In randomised clinical trials, these treatments can reduce fracture incidence by up to 50%. However, in routine care, these treatment benefits may be compromised by poor

adherence to treatment, with around 50% of women discontinuing treatment within 1 year [10, 11]. Suboptimal adherence to antiresorptive treatment has been shown to be associated with an increased risk of fracture [12–14]. Barriers to better adherence to osteoporosis treatment include the constraints associated with the administration of some of these agents, side-effects, the treatment regimen, the lack of a buy EVP4593 visible “read-out” of treatment benefit and inappropriate patient expectations and perceptions [15–17].

Improving Akt inhibitor adherence to osteoporosis treatment thus represents an important public health issue. Achieving this requires appropriate tools to measure adherence which 3-MA mw can be used to monitor improvements due to public health interventions. The notion of adherence involves a number of inter-related aspects. With regard to osteoporosis, an expert consensus recently described adherence as a general term encompassing both compliance and persistence [18]. Compliance was defined as the extent to which a patient acts in accordance with the prescribed interval and dose of a given treatment regimen, whereas persistence was defined as the cumulative time from initiation to discontinuation of therapy. Currently, three principal types of adherence measure have been developed, prescription follow-up or pharmacy claims to determine medication consumption over time, direct medication use measures (for example, pill counts, electronic measures or canister weights) or patient reports. Direct medication use measures are not particularly useful for naturalistic studies, since they may lead to bias due to potential

modification of adherence behaviour by implementation of the reporting measure. Of the prescription follow-up methods, the medication possession ratio (MPR) [19, 20] has Coproporphyrinogen III oxidase been widely used. A number of patient-reported measures of treatment adherence have been developed and validated, including the Morisky Medication Adherence Scale (MMAS) [21], the Medication Adherence Report Scale [22], the Adherence to Refills and Medications Scale [23], the ASK-20 [24] and the Hypertension Compliance Questionnaire [25]. However, none of these instruments were designed specifically with osteoporosis in mind, and it would therefore be of interest to develop a disease-specific adherence measure which would focus on adherence issues that are pertinent to osteoporosis and its treatment and may be more discriminating and sensitive to change than non-specific measures.

Cell 1997, 90:809–819.PubMedwww.selleckchem.com/products/MLN-2238.html CrossRef 65. Boominathan L: Some facts and thoughts: p73 as a tumour suppressor gene in the network of tumour suppressors. Mol Cancer

2007, 6:1–8.CrossRef see more 66. Levrero M, De Laurenzi V, Costanzo A, Gong J, Wang JY, Melino G: The p53/p63/p73 family of transcription factors: overlapping and distinct functions. J Cell Sci 2000, 113:1661–1670.PubMed 67. Alhosin M, Abusnina A, Achour M, Sharif T, Muller C, Peluso J, Chataigneau T, Lugnier C, Schini-Kerth VB, Bronner C, Fuhrmann G: Induction of apoptosis by thymoquinone in lymphoblastic leukemia Jurkat cells is mediated by a p73-dependent pathway which targets the epigenetic integrator UHRF1. Biochem Pharmacol 2010, 79:1251–1260.PubMedCrossRef 68. Bronner C, Chataigneau T, Schini-Kerth VB, Landry Y: The “”Epigenetic Code Replication Machinery”", ECREM: a promising drugable target of the epigenetic cell memory. Curr Med 2007, 14:2629–2641.CrossRef 69. Surh YJ: Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 2003, 3:768–780.PubMedCrossRef

70. Wu P, Dugoua JJ, Eyawo O, Mills EJ: Traditional Chinese Medicines in the treatment of hepatocellular cancers: a systematic review and meta-analysis. J Exp Clin Cancer Res 2009, 28:112.PubMedCrossRef 71. Lu Y, Li CS, Dong Q: Chinese herb related molecules of cancer-cell-apoptosis: a minireview of progress between mTOR inhibitor Kanglaite injection and related genes. J Exp Clin Cancer Res 2008, 27:31.PubMedCrossRef 72. Borek C: Dietary antioxidants and human cancer. Integr Cancer Ther 2004, 3:333–341.PubMedCrossRef 73. Zhang M, Holman

