Function and Distribution of Apolipoprotein A1 in The Artery Wall Are Markedly Distinct From Those in Plasma

Background—Prior studies show that apolipoprotein A1 (apoA1) recovered from human atherosclerotic lesions is highly oxidized. Ex vivo oxidation of apoA1 or high-density lipoprotein (HDL) cross-links apoA1 and impairs lipid binding, cholesterol efflux, and lecithin-cholesterol acyltransferase activities of the lipoprotein. Remarkably, no studies to date directly quantify either the function or HDL particle distribution of apoA1 recovered from the human artery wall. Methods and Results—A monoclonal antibody (10G1.5) was developed that equally recognizes lipid-free and HDL-associated apoA1 in both native and oxidized forms. Examination of homogenates of atherosclerotic plaque–laden aorta showed \u3e100-fold enrichment of apoA1 compared with normal aorta (P\u3c0.001). Surprisingly, buoyant density fractionation revealed that only a minority (\u3c3% of total) of apoA1 recovered from either lesions or normal aorta resides within an HDL-like particle (1.063≤d≤1.21). In contrast, the majority (\u3e90%) of apoA1 within aortic tissue (normal and lesions) was recovered within the lipoprotein-depleted fraction (d\u3e1.21). Moreover, both lesion and normal artery wall apoA1 are highly cross-linked (50% to 70% of total), and functional characterization of apoA1 quantitatively recovered from aorta with the use of monoclonal antibody 10G1.5 showed ≈80% lower cholesterol efflux activity and ≈90% lower lecithin-cholesterol acyltransferase activity relative to circulating apoA1. Conclusions—The function and distribution of apoA1 in human aorta are quite distinct from those found in plasma. The lipoprotein is markedly enriched within atherosclerotic plaque, predominantly lipid-poor, not associated with HDL, extensively oxidatively cross-linked, and functionally impaired

Function and Distribution of Apolipoprotein A1 in The Artery Wall Are Markedly Distinct From Those in Plasma

Background—Prior studies show that apolipoprotein A1 (apoA1) recovered from human atherosclerotic lesions is highly oxidized. Ex vivo oxidation of apoA1 or high-density lipoprotein (HDL) cross-links apoA1 and impairs lipid binding, cholesterol efflux, and lecithin-cholesterol acyltransferase activities of the lipoprotein. Remarkably, no studies to date directly quantify either the function or HDL particle distribution of apoA1 recovered from the human artery wall. Methods and Results—A monoclonal antibody (10G1.5) was developed that equally recognizes lipid-free and HDL-associated apoA1 in both native and oxidized forms. Examination of homogenates of atherosclerotic plaque–laden aorta showed \u3e100-fold enrichment of apoA1 compared with normal aorta (P\u3c0.001). Surprisingly, buoyant density fractionation revealed that only a minority (\u3c3% of total) of apoA1 recovered from either lesions or normal aorta resides within an HDL-like particle (1.063≤d≤1.21). In contrast, the majority (\u3e90%) of apoA1 within aortic tissue (normal and lesions) was recovered within the lipoprotein-depleted fraction (d\u3e1.21). Moreover, both lesion and normal artery wall apoA1 are highly cross-linked (50% to 70% of total), and functional characterization of apoA1 quantitatively recovered from aorta with the use of monoclonal antibody 10G1.5 showed ≈80% lower cholesterol efflux activity and ≈90% lower lecithin-cholesterol acyltransferase activity relative to circulating apoA1. Conclusions—The function and distribution of apoA1 in human aorta are quite distinct from those found in plasma. The lipoprotein is markedly enriched within atherosclerotic plaque, predominantly lipid-poor, not associated with HDL, extensively oxidatively cross-linked, and functionally impaired

Nanoparticles Containing a Liver X Receptor Agonist Inhibit Inflammation and Atherosclerosis

Liver X receptor (LXR) signaling pathways regulate lipid metabolism and inflammation, which has generated widespread interest in developing synthetic LXR agonists as potential therapeutics for the management of atherosclerosis. In this study, we demonstrate that nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (NP-LXR) exert anti-inflammatory effects and inhibit the development of atherosclerosis without causing hepatic steatosis. These NPs were engineered through self-assembly of a biodegradable diblock poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-b-PEG) copolymer. NP-LXR was significantly more effective than free GW3965 at inducing LXR target gene expression and suppressing inflammatory factors in macrophages in vitro and in vivo. Addtionally, the NPs elicited negligible lipogenic gene stimulation in the liver. Using the Ldlr−/− mouse model of atherosclerosis, we saw abundant co-localization of fluorescently labeled NPs within plaque macrophages following systemic administration. Notably, six intravenous injections of NP-LXR over two weeks markedly reduced the CD68-positive cell (macrophage) content of plaques (by 50%) without increasing total cholesterol or triglycerides in the liver and plasma. Together, these findings identify GW3965-encapsulated PLGA-b-PEG NPs as a promising nanotherapeutic approach to combat atherosclerosis, providing the benefits of LXR agonists without their adverse effects on hepatic and plasma lipid metabolism

