Keeping Authorities "Honest or Bust" with Decentralized Witness Cosigning

The secret keys of critical network authorities - such as time, name, certificate, and software update services - represent high-value targets for hackers, criminals, and spy agencies wishing to use these keys secretly to compromise other hosts. To protect authorities and their clients proactively from undetected exploits and misuse, we introduce CoSi, a scalable witness cosigning protocol ensuring that every authoritative statement is validated and publicly logged by a diverse group of witnesses before any client will accept it. A statement S collectively signed by W witnesses assures clients that S has been seen, and not immediately found erroneous, by those W observers. Even if S is compromised in a fashion not readily detectable by the witnesses, CoSi still guarantees S's exposure to public scrutiny, forcing secrecy-minded attackers to risk that the compromise will soon be detected by one of the W witnesses. Because clients can verify collective signatures efficiently without communication, CoSi protects clients' privacy, and offers the first transparency mechanism effective against persistent man-in-the-middle attackers who control a victim's Internet access, the authority's secret key, and several witnesses' secret keys. CoSi builds on existing cryptographic multisignature methods, scaling them to support thousands of witnesses via signature aggregation over efficient communication trees. A working prototype demonstrates CoSi in the context of timestamping and logging authorities, enabling groups of over 8,000 distributed witnesses to cosign authoritative statements in under two seconds.Comment: 20 pages, 7 figure

tlock: Practical Timelock Encryption from Threshold BLS

We present a practical construction and implementation of timelock encryption, in which a ciphertext is guaranteed to be decryptable only after some specified time has passed. We employ an existing threshold network, the League of Entropy, implementing threshold BLS [BLS01, B03] in the context of Boneh and Franklin\u27s identity-based encryption (IBE) [BF01]. At present this threshold network broadcasts BLS signatures over each round number, equivalent to the current time interval, and as such can be considered a decentralised key holder periodically publishing private keys for the IBE where identities are the round numbers. A noticeable advantage of this scheme is that only the encryptors and decryptors are required to perform any additional cryptographic operations; the threshold network can remain unaware of the TLE and does not have to change to support the scheme. We also release an open-source implementation of our scheme and a live web page that can be used in production now relying on the existing League of Entropy network acting as a distributed public randomness beacon service using threshold BLS signatures

N-Aryl-N'-(chroman-4-yl)ureas and thioureas display in vitro anticancer activity and selectivity on apoptosis-resistant glioblastoma cells: screening, synthesis of simplified derivatives, and structure-activity relationship analysis.

A series of chroman derivatives previously reported as potassium channel openers, as well as some newly synthesized simplified structures, were examined for their in vitro effects on the growth of three human high-grade glioma cell lines: U373, T98G, and Hs683. Significant in vitro growth inhibitory activity was observed with 2,2-dimethylchroman-type nitro-substituted phenylthioureas, such as compounds 4o and 4p. Interestingly, most tested phenylureas were found to be slightly less active, but more cell selective (normal versus tumor glial cells, such as 3d, 3e, and 3g), thus less toxic, than the corresponding phenylthioureas. No significant differences were observed in terms of chroman-derivative-induced growth inhibitory effects between glioma cells sensitive to pro-apoptotic stimuli (Hs683 glioma cells) and glioma cells associated with various levels of resistance to pro-apoptotic stimuli (U373 and T98G glioma cells), a feature that suggests non-apoptotic-mediated growth inhibition. Flow cytometry analyses confirmed the absence of pro-apoptotic effects for phenylthioureas and phenylureas when analyzed in U373 glioma cells and demonstrated U373 cell cycle arrest in the G0/G1 phase. Computer-assisted phase-contrast videomicroscopy revealed that 3d and 3g displayed cytostatic effects, while 3e displayed cytotoxic ones. As a result, this work identified phenylurea-type 2,2-dimethylchromans as a new class of antitumor agents to be further explored for an innovative therapeutic approach for high-grade glioma and/or for a possible new mechanism of action

Managing Identities Using Blockchains and CoSi

We combine collective signing and blockchains to create a secure and easy-to-use, decentralized SSH-key management system