CD, Huang JP, Xie X: Green tea and the prevention of breast cancer: a case-control study in Southeast China. Carcinogenesis 2007, 28:1074–1078.PubMedCrossRef 74. Gali-Muhtasib H, Roessner A, Schneider-Stock R: Thymoquinone: a promising anticancer drug from natural sources. Int J Biochem Cell Biol 2006, 38:1249–1253.PubMedCrossRef 75. Padhye S, Banerjee Telomerase S, Ahmad A, Mohammad R, Sarkar FH: From here to eternity – the secret of Pharaohs: Therapeutic potential of black cumin seeds and beyond. Cancer Ther 2008, 6:495–510.PubMed 76. Worthen DR, Ghosheh OA, Crooks PA: The in vitro anti-tumour activity of some crude and purified components of blackseed, Nigella sativa L. Anticancer Res 1998, 18:1527–1532.PubMed 77. Shoieb AM, Elgayyar M, Dudrick PS, Bell JL, Tithof PK: In vitro inhibition of growth and induction of apoptosis in cancer cell lines by thymoquinone. Int J Oncol 2003, 22:107–113.PubMed 78. Gali-Muhtasib HU, Abou Kheir WG, Kheir LA, Darwiche N, Crooks PA: Molecular pathway for thymoquinone-induced cell-cycle arrest and apoptosis in neoplastic keratinocytes. Anticancer Drugs 2004, 15:389–399.PubMedCrossRef 79.

05).

Subjects were allowed 60 minutes to consume the entire volume of beverage. Each condition was consumed on a different test day, with a minimum of five days separating mTOR inhibitor test visits. Table 2 Study timeline and outcome measures Time → Variable ↓ Pre Dehydrating Exercise Test Immediately Post Dehydrating Exercise Test 1 Hour Post Dehydrating Exercise Test 2 Hours Post Dehydrating Exercise Test 3 Hours Post Dehydrating Exercise Test† Immediately Post Performance Exercise Test Body Mass†† X X* X** X X   Plasma Osmolality X X     X   Urine Specific Gravity X X     X   Subjective Measures (VAS)   X X X X   Heart Rate X X     X X Blood Pressure X X     X X † The Performance

Exercise Test began following this measurement time (total exercise time was recorded) †† Body Mass was used to calculate fluid retention (as described in the Methods section) * For determination of fluid volume to consume ** For determination of “”baseline”" body mass Performance Exercise Test Three hours after the completion of the dehydrating exercise test (and HMPL-504 two hours after subjects consumed their assigned condition), a test of physical performance was conducted using a treadmill as previously done [20]. Specifically, subjects began walking on a motorized treadmill at a self-selected comfortable speed (0% grade) for five minutes. At the conclusion of the five-minute period,

the actual performance test began. The protocol involved an increase in intensity every three minutes. While the speed of the treadmill remained constant at 4.2 miles per hour throughout the test, the grade increase in the following manner: Rapamycin cost min 1-3, 0%; min 4-6, 2.5%; min 7-9, 5%; min 10-12, 7.5%; min 13-15, 10%; min 16-18, 12.5%; min 19-21, 15%. Subjects exercised until volitional exhaustion and the total exercise time was recorded. This identical protocol was administered at the screening visit (for familiarization) and on each of the four test day visits. Therefore, we do not believe that there was any significant degree of “”learning”" involved with this test. Outcome Measures In addition to the measure of total exercise time obtained in the performance test described above, the following variables were used as outcome measures; some of which have been discussed previously [21]. With regard to hydration status, body mass, fluid retention (based on body mass), plasma osmolality, and urine specific gravity were measured. Specifically, for fluid retention based on body mass, it was expected that the administration of test product at the amount prescribed would bring the subject’s body mass back to very near its P005091 research buy pre-exercise level.

