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The use of oncolytic viruses (OV) to precisely target and eliminate tumors ('virotherapy') is a rapidly evolving therapeutic approach to treating cancer. A major obstacle in virotherapy, especially for systemic administration, is the host's immune response towards the OV. In the case of measles virus (MeV), most individuals have been immunized against this agent leading to pre-existing neutralizing antibodies that can impair OV delivery to the tumor. These antibodies predominantly target the hemagglutinin (H) and fusion (F) envelope glycoproteins displayed at the particle's surface. Here, we introduce a novel and versatile pseudotyping platform for rapid envelope exchange of oncolytic MeV that allows for engineering of chimeric viruses invulnerable to pre-existing anti-MeV antibodies. Using this system, we have successfully exchanged the MeV F and H proteins with the glycoprotein G of vesicular stomatitis virus (VSV) and the surface proteins of Newcastle disease virus (NDV) or canine distemper virus (CDV), all of which are not endemic in the general human population. While the MeV-VSV and MeV-NDV pseudotypes were non-functional, the MeV-CDV pseudotype was successfully propagated to high-titer virus stocks. This study describes the successful generation of a robust envelope exchange platform for oncolytic MeV while also highlighting its intricate pseudotyping tolerance.

The insider threat is a significant security concern for Critical National Infrastructure (CNI) organizations. A successful insider act in one of the CNI sectors has potential to damage assets and interrupt the critical services that society depends upon. Existing research suggests that behavioral indicators are often evident prior to an act taking place, but that reporting of such behaviors does not usually happen. The aim of this study was to identify factors that influence employees’ intention to intervene when observing behavioral changes associated with insider acts. An online survey with employees within a large Critical National Infrastructure (CNI) energy sector organization (N = 55) explored factors including behavioral change type, relationship to the actor, employment status of the actor and actor motivations. Results supported existing research regarding reluctance to report behavioral indicators of attitude change, but also demonstrated that situations with sufficient evidence are more likely to be reported. Factors which inhibited intervention likelihood were relative seniority and perceived motivations of the actor, confidence of confidentiality and clarity of reporting processes. Primary barriers to intervention related to the observer's perceived ability to correctly interpret behavioral indicators and awareness of how to respond. Organizations need to provide training regarding behavioral indictors of insider threats, clear, confidential reporting processes, and a culture where respectful challenge is encouraged.

Patienten mit Hochrisikoblasentumoren, die nicht auf eine BCG-Immuntherapie ansprechen, stellen eine therapeutische Herausforderung dar. Als Second-line-Therapie wird derzeit haufig eine Kombination aus BCG plus Interferon empfohlen. Da jedoch ein Grosteil aggressiv wachsender Tumoren nicht sensibel auf Interferon reagiert, kame anstatt dessen der Einsatz onkolytischer Vesikular-Stomatitisviren (VSV) in Betracht, die speziell Interferon-refraktare Tumorzellen angreifen. In vitro toteten sowohl Wildtyp-VSV als auch ein attenuierter Subtyp, der eine gesteigerte Tumorselektivitat aufweist, bevorzugt aggressiv wachsende, Interferon-resistente Blasentumorzellen. Anschliesende In-vivo-Versuche in einem von uns validierten orthotopen Mausmodell konnten die viel versprechende antikanzerogene Aktivitat beider Viren nach intravesikaler Gabe eindrucksvoll bestatigen. Obwohl in diesem Modell immunkompromittierte Nacktmause verwendet werden, zeigte sich keine virale Toxizitat. Zusammenfassend scheinen fruhe klinische Studien zur intravesikalen Therapie mit VSV gerechtfertigt.

The structure and the rheological properties of the antiwear films from a zinc dialkyldithiophosphate (ZDTP) solution generated in a rolling/sliding contact simulating engine valve train conditions...

A multi-technique study of model automotive anti-wear films using SEM with quantitative electron microprobe analysis, reflection–absorption IR spectroscopy, SIMS imaging and XPS depth profiling is described. Constrained simulation of the XPS depth profiles allowed model cross-sections of the film structures to be constructed. With zinc dialkyl dithiophosphate as an anti-wear additive, the anti-wear films were found to have a thin inorganic mixed sulphide/oxide layer immediately above the Fe substrate. This formed the base for a thicker Zn-containing polyphosphate-like overlayer. Addition of detergent and dispersant to the lubricant formulation resulted in thicker, more patchy films, with a clearer differentiation between film and substrate.

