Toshiba (Switzerland)

This paper is co-authored by an informal group of experts from a broad range of backgrounds all of whom are active in standards groups, consortia and/or alliances in the Internet of Things (IoT) space. The ambition is to create mindshare on approaches to semantic interoperability and to actively encourage consensus building on what the co-authors regard as a key technical issue.

INTRODUCTION: Alzheimer's disease looms as a profound and growing threat to future human health. The disease is thought to be primarily driven by aberrant proteolysis of the amyloid precursor protein (APP) and amyloid beta (Aβ) plaque deposition. AREAS COVERED: We provide an overview of the molecular pathology that leads to an increase in Aβ peptide accumulation, of the mechanism of action for antibody mediated therapies and of the therapeutic vaccines that target Aβ under development. We also discuss the rationale for using vaccines in the early stages of the disease. EXPERT OPINION: peptides derived from the APP. Reducing these plaques by means of passive or active vaccination against Aβ-peptides has been a long-running endeavor but with disappointing results as the impact on disease progression has been minimal. The data gathered to date could suggest that antibodies do not work, mainly because the studies have not been performed in an optimal fashion. The emerging views are that patients should be treated earlier, ideally in the prodromal or symptom free stage, antibody levels have to be high and the correct epitope must be targeted. More clinical trials to fully explore the potential of vaccines are therefore warranted.

Abstract The ongoing coronavirus COVID-19 pandemic is caused by a new coronavirus (SARS-CoV-2) with its origin in the city of Wuhan in China. From there it has been rapidly spreading to many cities inside and outside China. Nowadays more than 33 millions with deaths surpassing 1 million have been recorded worldwide thus representing a major health issue. Rapid development of a protective vaccine against COVID-19 is therefore of paramount importance. Here we demonstrated that recombinantly expressed receptor binding domain (RBD) of the spike protein homologous to SARS binds to ACE2, the viral receptor. Higly repetitive display of RBD on immunologically optimized virus-like particles derived from cucumber mosaic virus (CuMV TT ) resulted in a vaccine candidate that induced high levels of specific antibodies in mice which were able to block binding of spike protein to ACE2 and potently neutralized COVID-19 virus in vitro .

BACKGROUND: -Ara h 2). We previously demonstrated the immunogenicity and the protective capacity of VLP Peanut-based immunization in a murine model for peanut allergy. Moreover, a Phase I clinical trial has been initiated using VLP Peanut material manufactured following a GMP-compliant manufacturing process. Key product characterization studies were undertaken here to understand the role and contribution of critical quality attributes that translate as predictive markers of immunogenicity and protective efficacy for clinical vaccine development. METHOD: The role of prokaryotic RNA encapsulated within VLP Peanut on vaccine immunogenicity was assessed by producing a VLP Peanut batch with a reduced RNA content (VLP Peanut low RNA). Immunogenicity and peanut allergen challenge studies were conducted with VLP Peanut low RNA, as well as with VLP Peanut in WT and TLR 7 KO mice. Furthermore, mass spectrometry and SDS-PAGE based methods were used to determine Ara h 2 antigen density on the surface of VLP Peanut particles. This methodology was subsequently applied to investigate the relationship between Ara h 2 antigen density and immunogenicity of VLP Peanut. RESULTS: A TLR 7 dependent formation of Ara h 2 specific high-avidity IgG antibodies, as well as a TLR 7 dependent change in the dominant IgG subclass, was observed following VLP Peanut vaccination, while total allergen-specific IgG remained relatively unaffected. Consistently, a missing TLR 7 signal caused only a weak decrease in allergen tolerability after vaccination. In contrast, a reduced RNA content for VLP Peanut resulted in diminished total Ara h 2 specific IgG responses, followed by a significant impairment in peanut allergen tolerability. The discrepant effect on allergen tolerance caused by an absent TLR 7 signal versus a reduced RNA content is explained by the observation that VLP Peanut-derived RNA not only stimulates TLR 7 but also TLR 3. Additionally, a strong correlation was observed between the number of Ara h 2 antigens displayed on the surface of VLP Peanut particles and the vaccine's immunogenicity and protective capacity. CONCLUSIONS: Our findings demonstrate that prokaryotic RNA encapsulated within VLP Peanut, including antigen density of Ara h 2 on viral particles, are key contributors to the immunogenicity and protective capacity of the vaccine. Thus, antigenicity and RNA content are two critical quality attributes that need to be determined at the stage of manufacturing, providing robust information regarding the immunogenicity and protective capacity of VLP Peanut in the mouse which has translational relevance to the human setting.