Farber (Health Canada) and Prof J. Park (Kyungwon University, Korea). Electronic supplementary material Additional file 1: MLST analysis of the Cronobacter isolates showing their source, geographic location and species. The data provided shows the spacial, temporal and source of strains used in this study, and reference where the strains have been used in previous publications. (DOC 205 KB) References 1. Farmer JJ III, Asbury MA, Hickman FW, Brenner DJ, The Enterobacteriaceae study group:Enterobacter Avapritinib research buy sakazakii : a new species of “” Enterobacteriaceae “” isolated from clinical specimens. Intl J System Bacteriol 1980,

30:569–584.CrossRef 2. Iversen C, Waddington buy AZD5582 M, On SLW, Forsythe S: Identification and phylogeny of Enterobacter sakazakii relative to Enterobacter and Citrobacter. J Clin Microbiol 2004, 42:5368–5370.CrossRefPubMed 3. Iversen C, Waddington M, Farmer JJ III, Forsythe S: The biochemical differentiation of Enterobacter sakazakii genotypes. BMC Microbiology PI3K Inhibitor Library 2006, 6:94.CrossRefPubMed 4. Iversen C, Lehner A, Mullane N, Bidlas E, Cleenwerck I, Marugg J, Fanning S, Stephan R, Joosten H: The taxonomy of Enterobacter sakazakii : proposal of a new genus Cronobacter gen. nov. and descriptions of Cronobacter sakazakii comb. nov. Cronobacter

sakazakii subsp. sakazakii, comb. nov., Cronobacter sakazakii subsp. malonaticus subsp. nov., Cronobacter turicensis sp. nov., Cronobacter muytjensii sp. nov., Cronobacter dublinensis sp. nov. and Cronobacter genomospecies 1. BMC Evol Biol 2007, 7:64.CrossRefPubMed 5. Iversen C, Mullane N, McCardell B, Tall BD, Lehner A, Fanning

S, Stephan R, Joosten H:Cronobacter gen. nov., a new genus to accommodate the biogroups of Enterobacter sakazakii, and proposal of Cronobacter sakazakii gen. nov., comb. nov., Cronobacter malonaticus sp. nov., Cronobacter turicensis sp. nov., Cronobacter muytjensii sp. nov., Cronobacter dublinensis sp. nov., Cronobacter BCKDHB genomospecies 1, and of three subspecies, Cronobacter dublinensis subsp. dublinensis subsp. nov., Cronobacter dublinensis subsp. lausannensis subsp. nov. and Cronobacter dublinensis subsp. lactaridi subsp. nov. Intl J System Evol Microbiol 2008, 58:1442–1447.CrossRef 6. Food and Agriculture Organization-World Health Organization (FAO-WHO): Joint FAO/WHO workshop on Enterbacter sakazakii and other microorganisms in powdered infant formula, Geneva, 2–5 February, 2004. [http://​www.​who.​int/​foodsafety/​publications/​feb2004/​en/​print.​html] 2004. 7. Food and Agriculture Organization-World Health Organization (FAO-WHO):Enterobacter sakazakii and Salmonella in powdered infant Formula. [http://​www.​who.​int/​foodsafety/​publications/​micro/​mra10/​en/​index.​html]Second Risk Assessment Workshop. 16–20th January. WHO Rome, Italy 2006. 8. Forsythe S:Enterobacter sakazakii and other bacteria in powdered infant milk formula.

Microbiology 1997,143(Pt 11):3443–3450.PubMedCrossRef 27. Li J, Jensen SE: Nonribosomal biosynthesis of fusaricidins by Paenibacillus polymyxa PKB1 involves direct activation of a D-amino acid. Chem Biol 2008,15(2):118–127.PubMedCrossRef 28. Steller S, Sokoll A, Wilde

