Identification of Small Molecules that Interfere with H1N1 Influenza A Viral Replication

Successful replication of the influenza A virus requires both viral proteins and host cellular factors. In this study we used a cellular assay to screen for small molecules capable of interfering with any of such necessary viral or cellular components. We used an established reporter assay to assess influenza viral replication by monitoring the activity of co‐expressed luciferase. We screened a diverse chemical compound library, resulting in the identification of compound 7 , which inhibits a novel yet elusive target. Quantitative real‐time PCR studies confirmed the dose‐dependent inhibitory activity of compound 7 in a viral replication assay. Furthermore, we showed that compound 7 is effective in rescuing high‐dose influenza infection in an in vivo mouse model. As oseltamivir‐resistant influenza strains emerge, compound 7 could be further investigated as a new and potentially suitable scaffold for the development of anti‐influenza agents that act on novel targets.     

Syndiotactic-specific polymerization of styrene: catalyst structure and polymerization mechanism

The mechanistic investigation of syndiotactic-specific polymerization of styrene is reviewed, mainly with reference to the research work carried out at the University of Salerno. NMR analysis of the stereochemical structure of s-PS macromolecules, in some cases suitably labelled, provided valuable information concerning the regiochemistry of polyinsertion, the type of addition to the monomer double bond, and the model of stereospecific propagation. Kinetic studies and spectroscopic investigation of the catalytic systems suggested a cationic Ti(III) complex with a strongly π-co-ordinated benzyl-type growing chain as the true active species. This revised version was published online in June 2006 with corrections to the Cover Date.     

Behavioural sensitization in 6-hydroxydopamine-lesioned rats is related to compositional changes of the AP-1 transcription factor: evidence for induction of FosB- and JunD-related proteins

Rats with unilateral dopamine denervation exhibit turning behaviour in response to the selective D1 agonist SKF 38393 only after a previous exposure to dopamine agonists. We demonstrate here that this 'priming' phenomenon is related to both an increased expression of the pre-existing AP-1 complex and the occurrence of novel AP-1 complexes which are formed by FosB- and JunD-related proteins. While the former protein is expressed as a consequence of the dopamine denervation, the latter is related to the first exposure to a dopamine agonist. Pre-treatment with MK-801, an antagonist for glutamatergic receptors, prevents both the priming development and the AP-1 compositional changes. Rotational behaviour induced by SKF 38393 closely correlates with the presence of the priming AP-1 complexes, regardless of the capability of the D1 agonist to induce the immediate-early gene cFos.     

Experience on Pre-Series and Series Production of LHC Dipoles Cold Masses in ASG Superconductors

In 1986 Ansaldo Magnet Dept. (now ASG Superconductors) started, in cooperation with CERN, the design activities of the first 1 m-8 T LHC prototype dipoles. After several design steps and the manufacturing of 1+3 prototype dipoles 10 m long, the final design configuration 15 m long was defined by CERN. During the following years, a very close collaboration with CERN engineers and technicians lead to define the parameters about the most critical manufacturing processes, in particular winding of s.c. cable, collaring of coils, cold mass welding and test procedures. In the meantime, installation and commissioning of all the manufacturing plants followed: winding machines, curing presses, collaring press and welding press were installed, as well as geometrical measurements stations and vacuum chamber for leak test. Finally two manufacturing halls were fully dedicated to LHC dipoles production. At the beginning of year 2002, all the manufacturing plants were coming to be operational, ready to start the large scale production of LHC cold masses: 30 pre-series, 386 series and 30 spare cold masses have been produced till May 2007, to get a total number of 446 cold masses. In this paper we summarize all the data collected during a five years production: main manufacturing data, test results and production rate are presented. Final results about tests performed at CERN in superfluid He at 1.9 K are also included as well as correlation between test result and manufacturing rate.     

Clostridium difficile colitis associated with treatment of Helicobacter pylori infection

Helicobacter pylori infection of the stomach is being detected and treated more often now than ever before. This is likely to result in an increase in complications such as antibiotic-associated diarrhea. However, there is no literature on the incidence of such diarrhea, particularly Clostridium difficile colitis, in patients treated for Helicobacter pylori infection. We report the case of a patient who developed Clostridium difficile colitis after treatment for Helicobacter pylori infection with metronidazole, amoxicillin, H2 blockers, and bismuth subsalicylate. This patient presented with severe diarrhea that responded to a course of metronidazole with rapid disappearance of symptoms. The incidence of Clostridium difficile colitis in patients treated for Helicobacter pylori infection has not been studied. This unique association, although not unexpected, has not yet been reported in the literature. The increasing number of patients being diagnosed and treated for this infection requires a heightened awareness on the part of physicians, to assure early diagnosis and treatment of this treatable, yet potentially dangerous, complication.     

Making driver modeling attractive

Automobile industry and academic researchers expend considerable effort to develop driver assistance systems. DASs are aware of certain driving situations and support drivers through information, warnings, or even intervention. Many DAS applications are safety oriented, such as lane departure warning systems. Some are comfort oriented, such as automated parking assistants. Moreover, DAS human-machine interfaces must support careful communication with potentially taxed drivers. Driver models support DAS design in several ways. Our work focuses on modeling the tactical level of driving decisions, such as when to brake and whether to accelerate and pass another vehicle. Such decisions are based on local, instantaneously available environmental information about the road and other cars in the same or an adjacent lane.     

Absorption into fluorescence. A method to sense biologically relevant gas molecules

In this work we present an innovative optical sensing methodology based on the use of biomolecules as molecular gating nano-systems. Here, as an example, we report on the detection of analytes related to climate change. In particular, we focused our attention on the detection of nitric oxide (NO) and oxygen (O2). Our methodology builds on the possibility of modulating the excitation intensity of a fluorescent probe used as a transducer and a sensor molecule whose absorption is strongly affected by the binding of an analyte of interest used as a filter. The two simple conditions that have to be fulfilled for the method to work are: (a) the absorption spectrum of the sensor placed inside the cuvette, and acting as the recognition element for the analyte of interest, should strongly change upon the binding of the analyte and (b) the fluorescence dye transducer should exhibit an excitation band which overlaps with one or more absorption bands of the sensor. The absorption band of the sensor affected by the binding of the specific analyte should overlap with the excitation band of the transducer. The high sensitivity of fluorescence detection combined with the use of proteins as highly selective sensors makes this method a powerful basis for the development of a new generation of analytical assays. Proof-of-principle results showing that cytochrome c peroxidase (CcP) for NO detection and myoglobin (Mb) for O2 detection can be successfully used by exploiting our new methodology are reported. The proposed technology can be easily expanded to the determination of different target analytes.