Distance measurements of the vascular system of the brain can be derived from biplanar digital subtraction angiography (2p-DSA). The measurements are used for planning of minimal invasive surgical procedures. Our 90 degree-fixed-angle G- ring angiography system has the potential of acquiring pairs of such images with high geometric accuracy. The sizes of vessels and aneurysms are estimated applying a fast and accurate extraction method in order to select an appropriate surgical strategy. Distance computation from 2p-DSA is carried out in three steps. First, the boundary of the structure to be measured is detected based on zero-crossings and closeness to user-specified end points. Subsequently, the 3D location of the center of the structure is computed from the centers of gravity of its two projections. This location is used to reverse the magnification factor caused by the cone-shaped projection of the x-rays. Since exact measurements of possibly very small structures are crucial to the usefulness in surgical planning, we identified mechanical and computational influences on the geometry which may have an impact on the measurement accuracy. A study with phantoms is presented distinguishing between the different effects and enabling the computation of an optimal overall exactness. Comparing this optimum with results of distance measurements on phantoms whose exact size and shape is known, we found, that the measurement error for structures of size of 20 mm was less than 0.05 mm on average and 0.50 mm at maximum. The maximum achievable accuracy of 0.15 mm was in most cases exceeded by less than 0.15 mm. This accuracy surpasses by far the requirements for the above mentioned surgery application. The mechanic accuracy of the fixed-angle biplanar system meets the requirements for computing a 3D reconstruction of the small vessels of the brain. It also indicates, that simple measurements will be possible on systems being less accurate.

In the current quest for a more sustainable, environment-friendly agriculture , variety mixtures are often suggested as a practical option to increase the stability of food production systems. Their effects on yield have been extensively researched, yet clear conclusions remain elusive, notably in terms of mechanistic processes and optimal variety combinations. Furthermore, in the case of wheat, yield is not the only component in the equation: grain quality is crucial for the bread value chain, yet the effects of variety mixtures on wheat quality and its stability have rarely been investigated. To that end, we conducted a multi-year, multi-site wheat variety mixture experiment investigating the role of variety mixtures on the performance and stability of five traits linked to grain yield and quality, and the mechanisms underlying these effects. Eight varieties were grown in pure stands and mixtures of 2 and 8 varieties, following a full diallel design. We considered the responses of grain yield, protein content, thousand kernel weight, hectoliter weight, and Zeleny sedimentation value. Results showed that mixtures generally outperformed pure stands in terms of global performance and stability for the 5 parameters. We particularly noticed an increase in quality stability and in Zeleny sedimentation value in mixtures, showing the potential of mixtures to improve crop quality. Moreover, we highlighted the important role of light interception for increased mixtures benefits. A more detailed investigation into individual mixture performances led us to some practical rules for optimal variety combinations: we advise combining varieties with similar heights and phenologies but different tillering abilities and yield potential. This study thus shows that variety mixtures represent a promising solution to sustainably increase the stability of wheat yield and quality. With practical recommendations, our results could benefit farmers but also processors and bakers, and promote the adoption of wheat variety mixtures.

Segmentation and 3D reconstruction of vessel center lines from subtraction angiography is difficult because of noise, an uneven distribution of the contrast agent, and bone structures concealing the vessels. In biplane images, some ambiguities in segmentation in one of the images can be resolved using image information from the other image. Images are first processed separately. A-priori vessel probabilities are computed using the grey value in the image. Gradients and second derivatives are computed using gaussian derivatives. Subsequently, 3D reconstruction is carried out in a line-by-line fashion between user-specified base lines on both images. The user is asked to point out corresponding vessel cross-sections on the frontal and lateral image. 3D locations are computed. Between adjacent 3D locations, intermediate 3D locations are estimated iteratively using location, curvature and size of the previously computed 3D vessel cross-section. The estimates are optimized evaluating local attributes in the two projection images, such as the grey level, the gradient and the closeness to the initial estimate. WE applied the method for the reconstruction of artificial and real structures. The artificial object consisted of metal wires with sizes ranging between 1 and 5 mm. Various parts of the structure were extracted and reconstructed successfully. Reconstructing center lines from real images was more difficult because of the image degrading influences. Structures with a size of about 1 mm were extracted and reconstructed successfully even though they were barely visible. The amount of user interaction depended on the visibility of the structures in the two images.

