IT Interdependence and the Economic Fairness of Cyber-security Regulations for Civil Aviation

Interviews about emerging cybersecurity threats and a cybersecurity public policy economic model for civil aviation illustrate stakeholders' concerns: interdependency issues can lead to aviation regulations that put smaller airports at a disadvantage

Global Antifungal Profile Optimization of Chlorophenyl Derivatives against Botrytis cinerea and Colletotrichum gloeosporioides

Twenty-two aromatic derivatives bearing a chlorine atom and a different chain in the para or meta position were prepared and evaluated for their in vitro antifungal activity against the phytopathogenic fungi Botrytis cinerea and Colletotrichum gloeosporioides. The results showed that maximum inhibition of the growth of these fungi was exhibited for enantiomers S and R of 1-(40-chlorophenyl)- 2-phenylethanol (3 and 4). Furthermore, their antifungal activity showed a clear structure-activity relationship (SAR) trend confirming the importance of the benzyl hydroxyl group in the inhibitory mechanism of the compounds studied. Additionally, a multiobjective optimization study of the global antifungal profile of chlorophenyl derivatives was conducted in order to establish a rational strategy for the filtering of new fungicide candidates from combinatorial libraries. The MOOPDESIRE methodology was used for this purpose providing reliable ranking models that can be used later

Proton-Ion Medical Machine Study (PIMMS), 2

The Proton-Ion Medical Machine Study (PIMMS) group was formed following an agreement between the Med-AUSTRON (Austria) and the TERA Foundation (Italy) to combine their efforts in the design of a cancer therapy synchrotron capable of accelerating either light ions or protons. CERN agreed to support and host this study in its PS Division. A close collaboration was also set up with GSI (Germany). The study group was later joined by Onkologie-2000 (Czech Republic). Effort was first focused on the theoretical understanding of slow extraction and the techniques required to produce a smooth beam spill for the conformal treatment of complex-shaped tumours with a sub-millimetre accuracy by active scanning with proton and carbon ion beams. Considerations for passive beam spreading were also included for protons. The study has been written in two parts. The more general and theoretical aspects are recorded in Part I and the specific technical design considerations are presented in the present volume, Part II. An accompanying CD-ROM contains supporting publications made by the team and data files for calculations. The PIMMS team started its work in January 1996 in the PS Division and continued for a period of four years

Raman spectroscopy uncovers biochemical tissue-related features of extracellular vesicles from mesenchymal stromal cells

Extracellular vesicles (EVs) from mesenchymal stromal cells (MSC) are emerging as valuable therapeutic agents for tissue regeneration and immunomodulation, but their clinical applications have so far been limited by the technical restraints of current isolation and characterisation procedures. This study shows for the first time the successful application of Raman spectroscopy as label-free, sensitive and reproducible means of carrying out the routine bulk characterisation of MSC-derived vesicles before their use in vitro or in vivo, thus promoting the translation of EV research to clinical practice. The Raman spectra of the EVs of bone marrow and adipose tissue-derived MSCs were compared with human dermal fibroblast EVs in order to demonstrate the ability of the method to distinguish the vesicles of the three cytotypes automatically with an accuracy of 93.7%. Our data attribute a Raman fingerprint to EVs from undifferentiated and differentiated cells of diverse tissue origin, and provide insights into the biochemical characteristics of EVs from different sources and into the differential contribution of sphingomyelin, gangliosides and phosphatidilcholine to the Raman spectra themselves

Perioperative outcome of laparoscopic left lateral liver resection is improved by using a bioabsorbable staple line reinforcement material in a porcine model

