Study of inelastic nuclear interactions of 400 GeV/c protons in bent silicon crystals for beam steering purposes.

Inelastic nuclear interaction probability of 400 GeV/c protons interacting with bent silicon crystals was investigated, in particular for both types of crystals installed at the CERN Large Hadron Collider for beam collimation purposes. In comparison to amorphous scattering interaction, in planar channeling this probability is for the quasi-mosaic type (planes (111)), and for the strip type (planes (110)). Moreover, the absolute inelastic nuclear interaction probability in the axial channeling orientation, along the axis, was estimated for the first time, finding a value of for a crystal 2 mm long along the beam direction, with a bending angle of 55 rad.

The FLUKA Code: An Accurate Simulation Tool for Particle Therapy.

Monte Carlo (MC) codes are increasingly spreading in the hadrontherapy community due to their detailed description of radiation transport and interaction with matter. The suitability of a MC code for application to hadrontherapy demands accurate and reliable physical models capable of handling all components of the expected radiation field. This becomes extremely important for correctly performing not only physical but also biologically based dose calculations, especially in cases where ions heavier than protons are involved.

Cold adaptation improves the growth of seasonal influenza B vaccine viruses.

Gene reassortment has proved useful in improving yields of influenza A antigens of egg-based inactivated vaccines, but similar approaches have been difficult with influenza B antigens. Current regulations for influenza vaccine seed viruses limit the number of egg passages and as a result resultant yields from influenza B vaccine seed viruses are frequently inconsistent. Therefore, reliable approaches to enhance yields of influenza B vaccine seed viruses are required for efficient vaccine manufacture.

Scientific investigations into febrile reactions observed in the paediatric population following vaccination with a 2010 Southern Hemisphere Trivalent Influenza Vaccine.

During the 2010 Southern Hemisphere (SH) influenza season, there was an unexpected increase in the number of febrile reactions reported in the paediatric population in Australia shortly after vaccination with the CSL 2010 trivalent influenza vaccine (TIV) compared to previous seasons. A series of scientific investigations were initiated to identify the root cause of these adverse events, including in vitro cytokine/chemokine assays following stimulation of adult and paediatric whole blood, as well as mammalian cell lines and primary cells, profiling of molecular signatures using microarrays, and in vivo studies in rabbits, ferrets, new born rats and rhesus non-human primates (NHPs). Various TIVs (approved commercial vaccines as well as re-engineered TIVs) and their individual monovalent pool harvest (MPH) components were examined in these assays and in animal models.

The development of vaccine viruses against pandemic A(H1N1) influenza.

Wild type human influenza viruses do not usually grow well in embryonated hens' eggs, the substrate of choice for the production of inactivated influenza vaccine, and vaccine viruses need to be developed specifically for this purpose. In the event of a pandemic of influenza, vaccine viruses need to be created with utmost speed. At the onset of the current A(H1N1) pandemic in April 2009, a network of laboratories began a race against time to develop suitable candidate vaccine viruses.

Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant.

Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant.

Chimeric potyvirus-like particles as vaccine carriers.

Presentation of subunit vaccines in a highly ordered aggregate form can result in enhanced immune responses. Coat protein (CP) monomers of a potyvirus (Johnsongrass mosaic virus) when produced in heterologous host expression systems (Escherichia coli, yeast and insect cells) self-polymerized to produce potyvirus-like particles (PVLPs). The N- and C-terminal regions of potyvirus CP are surface-exposed and are not required for assembly.

High level production of hybrid potyvirus-like particles carrying repetitive copies of foreign antigens in Escherichia coli.

Synthesis in E. coli of native coat protein of Johnsongrass mosaic virus, and hybrid protein molecules containing foreign antigens, resulted in the intracellular formation of potyvirus-like particles (PVLPs). The foreign antigens used were an octapeptide epitope from Plasmodium falciparum and a decapeptide hormone (luteinizing hormone releasing hormone) at the N- or at both N- and C-terminal regions of the coat protein molecule, and a full length protein antigen (Sj26-glutathione S-transferase of 26 kD from Schistosoma japonicum) replacing the N-terminal 62 amino acids of the coat protein.

The role of biotransformation in anthracycline-induced cardiotoxicity in mice.

