Immunogenicity of MultiTEP-Platform-Based Recombinant Protein Vaccine,PV-1950R,Targeting Three B-Cell Antigenic Determinants of Pathological α-Synuclein

Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are characterized by the aberrant accumulation of intracytoplasmic misfolded and aggregated α-synuclein (α-Syn), resulting in neurodegeneration associated with inflammation. The propagation of α-Syn aggregates from cell to cell is implicated in the spreading of pathological α-Syn in the brain and disease progression. We and others demonstrated that antibodies generated after active and passive vaccinations could inhibit the propagation of pathological α-Syn in the extracellular space and prevent/inhibit disease/s in the relevant animal models. We recently tested the immunogenicity and efficacy of four DNA vaccines on the basis of the universal MultiTEP platform technology in the DLB/PD mouse model. The antibodies generated by these vaccines efficiently reduced/inhibited the accumulation of pathological α-Syn in the different brain regions and improved the motor deficit of immunized female mice. The most immunogenic and preclinically effective vaccine, PV-1950D, targeting three B-cell epitopes of pathological α-Syn simultaneously, has been selected for future IND-enabling studies. However, to ensure therapeutically potent concentrations of α-Syn antibodies in the periphery of the vaccinated elderly, we developed a recombinant protein-based MultiTEP vaccine, PV-1950R/A, and tested its immunogenicity in young and aged D-line mice. Antibody responses induced by immunizations with the PV-1950R/A vaccine and its homologous DNA counterpart, PV-1950D, in a mouse model of PD/DLB have been compared.     

Volume Expansion of Compacted Graphite Iron Induced by Pearlite Decomposition and the Effect of Oxidation at Elevated Temperature

Engine cylinder blocks and heads, made of compacted graphite iron, are subjected to prolonged periods of cyclic heating and cooling. These conditions may give rise to the decomposition of the pearlite matrix accompanied by the formation of lower-density graphite and oxides, which will lead to an increase of material volume. The microstructural instability deteriorates the physical and mechanical properties of CGI and accordingly the thermal fatigue properties. In the present work it was shown that the extent and mechanism of volume change are drastically affected by the presence of an oxide atmosphere. It was found that after annealing under atmospheric conditions internal oxidation largely inhibited the progress of pearlite decomposition and therefore much smaller growth rates were obtained as compared to those observed under vacuum conditions in the dilatometer. After 16 h of annealing time at 700 °C in vacuum, the CGI samples exhibited 6 times faster growth kinetics as compared to annealing in open atmosphere.     

Mechanics of Intermittent Plasticity Punctuated by Fracture During Shear Deformation of Mg Alloys at Near-Ambient Temperatures

Microstructure evolution of basal-textured Mg alloy AZ31B (Mg: Al: Zn; 96: 3: 1 wt pct) during simple shear deformation at near-ambient temperatures was studied by plane-strain machining. Using Schmid factor calculations in conjunction with quantitative electron microscopy, it was found that plastic deformation in AZ31B in the primary deformation zone of machining commences by extension twinning followed by basal slip. Characteristics of twinning in individual grains were described by correlating the direction of twinning with the principal stress state. The implications of these deformation mechanics for the microstructure inherited by the freshly generated surfaces in shear-based material removal processes are examined. These include the identification of extensive surface texture reorientation at machined surfaces via extension twins, limits on surface integrities wrought by fracture events that punctuate plastic deformation, and their relationship to the cutting tool geometry.     

A modified sliding-mode observer design with application to diffusion equation

In many physical systems, the system's full state cannot be measured. An observer is designed to reconstruct the state from measurements. Disturbances often contribute to the dynamics of the system, and the designed observer must account for them. In this paper, a modified sliding-mode observer (SMO), a robust observer, is proposed that combines the efficiency of a nonlinear observer with the robustness of an SMO. The estimation error is proven to converge to zero under natural assumptions. This improved observer is compared with an extended Kalman filter and an unscented Kalman filter, as well as a standard SMO for three different versions of heat equation: a linear, a quasi-linear, and a nonlinear heat equation. The comparisons are done with and without an external disturbance. The simulations show improved performance of the modified SMO over other observers.     