C, Bernhard F, Franke P, Vater J: Initiation Small molecule library solubility dmso of surfactin biosynthesis and the role of the SrfD-thioesterase protein. Biochemistry 2004,43(35):11331–11343.PubMedCrossRef Competing interests The authors declare that they have no competing interests. Authors’ contributions CDQ was responsible for designing the study, bioinformatic analysis, and writing the manuscript. CDQ and TZL performed the recombinant protein preparation and biochemical experiments. SLZ made substantial contributions to data analyses and interpretation. WPZ, RD, and OL helped to revise the manuscript. XCW was responsible for the integrity of the work as a whole. All authors read and approved the final manuscript.”
“Background The main cause of morbidity and mortality in cystic fibrosis (CF) is EVP4593 datasheet chronic lung disease caused by a vicious cycle of infection and inflammation Ruboxistaurin datasheet which leads to progressive deterioration of pulmonary function, respiratory failure, and death [1]. Pseudomonas aeruginosa is the main bacteria associated

with pulmonary disease in CF. In vivo and in vitro evidence suggests that P. aeruginosa produce biofilm within the airways of chronic CF pulmonary infection patients,[2–5] which is a protective barrier around the bacterial cells and limits exposure to oxidative radicals, antibiotics, and phagocytes [6]. Bacterial biofilms

play a relevant role in persistent infections, which are rarely eradicated with antimicrobial therapy [7]. Despite the evidence of P. aeruginosa grown in the airways of CF patients in biofilm form, the susceptibility profile of the bacterium is usually evaluated, in vitro, in the planktonic state. However, the planktonic susceptibility profile may not represent the actual susceptibility of the bacteria [7]. To overcome the potential shortfalls of traditional (planktonic) microbiological methods to evaluate susceptibility, biofilm models have been proposed to Silibinin access susceptibility of P. aeruginosa in vitro[8]. Macrolide antibiotics are being evaluated for the treatment of chronic lung inflammatory diseases, including diffuse panbronchiolitis, CF, chronic obstructive pulmonary disease, and asthma. Although macrolides have no antimicrobial activity against P. aeruginosa at therapeutic concentrations, there is great interest in the evaluation of treatments of CF patients with these antibiotics, at least as complementary therapy [9–11]. Anti-inflammatory activity of macrolides has been showed in many studies, including clinical trials [12–17].

Moreover, DSF-family signals showed a high level of potency in interference of the morphology transition of C. albicans[14, 17, 22], which is a critical

feature associated with the virulence of this pathogen. Given the fact that biofilm formation is related to antibiotic resistance [26], together with the role of DSF-family signals in regulation of bacterial biofilm formation and antibiotic resistance, Evofosfamide research buy we speculate that DSF-family signals may have a role in modulation of bacterial antibiotic susceptibility. In this study, we report that in the presence of DSF signal and its derivatives, some of which were identified as bacterial quorum sensing (QS) signals [13, 14, 18, 22],

the minimum inhibitory concentrations (MIC) of a few antibiotics against the bacterial pathogens were significantly reduced. Furthermore, we showed that supplementation of DSF signal could substantially enhance the antimicrobial activity of gentamicin and selleckchem reduce the cytotoxicity of B. cereus in an in vitro infection model. Our findings suggest the promising potentials of DSF and its structurally related molecules as selleck chemicals llc putative antibiotic adjuvants for the control of bacterial infections. Results DSF and its structurally related molecules increase the antibiotic susceptibility of B. cereus Bacillus is a genus of Gram-positive, rod-shaped bacteria. They are ubiquitous in nature, and consisting Phosphatidylinositol diacylglycerol-lyase of both free-living and pathogenic species. Bacillus bacteria produce oval endospores to endure a wide range of extreme environmental conditions, while keeping the capacity to return to vegetative growth [27]. This remarkable characteristics of the endospore-vegetative cell transition of Bacillus pathogens allows them to be utilized as biological

weapons [28, 29]. Interestingly, our preliminary results showed that this morphological transition between the vegetative cell and endospore of Bacillus species could be stopped by exogenous addition of DSF-family signals (Deng, unpublished data). This finding, together with the previous observations that DSF signals are involved in regulation of bacterial biofilm formation, antibiotic tolerance and fungal morphological transition [15, 22–24], we speculated that DSF-family signals may affect the bacterial antibiotic sensitivity of Bacillus cells. To test this hypothesis, we firstly chose B. cereus, which is a common human pathogen and causes foodborne illness such as nausea, vomiting and diarrhea [30], to assay the antibiotic susceptibility in the presence of DSF signal or its derivatives (Table 1).

