Combinations of β-lactam or aminoglycoside antibiotics with plectasin are synergistic against methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87-89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We demonstrated that plectasin strongly rejuvenates the therapeutic potencies of existing antibiotics in vitro and in vivo. This is a novel strategy that can have major clinical implications in our fight against bacterial infections

Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production

The ever-increasing incidence of antibiotic-resistant infections combined with a weak pipeline of new antibiotics has created a global public health crisis1. Accordingly, novel strategies for enhancing our antibiotic arsenal are needed. As antibiotics kill bacteria in part by inducing reactive oxygen species (ROS)2–4, we reasoned that targeting microbial ROS production might potentiate antibiotic activity. Here we show that ROS production can be predictably enhanced in Escherichia coli, increasing the bacteria’s susceptibility to oxidative attack. We developed an ensemble, genome-scale metabolic modeling approach capable of predicting ROS production in E. coli. The metabolic network was systematically perturbed and its flux distribution analyzed to identify targets predicted to increase ROS production. In silico–predicted targets were experimentally validated and shown to confer increased susceptibility to oxidants. Validated targets also increased susceptibility to killing by antibiotics. This work establishes a systems-based method to tune ROS production in bacteria and demonstrates that increased microbial ROS production can potentiate killing by oxidants and antibiotics

Feedstock recycling of cable plastic residue via steam cracking on an industrial-scale fluidized bed

The use of plastic materials in a circular way requires a technology that can treat any plastic waste and produce the same quality of product as the original. Cable plastic residue from metal recycling of electric wires is composed of cross-linked polyethene (XLPE) and PVC, which is a mixture that cannot be mechanically recycled today. Through thermochemical processes, polymer chains are broken into syngas and monomers, which can be further used in the chemical industry. However, feedstock recycling of such a mixture (XLPE, PVC) has been scarcely studied on an industrial scale. Here, the steam cracking of cable plastic was studied in an industrial fluidised bed, aiming to convert cable plastics into valuable products. Two process temperatures were tested: 730 \ub0C and 800 \ub0C. The results show that the products consist of 27–31 wt% ethylene and propylene, 5–16% wt.% other linear hydrocarbons, and more than 10 wt% benzene. Therefore, 40%–60% of the products are high-value chemicals that could be recovered via steam cracking of cable plastic

High proportion of cactus species threatened with extinction

This is the author accepted manuscript. The final version is available from Nature Publishing Group via the DOI in this record.Consejo Nacional de Ciencia y Tecnologí

Data envelopment analysis in financial services: a citations network analysis of banks, insurance companies and money market funds

Development and application of the data envelopment analysis (DEA) method, have been the subject of numerous reviews. In this paper, we consider the papers that apply DEA methods specifically to financial services, or which use financial services data to experiment with a newly introduced DEA model. We examine 620 papers published in journals indexed in the Web of Science database, from 1985 to April 2016. We analyse the sample applying citations network analysis. This paper investigates the DEA method and its applications in financial services. We analyse the diffusion of DEA in three sub-samples: (1) banking groups, (2) money market funds, and (3) insurance groups by identifying the main paths, that is, the main flows of the ideas underlying each area of research. This allows us to highlight the main approaches, models and efficiency types used in each research areas. No unique methodological preference emerges within these areas. Innovations in the DEA methodologies (network models, slacks based models, directional distance models and Nash bargaining game) clearly dominate recent research. For each subsample, we describe the geographical distribution of these studies, and provide some basic statistics related to the most active journals and scholars

Early severe inflammatory responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection

