophys J Lett 732:L24. doi:10.​1088/​2041-8205/​732/​2/​L24 CrossRef Laughlin G, Steinacker A, Adams FC (2004) Type I planetary migration with MHD turbulence. Astrophys J 608:489–496CrossRef Lee MH (2004) Diversity and origin of 2:1 orbital resonances in extrasolar planetary systems.

Phthalates were present in all samples, presumably as trace conta

Phthalates were present in all samples, presumably as trace contaminants from plastic containers. The highest-temperature (175°C) sample from a borehole contained only polycyclic aromatic hydrocarbons (naphthalene, biphenyl, phenathrene, fluorene, 1-methylnaphtaline). These organic compounds characterize the deep sterile zone near the active Mutnovsky volcano (depth 200–600 m, temperature 175–250°C). Biphenyl

and phenathrene were absent in samples from lower temperature boreholes (95–124°C) and springs. However, numerous other aromatic hydrocarbons (benzenes, xylenes) and aliphatic hydrocarbons (decanes, isoalkanes) were present. The source of these compounds is not yet established. They may represent pre-existing organic material that has been chemically degraded by pyrolysis. For instance, Simoneit et al. (2008) established

that the light oil associated with the Uzon caldera in Kamchatka was formed by pyrolysis Sapanisertib manufacturer of buried algal mats. More interesting would be to determine that the aromatics and alkanes are products of a Fischer–Tropsch type synthesis. However, the original source of organics was not so important for the origin of life on the early Earth: these compounds Carbachol might as to be synthesized in hydrothermal medium as to be involved into hydrothermal circulation from other this website sources (synthesis at pre-geological stage of the Earth formation, synthesis in the atmosphere/ocean at the expense of ultraviolet radiation, delivering by comets, etc.). It seems that organic matter of any origin had a chance

to be transformed into a living unit under oscillating hydrothermal conditions through three successive stages: (1) an organic microsystem becomes unstable at the critical point of the bifurcate transition under conditions far from equilibrium; (2) relative stabilization of the microsystem due to the balanced oscillations around the critical point (appearance of the paradoxical state “stabilized instability”); (3) inversion of the energetic balance-free energy contribution begins to prevail over entropy contribution (Kompanichenko, 2008). Kompanichenko V.N. Three stages of the origin-of-life process: bifurcation, stabilization and inversion // International Journal of Astrobiology, 2008, Volume 7, Issue 01, p. 27–46. Simoneit, B., Deamer D.W. and Kompanichenko, V. 2008. Characterization of hydrothermally generated oil from the Uzon Caldera, Kamchatka. Applied Geochemistry (In press). E-mail: kompanv@yandex.

In five studies based on rat models, different vectors were used

In five studies based on rat models, different vectors were used to express therapeutic nucleic acids (transgenes or small interfering RNAs) Silmitasertib in vivo in peritoneal tissue [31, 40, 55–59]. However, no method has distinguished itself as the optimal means of preventing adhesion formation [59]. Current preventive approaches range from the use of physical barriers to the administration of pharmacological agents, recombinant proteins and antibodies, and gene therapy, yet they have all failed to consistently yield satisfactory results. Single therapeutic strategies are typically unsuccessful in preventing peritoneal adhesions due to the multi-factorial nature of adhesion pathogenesis.

Extensive literature on the subject demonstrates both the complexity of the issue and the myriad resources allocated HKI-272 in vitro to this condition, yet few interdisciplinary studies have been conducted involving experts from different fields. At this time the medical community only recognizes the “tip of the iceberg” and will continue treating the condition inadequately until it is more comprehensively explored. We are in agreement with Hellebrekers et al. and believe that additional prospective studies must be conducted to examine adhesion formation in relation

to factors of inflammation, coagulation, and fibrinolysis. To more effectively integrate the findings of different studies, specific attention should be paid to uniformity of measurement (what, where, and when to measure) [60]. We therefore suggest a regimented Carteolol HCl classification system for adhesions in an effort to standardize their definition and subsequent analysis. In this way, different surgeons in different treatment centers can more effectively evaluate patients and compare their conditions to past evaluations using a universal classification system (Figure 1). This classification is based on