CrossRef 13. Zhu YF, Kockrick E, Ikoma T, Hanagata N, Kaskel S: An efficient route to rattle-type Fe 3 O

4 @SiO 2 hollow mesoporous spheres using colloidal carbon spheres templates. Chem Mater 2009, 21:2547–2553.CrossRef 14. Neoh KG, Kang ET: Surface modification of magnetic nanoparticles for stem cell labeling. Soft Matter 2012, 8:2057–2069.CrossRef 15. Dandamudi S, Patil V, Fowle W, Khaw BA, Campbell RB: External magnet improves antitumor effect of vinblastine and the suppression of metastasis. Cancer Sci 2009, 100:1537–1543.CrossRef 16. Wang L, Neoh KG, Kang ET, Shuter B: Multifunctional polyglycerol-grafted Fe 3 O 4 @SiO 2 nanoparticles for targeting ovarian cancer cells. Biomaterials 2011, 32:2166–2173.CrossRef 17. Wang F, Chen XL, Zhao ZX, Tang SH, Huang XQ, Lin CH, Cai CB, Zheng NF, Mater J: Synthesis of learn more magnetic, fluorescent and mesoporous core-shell-structured nanoparticles for imaging, targeting and photodynamic therapy. J Mater Chem 2011, 21:11244–11252.CrossRef 18. Lin YS, Haynes CL: Synthesis and PF-562271 characterization of biocompatible and size-tunable multifunctional porous silica nanoparticles. Chem Mater 2009, 21:3979–3986.CrossRef 19. Chen Y, Chen HR, Shi JL: In vivo bio-safety evaluations

and diagnostic/therapeutic applications of chemically designed mesoporous silica nanoparticles. Adv Mater 2013, 25:3144–3176.CrossRef 20. Reddy LH, Arias JL, Nicolas J, Couvreur P: Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, LB-100 concentration pharmaceutical and biomedical applications. Chem Rev 2012, 112:5818–5878.CrossRef 21. Kim J, Kim HS, Lee N, Kim T, Kim H, Yu T, Song IC, Moon WK, Hyeon T: Multifunctional uniform nanoparticles composed of a magnetite nanocrystal core and a mesoporous silica shell for magnetic resonance and fluorescence imaging and for drug delivery. Angew Chem Int Ed 2008, 47:8438–8441.CrossRef 22. Laudenslager MJ, Schiffman JD, Schauer CL: Carboxymethyl chitosan as a matrix material for platinum, gold, and silver nanoparticles.

Biomacromolecules 2008, 9:2682–2685.CrossRef 23. Shi ZL, Neoh KG, Kang ET, Shuter B, Wang SC, Poh C, Wang W: (Carboxymethyl)chitosan modified superparamagnetic iron oxide nanoparticles for magnetic resonance imaging of stem cells. ACS Appl Mater Interfaces 2009, 1:328–335.CrossRef 24. Fan CX, Gao WH, Chen ZX, Fan HY, Li MY, Deng Galeterone FJ, Chen ZL: Tumor selectivity of stealth multi-functionalized superparamagnetic iron oxide nanoparticles. Int J Pharm 2011, 404:180–190.CrossRef 25. Oh JM, Choi SJ, Lee GE, Han SH, Choy JH: Inorganic drug-delivery nanovehicle conjugated with cancer-cell-specific ligand. Adv Funct Mater 2009, 19:1617–1624.CrossRef 26. Santra S, Kaittanis C, Santiesteban OJ, Perez JM: Cell-specific, activatable, and theranostic prodrug for dual-targeted cancer imaging and therapy. J Am Chem Soc 2011, 133:16680–16688.CrossRef 27. Peng S, Wang C, Xie J, Sun SH: Synthesis and stabilization of monodisperse Fe nanoparticles. J Am Chem Soc 2006, 128:10676–10677.