OmniLedger: A Secure, Scale-Out, Decentralized Ledger via Sharding

Designing a secure permissionless distributed ledger (blockchain) that performs on par with centralized payment processors, such as Visa, is a challenging task. Most existing distributed ledgers are unable to scale-out, i.e., to grow their total processing capacity with the number of validators; and those that do, compromise security or decentralization. We present OmniLedger, a novel scale-out distributed ledger that preserves longterm security under permissionless operation. It ensures security and correctness by using a bias-resistant public-randomness protocol for choosing large, statistically representative shards that process transactions, and by introducing an efficient crossshard commit protocol that atomically handles transactions affecting multiple shards. OmniLedger also optimizes performance via parallel intra-shard transaction processing, ledger pruning via collectively-signed state blocks, and low-latency “trust-butverify” validation for low-value transactions. An evaluation of our experimental prototype shows that OmniLedger’s throughput scales linearly in the number of active validators, supporting Visa-level workloads and beyond, while confirming typical transactions in under two seconds

CHAINIAC: Proactive Software-Update Transparency via Collectively Signed Skipchains and Verified Builds

Software-update mechanisms are critical to the security of modern systems, but their typically centralized design presents a lucrative and frequently attacked target. In this work, we propose CHAINIAC, a decentralized software-update framework that eliminates single points of failure, enforces transparency, and provides efficient verifiability of integrity and authenticity for software-release processes. Independent $\textit{witness servers}$ collectively verify conformance of software updates to release policies, $\textit{build verifiers}$ validate the source-to-binary correspondence, and a tamper-proof release log stores collectively signed updates, thus ensuring that no release is accepted by clients before being widely disclosed and validated. The release log embodies a $\textit{skipchain}$, a novel data structure, enabling arbitrarily out-of-date clients to efficiently validate updates and signing keys. Evaluation of our CHAINIAC prototype on reproducible Debian packages shows that the automated update process takes the average of 5 minutes per release for individual packages, and only 20 seconds for the aggregate timeline. We further evaluate the framework using real-world data from the PyPI package repository and show that it offers clients security comparable to verifying every single update themselves while consuming only one-fifth of the bandwidth and having a minimal computational overhead

Scalable Bias-Resistant Distributed Randomness

Bias-resistant public randomness is a critical component in many (distributed) protocols. Existing solutions do not scale to hundreds or thousands of participants, as is needed in many decentralized systems. We propose two large-scale distributed protocols, RandHound and RandHerd, which provide publicly-verifiable, unpredictable, and unbiasable randomness against Byzantine adversaries. RandHound relies on an untrusted client to divide a set of randomness servers into groups for scalability, and it depends on the pigeonhole principle to ensure output integrity, even for non-random, adversarial group choices. RandHerd implements an efficient, decentralized randomness beacon. RandHerd is structurally similar to a BFT protocol, but uses RandHound in a one-time setup to arrange participants into verifiably unbiased random secret-sharing groups, which then repeatedly produce random output at predefined intervals. Our prototype demonstrates that RandHound and RandHerd achieve good performance across hundreds of participants while retaining a low failure probability by properly selecting protocol parameters, such as a group size and secret-sharing threshold. For example, when sharding 512 nodes into groups of 32, our experiments show that RandHound can produce fresh random output after 240 seconds. RandHerd, after a setup phase of 260 seconds, is able to generate fresh random output in intervals of approximately 6 seconds. For this configuration, both protocols operate at a failure probability of at most 0.08% against a Byzantine adversary

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

TRPC1 protein channel is major regulator of epidermal growth factor receptor signaling.

TRP channels have been associated with cell proliferation and aggressiveness in several cancers. In particular, TRPC1 regulates cell proliferation and motility, two processes underlying cancer progression. We and others have described the mechanisms of TRPC1-dependent cell migration. However, the involvement of TRPC1 in cell proliferation remains unexplained. In this study, we show that siRNA-mediated TRPC1 depletion in non small cell lung carcinoma cell lines induced G(0)/G(1) cell cycle arrest resulting in dramatic decrease in cell growth. The expression of cyclins D1 and D3 was reduced after TRPC1 knockdown, pointing out the role of TRPC1 in G(1)/S transition. This was associated with a decreased phosphorylation and activation of EGFR and with a subsequent disruption of PI3K/Akt and MAPK downstream pathways. Stimulation of EGFR by its natural ligand, EGF, induced Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry through TRPC1. Ca(2+) entry through TRPC1 conversely activated EGFR, suggesting that TRPC1 is a component of a Ca(2+)-dependent amplification of EGF-dependent cell proliferation