the macroscopic appearance of adhesions and their extent to the different regions of the abdomen. Using specific scoring criteria, clinicians can assign a peritoneal adhesion index (PAI) ranging from 0 to 30, thereby giving a precise description of the intra-abdominal condition. Standardized classification and quantification of adhesions would enable researchers to integrate the results of different studies to more comprehensively CB-839 solubility dmso approach the treatment and management of adhesion-related pathology. Figure 1 Peritoneal adhesion index: by ascribing to each abdomen area an adhesion related score as indicated, the sum of the scores will result in the PAI. Furthermore, as asserted by other researchers [53], we must encourage greater collaboration among basic, material, and clinical sciences. Surgery is progressively becoming more dependent on the findings of research in the basic sciences, and surgeons must contribute by practicing research routinely in a clinical setting.

DLL4 expression was identified in the cytoplasm and cellular memb

DLL4 expression was identified in the cytoplasm and cellular membrane of cancer cells (Figure 2), and in the stromal cells (Figure 3). Ten representative tissue sections were observed by light microscropy and the percentage of DLL4 positive cancer cells was scored, averaged, and scored semiquantitatively. All immunostained slides were evaluated by two independent observers (SI and AT), who were unaware of the clinical data and disease outcome. If more than 10% of dominant staining learn more intensity in tumor cells or stromal cells was identified, the patients were regarded as DLL4 positive. After evaluation, patients were divided into two groups according

to DLL4 expression positivity. Clinicopathological factors of gastric cancer were assessed according to the General Rules of Gastric Cancer in Japan [18]. Figure 2 DLL4 expression in gastric cancer cells. Right: DLL4 expression was identified in the cellular membrane of gastric cancer cells. DLL positivity was found in the cytoplasm

and cellular membrane of gastric cancer (yellow arrow). Left: DLL4 expression was not found in gastric cancer (negative control). Figure 3 DLL4 expression in brain and stromal cells of gastric cancer. DLL4 positive Selleck JIB04 infiltrative cells were identified in cancer stroma (yellow arrow). Statistical analysis Statistical analysis of clinical features was performed using the χ2-test. Survival curves were constructed using the Kaplan-Meier method, and survival differences were analyzed by the generalized Wilcoxon selleck chemicals test. Multivariate

analysis was performed to determine prognostic factors. A p-value of less than 0.05 was considered to be statistically significant. Results DLL4 expression in gastric cancer tissues DLL4 positivity was identified in brain tissue as a positive control of DLL4 (Figure 1). DLL4 expression was primarily identified in the membranes and cytoplasm of cancer cells, regardless of tumor histology (Figure 2), as well as infiltrative cells in cancer stroma (Figure 3). 88 (49%) patients were classified as DLL4 positive (10% of DLL4 positive) group in cell lines; many 41 (23%) were positive in the stroma. DLL4 expression in gastric carcinoma cell lines Immunohistochemical staining showed DLL4 expression in cytoplasm of the four gastric cancer cell lines (Figure 4). Cell lysates extracted separately from the nucleus and cytoplasm in the gastric cancer cell lines were loaded and probed with anti-DLL4 antibody. DLL4 protein was identified in cytoplasm of the all gastric cancer cell lines, but not in the nucleus (Figure 5). Figure 4 DLL4 expression in gastric cancer cell lines. DLL4 expression was identified in the cellular membrane and cytoplasm of gastric cancer cells. Figure 5 DLL4 protein detection in gastric cancer cell lines by Western blot analysis.

