Computational-Driven Epitope Verification and Affinity Maturation of TLR4-Targeting Antibodies

Toll-like receptor (TLR) signaling plays a critical role in the induction and progression of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, experimental autoimmune encephalitis, type 1 diabetes mellitus and neurodegenerative diseases. Deciphering antigen recognition by antibodies provides insights and defines the mechanism of action into the progression of immune responses. Multiple strategies, including phage display and hybridoma technologies, have been used to enhance the affinity of antibodies for their respective epitopes. Here, we investigate the TLR4 antibody-binding epitope by computational-driven approach. We demonstrate that three important residues, i.e., Y328, N329, and K349 of TLR4 antibody binding epitope identified upon in silico mutagenesis, affect not only the interaction and binding affinity of antibody but also influence the structural integrity of TLR4. Furthermore, we predict a novel epitope at the TLR4-MD2 interface which can be targeted and explored for therapeutic antibodies and small molecules. This technique provides an in-depth insight into antibody–antigen interactions at the resolution and will be beneficial for the development of new monoclonal antibodies. Computational techniques, if coupled with experimental methods, will shorten the duration of rational design and development of antibody therapeutics.     

Cumin Prevents 17β-Estradiol-Associated Breast Cancer in ACI Rats

Breast cancer (BC) is a leading cause of cancer deaths in women in less developed countries and the second leading cause of cancer death in women in the U.S. In this study, we report the inhibition of E2-mediated mammary tumorigenesis by Cuminum cyminum (cumin) administered via the diet as cumin powder, as well as dried ethanolic extract. Groups of female ACI rats were given either an AIN-93M diet or a diet supplemented with cumin powder (5% and 7.5%, w/w) or dried ethanolic cumin extract (1%, w/w), and then challenged with subcutaneous E2 silastic implants (1.2 cm; 9 mg). The first appearance of a palpable mammary tumor was significantly delayed by both the cumin powder and extract. At the end of the study, the tumor incidence was 96% in the control group, whereas only 55% and 45% animals had palpable tumors in the cumin powder and extract groups, respectively. Significant reductions in tumor volume (660 ± 122 vs. 138 ± 49 and 75 ± 46 mm³) and tumor multiplicity (4.21 ± 0.43 vs. 1.16 ± 0.26 and 0.9 ± 0.29 tumors/animal) were also observed by the cumin powder and cumin extract groups, respectively. The cumin powder diet intervention dose- and time-dependently offset E2-related pituitary growth, and reduced the levels of circulating prolactin and the levels of PCNA in the mammary tissues. Mechanistically, the cumin powder diet resulted in a significant reversal of E2-associated modulation in ERα, CYP1A1 and CYP1B1. Further, the cumin powder diet reversed the expression levels of miRNAs (miR-182, miR-375, miR-127 and miR-206) that were highly modulated by E2 treatment. We analyzed the composition of the extract by GC/MS and established cymene and cuminaldehyde as major components, and further detected no signs of gross or systemic toxicity. Thus, cumin bioactives can significantly delay and prevent E2-mediated mammary tumorigenesis in a safe and effective manner, and warrant continued efforts to develop these clinically translatable spice bioactives as chemopreventives and therapeutics against BC.     

Facile Deposition of Silver Nanoparticles on Photonic Cellulose Nanocrystals Films: A Study on Solvent Stability and Post Antibacterial Activity

Cellulose nanocrystals (CNCs) incorporated with silver nanoparticles (AgNPs) photonic films have drawn considerable attention due to their plasmonic chiroptical activity. However, the exploitation of some fundamental properties for practical use such as the affinity analysis of metal nanoparticles attached to the surface of photonic films according to the solvent compatibility and antibacterial activity under physical conditions has yet not been studied. Hence, a facile process of in situ deposition of AgNPs into the chiral structure of CNC films is proposed. CNC photonic films, cross-linked by glutaraldehyde are prepared. This interaction generated the solvents-stable photonic film with a considerable amount of unreacted aldehyde functional groups that facilitates the reduction of Ag salt to AgNPs. The formed AgNPs in the photonic films show excellent stability over immersion in various polar and non-polar solvents. The post-solvent treated photonic films display excellent contact-based antibacterial behavior against gram-negative Escherichia coli.     

Radiation-induced wood plastic composites under combinations of monomers

Radiation-induced wood plastic composites (WPC) were prepared from five varieties of Bangladeshi timbers, using seven different types of monomers. The mixtures of double and triple monomers were investigated along with the single-monomer system for the preparation of composites. Among the three systems, single-monomer process showed the highest polymer loading with butylmethacrylate (BMA). Tensile strength (TS) property, represented as T_f = TS_wpc/TS_wood was determined. Highest T_f values were achieved with the soft wood. The effects of dose and dose rate, monomer concentration, and swelling agent were also studied. Suitable total dose was found to be 3 Mrad at 0.8 Mrad/h, and methanol exhibited the best swelling ability for the woods at a ratio of 1 : 9 v/v in all the monomer investigated.     

