GD3/proteosome vaccines induce consistent IgM antibodies against the ganglioside GD3

The gangliosides of melanoma and other tumours of neuroectodermal origin are suitable targets for immune intervention with tumour vaccines. The optimal vaccines in current use contain ganglioside plus bacillus Calmette-Guérin and induce considerable morbidity. We have screened a variety of new adjuvants in the mouse, and describe one antigen-delivery system, proteosomes, which is especially effective. Highly hydrophobic Neisserial outer membrane proteins (OMP) form multimolecular liposome-like vesicular structures termed proteosomes which can readily incorporate amphiphilic molecules such as GD3 ganglioside. The optimal GD3/proteosome vaccine formulation for induction of GD3 antibodies in the mouse is determined. Interestingly, the use of potent immunological adjuvants in addition to proteosomes augments the IgM and IgG antibody titres against OMP in these vaccines but GD3 antibody titres are unaffected. The application of proteosomes to enhance the immune response to GD3 extends the concept of the proteosome immunopotentiating system from lipopeptides to amphipathic carbohydrate epitopes such as cell-surface gangliosides. The demonstrated safety of meningococcal OMP in humans and the data in mice presented here suggest that proteosome vaccines have potential for augmenting the immunogenicity of amphipathic tumour antigens in humans.     

The incorporation of yield surface distortion into a unified constitutive model,part 2: Predictive capabilities

Summary The MATMOD-4V-DISTORTION model has been derived [1] with the intent of improving the MATMOD-4V model by adding the capability to predict distortions of small strain offset yield surfaces. This model is compared against a variety of experimental data to verify its behavior. Model simulations are compared with experimental data for proportional and nonproportional prestress histories and the effect of yield definition is also investigated. Finally, the same model which predicts a flattening of the yield surface in space is used to predict a rotation of the yield surface in ₁-₂ coordinates.With 9 Figures     

Inversion handling for stable deformable modeling

In 3D deformable modeling approaches based on FEM, inverted tetrahedral elements can cause undesired visual artifacts and the breakdown of the simulation. As inversion can never be avoided and sometimes is even the correct behavior of elements, there is a strong need for stable inversion handling. In this paper, we propose a novel method to resolve inverted elements which is motivated by previous work of Irving et al. [6]. In combination with an efficient handling of degenerated elements, our approach yields a stable simulation of arbitrary deformations. Although we focus on the corotational formulation of linear FEM, the method can be implemented within arbitrary constitutive models.     

Determination of epoxidized soy bean oil (ESBO) in oily foods by GC–FID or GC–MS analysis of the methyl diepoxy linoleate

A simplified method is presented for determining epoxidized soy bean oil (ESBO) in food or food simulants, such as olive oil. ESBO is transesterified with methoxide/methanol directly in the homogenated food, i.e. without prior extraction, and analyzed on a cyanopropyl or phenyl polysiloxane stationary phase without formation of dioxolanes. For most foods, flame ionization detection (FID) was appropriate, but for samples with interfering components, GC–MS was needed. Chemical ionization (CI) with ammonia is more sensitive and more selective than electron impact ionization (EI). In CI, positive and negative ion monitoring (PCI and NCI) are similar in sensitivity, but different in selectivity, i.e. the combination of the two is well suited for confirmation. Results are shown to be in agreement with on-line LC–GC–FID.     

Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure

Currently, in developed countries, nights are excessively illuminated (light at night), whereas daytime is mainly spent indoors, and thus people are exposed to much lower light intensities than under natural conditions. In spite of the positive impact of artificial light, we pay a price for the easy access to light during the night: disorganization of our circadian system or chronodisruption (CD), including perturbations in melatonin rhythm. Epidemiological studies show that CD is associated with an increased incidence of diabetes, obesity, heart disease, cognitive and affective impairment, premature aging and some types of cancer. Knowledge of retinal photoreceptors and the discovery of melanopsin in some ganglion cells demonstrate that light intensity, timing and spectrum must be considered to keep the biological clock properly entrained. Importantly, not all wavelengths of light are equally chronodisrupting. Blue light, which is particularly beneficial during the daytime, seems to be more disruptive at night, and induces the strongest melatonin inhibition. Nocturnal blue light exposure is currently increasing, due to the proliferation of energy-efficient lighting (LEDs) and electronic devices. Thus, the development of lighting systems that preserve the melatonin rhythm could reduce the health risks induced by chronodisruption. This review addresses the state of the art regarding the crosstalk between light and the circadian system.     