Likewise, the phage is able to propagate in different strains of

Likewise, the phage is able to propagate in different strains of Escherichia, Salmonella, Klebsiella, Proteus and Serratia, provided they contain an IncM plasmid. To obtain more insight in plasmid-specific RNA phages, we determined the genome sequence of phage M and present here its analysis and check details comparison to the genomes of other RNA phages of the Leviviridae family. Results and discussion Overall structure of the genome The genome of phage M is 3405 nucleotides long and follows the canonical Leviviridae

genome organization with maturation, coat and replicase cistrons following each other in CUDC-907 cost the 5′-3′ direction (Figure 1). An unusual feature of the genome is that the lysis gene appears to be located in a different position than in other leviviruses, as discussed below. It is also the smallest known

Leviviridae genome to date, about 60 nucleotides shorter than that of the group II F-specific phage GA [28]. The protein coding regions of phage M are of similar length to those of phage GA, with maturation and coat genes PRN1371 cell line being a bit longer and replicase somewhat shorter; the greatest savings in M’s genome come from terminal untranslated regions (UTRs), the 5′ UTR being about 45 nucleotides and the 3′ UTR about 20 nucleotides shorter. Figure 1 Genome organization of phage M. Start and end positions of phage genes are indicated. For comparison, the other known genome organizations of Leviviridae phages are represented on the right with genes color-coded as in the M genome. In phage Qβ, protein A1 (bright green) is an extended read-through variant of the coat protein and the lysis function is performed by the maturation

protein. Identification of the lysis gene All members of the levivirus genus encode a short polypeptide that mediates cell lysis. Amino acid sequences of lysis proteins show great variation and their only unifying feature is the existence of a hydrophobic transmembrane helix within the protein [29]. Lysis proteins have been shown to accumulate in the bacterial membrane Pregnenolone where they presumably form pores that lead to cell lysis [30]. In all of the known Enterobacteria-infecting leviviruses, the lysis gene overlaps with coat and replicase genes in a different reading frame and is translationally coupled with the coat gene [1]. However, in the genome of phage M, no candidate ORFs at this location could be identified: in the +2 frame relative to the coat gene there are no termination codons until the start of replicase and in the +1 frame only a 17 amino acid long ORF that would encode a non-hydrophobic peptide is found. Up to now, there have been two reported cases in the Leviviridae family where the lysis gene in is in a different location: Acinetobacter phage AP205 has a short lysis gene preceding the maturation gene [31], while Caulobacter phage ϕCb5 codes for a longer, two-helix protein that completely overlaps with the replicase gene [32].

However, the function of miR-203 in breast cancer remains unclear

However, the function of miR-203 in breast cancer remains unclear, especially in TNBC. In this paper, we showed that miR-203 was down-regulated in TNBC cell lines and that the ectopic over-CB-839 molecular weight Expression of miR-203 blocked tumor cell proliferation and migration in vitro. Furthermore, BIRC5 and LASP1 were identified as two direct functional BVD-523 cell line targets of miR-203 in TNBC cells. These data suggest that the reduced expression of miR-203 facilitates the development and metastasis of TNBC. Materials and methods Cell culture and treatment Human triple-negative breast cancer cell lines

(MDA-MB-468 and MDA-MB-231) and normal breast cell line MCF-10A, were purchased from the American Type Culture Collection. MDA-MB-468 and MDA-MB-231 cells were maintained in DMEM (Gibco) supplemented with

10% FBS and 100 U/ml penicillin and 100 μg/ml streptomycin. MCF-10A cells were maintained in DMEM/F-12 supplemented with 10% FBS, insulin (10 μg /ml), hydrocortisone (500 ng/ml) and EGF (20 ng/ml). The cells were collected using 0.05% trypsin EDTA following the specified incubation period. Precursor miRNA/siRNA/plasmid transfection Cells were seeded in 6-well plates check details at a concentration of 1 × 105 and cultured in medium without antibiotics for approximately 24 h before transfection. Cells were transiently transfected with miR-203 precursor (Applied Biosystems) or negative control miRNA, BIRC5 siRNA (Sigma), LASP1 siRNA (Sigma) or control siRNA at a final concentration of 200nM. PcDNA-BIRC5 or pcDNA-LASP1 plasmid was also transfected into MDA-MB-231 cells using Lipofectamine 2000 (Invitrogen) according to the manufacturer’s protocol.

