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The direct current (dc) conductivities and organic field-effect transistor (OFET) characteristics of a class of octa-substituted liquid crystalline (discotic mesophase) phthalocyanines (Pcs) are discussed. These molecules self-organize into columnar aggregates with large coherence lengths (up to approximately 300 nm). Langmuir–Blodgett films of these molecules were horizontally transferred to either interdigitated microelectrodes (IME) or OFET substrates, so that current flow could be measured either parallel or perpendicular to the column axis. Twenty-eight bilayer films of these Pcs on the IME substrates showed anisotropies in dc conductivity up to 50:1, whereas similar Pc films showed anisotropies in field effect mobilities of approximately 10:1, for a variety of W/L ratios (source/drain dimensions and spacing). Field-effect mobilities of 1 to 5 × 10-6 cm2·V-1·s-1 were determined from OFET measurements, along the Pc column axis, whereas charge mobilities measured from the space charge limited current regime on the IME substrates were in the range of 10-4 cm2·V-1·s-1. Conductive tip atomic force microscopy measurements on the apprximately 500-nm length scale showed that the conductivity anisotropy can be as high as 1000:1 when the Pc columns are intimately contacted to an adjacent Au bond pad.

Bendamustine is an alkylating agent that can form interstrand DNA crosslinks (ICLs) and cause cell death via several pathways, including intrinsic apoptosis. Bendamustine has proven to be a potent and effective treatment for patients with chronic lymphocytic leukemia (CLL) and rituximab-refractory indolent non-Hodgkin's lymphoma (NHL), with additional clinical activity seen in other B-cell malignancies and in multiple myeloma (MM). However, the activity of bendamustine in the treatment of solid tumor malignancies has been less impressive, possibly due to the pharmacokinetic and biodistribution properties of bendamustine. RXDX-107 is a dodecanol alkyl ester of bendamustine, and the clinical drug product is encapsulated in human serum albumin (HSA) to form nanoparticles. RXDX-107 was designed to improve tissue biodistribution over bendamustine, which may result in superior efficacy and tolerability in patients with solid tumors. In in vitro anti-proliferative studies, RXDX-107 displayed dose-dependent cytotoxicity against multiple solid tumor cell lines, including non-small lung cancer (NSCLC), breast and ovarian cancer. While the IC50s of RXDX-107 were comparable to those of bendamustine, RXDX-107 displayed stronger induction of pH2AX (a biomarker for DNA damage) and more complete cell killing than bendamustine in multiple cell lines. Furthermore, RXDX-107 potently inhibited subcutaneous tumor growth in cell line-derived xenograft (CDX) models of human NSCLC and breast cancer. Importantly, RXDX-107 also showed single agent anti-tumor activities, including tumor regression in multiple patient-derived xenograft (PDX) models of advanced solid tumors, such as breast, lung, and ovarian cancer. In conclusion, our preclinical data demonstrate potent and broad anti-tumor activity of RXDX-107 across a variety of solid tumor types, and support further clinical development of this novel drug candidate for the treatment of solid tumors. Citation Format: Leenus Martin, Roopal Patel, Anthony Drager, Renee Roemmele, Bradley McIntyre, Robert McKean, Piyush Patel, Peter Chua, Jerry Cao, Robert Shoemaker, Peter Brown, Pratik Multani, Robert Wild, Ralph Lin, Gang Li. RXDX-107, a dodecanol alkyl ester of bendamustine, demonstrates improved pharmacokinetic properties and significant anti-tumor efficacy in preclinical models of solid tumors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B177.

There currently exists the need for fusion systems that can provide an accurate and comprehensive assessment of military situations in real-time. The objective of this effort was to define, prototype, and demonstrate an affordable next-generation JDL Level 2 fusion and exploitation architecture. The scope of this effort included the identification of the limiting criteria in current Level 2 fusion assessment systems that inhibit them from providing real-time assessment. Using this criterion and assessment of the hardware requirements trade space, solutions were proposed consisting of both hardware and software approaches including an assessment of cost impact. The validity of the solutions were then validated by applying them to an existing state-of-the-art Level 2 fusion system, the Nodal Exploitation Application Toolkit developed by Sterling Software; Rome, NY. The effort succeeded in providing a demonstration of the prototype on a Linux Cluster at the Air Force Research Laboratorys' Rome Research Site, in Rome, NY. Performance improvements were not limited to parallelizing existing algorithms across multiple processors. The sequential algorithmic processing was optimized as well. Compared to the original software running on a Linux PC, results show 30 times speed improvement on a single processor, 63 times speed improvement when run in parallel across 4 processors.