The friction and wear characteristics of combinations of silicon nitride, alumina and AISI 52100 steel in the presence of mineral oil containing anti-wear, dispersant and detergent additives have been investigated in a tri-pin-on-disc machine. The tests were carried out at a nominal temperature of 100°C for a range of sliding speeds, loads and total sliding distances. In Part II of this two-part paper a comparison will be made between the tribological performance of these sliding pairs of materials in mineral oil and ester based lubricant environments. The results of the investigation showed that the alumina performed relatively poorly under these test conditions, whereas silicon nitride showed good potential as an improved wear resisting material compared with 52100 steel. Wear factors of the order of 10−10 mm3/Nm were deduced for the alumina, while values as low as 10−11 mm3/Nm were typical of the silicon nitride sliding against 52100 steel discs. The alumina pins wore by a process of brittle fracture at the surface, whereas the silicon nitride pins wore primarily by a tribochemical polishing mechanism. The rate of tribo-chemical wear was found to be proportional to the nominal contact area.

The surface films formed by a set of oils of related additive chemistry, but with differing detergent and dispersant contents, have been chemically characterized using a combination of surface analysis techniques. The films were formed in a cam/tappet friction apparatus with a direct acting bucket tappet geometry. In the absence of overbased detergent, the amorphous films were composed essentially of inorganic zinc phosphates formed by the ZDTP anti-wear additive, and evidence of higher molecular weight phosphates (e.g. metaphosphates) was found. Adding overbased detergent and dispersant resulted in partial replacement of zinc by the detergent metal and loss of the higher molecular weight phosphates in favour of ortho- and pyro-phosphates.

Pivoted follower valve train systems are now widely used in modern high-speed automotive engines, and because of their proneness to wear they feature prominently in lubricant specification test requirements. Critical conditions for wear in these systems have been identified by the application of a new model for steady, non-catastrophic,wear processes to the kinematic analysis of the cam/follower contact cycle. It is shown that using this technique, the positions of maximum wear and the reasons for the observed wear severity of pivoted follower systems can be more accurately identified than previously.

The Standard-C system, when integrated with a suitable navigation system and other vehicle sensors, offers a unique low-cost global solution for automatic vehicle location, messaging, and fleet management. For haulers engaged in just-in-time deliveries such a combination offers to the dispatcher a near real-time display of the truck's progress, while also providing a means of rapidly exchanging messages between the driver and dispatcher whenever the need occurs. The range of Standard-C capabilities includes two-way store and forward data/messaging; a short burst transmission mode for position and data reporting; polling; and an enhanced group call facility. The flexibility of the system ensures that it is able to satisfy the long-range communications requirements of truck companies throughout the world, operating as a closed user group or via the public network. >

For many years, zinc dialkyldithiophosphate (ZDTP) lubricant additives have been extensively used for their anti-oxidant and anti-wear properties in rubbing systems but due to environmental considerations, there is now a need to develop new anti-wear additives with different chemistry but comparable anti-wear efficiency. As the anti-wear action of ZDTP additives is associated to the formation of a protective solid film onto friction surfaces under boundary lubrication conditions, the knowledge of the anti-wear film behaviour is a key point.

An improved understanding of lubrication within the piston ring pack is expected to contribute to efforts aimed at improving the fuel economy of automotive engines. However, most studies of frictional losses within the piston ring-pack use viscometric data for ‘fresh’ lubricants. The changes that occur to the viscometric properties of the lubricant in a working engine are not generally taken into account. The lubricant in an engine is subjected to a harsh physical environment, and the aggressive chemistry that takes place in the vicinity of the top piston ring causes lubricant degradation by both evaporation of the lower boiling point components and by oxidation. Top ring zone oil sampling studies show that this degradation changes the viscometric properties of the lubricant. Measured viscometric data have been used in a piston ring pack model to estimate the effects of oil degradation on frictional power losses within the ring pack. In an extreme case, degradation increased these losses by up to 40%.

The composition and structure of well-developed zinc dialkyldithiophosphate (ZDTP) anti-wear films, formed under factional conditions, has been examined by scanning electron microscopy/electron probe microanalysis (SEM/EPMA) and secondary ion mass spectrometry (SIMS), without solvent washing. The presence of the molecular groups identified by SIMS was confirmed to depths of at least 100 nm by X-ray photoelectron spectroscopy (XPS) depth profiling. The main constituent of the film approximated closely to P2O5, with varying amounts of organic material, and sulphides and oxides of zinc and iron. A model is proposed for a glassy polyphosphate film whose physical properties vary with depth as a result of varying modifier contents. The consequences of such a structure for film adhesion and for the physical and chemical processes of removal of substrate material are discussed.

