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Big data usually means big sample size with many outliers, in which traditional scalable L2-norm principal component analysis (L2-PCA) will fail. Current existing L1-norm PCA (L1-PCA) methods can improve robustness over outliers, however, its scalability is usually limited in either sample size or dimension size.  The inventor proposes an online flipping method to solve L1-PCA challenges, which is not only convergent asymptotically (or with big data), but also achieves most efficiency in the sense each sample is visited only once to extract one principal component (PC).

Retinal Degenerations (RD) are the leading cause of blindness in the United States. The degeneration of the Retinal Pigment Epithelium (RPE) is associated with various types of RD such as Stargardt’s disease, retinitis pigmentosa, choroideremia, Late-Onset Retinal Degeneration (L-ORD), and Age-related Macular Degeneration (AMD). The RPE as a layer of cells in the back of the eye. Therefore, it is essential to maintain the health and integrity of retinal photoreceptors.

The chemokine receptor, CCR4 is a seven transmembrane G protein-coupled cell surface receptor molecule with selective expression on cells of the hematopoietic system. In adult T cell leukemia (ATL), the cell-surface expression of CCR4 on leukemic cells has been found to be nearly universal. Therefore, a CCR4-directed chimeric antigen receptor (CAR) -cell may provide an effective therapeutic against ATL.

RNA interference (RNAi) is a biological response to double-stranded RNA that regulates expression of protein-coding genes and is a natural mechanism for gene silencing. Delivery of short, interfering RNA (siRNA) leads to RNAi of the targeted genes. 

The tumor-suppressor p53 protein plays a major role in tumor development. Most human cancers fail to normally activate wild-type p53, which is at least partly responsible for the unregulated growth of cancer cells and their failure to undergo apoptosis. While many chemotherapeutics enhance p53 levels, their non-specific DNA damage (genotoxicity) causes unfavorable side effects.
 

Tumor necrosis factor receptor type 2 (TNFR2)-expressing regulatory T cells (Tregs), present in the tumor microenvironment, play an important role in tumor immune evasion. TNFR2 plays a crucial role in stimulating the activation and proliferation of Tregs, a major checkpoint of antitumor immune responses. In addition to its expression on Tregs, TNFR2 is also known to be overexpressed on some types of tumors and the survival and growth of these tumor cells is promoted by ligands of TNFR2.

Soluble forms of human CD4 (sCD4) inhibit HIV-1 entry into immune cells.  Different forms of sCD4 and their fusion proteins have been extensively studied in animal models and clinical trials as promising HIV-1 inhibitors. However, they have not been successful in clinical trials due to their transient efficacy.  sCD4 is also known to interact with class II major histocompatibility complex (MHCII) and, at low concentrations, could enhance HIV-1 infectivity. 

The HIV-positive population continues to rise despite a worldwide decline in the rates of infection caused by human immunodeficiency virus (HIV).  The HIV virus continues to spread due to a lack of effective vaccines and pre-exposure prophylaxis methods, even though the availability and effectiveness of antiretroviral therapy has helped reduce acquired immunodeficiency syndrome (AIDS)-related deaths. 

The technology is directed to compositions and methods of designing nucleic acid nanoparticles (NANPs) composed entirely of DNA, RNA, or DNA and RNA to achieve desirable immunostimulation and decrease undesirable effects on the immune system by changing the composition of the NANP. Benefits of the invention include the desirable activation of the immune system by these particles to increase the efficacy of vaccines and immunotherapies.

Englerin A, a natural product, has shown growth-inhibiting activity against renal cancer cell lines. The compound is an agonist of protein kinase C (PCK) theta, which results in cell cytotoxicity, insulin inhibition, and selective activation of viral replication in T cells.  Englerin A derivatives are promising treatment strategies for any diseases associated with PKC theta and/or ion channel proteins.