Density-Dependence of Surface Transport in Tellurium-Enriched Nanograined Bulk Bi2Te3

Three-dimensional topological insulators (3D TI) exhibit conventional parabolic bulk bands and protected Dirac surface states. A thorough investigation of the different transport channels provided by the bulk and surface carriers using macroscopic samples may provide a path toward accessing superior surface transport properties. Bi₂Te₃ materials make promising 3D TI models; however, due to their complicated defect chemistry, these materials have a high number of charge carriers in the bulk that dominate the transport, even as nanograined structures. To partially control the bulk charge carrier density, herein the synthesis of Te-enriched Bi₂Te₃ nanoparticles is reported. The resulting nanoparticles are compacted into nanograined pellets of varying porosity to tailor the surface-to-volume ratio, thereby emphasizing the surface transport channels. The nanograined pellets are characterized by a combination of resistivity, Hall- and magneto-conductance measurements together with (THz) time-domain reflectivity measurements. Using the Hikami-Larkin-Nagaoka (HLN) model, a characteristic coherence length of ≈200 nm is reported that is considerably larger than the diameter of the nanograins. The different contributions from the bulk and surface carriers are disentangled by THz spectroscopy, thus emphasizing the dominant role of the surface carriers. The results strongly suggest that the surface transport carriers have overcome the hindrance imposed by nanoparticle boundaries.     

Fecal Microbiota Transplantation during and Post-COVID-19 Pandemic

COVID-19 is a major pandemic facing the world today, which has implications on current microbiome-based treatments such as fecal microbiota transplantation (FMT) used for recurrent Clostridioides difficile infections. The bidirectional relationship between the inhabitants of our gut, the gut microbiota, and COVID-19 pathogenesis, as well as the underlying mechanism involved, must be elucidated in order to increase FMT safety and efficacy. In this perspective, we discuss the crucial cross-talk between the gut microbiota and the lungs, known as the gut–lung axis, during COVID-19 infection, as well as the putative effect of these microorganisms and their functional activity (i.e., short chain fatty acids and bile acids) on FMT treatment. In addition, we highlight the urgent need to investigate the possible impact of COVID-19 on FMT safety and efficacy, as well as instilling stringent screening protocols of donors and recipients during COVID-19 and post-COVID-19 pandemic to produce a cohesive and optimized FMT treatment plan across all centers and in all countries across the globe.     

Modeling the inactivation of Bacillus cereus by infrared radiation in paprika powder (Capsicum annuum)

Infrared (IR) irradiation, a novel technology for modeling of decontamination of Bacillus cereus in paprika powder was evaluated and the effect on temperature profiles and total phenolic content was determined. The highest reduction in B. cereus count (2.3 log CFU/g) was achieved after a holding time of 1 min at 200 W IR power and 5 cm distance. The rapid rise in temperature was observed in surface paprika powder and the highest temperature at 200 W IR power and 5 cm distance reaching to 127.8°C. An increase in IR power and a decrease in sample distance of the IR lamp caused a significant decrease in the total phenolic content. The Double Weibull model closely predicted the inactivation of B. cereus in paprika powder by IR irradiation.     

Effect of Eryngium caeruleum essential oil on microbial and sensory quality of minced fish and fate of Listeria monocytogenes during the storage at 4°C

The present study investigated in vitro antimicrobial activity of Eryngium caeruleum essential oil (EEO) against five foodborne pathogenic bacteria based on microdilution and disk diffusion methods. Moreover, its effects on specific spoilage microorganisms, inoculated Listeria monocytogenes, and its sensory changes in minced fish were evaluated during 12 days of storage at refrigeration temperature. The results showed that Staphylococcus aureus and Escherichia coli were the most sensitive and the most resistant bacteria with a minimum inhibitory concentration of 0.125 and 1 mg/ml, as well as inhibition zones of 15.66 and 11.66 mm, respectively. Regarding the antimicrobial effect of EEO on the microbial profile and inoculated L. monocytogenes, treating with 0.4% EEO caused a significant decrease in the studied microorganisms when compared to the control group (p < 0.05). In addition, considering the sensory evaluation, the best scores were observed for the samples treated with 0.2% and 0.4% EEO. However, none of the groups obtained acceptable scores until the final day of storage except for the color attribute. In general, sensory evaluation and its correlation with microbial counting indicated that the treatment with 0.4% EEO was able to preserve the microbial quality of the minced fish at refrigeration temperature without any undesirable sensory effects.