Piston ring/cylinder contacts in modern automotive engines are being exposed to increasingly high temperatures, gas pressure loading and combustion contamination. Conventional ferrous materials and wear-resistant coatings appear to be reaching their limit of reliability and a variety of novel materials, notably ceramics, are being applied to combat the tribological problems resulting from these developments. The tribological behaviour of ceramics in an engine environment is, as yet, not well understood. In particular, there is inadequate knowledge of how lubricants can affect the wear processes, and hence the durability, of ceramics in these applications. As a first step in clarifying these questions, the wear of an alumina-based plasma coating has been compared with that of conventional chromium plating in the Plint reciprocating wear machine. The temperatures, contact loadings and sliding speeds pertaining close to the top reversal point in a high temperature, heavy-duty diesel engine were closely simulated, and the experimental specimens were prepared from real engine components. The wear of the two piston ring coatings responded differently to lubricant additives. The alumina-based coating gave generally lower wear than the chromium plating. Examination of the worn surfaces by scanning electron microscopy and electron probe microanalysis revealed markedly different material removal processes for the two coatings. In these thick coatings damage appeared always to have been initiated at the surface rather than at the interface with the substrate. The possible influences of film formed on the surface by the lubricant are discussed.

During the period 1973 to 1979 the number of recorded incidents of equine salmonellosis increased from 23 in 1973 to a peak of 111 incidents in 1976, but has since decreased to 32 in 1979. Of the 416 incidents recorded during the period of the survey 292 were caused by Salmonella typhimurium and 121 by 33 different serotypes; in three instances rough strains of salmonella were involved. The number of incidents caused by serotypes other than S typhimurium increased from one in 1973 to 32 in 1976. The number of different salmonella serotypes increased from two in 1973 to 23 in 1977 and has subsequently declined. Drug resistance monitoring of salmonella strains from horses showed that most of the strains were resistant to streptomycin and sulphonamides, although resistance to other antibacterial drugs used was low. Seventeen different patterns of antibiotic resistance were observed but resistance to more than two antibiotics was uncommon.

A new form of elemental surface load on a half space is introduced, presuming a quasi-pyramidal variation of load which is doubly linear in each of four rectangular parts of a surface rectangle. Approximations of arbitrary load distributions by sums of such elements are continuous, piecewise linear in two directions and well adaptable. The loads may be normal or tangential. The explicit solutions obtained for all stress and displacement components due to each elemental load involve only elementary functions, are free of the discontinuities which arise with stepwise elements, and are suitable for computing. Some illustrative stress distributions are presented for elemental loads and for multiple pyramidal loads involving both normal and tangential loads. The value of the load continuity in the more complicated analyses of surface cracks is also illustrated.

SUMMARY A total of 353 incidents of ovine salmonellosis caused by 44 different serotypes was recorded for England and Wales from 1975 to 1981 inclusive. The commonest serotypes were S. typhimurium (92 incidents), S. dublin (85), S. Montevideo (39) and S. arixonae 61:k:1,5,7 (30). Since 1969 there has been a reduction in incidents due to S. dublin whilst S. abortus ovis has not been recorded since 1976. S. arizonae was first recorded in sheep in England and Wales in 1976; isolates examined have been of serotype 61:k:1,5,7 which is well adapted to sheep. Abortions occurred in nine out of 30 incidents due to this serotype but in eight of these other abortion agents were demonstrated. S. arizonae appeared to be implicated in four cases of enteritis but it was considered secondary to some other disease condition in 10 incidents and an incidental finding in the remaining seven incidents involving apparently healthy animals. Most incidents occurred in Yorkshire.

Data on collisions of electrons with molecules of carbon dioxide, carbon monoxide, and nitrogen are used to compute the elevation of electron temprature above gas temperature for different degrees of excitation of carbon dioxide beyond that for equilibrium. Extra-equilibrium excitations of vibrational and electronic levels are considered. Under certain conditions the electron temperature closely follows the carbon dioxide vibrational temperature. Numerical results are presented to show the effects of the different gases. The rates for ionization of molecules by collisions with electrons are calculated for different values of electron temperature, and the possibility of electron ionizing collisions in flame gases is discussed.

The binding of water, methanol, ethanol, propanol, and isopropanol by hair keratin and tendon collagen was measured. Water was found to be taken up preferentially from aqueous solutions of the higher alcohol homologues, whereas in the case of methanol-water mixtures the absorption of the alcoholic component was slightly favored. Attempts to interpret the experimental results by using absorption models based on stoichiometric interactions failed. The data could be fitted to a phase-partition model based on the assumption that considerable internal pressure exists in the protein phase favoring the absorption of the smaller molecules. The standard free energies of transfer from the solution into the protein phase were found to be very nearly the same for all components, including water, and were independent of the hydrocarbon chain lengths, implying that hydrophobic interactions play only an insignificant role in the binding of alcohols to keratin and collagen.

