Confinement-induced nonlocality and casimir force in transdimensional systems.

We study within the framework of the Lifshitz theory the long-range Casimir force for in-plane isotropic and anisotropic free-standing transdimensional material slabs. In the former case, we show that the confinement-induced nonlocality not only weakens the attraction of ultrathin slabs but also changes the distance dependence of the material-dependent correction to the Casimir force to go as contrary to the ∼1/ dependence of that of the local Lifshitz force. In the latter case, we use closely packed array of parallel aligned single-wall carbon nanotubes in a dielectric layer of finite thickness to demonstrate strong orientational anisotropy and crossover behavior for the inter-slab attractive force in addition to its reduction with decreasing slab thickness.

Targeting folate receptor beta on monocytes/macrophages renders rapid inflammation resolution independent of root causes.

Provoked by sterile/nonsterile insults, prolonged monocyte mobilization and uncontrolled monocyte/macrophage activation can pose imminent or impending harm to the affected organs. Curiously, folate receptor beta (FRβ), with subnanomolar affinity for the vitamin folic acid (FA), is upregulated during immune activation in hematopoietic cells of the myeloid lineage. This phenomenon has inspired a strong interest in exploring FRβ-directed diagnostics/therapeutics.

Efficacy and tolerability of folate-aminopterin therapy in a rat focal model of multiple sclerosis.

Background: Activated macrophages in the experimental model of multiple sclerosis (MS) express folate receptor-β (FR-β), representing a promising target for the treatment of MS. Here, we both evaluated the efficacy of a novel folate-aminopterin construct (EC2319) in a rat focal model of multiple sclerosis (MS) and investigated the utility of Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated folate (Ga-FOL) for assessing inflammatory lesions. In addition, we investigated whether FR-β is expressed in the brain of patients with MS.

Pre-clinical studies of EC2629, a highly potent folate- receptor-targeted DNA crosslinking agent.

Folate receptor (FR)-targeted small molecule drug conjugates (SMDCs) have shown promising results in early stage clinical trials with microtubule destabilizing agents, such as vintafolide and EC1456. In our effort to develop FR-targeted SMDCs with varying mechanisms of action, we synthesized EC2629, a folate conjugate of a DNA crosslinking agent based on a novel DNA-alkylating moiety. This agent was found to be extremely potent with an in vitro IC50 ~ 100× lower than folate SMDCs constructed with various microtubule inhibitors.

Phase I/II clinical trial of the targeted chemotherapeutic drug, folate-tubulysin, in dogs with naturally-occurring invasive urothelial carcinoma.

Purpose: The purpose was to determine the safety and antitumor activity of a folate-tubulysin conjugate (EC0531) in a relevant preclinical animal model, dogs with naturally-occurring invasive urothelial carcinoma (iUC). Canine iUC is an aggressive cancer with high folate receptor (FR) expression similar to that in certain forms of human cancer.

Experimental Design: A 3+3 dose escalation study of EC0531 (starting dose 0.

Development and validation of a UPLC-MS/MS method for the novel folate-targeted small molecule drug conjugate EC1456 and its metabolites in tumor homogenates from mice.

EC1456 is a novel folate-targeted small molecule drug conjugate of tubulysin B hydrazide being developed as an anticancer agent for patients with advanced solid tumors expressing the folate receptor. To try and correlate circulating systemic levels of EC1456 and its metabolites to tumor concentrations and potentially develop a PK/PD model, a sensitive bioanalytical method was developed and validated for the quantitation of the analytes in KB tumor homogenates. The method involved homogenizing tumors with buffer containing N-maleoyl-β-alanine, mannitol and acetic acid, precipitation of the homogenate with acetone followed by heating at 55°C for 1h to convert tubulysin B hydrazide to its corresponding hydrazone.

Applied spectrophotometry: analysis of a biochemical mixture.

Spectrophotometric analysis is essential for determining biomolecule concentration of a solution and is employed ubiquitously in biochemistry and molecular biology. The application of the Beer-Lambert-Bouguer Lawis routinely used to determine the concentration of DNA, RNA or protein. There is however a significant difference in determining the concentration of a given species (RNA, DNA, protein) in isolation (a contrived circumstance) as opposed to determining that concentration in the presence of other species (a more realistic situation).

Going paperless: implementing an electronic laboratory notebook in a bioanalytical laboratory.

AIT Bioscience, a bioanalytical CRO, implemented a highly configurable, Oracle-based electronic laboratory notebook (ELN) from IDBS called E-WorkBook Suite (EWBS). This ELN provides a high degree of connectivity with other databases, including Watson LIMS. Significant planning and training, along with considerable design effort and template validation for dozens of laboratory workflows were required prior to EWBS being viable for either R&D or regulated work.

The EU precautionary bans of animal feed additive antibiotics.

Toxicologists, with good reason, will feel that the biological safety of chemical products across the market sectors rests largely on their efforts. However, one sector has received much adverse attention from the media, consumers, politicians, legislators and advisory groups in recent years. It is food animal production in intensive systems and, within those, various types of chemical additives included in the compound diets fed.