Ricinoleic acid inPhyllanthus niruri seed oil

Seed oil ofPhyllanthus niruri (Euphorbiaceae) contains 1.2% ricinoleic (12-hydroxy-cis-9-octadecenoic) acid, previously unknown in the genusPhyllanthus. Identification is based on thin layer and gas liquid chromatography, infrared, nuclear magnetic resonance, and mass spectrometry analysis as well as chemical methods. Other major components of the oil are linoleic acid (21%) and linolenic acid (51.4%). Presented at the ISF/AOCS World Congress, April 1980, New York City.     

Reaction of Hydrogen Bromide with Long Chain 1,2-Diols

The reactions of 1,2-hexadecanediol and 1,2-octadecanediol with hydrogen bromide in the presence of acetic anhydride have been investigated. The treatment of hydrogen bromide (48%) in acetic anhydride with 1,2-hexadecanediol gives mainly 1-bromo-2-acetoxy hexadecane (66%), 2-acetoxy hexadecanol (26%), and 1,3-hexadecanediol (8%). Similar products result from 1,2-octadecanediol. The structures of the products are based on combustion data, spectroscopic, and chemical evidences. The mechanism of the reaction has been discussed.     

Ambient‐cured polyesteramide‐based anticorrosive coatings from linseed oil—A sustainable resource

Ambient‐cured polyesteramide (APEA) coating resin synthesized from dihydroxy fatty amide obtained from linseed oil, a sustainable resource, and poly(styrene‐co‐maleic anhydride), a bifunctional acid component, was found to exhibit improved physicomechanical and anticorrosive properties. The structural elucidation of APEA resin has been carried out by FTIR, ¹H‐NMR, and ¹³C‐NMR spectroscopies. The physicomechanical and chemical resistance properties were investigated by standard methods. The corrosion resistance performance was evaluated in acid, alkali, and organic solvent. The thermal behavior was studied by TGA technique. A comparative study of these properties of APEA with reported baked polyesteramide (PEA) coatings was carried out. A remarkable improvement in the drying property of APEA was observed. The APEA coatings also showed improved physicomechanical and anticorrosive properties as compared to the baked PEA coatings. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 1818–1824, 2005     

Overview of Fine-Scale Piezoelectric Ceramic/Polymer Composite Processing

In the past two decades, piezoelectric ceramic/polymer composites with different connectivities have been developed for transducer applications such as hydrophones, biomedical imaging, nondestructive testing, and air imaging. Recently, much attention has been given to fine-scale piezoelectric ceramic/polymer composites. These composites allow higher operating frequencies, and thus increased resolution, in medical imaging transducers. In this review, methods for processing fine-scale piezoelectric ceramic/polymer composites are discussed. The current capabilities, strengths, and weaknesses of each method are compared. The importance of spatial scale in composite performance is also reviewed. Several of the processing methods have demonstrated composites with fine-scale ceramic phases (<50 μm), and others have potential to form composites with a ceramic scale of under 20 μm.     

Thermoelectric properties of SbNCa3 and BiNCa3 for thermoelectric devices and alternative energy applications

Thermoelectric properties of two antiperovskites SbNCa₃ and BiNCa₃ are calculated using first principles calculations. High values of Seebeck coefficients are observed for these materials. Electrical and thermal conductivities are also calculated. Increase in thermal conductivity and decrease in electrical conductivity are found with increasing temperature. The maximum values of thermal conductivity are 92×10¹⁴  W/m K s and 88×10¹⁴  W/m K s for SbNCa₃ and BiNCa₃ respectively at a temperature of 900 K. The peak values of 5×10²⁰/Ω m s and 5.2×10²⁰/Ω m s are achieved for n-type SbNCa₃ and BiNCa₃ respectively at a temperature of 300 K. Figure of merit is achieved for these materials at room temperature which shows that these materials can be useful for thermoelectric devices and alternative energy sources.     

Growth and formation mechanism of sea urchin-like ZnO nanostructures on Si

Sea urchin-like nanostructures of ZnO consisting of ZnO nanowires with blunt faceted ends were grown on Si (100) substrates by oxidation of metallic Zn at 600 °C. ZnO nanowires having a diameter of 30–60 nm and length of 2–4 Μm were in similar shape with uniform diameter along its entire length with well faceted blunt ends. X-ray diffraction and transmission electron microscope analysis showed that the as-grown nanostructures were highly crystalline with wurtzite hexagonal structure having lattice constants of a=b=3.25 å and c=5.21 å. Room temperature photoluminescence (PL) measurements showed a weak near band-edge emission at 380 nm, but a strong green emission at 500–530 nm. A model for vapor-solid (VS) growth mechanism of ZnO nanowires was presented, in which nucleation of ZnO is crucial for the growth of the nanostructures.