Smoothing the Nonsmoothness

To tackle difficulties for theoretical studies in situations involving nonsmooth functions, we propose a sequence of infinitely differentiable functions to approximate the nonsmooth function under consideration. A rate of approximation is established and an illustration of its application is then provided

Monoclonal antibody humanness score and its applications

BACKGROUND: Monoclonal antibody therapeutics are rapidly gaining in popularity for the treatment of a myriad of diseases, ranging from cancer to autoimmune diseases and neurological diseases. Multiple forms of antibody therapeutics are in use today that differ in the amount of human sequence present in both the constant and variable regions, where antibodies that are more human-like usually have reduced immunogenicity in clinical trials. RESULTS: Here we present a method to quantify the humanness of the variable region of monoclonal antibodies and show that this method is able to clearly distinguish human and non-human antibodies with excellent specificity. After creating and analyzing a database of human antibody sequences, we conducted an in-depth analysis of the humanness of therapeutic antibodies, and found that increased humanness score is correlated with decreased immunogenicity of antibodies. We further discovered a surprisingly similarity in the immunogenicity of fully human antibodies and humanized antibodies that are more human-like based on their humanness score. CONCLUSIONS: Our results reveal that in most cases humanizing an antibody and confirming the humanness of the final form may be sufficient to eliminate immunogenicity issues to the same extent as using fully human antibodies. We created a public website to calculate the humanness score of any input antibody sequence based on our human antibody database. This tool will be of great value during the preclinical drug development process for new monoclonal antibody therapeutics

Theaflavin-3, 3\u27-digallate decreases human ovarian carcinoma OVCAR-3 cell-induced angiogenesis via Akt and Notch-1 pathways, not via MAPK pathways

Theaflavin-3, 3\u27-digallate (TF3) is a black tea polyphenol produced from polymerization and oxidization of the green tea ployphenols epicatechin gallate and (-)-epigallocatechin-3-gallate (EGCG) during fermentation of fresh tea leaves. TF3 has been reported to have anticancer properties. However, the effect of TF3 on tumor angiogenesis and the underlying mechanisms are not clear. In the present study, TF3 was verified to inhibit tumor angiogenesis. Compared with EGCG, TF3 was more potent. TF3 inhibited human ovarian carcinoma OVCAR-3 cell-induced angiogenesis in human umbilical vein endothelial cell model and in chick chorioallantoic membrane model. TF3 reduced tumor angiogenesis by downregulating HIF-1α and VEGF. One of the mechanisms was TF3 inactivated Akt/mTOR/p70S6K/4E-BP1 pathway and Akt/c-Myc pathway. Besides, TF3 suppressed the cleavage of Notch-1, subsequently decreased the expression of c-Myc, HIF-1α and VEGF, and finally the impaired cancer cells induced angiogenesis. Nevertheless, TF3 did not have any influence on the MAPK pathways. Taken together, these findings suggest that TF3 might serve as a potential anti-angiogenic agent for cancer treatment

Era of Digital Health: A Review of Portable and Wearable Affinity Biosensors

Digital health facilitated by wearable/portable electronics and big data analytics holds great potential in empowering patients with real‐time diagnostics tools and information. The detection of a majority of biomarkers at trace levels in body fluids using mobile health (mHealth) devices requires bioaffinity sensors that rely on “bioreceptors” for specific recognition. Portable point‐of‐care testing (POCT) bioaffinity sensors have demonstrated their broad utility for diverse applications ranging from health monitoring to disease diagnosis and management. In addition, flexible and stretchable electronics‐enabled wearable platforms have emerged in the past decade as an interesting approach in the ambulatory collection of real‐time data. Herein, the technological advancements of mHealth bioaffinity sensors evolved from laboratory assays to portable POCT devices, and to wearable electronics, are synthesized. The involved recognition events in the mHealth affinity biosensors enabled by bioreceptors (e.g., antibodies, DNAs, aptamers, and molecularly imprinted polymers) are discussed along with their transduction mechanisms (e.g., electrochemical and optical) and system‐level integration technologies. Finally, an outlook of the field is provided and key technological bottlenecks to overcome identified, in order to achieve a new sensing paradigm in wearable bioaffinity platforms