Anthracyclines are highly efficacious antineoplastic agents but they become cardiotoxic after repeated dosing. For the major anthracycline, doxorubicin (Dox), this toxicity is thought to be associated with the formation of the 13-dihydro metabolite. Paced mouse left atria were used to assess the cardiotoxicity of Dox, 4'-epidoxorubicin (Epi), daunorubicin (Dauno) and their major metabolites.

Simple and sensitive quantification of anthracyclines in mouse atrial tissue using high-performance liquid chromatography and fluorescence detection.

Anthracyclines are very effective against soft tissue sarcomas, with cardiotoxicity being an important side effect after repeated administration. To estimate the relative cardiotoxicity of various anthracyclines and their metabolites, we developed an isolated mouse left atrium model. To relate an effect of doxorubicin, 4'-epidoxorubicin and their four main metabolites (doxorubicinol, epidoxorubicinol and the aglycons 7-deoxydoxorubicinon and 7-deoxydoxorubicinolon) to concentrations in the tissue instead of the incubation bath, a method of quantifying the anthracyclines in small tissue samples was developed.

Isolated mouse atrium as a model to study anthracycline cardiotoxicity: the role of the beta-adrenoceptor system and reactive oxygen species.

Cancer chemotherapy with anthracyclines, of which doxorubicin (DX2) is the main representative, is limited by cardiomyopathy developing in animals and patients after cumulative dosing. The toxicity is probably related to free radical formation by the anthracycline as well as its metabolites with concomitant O2.- and .

Clinical experience with an ethinyl estradiol-desogestrel oral contraceptive.

Desogestrel (150 micrograms), a potent progestogen virtually devoid of androgenic activity, was used in combination with 30 micrograms ethinyl estradiol as an oral contraceptive preparation (Marvelon). 219 women completed a total of 4074 cycles, and the use-effectiveness was 0.58 Pearl Units.

Preterm labor: the role of amnionitis.

This prospective study represents an attempt to find a link between subclinical intra-amniotic infection and preterm singleton labor in 27 asymptomatic patients with intact membranes. Liquor amnii was obtained by transabdominal amniocentesis and cultured for anaerobic and aerobic bacteria and mycoplasmas. None of these cultures was positive.

Epitopes of an influenza viral peptide recognized by antibody at single amino acid resolution.

Antibodies raised against the synthetic peptide corresponding to the carboxy-terminal 24 amino acids (305-328) of the heavy chain of the hemagglutinin molecule of influenza virus A/X-31 (H3) bind this peptide at three antigenic sites. These sites were identified by assaying binding of polyclonal BALB/c mouse antipeptide sera to the complete set of all possible di-, tri, tetra-, penta-, hexa-, hepta-, and octapeptides homologous with the 24-residue sequence. Individual epitopes were defined and essential residues identified by testing the binding of monoclonal antibodies to sets of peptide analogues in which every one of the homologous residues was replaced in turn by each of the 19 alternative genetically coded amino acids.

Nephrotoxicity and hepatotoxicity of 1,1-dichloro-2,2-difluoroethylene in the rat. Indications for differential mechanisms of bioactivation.

1,1-Dichloro-2,2-difluoroethylene (DCDFE) produced marked nephrotoxicity in rats upon an i.p. dose of 150 mumole/kg.

Strategies for epitope analysis using peptide synthesis.

A recently developed approach to the synthesis and ELISA screening of large numbers of peptides is described. The method has created the opportunity to tackle questions about the sites and specificity of antigenic determinants which were formerly thought to be too difficult to answer. The various strategies for application of this method are described along with examples of their successful use.

Laparoscopic diagnosis of mesenteric venous thrombosis.

Diagnosis of mesenteric venous thrombosis is almost always delayed, due to the aspecificity of the complaints and the clinical findings, as well as the laboratory investigations. Earlier diagnosis is essential to improve the present grim mortality rate. We report a case of mesenteric venous thrombosis in a 25-year-old female.

The antibody response to myoglobin--I. Systematic synthesis of myoglobin peptides reveals location and substructure of species-dependent continuous antigenic determinants.

Sets of peptides representing all the possible hepta-, octa-, nona- and decapeptides of sperm whale myoglobin were synthesized. An ELISA method was used to detect the ability of antibodies, present in antisera raised against native sperm whale myoglobin, to bind to these peptides. Antisera made in two species were compared.