Applied Science Laboratories (United States)

BackgroundOften thought of as a minor health concern, sore throat or pharyngitis is an important public health issue. It is one of the most common symptoms of upper respiratory diseases including COVID‐19 and is a leading cause of physician visits and antibiotic prescriptions. However, few over‐the‐counter medications are proven to heal sore throat inflammation.MethodsAdenocarcinomic human alveolar basal epithelial cells (A549 cells) and three dimensional organotypic human respiratory tissues were used to study inflammation and various treatment effects on respiratory epithelia. The cells and tissues were studied both in the presence and absence of bradykinin, one of the first inflammatory mediators of pharyngitis. Inflammation was measured by analyzing the levels of prostaglandin E2 (PGE2), interleukin 8 (IL‐8), and leukotriene B4 (LTB4), transepithelial electrical resistance (TEER), and lactate dehydrogenase (LDH) release. Tissue morphology was analyzed by immunohistochemistry.ResultsIn studying pharyngitis using organotypic human respiratory tissue stimulated with bradykinin, we saw an increase in PGE2 and interleukin‐8 (IL‐8) in response to bradykinin. Acetyl salicylic acid (ASA), a nonspecific COX inhibitor, was able to mitigate a bradykinin‐induced increase in PGE2 in our studies. However, ASA was inflammatory above its therapeutic window, increasing the levels of PGE2 and IL‐8 above those seen with bradykinin stimulation alone. We describe a novel, scientifically validated treatment for sore throat, that contains a low dose of ASA and other anti‐inflammatory ingredients.ConclusionThis study elucidates the complex mechanisms involved in healing pharyngitis, an inflammatory condition of the upper respiratory epithelia. An ASA‐based formula (Biovanta) mitigated bradykinin‐induced inflammation more strongly than ASA alone in organotypic human respiratory tissues. Surprisingly, we found that many of the most common over the counter sore throat therapies exacerbate inflammation and IL‐8 in organotypic human respiratory tissues, suggesting these common treatments may increase the likelihood of further respiratory complications.

Fusion genes including NPM-ALK can promote T-cell transformation, but the signals required to drive a healthy T cell to become malignant remain undefined. In this study, we introduce NPM-ALK into primary human T cells and demonstrate induction of the epithelial-to-mesenchymal transition (EMT) program, attenuation of most T-cell effector programs, reemergence of an immature epigenomic profile, and dynamic regulation of c-Myc, E2F, and PI3K/mTOR signaling pathways early during transformation. A mutant of NPM-ALK failed to bind several signaling complexes including GRB2/SOS, SHC1, SHC4, and UBASH3B and was unable to transform T cells. Finally, T-cell receptor (TCR)-generated signals were required to achieve T-cell transformation, explaining how healthy individuals can harbor T cells with NPM-ALK translocations. These findings describe the fundamental mechanisms of NPM-ALK-mediated oncogenesis and may serve as a model to better understand factors that regulate tumor formation. SIGNIFICANCE: This investigation into malignant transformation of T cells uncovers a requirement for TCR triggering, elucidates integral signaling complexes nucleated by NPM-ALK, and delineates dynamic transcriptional changes as a T cell transforms.See related commentary by Spasevska and Myklebust, p. 3160.

Welcome Message from the President of Applied Science University - Prof. Mahfuz Judeh

Abstract A novel emulsion and its preparation route were established in a quasi-ternary system with a nonionic surfactant, water, glycerol, and squalane. This emulsion is simply obtained by diluting a discontinuous cubic liquid crystal. It consists of giant floc in part, corresponding to the fraction of the discontinuous cubic liquid crystal. Contrary to common emulsification, our emulsion has an unique and abnormal shear-response: the semistable structure is breaking down gradually by applying a mechanical energy.

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The synthesis and characterization of the stable carbene perdeuterio-1,3,4,5-tetramethylimidazol-2-ylidene (2) are reported. The neutron and X-ray diffraction data from single crystals of this perdeuterocarbene are used to determine the electron distribution in the molecule. Neutron diffraction data were collected at 80 and 173K on 2. The experimentally determined electron density is very closely matched by density functional calculations which show that 2 is a true carbene with negligible ylidic character. 71 refs., 6 figs., 5 tabs.

Abstract Several 304H stainless steel superheater tubes fractured in stressed areas within hours of a severe caustic upset in the boiler feedwater system. Tests performed on a longitudinal weld joint, which connected two adjacent tubes in the tertiary superheater bank, confirmed caustic-induced stress-corrosion cracking, promoted by the presence of residual welding stresses. Improved maintenance of check valves and routine inspection of critical monitoring systems (conductivity alarms, sodium analyzers, etc.) were recommended to help avoid future occurrences of severe boiler feedwater contamination. Additional recommendations were to eliminate these short longitudinal weld joints by using a bracket assembly joint between the tubes, use a post-weld heat treatment to relieve residual welding stress or select a more stress-corrosion cracking resistant alloy for this particular application.

Abstract A type 410 stainless steel circulating water pump shaft used in a fossil power steam generation plant failed after more than 7 years of service. Visual examination showed the fracture surface to be coated with a thick, spalling, rust-colored scale, along with evidence of pitting. Samples for SEM fractography, EDS analysis, and metallography were taken at the crack initiation site. Hardness testing produced a value of approximately 27 HRC. The examinations clearly established that the shaft failed by fatigue. The fatigue crack originated at a localized region on the outside surface where pitting and intergranular cracking had occurred. The localized nature of the initial damage indicated that a corrosive medium had concentrated on the surface, probably due to a leaky seal. Reduction of hardness to 22 HRC or lower and inspection of seals were recommended to prevent future failures.

Electrochemical techniques used in the study of corrosion are particularly susceptible to errors due to IR drop when used to study systems such as the corrosion of steel in natural waters. The influence of the electrochemical measurement cell geometry on both the nature and the magnitude of the expected errors is reviewed. Also, the effect of a non uniform current distribution on the working electrode is examined. Expected errors for a range of corrosion rates and water conductivities that are typical of steel in cooling systems are presented for three types of experiments. These experiments are: simple linear polarization (polarization resistance), small range polarization, which is computer-fit to extract the corrosion rate and Tafel parameters, and full polarization.