Stealth Game !NEW! Download
Vanesa Domagala
I was wondering if it is possible to either jam radars, or somehow diminish an aircraft's radar signature, to give it stealth capabilities. I am currently working on an F-35 C-inspired stealth multi-purpose jet, and I would like to give it stealth capabilities like the real jets.
Regarding MPS uptake, Blume et al have found that the increased blood circulation time is due to a reduced interaction with plasma proteins and cell-surface proteins (Blume 1993; Vert and Domurado 2000), although other studies have found no direct evidence of this reduced interaction with plasma components (Johnstone et al 2001). One possible explanation for the reduced interaction is the steric hindrance effect, which is generated by the surface-grafted methoxy-PEG molecules. Complement fixation on PEG-bearing liposomes thus appears to occur in a cryptic location inaccessible to ligation to complement receptors. Another possible contributor to the stealth behavior of such vesicles is competition for CR3 between surface-bound and free-complement proteins iC3b. Furthermore, degradation of surface-bound C3b to fragments inhibiting recognition by phagocytic complement receptors might also explain the anti-phagocytic effect. Studies with freshly isolated macrophages have also indicated the presence of unidentified serum factors (called dysopsonins) that act synergistically with the steric barrier of long circulating particles, thereby further suppressing particle recognition by phagocytic cells (Moghimi et al 1993; Johnstone et al 2001).
Recently, S-CKD602 (Alza Corporation), a PEGylated stealth liposomal formulation of CKD-602, which is a semi-synthetic analog of camptothecin, was submitted for a Phase I trial. After administration of S-CKD602 at doses of 0.5 mg/m2, the plasma AUC was 50-fold that of non-liposomal CKD-602; S-CKD602 showed minimal toxicity and interesting activity (Zamboni et al 2005).
In order to behave in this fashion, immunoliposomes are built so as to be long-circulating and non-immunogenic, using the stealth technique. Briefly, a PEG (MW 3400) derivative of PE or DSPE containing a maleimide group at the end of the PEG chain is mixed into the liposome formulation (Figure 2). After liposome preparation, reduced thiol groups of Fab or scFv fragments are joined via surface linkage to the maleimide group of the aforementioned PEG-liposome, obtaining a stable thioether bond. This method for preparing immunoliposomes starting from preformed liposomes is the most widely used. Alternatively, commercially available doxorubicin-loaded long-circulating liposomes (DOXIL) have been modified by post-insertion of a monoclonal antibody. MAb, modified with DSPE-PEG conjugate, in which the free PEG terminus is activated with the p-nitrophenylcarbonyl group, has been inserted into preformed liposomes (Lukyanov et al 2004). Therapeutic targets and immunoliposomal compositions are reported in Table 2.
Other ligands have been used to specifically target stealth liposomes to receptors over-expressed in cancer cells. Folic acid, which has been used for liposome-specific targeting of DXR, daunorubicin, cisplatin, and other drugs, is one of the most extensively studied (for a recent review (Stephenson et al 2004)) and it has been proposed for boron neutron capture therapy (Stephenson et al 2003). Transferrin is a popular ligand for specific delivery of anticancer drugs, proteins and genes to malignant cells (Ishida et al 2001) as well as for boron neutron capture therapy (Maruyama et al 2004).
Sigma receptors (subtype of opioid receptor) have recently been proposed as an interesting target for different malignancies (breast, melanoma, prostate). An anisamide-derivatized stealth liposomal formulation (DXR) showed high specific toxicity and superior therapeutic effect versus untargeted liposomes (Banerjee et al 2004) and recently haloperidol-associated stealth liposomes can efficiently target genes to sigma receptor overexpressing breast cancer cells (Mukherjee et al 2005).
Authoritarianism has been undergoing a metamorphosis. Historically, authoritarians openly repressed opponents by violence and harassment and subverted the rule of law to perpetuate their rule. The post-Cold War crackdown on these transparently authoritarian practices provided significant incentives to avoid them. Instead, the new generation of authoritarians learned to perpetuate their power through the same legal mechanisms that exist in democratic regimes. In so doing, they cloak repressive practices under the mask of law, imbue them with the veneer of legitimacy, and render anti-democratic practices much more difficult to detect and eliminate. This Article offers a comprehensive cross-regional account of that phenomenon, which I term stealth authoritarianism. Drawing on rational-choice theory, the Article explains the expansion of stealth authoritarianism across different case studies. The Article fills a void in the literature, which has left undertheorized the authoritarian learning that occurred after the Cold War and the emerging reliance on legal, particularly sub-constitutional, mechanisms to perpetuate political power. Although stealth authoritarian practices are more prevalent in nondemocracies, the Article illustrates that they can also surface in regimes with favorable democratic credentials, including the United States. In so doing, the Article aims to orient the scholarly debate towards regime practices rather than regime types. The Article concludes by discussing the implications of stealth authoritarianism for scholars and policymakers. The existing democracy-promotion mechanisms in the United States and elsewhere are of limited use in detecting stealth authoritarian tactics. Paradoxically, these mechanisms, which have narrowly focused on eliminating transparent democratic deficiencies, have provided legal and political cover to stealth authoritarian practices and created the very conditions in which these practices thrive. In addition, stealth authoritarianism can ultimately make authoritarian governance more durable by concealing anti-democratic practices under the mask of law. At the same time, however, stealth authoritarianism is less insidious than its traditional, more repressive alternative and can, under some circumstances, produce the conditions by which democracy can expand and mature, in a two-steps-forward-one-step-backward dynamic.
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