Activity of AMP2041 against human and animal multidrug resistant Pseudomonas aeruginosa clinical isolates

Background: Antimicrobial resistance is a growing threat to public health. Pseudomonas aeruginosa is a relevant pathogen causing human and animal infections, frequently displaying high levels of resistance to commonly used antimicrobials. The increasing difficulty to develop new effective antibiotics have discouraged investment in this area and only a few new antibiotics are currently under development. An approach to overcome antibiotic resistance could be based on antimicrobial peptides since they offer advantages over currently used microbicides. Methods: The antimicrobial activity of the synthetic peptide AMP2041 was evaluated against 49 P. aeruginosa clinical strains with high levels of antimicrobial resistance, isolated from humans (n = 19) and animals (n = 30). In vitro activity was evaluated by a microdilution assay for lethal dose 90% (LD90), while the activity over time was performed by time-kill assay with 12.5 μg/ml of AMP2014. Evidences for a direct membrane damage were investigated on P. aeruginosa ATCC 27853 reference strain, on animal isolate PA-VET 38 and on human isolate PA-H 24 by propidium iodide and on P. aeruginosa ATCC 27853 by scanning electron microscopy. Results: AMP2041 showed a dose-dependent activity, with a mean (SEM) LD90 of 1.69 and 3.3 μg/ml for animal and human strains, respectively. AMP2041 showed microbicidal activity on P. aeruginosa isolates from a patient with cystic fibrosis (CF) and resistance increased from first infection isolate (LD90 = 0.3 μg/ml) to the mucoid phenotype (LD90 = 10.4 μg/ml). The time-kill assay showed a time-dependent bactericidal effect of AMP2041 and LD90 was reached within 20 min for all the strains. The stain-dead assay showed an increasing of membrane permeabilization and SEM analysis revealed holes, dents and bursts throughout bacterial cell wall after 30 min of incubation with AMP2041. Conclusions: The obtained results assessed for the first time the good antimicrobial activity of AMP2041 on P. aeruginosa strains of human origin, including those deriving from a CF patient. We confirmed the excellent antimicrobial activity of AMP2041 on P. aeruginosa strains derived from dog otitis. We also assessed that AMP2041 antimicrobial activity is linked to changes of the P. aeruginosa cell wall morphology and to the increasing of membrane permeability

Residual stress investigation on Ti-48Al-2Cr-2Nb samples produced by Electron Beam Melting process

Abstract Ti-48Al-2Cr-2Nb (Ti-48-2-2) is an intermetallic alloy belonging to a family of gamma-TiAl intermetallic alloys that are attracting significant attention. Electron Beam Melting (EBM) process is today the only manufacturing process that allows effective production of parts made by these kinds of alloys. Proper process control avoids high temperatures in the surrounding areas that may generate significant residual stresses that could cause micro-cracks. In this paper, an investigation on the residual stress state on Ti-48-2-2 parts is carried out using the hole drilling method. In particular, the influence of EBM process parameters is evaluated in order to understand the effects of the residual stresses on part integrity

in vitro antimicrobial activity of a gel containing antimicrobial peptide amp2041 chlorhexidine digluconate and tris edta on clinical isolates of pseudomonas aeruginosa from canine otitis

Background Pseudomonas aeruginosa (PA) may cause suppurative otitis externa with severe inflammation and ulceration in dogs. Multidrug resistance is commonly reported for this organism, creating a difficult therapeutic challenge. Objective The aim of this study was to evaluate the in vitro antimicrobial activity of a gel containing 0.5 μg/mL of antimicrobial peptide AMP2041, 0.07% chlorhexidine digluconate (CLX), 0.4% Tris and 0.1% EDTA on 30 clinical isolates of PA from canine otitis externa. Materials and Methods Antimicrobial activity was evaluated through minimal bactericidal concentration (MBC). Standardized bacterial suspensions were incubated with different concentrations of the gel at 37°C for 30 min and plated for colony forming unit (CFU) counts. Time-to-kill kinetics were evaluated with the undiluted product and at MBC for each PA strain at 30 s, 1, 5, 10, 15, 30 min, 24 and 48 h. Results The MBC was 1:64 for two of 30 strains, 1:128 for 15 of 30 strains and 1:256 for 13 of 30 strains. The geometric mean was 1:165, equivalent to a concentration of 0.003 μg/mL AMP2041 + 0.0004% CLX + 0.0024%Tris + 0.0006% EDTA. Time-to-kill assays with the undiluted product showed complete bactericidal effect within 30 s for all isolates, whereas at the MBC this effect was reached within 5 min for 20 of 30 isolates and within 30 min for all isolates. Bactericidal activity was maintained after 48 h for all isolates. Conclusion This gel has shown rapid, complete and long-lasting activity against a panel of 30 PA isolates from cases of canine otitis externa

