Syntheses of aza analogs of kainoids

The kainoids are a class of non-proteinogenic pyrrolidine dicarboxylates that exhibit both excitatory and excitotoxic activities. These activities are a result of the ability of the kainoids to act as glutamate receptor agonists by activating ionotropic glutamate receptors. The parent of this group of compounds is α-kainic acid. Kainic acid is isolated from the seaweed Diginea simplex and has been used in Asian countries as a treatment for intestinal worms in children. In addition it is used extensively by neuropharmacologists for the study of glutamate receptors. Several years ago, the world's sole supplier of kainic acid discontinued this product. Since that time, other sources have appeared, however, the price of kainic acid remains significantly higher than it once was. We have thus been working on synthesizing aza analogs of kainoids which would be less costly but potentially potent alternatives to kainic acid via the dipolar cycloadditions of diazoalkanes with trans diethyl glutaconate. These 1, 3-dipolar cycloadditions yielded 2-pyrazolines or pyrazoles. The 2-pyrazolines may be precursors to aza analogs of kainoids. The regioselectivity of these 1, 3-dipolar cycloadditions and isomerization of the 1-pyrazolines to 2-pyrazolines was evaluated. Reductions of the 2-pyrazolines yielded aza analogs of kainoids.^ TMS diazomethane, due to the commercial availability, has been frequently used as a synthetic reagent in 1, 3-dipolar cycloadditions, particularly in the preparation of novel amino acid analogs. A survey of the recent literature indicates that the regioselectivity of the double bond isomerization of TMS substituted 1-pyrazolines is variable and at first glance, unpredictable. In an effort to develop a mechanistic rational for the isomerization which could account for the products obtained, a systematic survey of dipolar cycloadditions between TMS diazomethane and α, β-unsaturated dipolarophiles was undertaken. It was suggested that the steric demand of the dipolarophiles had a profound effect on both the relative stereochemistry of dipolar cycloaddition reactions of TMSCHN2 and the preferred direction of isomerization of the resulting 1-pyrazoline.^

Characterizing Internet worm spatial-temporal infection structures

Since the Morris worm was released in 1988, Internet worms continue to be one of top security threats. For example, the Conficker worm infected 9 to 15 million machines in early 2009 and shut down the service of some critical government and medical networks. Moreover, it constructed a massive peer-to-peer (P2P) botnet. Botnets are zombie networks controlled by attackers setting out coordinated attacks. In recent years, botnets have become the number one threat to the Internet. The objective of this research is to characterize spatial-temporal infection structures of Internet worms, and apply the observations to study P2P-based botnets formed by worm infection. First, we infer temporal characteristics of the Internet worm infection structure, i.e., the host infection time and the worm infection sequence, and thus pinpoint patient zero or initially infected hosts. Specifically, we apply statistical estimation techniques on Darknet observations. We show analytically and empirically that our proposed estimators can significantly improve the inference accuracy. Second, we reveal two key spatial characteristics of the Internet worm infection structure, i.e., the number of children and the generation of the underlying tree topology formed by worm infection. Specifically, we apply probabilistic modeling methods and a sequential growth model. We show analytically and empirically that the number of children has asymptotically a geometric distribution with parameter 0.5, and the generation follows closely a Poisson distribution. Finally, we evaluate bot detection strategies and effects of user defenses in P2P-based botnets formed by worm infection. Specifically, we apply the observations of the number of children and demonstrate analytically and empirically that targeted detection that focuses on the nodes with the largest number of children is an efficient way to expose bots. However, we also point out that future botnets may self-stop scanning to weaken targeted detection, without greatly slowing down the speed of worm infection. We then extend the worm spatial infection structure and show empirically that user defenses, e.g. , patching or cleaning, can significantly mitigate the robustness and the effectiveness of P2P-based botnets. To counterattack, we evaluate a simple measure by future botnets that enhances topology robustness through worm re-infection.