Disparities between Antibody Occupancy,Orientation, and Cytotoxicity in Immunotherapy

We report fusion proteins designed to bind spatially distinct epitopes on the extracellular portion of HER2, a breast cancer biomarker and established therapeutic target, and recruit IgG (either anti-His₆ or serum IgG) to the cell surface. When the proteins were incubated with anti-His₆ antibody and various concentrations of a single HER2-binding protein His₆ fusion, we observed interference and a decrease in antibody recruitment at HER2-binding protein concentrations exceeding ∼30 nM. In contrast, concomitant treatment with two or three distinct HER2-binding protein His₆ fusions, and anti-His₆, results in increased antibody recruitment, even at relatively high HER2-binding protein concentration. In some instances, increased antibody recruitment leads to increased antibody-dependent cellular cytotoxicity (ADCC) activity. While a fusion protein consisting of a HER2-binding nanobody and Sac7d, a protein evolved to recognize the Fc domain of IgG, binds IgG from serum, antibody recruitment does not lead to ADCC activity. Rationales for these disparities are provided. Collectively, our findings have implications for the design of efficacious targeted immunotherapeutic biologics, and ensembles thereof.     

Speed enhancement techniques for Clock-Delayed Dual Keeper Domino logic style

ABSTRACT

Domino circuit topology for high-speed operation, robustness and lower power consumption is quintessential in design of digital systems. In this paper, various high speed and robust mechanisms are proposed to enhance the speed of Clock-Delayed Dual Keeper Domino (CDDK) circuit. Delayed enabling of keeper circuit in CDDK domino circuit reduces contention between keeper circuit and Pull-Down network (PDN). The speed of transition at the dynamic node of the CDDK domino circuit is enhanced through imposing techniques namely (i) controlled clock delay time in enabling the keeper transistor, (ii) keeper control signal voltage swing variation, (iii) sizing of keeper transistors and (iv) deploying an additional conditional discharge path. The robustness of CDDK circuit is increased by upsizing the keeper transistor without degrading the speed by stack arrangement of dual keeper transistors. The simulation of enhancement techniques has been performed using Cadence® Virtuoso ADEL and ADEXL environments employing UMC 90nm technology library. The simulation results of wide fan-in 64-input OR gate demonstrate that CDDK technique with additional discharge path offer 38% increase in speed and CDDK technique with keeper transistor upsizing offers 52% increase in noise gain margin without speed degradation while comparing with the conventional domino logic circuit.     

Enhancement of mechanical properties and chemical durability of Soda-lime silicate glasses treated by DC gas discharges

We report for the first time a study on non-contact thermal poling of soda lime silicate glasses using DC gas discharge. In this work, the formation of a glow discharge is evidenced during the thermal poling treatment (longer than 30 minutes). The hardness and the chemical durability of glasses poled under different conditions (contact or non-contact) and atmospheres (nitrogen or air) are measured and compared to that of un-poled reference glass. The results reveal enhanced mechanical and chemical properties for samples poled under nitrogen as compare to air poled or soda lime silicate glass samples. A structural and chemical analysis of surface of the glass using IR-reflectance measurement and ToF-SIMS is also presented. The formation of a “silica-like” layer on the surface of nitrogen poled glasses is observed, which is likely associated with the enhancement of surface properties. On the other hand, the introduction of protons beneath the surface of glasses poled under air leads to the formation of a hydrated alkaline earth silica layer. Based on the observations a mechanism behind the sustainability of the plasma under DC conditions is proposed.     

Characterization of biodegradable core–clad borosilicate glass fibers with round and rectangular cross-section

Here, we report on core–clad bioactive borosilicate fibers, that we have prepared both with round and rectangular cross-section profile. The exposed approach, which relies on the stacking and drawing of glass slabs, demonstrates our ability to develop bioactive-based glass fibers with tailored cross-section profiles. Tens-of-meters-long fibers were successfully drawn, although suffering from elevated losses in the case of the rectangular ones. The response of the fibers in simulated body fluid was studied for both geometries. We found that a round cladding can act as protective layer, tempering effects of the corrosion. We also noticed that rectangular fibers are more prone to degradation, the enhanced corrosion beginning from their sharp corners as they accumulated residual tensile stress during drawing. To the best of our knowledge, this is the first report on the effect of residual tensile stresses from surface tension deformations applied to the corrosion of rectangular fibers. As geometry plays a critical role on the biodegradation behavior of the fiberglass, we believe the enclosed results could lead to the design of fiber devices with tailored cross-section profile in order to tune their rate of degradation on solely based geometrical effects.     

The effects of environmental factors on the prevalence and diversity of bacteriophages lytic against the top six non-O157 Shiga toxin-producing Escherichia coli on an organic farm

Bacteriophages (or phages) specific to Shiga toxin-producing Escherichia coli (STEC) strains are frequently isolated from animal-associated environments primarily because ruminant animals are the natural reservoir of STEC. However, little is known about these phages in produce-growing environments. The objective of this study was to determine the effects of environmental factors on the prevalence of the phages lytic against O157 and the top six non-O157 STEC on an organic farm. A total of 370 samples were collected from an organic farm, containing animal-active and produce-growing areas, for 1 year. A bacterial cocktail, including nonpathogenic and pathogenic E. coli strains, was used for phage isolation. Meanwhile, culture methods and PCR were used to isolate STEC strains. Weather information was also collected for each sampling trip. Twenty-eight samples contained phages lytic against STEC (or STEC-infecting phages), of which 26 were collected from the animal-active area. Moreover, the winter season had a higher phage prevalence than other seasons, likely due to high rain precipitation. The phages belonging to the Myoviridae family and those lytic against STEC O103 were the most prevalent. One E. coli O103:H2 was isolated from a water sample where no STEC O103-infecting phages were found. Additionally, no STEC O103 was present in the samples containing STEC O103-infecting phages. The findings indicate that animal is the primary factor contributing to the prevalence of the STEC-infecting phages in the surrounding environment of the organic farm, and the presence of these phages contributes to a negative correlation with their STEC hosts.