Efficient traceable oblivious transfer and its applications

Oblivious transfer (OT) has been applied widely in privacy-sensitive systems such as on-line transactions and electronic commerce to protect users\u27 private information. Traceability is an interesting feature of such systems that the privacy of the dishonest users could be traced by the service provider or a trusted third party (TTP). However, previous research on OT mainly focused on designing protocols with unconditional receiver\u27s privacy. Thus, traditional OT schemes cannot fulfill the traceability requirements in the aforementioned applications. In this paper, we address this problem by presenting a novel traceable oblivious transfer (TOT) without involvement of any TTP. In the new system, an honest receiver is able to make a fixed number of choices with perfect receiver privacy. If the receiver misbehaves and tries to request more than a pre-fixed number of choices, then all his previous choices could be traced by the sender. We first give the formal definition and security model of TOT, then propose an efficient TOT scheme, which is proven secure under the proposed security model

New Vaccines Against Influenza Virus

Vaccination is one of the most effective and cost-benefit interventions that prevent the mortality and reduce morbidity from infectious pathogens. However, the licensed influenza vaccine induces strain-specific immunity and must be updated annually based on predicted strains that will circulate in the upcoming season. Influenza virus still causes significant health problems worldwide due to the low vaccine efficacy from unexpected outbreaks of next epidemic strains or the emergence of pandemic viruses. Current influenza vaccines are based on immunity to the hemagglutinin antigen that is highly variable among different influenza viruses circulating in humans and animals. Several scientific advances have been endeavored to develop universal vaccines that will induce broad protection. Universal vaccines have been focused on regions of viral proteins that are highly conserved across different virus subtypes. The strategies of universal vaccines include the matrix 2 protein, the hemagglutinin HA2 stalk domain, and T cell-based multivalent antigens. Supplemented and/or adjuvanted vaccination in combination with universal target antigenic vaccines would have much promise. This review summarizes encouraging scientific advances in the field with a focus on novel vaccine designs

Modular Verification of Protocol Equivalence in the Presence of Randomness

Security protocols that provide privacy and anonymity guarantees are growing increasingly prevalent in the online world. The highly intricate nature of these protocols makes them vulnerable to subtle design flaws. Formal methods have been successfully deployed to detect these errors, where protocol correctness is formulated as a notion of equivalence (indistinguishably). The high overhead for verifying such equivalence properties, in conjunction with the fact that protocols are never run in isolation, has created a need for modular verification techniques. Existing approaches in formal modeling and (compositional) verification of protocols for privacy have abstracted away a fundamental ingredient in the effectiveness of these protocols, randomness. We present the first composition results for equivalence properties of protocols that are explicitly able to toss coins. Our results hold even when protocols share data (such as long term keys) provided that protocol messages are tagged with the information of which protocol they belong to.Ope

Statistical nonrecursive spatial-temporal focal plane processing for background clutter suppression and target detection.

Advanced surveillance and weapon guidance systems using new mosaic sensor arrays and large scale integration (LSI) electronic data processors on the same focal plane require detection of weak targets deeply buried in background clutter noise by many tens of db's. This investigation reports on the focal plane processing techniques to accomplish these heretofore unachievable goals. Five focal plane processing algorithms are developed consisting of nonrecursive statistical spatial-temporal filters for clutter suppression followed by thresholding for initialization of target detection. These filters are based on either the minimization of mean square error criterion (for MMSE filters) or the maximization of signal to noise ratio criterion (for matched filters). Two are nonadaptive spatial filters and two are nonadaptive spatial-temporal filters. The fifth type is an adaptive spatial filter based on the minimization of mean square error criterion. These filters have been investigated analytically and by computer simulation using computer generated images containing correlated clutter noises modeled by Markov processes and also real world infrared images. Using an infrared image in the red spike spectral band, a single frame statistical spatial filter can suppress the clutter by 27 db. A five frame sequential statistical spatial-temporal filter was found to have a clutter suppression of 87 db.http://archive.org/details/statisticalnonre00evenLieutenant Commander, Israeli NavyApproved for public release; distribution is unlimited

Abuse-free optimistic contract signing

Abstract. We introduce the notion of abuse-free distributed contract signing, that is, distributed contract signing in which no party ever can prove to a third party that he is capable of choosing whether to validate or invalidate the contract. Assume Alice and Bob are signing a contract. If the contract protocol they use is not abuse-free, then it is possible for one party, say Alice, at some point to convince a third party, Val, that Bob is committed to the contract, whereas she is not yet. Contract protocols with this property are therefore not favorable to Bob, as there is a risk that Alice does not really want to sign the contract with him, but only use his willingness to sign to get leverage for another contract. Most existing optimistic contract signing schemes are not abuse-free. (The only optimistic contract signing scheme to date that does not have this property is inefficient, and is only abuse-free against an off-line attacker.) We give an efficient abuse-free optimistic contract-signing protocol based on ideas introduced for designated verifier proofs (i.e., proofs for which only a designated verifier can be convinced). Our basic solution is for two parties. We show that straightforward extensions to n>2 party contracts do not work, and then show how to construct a three-party abuse-free optimistic contract-signing protocol. An important technique we introduce is a type of signature we call a private contract signature. Roughly, these are designated verifier signatures that can be converted into universally-verifiable signatures by either the signing party or a trusted third party appointed by the signing party, whose identity and power to convert can be verified (without interaction) by the party who is the designated verifier.