In vitro

Background – Pseudomonas aeruginosa (PA) may cause suppurative otitis externa with severe inflammation and ulceration in dogs. Multidrug resistance is commonly reported for this organism, creating a difficult therapeutic challenge. Objective – The aim of this study was to evaluate the in vitro antimicrobial activity of a gel containing 0.5 lg/mL of antimicrobial peptide AMP2041, 0.07% chlorhexidine digluconate (CLX), 0.4% Tris and 0.1% EDTA on 30 clinical isolates of PA from canine otitis externa. Materials and Methods – Antimicrobial activity was evaluated through minimal bactericidal concentration (MBC). Standardized bacterial suspensions were incubated with different concentrations of the gel at 37°C for 30 min and plated for colony forming unit (CFU) counts. Time-to-kill kinetics were evaluated with the undiluted product and at MBC for each PA strain at 30 s, 1, 5, 10, 15, 30 min, 24 and 48 h. Results – The MBC was 1:64 for two of 30 strains, 1:128 for 15 of 30 strains and 1:256 for 13 of 30 strains. The geometric mean was 1:165, equivalent to a concentration of 0.003 lg/mL AMP2041 + 0.0004% CLX + 0.0024% Tris + 0.0006% EDTA. Time-to-kill assays with the undiluted product showed complete bactericidal effect within 30 s for all isolates, whereas at the MBC this effect was reached within 5 min for 20 of 30 isolates and within 30 min for all isolates. Bactericidal activity was maintained after 48 h for all isolates. Conclusion – This gel has shown rapid, complete and long-lasting activity against a panel of 30 PA isolates from cases of canine otitis externa

Effective work function engineering by sacrificial lanthanum diffusion on HfON-based 14 nm NFET devices

session C2L-E: Advanced CMOS Device and TechnologyInternational audienceIn this paper, the impact of metallic lanthanum (La) deposited by Radio-Frequency PVD on effective work function (WF eff ) of HfON-based NFET devices in a sacrificial metal gate-first approach is evaluated for the first time. Engineering of WF eff towards N+ without leakage degradation is demonstrated by tuning both the pedestal TiN thickness and the as-deposited metallic La dose. WF eff shift is related to a La-induced interfacial dipole (5), whose value has been correlated to the effective La dose into HfON/SiON stack after diffusion annealing, which has been accurately measured through a spectroscopic method based on La X-Ray Fluorescence (XRF)

Effect of La and Al addition used for threshold voltage shift on the BTI reliability of HfON-based FDSOI MOSFETs

session 2B: Process IntegrationInternational audienceIn this paper, the Bias Temperature Instability effects of Lanthanum (La) and Aluminum (Al) incorporation, used for threshold voltage adjustment by dipole formation at the SiO2/HfON interface into the FDSOI gate dielectrics has been studied. When compared at the same oxide electric field (Eox), incorporation of La causes significant enhancement of intrinsic NBTI (Negative Bias Temperature Instability) effect and it reduces the already low PBTI (Positive Bias Temperature Instability) effect. On the other hand, comparison at the same Gate voltage (Vg) does not show the same behavior possibly due to the reduction of oxide field (Eox) by La dipole effect. Incorporation of Al does not have a significant impact on NBTI but it causes significant enhancement of PBTI, when compared both at the same Eox or same Vg. NBTI/PBTI degradations well correlate to the La and Al effective doses in the gate dielectrics

Precise EOT regrowth extraction enabling performance analysis of Low Temperature Extension First devices

session B2L-G: Advanced CMOS Characterization and ReliabilityInternational audience— 3D sequential integration requires top FETs processing with a low thermal budget (500°C). The analysis of the origin of the performance difference between Low Temperature (LT) MOSFET and high temperature standard process must take into account a potential EOT modification for short gate lengths. In this work, the difficulty of precise EOT extraction for scaled devices is observed by CV measurements and an alternative methodology using IV measurements is proposed. This methodology has been applied to an extension first integration, and the extraction accuracy is high enough to conclude to an EOT regrowth for the low temperature nFETs only. Thus, the origin of performance degradation between LT and HT, previously attributed to larger access resistance, highlights also a detrimental role of gate stack instability. The origin of this variation is attributed to oxygen ingress, through the thin extension first liner which should be suppressed by minor process optimizations

Change in diversity, ecological significance and biogeographical relationships of the Mediterranean Miocene toothed whale fauna

The main evolutionary trend in the Mediterranean Miocene toothed whale fauna is related (1) to the change in diversity and (2) to the turnover in community structure. Diversity increases from Upper Aquitanian-Lower Burdigalian to Burdigalian-Langhian, when it reaches its maximum. Starting from this time, diversity decreases progressively. The Early Miocene (Upper Aquitanian-Lower Burdigalian) Mediterranean toothed whale fauna, as well as the extramediterranean ones, is characterised by a high number of endemic taxa and by the prevalence of longirostral forms living in estuarine-neritic environments. A more diversified fauna spreading in neritic and pelagic environments characterises the Burdigalian-Langhian age, while an increase in pelagic forms and the nearly complete disappearance of some archaic longirostral taxa is typical of the Serravallian-Messinian fauna. Decrease in diversity and disappearance of archaic longirostral taxa are also recorded, at more general scale, in the Late Miocene extramediterranean fossil bearing deposits. These events can be related to the progressive global climatic deterioration, starting from Middle Miocene. From a biogeographic point a view, we can outline some relationships between the Mediterranean and western North Atlantic Miocene faunas. Closer affinities are observed between the Baltringen fauna and the northern Atlantic one, because of the presence of the genera Pomatodelphis and Zarhachis (platanistids) in both areas. In the Miocene Mediterranean and in North Atlantic, the delphinids are apparently absent as well as other extant delphinoid groups even if erroneously recorded in the past