Silk‐Based antimicrobial polymers as a new platform to design drug‐free materials to impede microbial infections

Surgical site infections (SSI) represent a serious health problem that occur after invasive surgery, thus new antimicrobial biomaterials able to prevent SSI are needed. Silks are natural biopolymers with excellent biocompatibility, low immunogenicity and controllable biodegradability. Spider silkbased materials can be bioengineered and functionalized with specific peptides, such as antimicrobial peptides, creating innovative polymers. Herein, we explored new drugfree multifunctional silk films with antimicrobial properties, specifically tailored to hamper microbial infections. Different spider silk domains derived from the dragline sequence of the spider Nephila clavipes (6mer and 15mer, 27 and 41 kDa proteins, respectively) were fused with the two antimicrobial peptides, Hepcidin (Hep) and Human Neutrophil peptide 1 (HNP1). The selfassembly features of the spider silk domains (sheets) were maintained after functionalization. The bioengineered 6merHNP1 protein demonstrated inhibitory effects against microbial pathogens. Silkbased films with 6merHNP1 and different contents of silk fibroin (SF) significantly reduced bacterial adhesion and biofilm formation, whereas higher bacterial counts were found on the films prepared with 6mer or SF alone. The silkbased films showed no cytotoxic effects on human foreskin fibroblasts. The positive cellular response, together with structural and antimicrobial properties, highlight the potential of these multifunctional silkbased films as new materials for preventing SSI.The Portuguese Foundation for Science and Technology (FCT) under the project PTDC/BBB-BIO/0827/2012 and by the European Regional Development Fund (FEDER) through the "COMPETE" - Operational Programme for Competitiveness factors (FCOMP-01-0124-FEDER-028120) supported this work. The authors would like to thank Prof. Celia Manaia from the Escola Superior de Biotecnologia (Porto, Portugal) for providing the Pseudomonas sp. bacteria; and Dr. Alberta Faustino from the Hospital de S. Marcos (Braga, Portugal) for providing the other bacterial strains. A. R. Franco thanks FCT through the PostDoctoral scholarship SFRH/BPD/100760/2014.info:eu-repo/semantics/publishedVersio

Role of deep levels and interface states in the capacitance characteristics of all‐sputtered CuInSe2/CdS solar cell heterojunctions

All‐sputtered CuInSe2/CdS solar cellheterojunctions have been analyzed by means of capacitance‐frequency (C‐F) and capacitance‐bias voltage (C‐V) measurements. Depending on the CuInSe2 layer composition, two kinds of heterojunctions were analyzed: type 1 heterojunctions (based on stoichiometric or slightly In‐rich CuInSe2 layers) and type 2 heterojunctions (based on Cu‐rich CuInSe2 layers). In type 1 heterojunctions, a 80‐meV donor level has been found. Densities of interface states in the range 101 0–101 1 cm2 eV− 1 (type 1) and in the range 101 2–101 3 cm− 2 eV− 1 (type 2) have been deduced. On the other hand, doping concentrations of 1.6×101 6 cm− 3 for stoichiometric CuInSe2 (type 1 heterojunction) and 8×101 7 cm− 3 for the CdS (type 2 heterojunction) have been deduced from C‐Vmeasurements

The strategic calculus of terrorism: Substitution and competition in the Israel—Palestine conflict

Previous work on the dynamics of conflicts where we see terrorism has tended to focus on whether we see shifts in attack mode following government countermeasures. We contend that many factors other than counterinsurgency can influence whether groups resort to terrorism, including competition between groups, as well as their relationship to public opinion and other political events. Hence, understanding terrorist tactics in prolonged conflicts with multiple actors requires us to consider a more general framework of innovation, imitation, competition and dependence between actors. We use disaggregated data on terrorist attacks, counterterrorism and public opinion in the Israel—Palestine conflict to jointly evaluate predictions derived from several conventional theories of strategic behaviour. We find that the strategic calculus of Palestinian groups is complex and cannot be treated as time invariant. Our results suggest that factors such as the degree of public support, inter-group competition, the anticipation of countermeasures and non-trivial non-violent payoffs have an observable effect on the strategic behaviour of the Palestinian groups, and that structural relationships are often far from constant over time. </jats:p

Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis

<p>Abstract</p> <p>Background</p> <p>Rifampin is a key drug in antituberculosis chemotherapy because it rapidly kills the majority of bacilli in tuberculosis lesions, prevents relapse and thus enables 6-month short-course chemotherapy. Little is known about the pharmacokinetics of rifampin in children. The objective of this study was to evaluate the pharmacokinetics of rifampin in children with tuberculosis, both human immunodeficiency virus type-1-infected and human immunodeficiency virus-uninfected.</p> <p>Methods</p> <p>Fifty-four children, 21 human immunodeficiency virus-infected and 33 human immunodeficiency virus-uninfected, mean ages 3.73 and 4.05 years (<it>P </it>= 0.68), respectively, admitted to a tuberculosis hospital in Cape Town, South Africa with severe forms of tuberculosis were studied approximately 1 month and 4 months after commencing antituberculosis treatment. Blood specimens for analysis were drawn in the morning, 45 minutes, 1.5, 3.0, 4.0 and 6.0 hours after dosing. Rifampin concentrations were determined by liquid chromatography tandem mass spectrometry. For two sample comparisons of means, the Welch version of the t-test was used; associations between variables were examined by Pearson correlation and by multiple linear regression.</p> <p>Results</p> <p>The children received a mean rifampin dosage of 9.61 mg/kg (6.47 to 15.58) body weight at 1 month and 9.63 mg/kg (4.63 to 17.8) at 4 months after commencing treatment administered as part of a fixed-dose formulation designed for paediatric use. The mean rifampin area under the curve 0 to 6 hours after dosing was 14.9 and 18.1 μg/hour/ml (<it>P </it>= 0.25) 1 month after starting treatment in human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children, respectively, and 16.52 and 17.94 μg/hour/ml (<it>P </it>= 0.59) after 4 months of treatment. The mean calculated 2-hour rifampin concentrations in these human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children were 3.9 and 4.8 μg/ml (<it>P </it>= 0.20) at 1 month after the start of treatment and 4.0 and 4.6 μg/ml (<it>P </it>= 0.33) after 4 months of treatment. These values are considerably less than the suggested lower limit for 2-hour rifampin concentrations in adults of 8.0 μg/ml and even 4 μg/ml</p> <p>Conclusion</p> <p>Both human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children with tuberculosis have very low rifampin serum concentrations after receiving standard rifampin dosages similar to those used in adults. Pharmacokinetic studies of higher dosages of rifampin are urgently needed in children to assist in placing the dosage of rifampin used in childhood on a more scientific foundation.</p

Foreign policy and globalization theory: The case of Israel

Since the early 1990s, international relations has witnessed a stimulating debate on globalization. This debate laid the foundations for globalization theory (GT), providing the tools for an empirical examination of the globalization of multiple activities: from politics and organized violence, to finance, trade and production, through culture and environmental degradation. However, examination of what appear to be the best-known works on globalization reveals that foreign policy has been virtually excluded from GT. In this context, based on what is described here as a synergistic transformationalist approach (STA) to globalization, I provide a critique of GT. The critique is geared towards examining why foreign policy hitherto has been overlooked by contemporary GT. I expose the problems this generates and address them by exploring how STA enables GT to incorporate foreign policy. I use the case of Israel heuristically to elicit how incorporating foreign policy into GT may provide a better understanding of the relationship between foreign policy and globalization. Three themes are highlighted: the role of foreign policy in inducing and reproducing globalization; determining the mutually constitutive relationship between globalization and the state; and shaping the interfacing between international politics and globalization