The maximum extent of reaction in gelled systems

Just how far reactions can go after gelation during the cure of telechelic prepolymers has been a debatable point for some time. Utilizing a recently devised method,⁷ the curing reactions of some telechelic prepolymers were followed after the gel point. Extents of reaction above 90% occurred only in systems of average functionality close to two, functionality being the average number of reactive groups per molecule. Among systems of higher functionality, maximum extents of reaction of about 70% were most common. The final extent of reaction was only a few per cent above the extent of reaction at the gel point. The maximum extent of reaction varied with the concentration of reactive species and the relationship was a linear one at each functionality of the system. The data were consistent with P_A²/r = {0.88/[(h ? 1)(j ? 1)]} + 0.10 where P_A is the fraction of prepolymer reactive groups initially present which have reacted, r is the ratio of the initial number of crosslinking groups to prepolymer reactive groups, and h and j are weighted average functionalities of the two reactants. It is suggested that the limiting factor in defining the final extent of reaction in these systems is the accessibility of reactive groups as determined by solid geometry rather than thermodynamics or reaction kinetics. The final extent of cure is regularly dependent on functionality and one cannot regard functionality and maximum extent of reaction as independent variables.     

Analysis of the temperature dependence of the fracture stress of sharp notched bending specimens of a structural steel with respect to intermediate transitions

The flow and fracture stresses, σ_y^g and σ_f^g (δ = crack tip displacement), of sharply notched bending specimens of a structural steel U St 37-1 are measured in the temperature range from full scale to small scale yielding. The best adaption of the experimental results for σ_f^g is obtained by a curve which exhibits an intermediate transition, i.e. which follows in a temperature range between an upper, T_tM¹ and a lower, T_tl¹, transition temperature to the curve σ_y^g(T) for the flow stress with a constant δ = δ₁. This transition corresponds to that of the slip to the twin nucleated fracture. Two analyses [3,5] according to the local fracture stress, σ_f^*, concept show that the amount and the temperature dependence of σ_f^* are somewhat different for both methods, but that both exhibit an increase of σ_f^* in the transition range. It is concluded that each transition in the nucleation mode of the fracture is connected with such a transition in the fracture stress. It may, however, become indistinct or even be covered by the scatter of the experimental points.     

Radio fluorination and positron emission tomography (PET) as a new approach to study the in vivo distribution and elimination of the advanced glycation endproducts N epsilon-carboxymethyllysine (CML) and N epsilon-carboxyethyllysine (CEL).

After synthesis of fluorine-18 labelled analogues by [18F]fluorobenzoylation at the alpha-amino group, biodistribution and elimination of individual advanced glycation endproducts, namely N epsilon-carboxymethyllysine and N epsilon-carboxyethyllysine, were studied in comparison to lysine in rats after intravenous injection using positron emission tomography (PET). The [18F]radiofluorinated amino acids were fast distributed via the blood, followed by a rapid excretion through the kidneys. Elimination kinetics were similar for both AGEs and lysine. For CML and CEL, but not for lysine, a temporary liver accumulation could be observed, which was not connected with any metabolisation or enterohepatic circulation. No further accumulation in any tissues was observable, indicating that increased tissue levels of CML or CEL, which have been described for certain disorders, are exclusively derived from endogenous origin and should not depend on a dietary intake. However, under uremic conditions, an impaired kidney function might result in a significant increase of the AGE-load of blood and tissues. PET based on 18F-labelled AGEs proved to be a promising tool to elucidate the physiological fate of post-translationally modified amino acids and to clarify the role of AGEs as possible "glycotoxins".     

Applying a physics-of-failure model to predicting surface mount solder joint reliability

To address the wide variety of solder joint configurations, the authors have developed and applied a physics-of-failure model to predicting the service life of solder joints under thermal cycling conditions. The wide variety of solder joint geometries, materials and environments makes it impractical to develop and apply empirical models to predicting the service life of solder joint interconnects. On the other hand, a physics-of-failure model that describes the failure mechanisms in solder joints can be applied to a wide range of conditions. The physics-of-failure model framework is described and a model is demonstrated for predicting the failure of a leadless surface mount solder joint under slow thermal cycling conditions.     

Determination of the overall migration from silicone baking moulds into simulants and food using 1H-NMR techniques

Different silicone baking moulds (37 samples) were characterized with respect to potential migrating substances using ¹H-NMR, RP-HPLC–UV/ELSD and GC techniques. In all cases cyclic organosiloxane oligomers with the formula [Si(CH₃)₂–O] _n were identified (n = 6 … 50). Additionally, linear, partly hydroxyl-terminated organosiloxanes HO–[Si(CH₃)₂–O] _n –H (n = 7 … 20) were found in 13 samples. No substances other than siloxanes could be detected, meaning the migrants mainly consist of organopolysiloxanes. Based on this knowledge, a ¹H-NMR quantification method for siloxanes was established for the analysis of both simulants and foodstuffs. Validation of the ¹H-NMR method gave suitable performance characteristics: limit of detection 8.7 mg kg^–1 oil, coefficient of variation 7.8% (at a level of 1.0 mg kg^–1 food). Migration studies were carried out with simulants (olive oil, isooctane, ethanol (95%), Tenax) as well as preparation of different cakes. From the 1st to 10th experiment, siloxane migration into cakes only slightly decreased, with a significant dependence on fat content. Migration never exceeded a level of 21 mg kg^–1 (3 mg dm^–2) and was, therefore, well below the overall migration limit of 60 mg kg^–1 (10 mg dm^–2). However, migration behaviour into simulants differed completely from these results.