Biofilm Eradication Kinetics of the Ultrashort Lipopeptide C12-OOWW-NH2 Utilizing a Modified MBEC Assay™

In this study, we report the antimicrobial planktonic and biofilm kill kinetics of ultrashort cationic lipopeptides previously demonstrated by our group to have a minimum biofilm eradication concentration (MBEC) in the microgram per mL (μg/mL) range against clinically relevant biofilm-forming micro-organisms. We compare the rate of kill for the most potent of these lipopeptides, dodecanoic (lauric) acid-conjugated C₁₂-Orn-Orn-Trp-Trp-NH₂ against the tetrapeptide amide H-Orn-Orn-Trp-Trp-NH₂ motif and the amphibian peptide Maximin-4 via a modification of the MBEC Assay™ for Physiology & Genetics (P&G). Improved antimicrobial activity is achieved upon N-terminal lipidation of the tetrapeptide amide. Increased antimicrobial potency was demonstrated against both planktonic and biofilm forms of Gram-positive micro-organisms. We hypothesize rapid kill to be achieved by targeting of microbial membranes. Complete kill against established 24-h Gram-positive biofilms occurred within 4 h of exposure to C₁₂-OOWW-NH₂ at MBEC values [methicillin-resistant Staphylococcus epidermidis (ATCC 35984): 15.63 μg/mL] close to the values for the planktonic minimum inhibitory concentration (MIC) [methicillin-resistant Staphylococcus epidermidis (ATCC 35984): 1.95 μg/mL]. Such rapid kill, especially against sessile biofilm forms, is indicative of a reduction in the likelihood of resistant strains developing with the potential for quicker resolution of pathogenic infection. Ultrashort antimicrobial lipopeptides have high potential as antimicrobial therapy.

Transatlantic distribution of the Alaskan White River Ash

Volcanic ash layers preserved within the geologic record represent precise time markers that correlate disparate depositional environments and enable the investigation of synchronous and/or asynchronous behaviors in Earth system and archaeological sciences. However, it is generally assumed that only exceptionally powerful events, such as supereruptions (≥450 km3 of ejecta as dense-rock equivalent; recurrence interval of ∼105 yr), distribute ash broadly enough to have an impact on human society, or allow us to address geologic, climatic, and cultural questions on an intercontinental scale. Here we use geochemical, age, and morphological evidence to show that the Alaskan White River Ash (eastern lobe; A.D. 833–850) correlates to the “AD860B” ash (A.D. 846–848) found in Greenland and northern Europe. These occurrences represent the distribution of an ash over 7000 km, linking marine, terrestrial, and ice-core records. Our results indicate that tephra from more moderate-size eruptions, with recurrence intervals of ∼100 yr, can have substantially greater distributions than previously thought, with direct implications for volcanic dispersal studies, correlation of widely distributed proxy records, and volcanic hazard assessment.

A worldwide survey of chronic cough: A manifestation of enhanced somatosensory response:A manifestation of enhanced somatosensory response

Reports from individual centres suggest a preponderance of females with chronic cough. Females also have heightened cough reflex sensitivity. Here we have reviewed the age and sex of unselected referrals to 11 cough clinics. To investigate the cause of any observed sex dimorphism, functional magnetic resonance imaging of putative cough centres was analysed in normal volunteers. The demographic profile of consecutive patients presenting with chronic cough was evaluated. Cough challenge with capsaicin was undertaken in normal volunteers to construct a concentration-response curve. Subsequent functional magnetic resonance imaging during repeated inhalation of sub-tussive concentrations of capsaicin observed areas of activation within the brain and differences in the sexes identified. Of the 10 032 patients presenting with chronic cough, two-thirds (6591) were female (mean age 55 years). The patient profile was largely uniform across centres. The most common age for presentation was 60-69 years. The maximum tolerable dose of inhaled capsaicin was lower in females; however, a significantly greater activation of the somatosensory cortex was observed. Patients presenting with chronic cough from diverse racial and geographic backgrounds have a strikingly homogeneous demographic profile, suggesting a distinct clinical entity. The preponderance of females may be explained by sex-related differences in the central processing of cough sensation.

Photodynamic antimicrobial polymers for infection control

Hospital-acquired infections pose both a major risk to patient wellbeing and an economic burden on global healthcare systems, with the problem compounded by the emergence of multidrug resistant and biocide tolerant bacterial pathogens. Many inanimate surfaces can act as a reservoir for infection, and adequate disinfection is difficult to achieve and requires direct intervention. In this study we demonstrate the preparation and performance of materials with inherent photodynamic, surface-active, persistent antimicrobial properties through the incorporation of photosensitizers into high density poly(ethylene) (HDPE) using hot-melt extrusion, which require no external intervention except a source of visible light. Our aim is to prevent bacterial adherence to these surfaces and eliminate them as reservoirs of nosocomial pathogens, thus presenting a valuable advance in infection control. A two-layer system with one layer comprising photosensitizer-incorporated HDPE, and one layer comprising HDPE alone is also described to demonstrate the versatility of our approach. The photosensitizer-incorporated materials are capable of reducing the adherence of viable bacteria by up to 3.62 Log colony forming units (CFU) per square centimeter of material surface for methicillin resistant Staphylococcus aureus (MRSA), and by up to 1.51 Log CFU/cm2 for Escherichia coli. Potential applications for the technology are in antimicrobial coatings for, or materials comprising objects, such as tubing, collection bags, handrails, finger-plates on hospital doors, or medical equipment found in the healthcare setting.

Photosensitisers - the progression from photodynamic therapy to anti-infective surfaces

Introduction: The application of light as a stimulus in pharmaceutical systems and the associated ability to provide precise spatiotemporal control over location, wavelength and intensity, allowing ease of external control independent of environmental conditionals, has led to its increased use. Of particular note is the use of light with photosensitisers.

Areas covered: Photosensitisers are widely used in photodynamic therapy to cause a cidal effect towards cells on irradiation due to the generation of reactive oxygen species. These cidal effects have also been used to treat infectious diseases. The effects and benefits of photosensitisers in the treatment of such conditions are still being developed and further realised, with the design of novel delivery strategies. This review provides an overview of the realisation of the pharmaceutically relevant uses of photosensitisers, both in the context of current research and in terms of current clinical application, and looks to the future direction of research.

Expert opinion: Substantial advances have been and are being made in the use of photosensitisers. Of particular note are their antimicrobial applications, due to absence of resistance that is so frequently associated with conventional treatments. Their potency of action and the ability to immobilise to polymeric supports is opening a wide range of possibilities with great potential for use in healthcare infection prevention strategies.

New modular structure DC-DC converter without electrolytic capacitors for renewable energy applications

Intelligent Computing for Sustainable Energy and Environment (ICSEE 2012)

No Abstract available

Prediction of integral type failures in semiconductor manufacturing through classification methods

Smart management of maintenances has become fundamental in manufacturing environments in order to decrease downtime and costs associated with failures. Predictive Maintenance (PdM) systems based on Machine Learning (ML) techniques have the possibility with low added costs of drastically decrease failures-related expenses; given the increase of availability of data and capabilities of ML tools, PdM systems are becoming really popular, especially in semiconductor manufacturing. A PdM module based on Classification methods is presented here for the prediction of integral type faults that are related to machine usage and stress of equipment parts. The module has been applied to an important class of semiconductor processes, ion-implantation, for the prediction of ion-source tungsten filament breaks. The PdM has been tested on a real production dataset. © 2013 IEEE.