THE ORIGINAL RESEARCH of Britton and Silvette in 1932 definitely established the relationship of the adrenal to carbohydrate metabolism. These authors showed that extracts of this gland were capable not only of restoring the blood sugar and liver and muscle glycogen stores in adrenalectomized animals but also would influence carbohydrate metabolism in the normal animal. At that time they suggested that the increase in hepatic glycogen might form the basis of a test for measuring the potency of adrenal extracts. It was not, however, until 1942, that Reinecke and Kendall published a quantitative method for the assay of adrenal hormones based upon the ability of these substances to cause deposition of glycogen in the livers of adrenalectomized fasted rats. More recently, in 1944, Olsen and his associates have evaluated the Reinecke Kendall test and have suggested certain modifications such as the pre-feeding of a high protein diet to increase the total response of the animal to a given dose of adrenal cortic...

Electrostatic probes have been used to obtain positive-ion concentrations and electron temperatures in methane-air and ethylene-air flames on a low-pressure flat-flame burner. The following measurements were also taken: gas temperatures, using thermocouples; gas velocities, using the particle-tracking technique; emission intensities from excited OH, C 2 , CH, and CO 2 , using a monochromator. It was found that electron temperatures were higher than gas temperatures in the reaction zone and the peak value of the former coincided with the peak in OH emission. This elevation of electron temperature is possibly attributable to electron collisions with excited OH and C 2 . Theoretical values of the rate constant for electron ionizing collisions are presented for CO, O 2 , NO, and Na, and it is concluded that this type of collision does not seem to be significant in methane-air and ethylene-air flames. It might be more significant in higher-temperature flames and in flames seeded with alkali. For the stoichiometric methane-air flame, the maximum rate of ion production occurred downstream of the peak electron temperature and was 1.9×10 12 ions cm −3 sec −1 . The value of the ion-recombination coefficient was (1.1.±0.2)×10 −7 cm 3 sec −1 .

This work was carried out as part of the instrumented fuel stringer programme in Civil Advanced Gas-cooled Reactors. The overall aim of the project was to assess the coolant temperature distribution in the CAGR fuel cluster on the basis of thermocouple measurements in the coolant downstream of the fuel exit. This was achieved by use of an air rig simulating an AGR channel and the subsequent development of a model was based on a diffusivity analysis. This paper describes points of general interest arising from this work.

A study of the separate influences of hardness and microstructure on wear rate has been attempted, by the selective thermal treatment of AISI 4340 Steel. Martensitic microstructures gave consistently higher wear, for a given hardness, than the bainite-and ferrite/pearlite-containing microstructures that were examined. There was evidence that the predominant wear processes were different for different microstructures. A transition to relatively high rates of wear was observed with the softer martensitic structures. This transition has been qualitatively modelled by combining criteria for the plastic flow of areas of contact with an existing elastic model for the contact of rough surfaces. Significant influences of surface topography and boundary friction on the transition to high wear are indicated, which could have consequences for the manufacture and lubrication of critical mechanisms, e.g. gear and cam systems.

The stress-strain properties of the APDA reference alloy of uranium- 10 wt.% molybdenum at various burnups up to 2.1 total at. % are described. Data were ob tained on both irradiated and unirradiated specimens of the alloy by the use of a remotely operated bend-testing machine. Tensile properties of unirradiated material are also reported for comparison with data obtained from the bend tests. The mathematical procedure used in obtainirg equivalent uniaxial stress-strain properties from the bend-test data is described in the Appendix. The results of the bend tests indicate that the physical properties of the reference alloy were severely affected by irradiation to burnups as high as 2.1 total at.%. At a test temperature of 500 deg C, the modulus of elasticity, ultimate strength, and strain at fracture decreased rapidly up to a burnup of about 0.5 to 1.0 total at.% with the rate of change decreasing thereafter. No important differences were noted between coextruded and hot-rolled material. An indication was obtained that the ultimate strength of the alloy was improved with increasing irradiation temperatures up to about 500 deg C. Data obainined on unirradiated material indicated that ductility of the reference alloy was lower at 500 deg C thanmore » at room temperature. Stress-strain curves for the irradiated specimens are included. The value of these data is limited because of the large number of variables encountered in the specimen histories and the small number of tests involved in this program. (auth)« less