Hypothesis Laparoscopic liver surgery is significantly limited by the technical difficulty encountered during transection of substantial liver parenchyma, with intraoperative bleeding and bile leaks. This study tested whether the use of a bioabsorble staple line reinforcement material would improve outcome during stapled laparoscopic left lateral liver resection in a porcine model. Study design A total of 20 female pigs underwent stapled laparoscopic left lateral liver resection. In group A (n = 10), the stapling devices were buttressed with a bioabsorbable staple line reinforcement material. In group B (n = 10), standard laparoscopic staplers were used. Operative data and perioperative complications were recorded. Necropsy studies and histopathological analysis were performed at 6 weeks. Data were compared between groups with the Student's t-test or the chi-square test. Results Operating time was similar in the two groups (64 +/- 11 min in group A versus 68 +/- 9 min in group B, p = ns). Intraoperative blood loss was significantly higher in group B (185 +/- 9 mL versus 25 +/- 5 mL, p <0.05). There was no mortality. There was no morbidity in the 6-week follow-up period; however, two animals in group B had subphrenic bilomas (20%) at necropsy. At necropsy, methylene blue injection via the main bile duct revealed leakage from the biliary tree in four animals in group B and none in group A (p <0.05). Histopathological examination of the resection site revealed minor abnormalities in group A while animals in group B demonstrated marked fibrotic changes and damaged vascular and biliary endothelium. Conclusion Use of a bioabsorbable staple line reinforcement material reduces intraoperative bleeding and perioperative bile leaks during stapled laparoscopic left lateral liver resection in a porcine model

Prediction of Promiscuous P-Glycoprotein Inhibition Using a Novel Machine Learning Scheme

BACKGROUND: P-glycoprotein (P-gp) is an ATP-dependent membrane transporter that plays a pivotal role in eliminating xenobiotics by active extrusion of xenobiotics from the cell. Multidrug resistance (MDR) is highly associated with the over-expression of P-gp by cells, resulting in increased efflux of chemotherapeutical agents and reduction of intracellular drug accumulation. It is of clinical importance to develop a P-gp inhibition predictive model in the process of drug discovery and development. METHODOLOGY/PRINCIPAL FINDINGS: An in silico model was derived to predict the inhibition of P-gp using the newly invented pharmacophore ensemble/support vector machine (PhE/SVM) scheme based on the data compiled from the literature. The predictions by the PhE/SVM model were found to be in good agreement with the observed values for those structurally diverse molecules in the training set (n = 31, r(2) = 0.89, q(2) = 0.86, RMSE = 0.40, s = 0.28), the test set (n = 88, r(2) = 0.87, RMSE = 0.39, s = 0.25) and the outlier set (n = 11, r(2) = 0.96, RMSE = 0.10, s = 0.05). The generated PhE/SVM model also showed high accuracy when subjected to those validation criteria generally adopted to gauge the predictivity of a theoretical model. CONCLUSIONS/SIGNIFICANCE: This accurate, fast and robust PhE/SVM model that can take into account the promiscuous nature of P-gp can be applied to predict the P-gp inhibition of structurally diverse compounds that otherwise cannot be done by any other methods in a high-throughput fashion to facilitate drug discovery and development by designing drug candidates with better metabolism profile

Assessment of phenolic herbicide toxicity and mode of action by different assays

A phytotoxicity assay based on seed germination/root elongation has been optimized and used to evaluate the toxic effects of some phenolic herbicides. The method has been improved by investigating the influence of experimental conditions. Lepidium sativum was chosen as the most suitable species, showing high germinability, good repeatability of root length measurements, and low sensitivity to seed pretreatment. DMSO was the most appropriate solvent carrier for less water-soluble compounds. Three dinitrophenols and three hydroxybenzonitriles were tested: dinoterb, DNOC, 2,4-dinitrophenol, chloroxynil, bromoxynil, and ioxynil. Toxicity was also determined using the Vibrio fischeri MicrotoxA (R) test, and a highly significant correlation was found between EC50 values obtained by the two assays. Dinoterb was the most toxic compound. The toxicity of hydroxybenzonitriles followed the order: ioxynil > bromoxynil > chloroxynil; L. sativum exhibited a slightly higher sensitivity than V. fischeri to these compounds. A QSAR analysis highlighted the importance of hydrophobic, electronic, and hydrogen-bonding interactions, in accordance with a mechanism of toxic action based on protonophoric uncoupling of oxidative phosphorylation. The results suggest that the seed germination/root elongation assay with L. sativum is a valid tool for the assessment of xenobiotic toxicity and can be recommended as part of a test battery