Immune stimulatory oligodeoxynucleotides (ODN) with unmethylated CpG motifs are potent inducers of both innate and adaptive immunity. It initially appeared that a single type of optimal CpG motif would work in all applications. We now report that specific motifs of CpG ODN can vary dramatically in their ability to induce individual immune effects and that these differences impact on their antitumor activity in different tumor models. In particular, a distinct type of CpG motif, which has a chimeric backbone in combination with poly(G) tails, is a potent inducer of NK lytic activity but has little effect on cytokine secretion or B cell proliferation. One such NK-optimized CpG ODN (1585) can induce regression of established melanomas in mice. Surprisingly, no such therapeutic effects were seen with CpG ODN optimized for activation of B cells and Th1-like cytokine expression (ODN 1826). The therapeutic effects of CpG 1585 in melanoma required the presence of NK but not T or B cells and were not associated with the induction of a tumor-specific memory response. In contrast, CpG 1826, but not CpG 1585, was effective at inducing regression of the EL4 murine lymphoma; this rejection was associated with the induction of a memory response and although NK cells were necessary, they were not sufficient. These results demonstrate that selection of optimal CpG ODN for cancer immunotherapy depends upon a careful analysis of the cellular specificities of various CpG motifs and an understanding of the cellular mechanisms responsible for the antitumor activity in a particular tumor.

a b s t r a c tIn this paper, we develop a new non-ordinary state-based peridynamic method to solve transient dynamic solid mechanics problems. This new peridynamic method has advantages over the previously developed bond-based and ordinary state-based peridynamic methods in that its bonds are not restricted to central forces, nor is it restricted to a Poisson's ratio of 1/4 as with the bond-based method. First, we obtain non-local nodal deformation gradients that are used to define nodal strain tensors. The deformation gradient tensors are used with the nodal strain tensors to obtain rate of deformation tensors in the deformed configuration. The polar decomposition of the deformation gradient tensors are then used to obtain the nodal rotation tensors which are used to rotate the rate of deformation tensors and previous Cauchy stress tensors into an unrotated configuration. These are then used with conventional Cauchy stress constitutive models in the unrotated state where the unrotated Cauchy stress rate is objective. We then obtain the unrotated Cauchy nodal stress tensors and rotate them back into the deformed configuration where they are used to define the forces in the nodal connecting bonds. As a first example we quasi-statically stretch a bar, hold it, and then rotate it ninety degrees to illustrate the methods finite rotation capabilities. Next, we verify our new method by comparing small strain results from a bar fixed at one end and subjected to an initial velocity gradient with results obtained from the corresponding onedimensional small strain analytical solution. As a last example, we show the fracture capabilities of the method using both a notched and un-notched bar.

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We conducted an experimental and analytical study to understand the mechanisms and dominant parameters for ogive-nose rods and 7.62 mm APM2 bullets that perforate 5083-H116 aluminum armor plates. The 20-mmdiameter, 95-mm-long, ogive-nose, 197 g, hard steel rods were launched with a gas gun to striking velocities between 230-370 m/s. The 7.62-mm-diameter, 10.7 g, APM2 bullet consists of a brass jacket, lead filler, and a 5.25 g, ogivenose, hard steel core. The brass and lead were stripped from the APM2 bullets by the targets, so we conducted ballistic experiments with both the APM2 bullets and only the hard steel cores. These projectiles were fired from a rifle to striking velocities between 480-950 m/s. Targets were 20, 40, and 60-mm-thick, where the 40 and 60-mm-thick targets were made up of layered 20-mm-thick plates in contact with each other. The measured ballistic-limit velocities for the APM2 bullets were 4, 6, and 12% smaller than that for the hard steel cores for the 20, 40, and 60-mmthick targets, respectively. Thus, the brass jacket and lead filler had a relatively small effect on the perforation process. In addition, we conducted large strain, compression tests on the 5083-H116 aluminum plate material for input to perforation equations derived from a cavityexpansion model for the ogive-nose rods and steel core projectiles. Predictions for the rod and hard steel core projectiles are shown to be in good agreement with measured ballistic-limit and residual velocity data. These experimental results and perforation equations display the dominant problem parameters.