Methods Patients Two groups of children referred to the Pediatric Gastroenterology and Liver Unit of the “”Sapienza”" University of Rome were included in this study: 20 CD (mean age 8.3 years, range 1.2-16.1 years) in active and in remission state

(at AZD5363 supplier diagnosis and after at least 9 months of gluten-free diet, respectively) and 10 controls undergoing upper gastrointestinal endoscopy for functional dyspepsia (mean age 11.7 years, range 7.8-20.8 years). The latter tested negative for antitransglutaminase and antiendomysial antibodies with normal IgA levels, while histology of duodenum did not reveal features of CD. Diagnosis of CD MI-503 had been performed according to ESPGHAN criteria [15]. Table 2 summarizes clinical features of the

studied population. selleck chemicals Size appropriate and well oriented endoscopic biopsy specimens were obtained from the second part of the duodenum. The histopathological diagnosis was based on typical mucosal lesions with crypt cell hyperplasia, villous atrophy, and increased number of intra-epithelial lymphocytes (IELs) [16]. All untreated CD patients were positive for antiendomysial and antitransglutaminase antibodies at the time of diagnosis. In all patients there was an endoscopic improvement of duodenal mucosa following gluten withdrawal, but only in 2 of them (patients number 12 and 19) there was also a full histological improvement. None of the children included in the study was treated with antibiotics for at least 3 months before the sampling time. The study protocol was approved by the Committee on Ethical Practice of the ‘Policlinico Umberto I’ hospital. Children were enrolled in the study after written informed consent from their parents. The biopsy

samples were placed in liquid nitrogen immediately after their emission and stored at -80°C until analysis. Bacterial strains The strains listed below were obtained from the American Type Culture Collection (ATCC) and used MTMR9 as marker on TTGE gel electrophoresis: Bacteroides fragilis ATCC 23745, Bacteroides thetaiotaomicron ATCC 29148, Bacteroides vulgatus ATCC 8482, Parabacteroides distasonis ATCC 8503, Escherichia coli MG1655. Bacterial DNA was extracted with UltraClean kit (MO BIO Laboratories, Solana Beach, California, USA) according to the manufacturer’s instructions. DNA extraction Duodenal biopsy specimens from CD and control patients were first quickly washed in 500 μL of physiologic saline with 0.016% dithiothreitol to remove luminal bacteria from the mucus, and then utilized for DNA extraction procedure by DNeasy tissue kit (Qiagen, Hilden, Germany) according to the manufacturer’s instructions. In order to obtain maximum yield of both Gram-positive and Gram-negative bacteria, a special step in DNA purification protocol was added, following DNeasy tissue kit manual.

fumigatus survival and dissemination during invasive aspergillosis [35, 36]. Figure 2 Proteomic analysis of the 4SC-202 clinical trial temperature www.selleckchem.com/HDAC.html effects. The hierarchical clustering obtained on CM10 ProteinChips® with metabolic extracts (A) and somatic

extracts (B) with the three wild-type A. fumigatus strains (IHEM 18963, IHEM 22145, IHEM 9599). The three extracts, one for each strain, obtained at 25°C (in red) and at 37°C (in blue) are indicated on the top of the figure. Values on the right indicate the molecular mass of protein differentially expressed according to the laser intensities used (in red 2000 nanoJoule (nJ) and in blue 4000 nJ). Two clusters were observed according to growth temperatures with the metabolic and the somatic extracts. Higher number of proteins was up regulated at 37°C than at 25°C in both fractions. In the dendrograms shown, the red, black or green colour indicates that the relative intensity of the protein concentration is respectively higher, intermediate or lower than