Introduction: SARS-CoV-2 has developed a number of Variants of Concern (VOC) with increased infectivity and/or reduced recognition by neutralizing antibodies specific for the receptor binding domain (RBD) of the spike protein. Extended studies of other viruses have shown that strong and broad viral escape from neutralizing serum antibodies is typically associated with the formation of serotypes. Methods: To address the question of serotype formation for SARS-CoV-2 in detail, we generated recombinant RBDs of VOCs and displayed them on virus-like particles (VLPs) for vaccination and specific antibody responses. Results: As expected, mice immunized with wild type (wt) RBD generated antibodies that recognized wt RBD well but displayed reduced binding to VOC RBDs, in particular those with the E484K mutation. Unexpectedly, however, antibodies induced by the VOC vaccines typically recognized best the wt RBDs, often more than the homologous VOC RBDs used for immunization. Hence, these data do not reveal different serotypes but represent a newly observed viral evolution, suggesting a unique situation where inherent differences of RBDs are responsible for induction of neutralizing antibodies. Discussion: Therefore, besides antibody (fine) specificity, other qualities of antibodies (e.g. their affinity) determine neutralizing capability. Immune escape of SARS-CoV-2 VOCs only affects a fraction of an individual's serum antibodies. Consequently, many neutralizing serum antibodies are cross-reactive and thus protective against multiple current and future VOCs. Besides considering variant sequences for next generation vaccines, broader protection will be achieved with vaccines that induce elevated titers of high-quality antibodies.

Abstract The investigations in epoxy resins and other polymers have shown that by selecting the structure of the segments between the crosslinks it is possible to vary to a great extend the morphology and the physical properties. In a survey, a classification of 7 systems is given, cach of them characterized by specific morphological and physical properties. It is demonstrated that conventional epoxide resins show a distinct maximum of the mechanical damping and elongation at rupture nearly at the same temperature. The toughness‐temperature characteristic however shows a maximum 20°–30°C below the glass transition temperature. One system, the slightly crosslinked epoxy resins e.g. obtained by reacting long chain acid polyesters and diepoxides show a very high toughness in the transition range, compared to the conventional high crosslinked polymers.

In the context of AIOTI (Alliance for Internet of Things Innovation) WG03 and by following the evolution on IoT architectural aspects and available specifications, AIOTI WG03 has developed a High Level Architecture (HLA) for IoT that should be applicable to AIOTI Large Scale Pilots. The HLA takes into account existing SDOs and alliances architecture specifications

Although diagnosed concussions affect balance control, dual-task abilities, visual functions, and neurocognitive functions, few prospective investigations have examined how head impacts sustained during an Olympic-style boxing tournament that do not result in a concussion, so-called sub-concussive blows, affect performance. Female boxers, in particular, have received scant attention in the boxing literature to date. PURPOSE: To prospectively examine the neurocognitive, postural control, dual-task, and visual abilities of female Olympic-style boxers before and after participation in a boxing tournament. METHODS: Sixty-one females completed the modified Balance Error Scoring System (mBESS), King-Devick test, and 3m timed-up-and-go (TUG) test in single-task and dual-task conditions. A subset (n= 31) also completed the CogState computerized neurocognitive test. Initial testing was completed prior to the 2016 Women’s World Boxing Championships and each participant repeated the testing protocol within a day of elimination. Pre-tournament and post-tournament performance variables were compared using paired samples t-tests. RESULTS: Participants (mean age = 26.1 ± 4.6 years) completed a mean of 7.5 ± 4.5 rounds of Olympic-style boxing over the course of 2-8 days. Pre-tournament scores were significantly worse than post-tournament scores for total mBESS (5.5±2.9 errors vs. 2.2±1.9 errors, p< .001, d= 1.23) and King-Devick time (18.0±8.3 s vs. 14.2±3.9 s, p= .002, d= 0.53). Processing speed was significantly slower prior to the boxing tournament (maze chase task: 1.17±0.44 correct moves/second vs. 1.39±0.34 correct moves/second, p= .001, d= 0.58). No significant changes between testing sessions were detected for the other obtained outcome variables. CONCLUSION: Female boxers demonstrated either improvement or no significant change after competing in an Olympic-style boxing tournament, relative to pre-tournament performance. As many of the tasks employed in our testing battery are novel, practice effects may have contributed to improved performance. Given the relatively short time frame between assessments, clinicians should be aware of potential practice effects when using ringside tests in the diagnosis and management of concussion.