Chronic infections are an increasing problem due to the aging population and the increase in antibiotic resistant organisms. Therefore, understanding the host-pathogen interactions that result in chronic infection is of great importance. Here, we investigate the molecular basis of chronic bacterial cystitis. We establish that introduction of uropathogenic E. coli (UPEC) into the bladders of C3H mice results in two distinct disease outcomes: resolution of acute infection or development of chronic cystitis lasting months. The incidence of chronic cystitis is both host strain and infectious dose-dependent. Further, development of chronic cystitis is preceded by biomarkers of local and systemic acute inflammation at 24 hours post-infection, including severe pyuria and bladder inflammation with mucosal injury, and a distinct serum cytokine signature consisting of elevated IL-5, IL-6, G-CSF, and the IL-8 analog KC. Mice deficient in TLR4 signaling or lymphocytes lack these innate responses and are resistant, to varying degrees, to developing chronic cystitis. Treatment of C3H mice with the glucocorticoid anti-inflammatory drug dexamethasone prior to UPEC infection also suppresses the development of chronic cystitis. Finally, individuals with a history of chronic cystitis, lasting at least 14 days, are significantly more susceptible to redeveloping severe, chronic cystitis upon bacterial challenge. Thus, we have discovered that the development of chronic cystitis in C3H mice by UPEC is facilitated by severe acute inflammatory responses early in infection, which subsequently are predisposing to recurrent cystitis, an insidious problem in women. Overall, these results have significant implications for our understanding of how early host-pathogen interactions at the mucosal surface determines the fate of disease

Thermochemical recycling of tall oil pitch in a dual fluidized bed

Crude tall oil is a by-product obtained from the manufacture of chemical wood pulp. The residue obtained after the distillation of this product is known as tall oil pitch (TOP). This complex fraction is a highly viscous liquid that consists mainly of free fatty acids, fatty acids derivatives, rosin acids and additives. Given its complex composition, it is commonly used as fuel for heat production. In this work, steam cracking is proposed as an alternative treatment for this residue. Steam cracking can convert TOP into a valuable product gas that can be used in different applications including the production of green chemicals, moving towards a carbon circular economy. The experimental tests were performed in the Chalmers pilot scale Dual Fluidized Bed, consisting of a steam cracker and a combustor. For these experiments, the thermochemical decomposition of 150–175 kg/h TOP was performed at the steam cracker at two different temperatures (775 and 825 \ub0C) to evaluate the influence of this parameter on the obtained products. Wood pellets were also tested as reference material for the highest temperature. The distribution of the obtained products was analysed. Results show that TOP can be regarded as a by-product instead of a residue and used as feedstock for the recovery of chemical building blocks and syngas via thermochemical recycling. Between 40 and 50 % of the carbon present in the fuel is kept in the permanent gases, while about 20 % is in aromatic hydrocarbons. Compared to biomass, the aromatics yield obtained for TOP is much higher (190 g/kg for TOP and 13 g/kg for biomass). Among the species found, benzene, toluene and xylene, represent between 62 and 72 % of the total measured aromatics. Regarding the gas fraction, the production of valuable light hydrocarbons (such as ethylene and propylene) is more pronounced in the TOP residue than in the biomass. In addition, an energy balance over the system was estimated and showed that TOP thermochemical recycling can be self-sustained in a Dual Fluidized Bed if the non-valuable products are combusted. The results obtained in this work indicate that this TOP could be an appealing option to consider as a source of biorefinery revenue leading to the circular use of waste

What is a smart device? - a conceptualisation within the paradigm of the internet of things

The Internet of Things (IoT) is an interconnected network of objects which range from simple sensors to smartphones and tablets; it is a relatively novel paradigm that has been rapidly gaining ground in the scenario of modern wireless telecommunications with an expected growth of 25 to 50 billion of connected devices for 2020 Due to the recent rise of this paradigm, authors across the literature use inconsistent terms to address the devices present in the IoT, such as mobile device, smart device, mobile technologies or mobile smart device. Based on the existing literature, this paper chooses the term smart device as a starting point towards the development of an appropriate definition for the devices present in the IoT. This investigation aims at exploring the concept and main features of smart devices as well as their role in the IoT. This paper follows a systematic approach for reviewing compendium of literature to explore the current research in this field. It has been identified smart devices as the primary objects interconnected in the network of IoT, having an essential role in this paradigm. The developed concept for defining smart device is based on three main features, namely context-awareness, autonomy and device connectivity. Other features such as mobility and userinteraction were highly mentioned in the literature, but were not considered because of the nature of the IoT as a network mainly oriented to device-to-device connectivity whether they are mobile or not and whether they interact with people or not. What emerges from this paper is a concept which can be used to homogenise the terminology used on further research in the Field of digitalisation and smart technologies