the mean value. Oxygenation On CM10 and NP20 ProteinChips®, two distinct clusters were obtained depending on oxygenation conditions for all the fungal samples analyzed whatever the temperature and media applied to growth conditions (data not shown). Oxygen and a functional respiratory chain have been demonstrated to be essential for the germination process and mycelial development of A. fumigatus [37]. The protein patterns for both the metabolic and somatic GANT61 fractions are notably influenced by oxygenation. From cultures with modified Sabouraud medium at 37°C, we observed 65 significant peaks out of 122 between static and shaken cultures for the somatic A. fumigatus extracts and 55 out of 112 for the metabolic fractions (p < 0.05) (data not shown). Aspergillus fumigatus is exposed to rapid changes in hypoxic conditions at sites of inflammation. The response to stressful conditions is likely to be an important virulence attribute of this pathogenic mold [5, 38]. Medium On modified Sabouraud medium the number of upregulated proteins was higher than in the modified Czapeck medium for the three wild-types

strains of A. fumigatus. The medium composition obviously acts on fungal growth. The medium influence has already Tacrolimus (FK506) been shown using 2-D electrophoresis for A. fumigatus [12] and MALDI-TOF analysis for A. oryzae [39]. In conclusion, the results obtained clearly show that A. fumigatus proteome is dynamic and will adapt to its immediate environment as described for Aspergillus nidulans [40] and bacteria [41]. The three strains of A. fumigatus responded in the same way according to the variations of environmental factors such as temperature, medium and oxygenation. For comparative analysis applied to discriminate strains and species, the modified Sabouraud medium and incubation temperature at 37°C were selected. Comparison of atypical pigmented A.

On the other hand, little or weak correlations between I d and the number of As https://www.selleckchem.com/products/Vorinostat-saha.html dopants are found. The weak positive correlations with N s see more and N at the off-state are attributed to a tendency that a larger number of dopants lead to smaller L g *. In order to further investigate the effect of the number of As, I d-V g characteristics

of NWs implanted at a smaller dose of 2 × 1014 cm−2 were calculated. The average number of active As atoms in this NW is 16, which averages 1.8 × 1020 cm−3. The average and standard deviation of the on-current in this NW are almost the same as those in the 1 × 1015 cm−2 NW. This is consistent with little or weak correlations between I d and the number of As dopants as we mentioned above. However, a few out of 100 NW devices of 2 × 1014 PS-341 research buy cm−2 have on-current which is only about one half its average. This is attributable to the large interatomic distances of discrete As atoms in these devices. These results indicate that the on-current fluctuation

is caused by the fluctuation of interatomic distances of discrete As atoms, not by the fluctuation of the number of As. The off-current fluctuation can be reduced by a process in which dopants in the S/D extensions are likely to exist near the channel region. In contrast, the on-current fluctuation may be inherent in ultra-small NW transistors because interatomic distance is determined by random atomic movement. Conclusions We have theoretically investigated the effects of random discrete distribution of implanted and annealed As atoms in the S/D extensions on the device characteristics of n-type GAA Si NW transistors. KMC simulation is used for generating realistic random distribution of active As atoms in Si NWs, and the current–voltage characteristics are calculated using the TCL NEGF method. The fluctuation of drain current

is observed with the normalized standard deviation of approximately 0.2. The correlation between the drain current and the factors related to random As distribution is examined. The results indicate that the on-current fluctuation is not directly due to the fluctuation of the number of dopants in the S/D extensions. The on-current fluctuation may be caused by the randomness of As dopant positions in the S/D extensions and hence is inherent in ultra-small NW transistors. Acknowledgments We acknowledge Dr. Ignacio Martin Bragado for the fruitful discussions on KMC modeling. References 1. Roy S, Asenov A: Where do the dopants go? Science 2005, 309:388–390. 2. Martinez A, Aldegunde M, Seoane N, Brown AR, Barker JR, Asenov A: Quantum-transport study on the impact of channel length and cross sections on variability induced by random discrete dopants in narrow gate-all-around silicon nanowire transistors. Electron Devices, IEEE Transactions 2011, 58:2209–2217.CrossRef 3. Wang X, Brown AR, Cheng B, Asenov A: Statistical variability and reliability in nanoscale FinFETs.