Real-time PCR assay Total RNA was extracted from cultured cells using the TRIzol reagent (Invitrogen). cDNA was obtained by reverse transcription of total RNA using a TaqMan Reverse Transcription Kit (Applied Biosystems) and iScript cDNA Synthesis kit (BIO-RAD), respectively. The expression level of mature miR-203 was measured using a TaqMan miRNA assay (Applied Biosystems) according to the provided Protein Tyrosine Kinase inhibitor protocol and using U6 small nuclear RNA as an internal control. Expression of BIRC5 and LASP1mRNA was detected using Power SYBR Green kit (Applied Biosystems). All experiments were performed in triplicate. Colony formation assay Cells were seeded into a 12-well cell culture plate and incubated for 2 weeks at 37 °C after treatment. Then, cells were washed twice with PBS, fixed with cold methanol, stained with 0.1% crystal violet, washed and air dried. Migration assay Cells were harvested and re-suspended in serum-free DMEM medium. For the migration assay, 5 × 104 cells were added into the upper chamber of the insert (BD Bioscience, 8 μm pore size). Cells were plated in medium without serum, and medium containing 10% fetal bovine serum in the lower chamber served as the chemoattractant. After 6 h of incubation, cells were fixed with 3.

At elevated temperature (85°C), even with descents of both LRS an

At elevated temperature (85°C), even with descents of both LRS and HRS, the memory window is still in accordance with excellent thermal stability, and a 10-year usage is still possible, with the resistance ratio larger than 10. Figure 4 Read disturbance test for device after 10 4 -s retention time under room temperature and at 85°C. No significant degradation of resistance ratio

was observed under room temperature, and there is a slightly parallel descent of the HRS and LRS at 85°C. The speed of the set and reset operations with different pulse widths at ±5 V is exhibited in Figure 5, and the resistance state of the device after the pulse was read at 0.1 V. We found that the resistive switching phenomenon occurs when the pulse width is larger than 500 ns for reset check details operation and 800 ns for set operation. The operation speed of the memory cell is a little faster than some cases before [22, 30]. Figure 5 The behavior of the TiN/HfO 2 /Al 2 O 3 /ITO/PET memory cell under different pulses. HRS and LRS are read at 0.1 V, and the set and reset operations of the devices were achieved with different pulsing widths at ±5 V. Stable and reproducible switching characteristics have

been displayed in Figure 6 with a consistent 400 switching cycle without failures by DC sweeping. The sweeping voltage was applied from 0 to 2 V for set and 0 to −2 V for reset with a reading voltage of 0.1 V at room temperature. In Figure 6a, the result of the endurance test shows that memory ratio remains above 10:1 all along. Foretinib nmr Furthermore, statistics of the resistances and operation voltages are conducted separately according to the endurance test result. The resistance distributions of the LRS and HRS have been shown in Figure 6b, and we can find that only a small dispersion, with almost 90% of the LRS around 0.6 kΩ and 80% of the HRS around 10 kΩ, existed during the switching. In addition, Figure 6c shows the operation voltage

distributions for set and reset. It can be obviously observed that almost 99% of the reset Amobarbital voltages are near −2 V and almost 85% of the set voltages are around 1 V. Through all the statistical results and previous test result, we can conclude that our flexible RRAM is characterized with high uniformity and reliability. Figure 6 The DC endurance test of the device. Voltage sweeping was from 0 V to 2 V for set and from 0 V to −2 V for reset at room temperature, with a reading voltage of 0.1 V. (a) The continuous program and erase test, (b) the statistical result of the set and reset voltages, and (c) the statistical result of the resistance distributions of the LRS and HRS. To inspect the equivalent circuit model of the device, we measured the impedance of the device in HRS and LRS in the Z-Z (θ) mode by applying 20 mV of AC small signal (40 Hz to 110 MHz) to the device. Figure 7 shows the Nyquist plot (Z″-Z ′, Z″, and Z ′ represent the absolute value of imaginary parts and real parts of the impedance) of the device in the LRS and HRS.