Iniva: Inclusive and Incentive-compatible Vote Aggregation

Many blockchain platforms use committee-based consensus for scalability, finality, and security. In this consensus scheme, a committee decides which blocks get appended to the chain, typically through several voting phases. Platforms typically leverage the committee members' recorded votes to reward, punish, or detect failures. A common approach is to let the block proposer decide which votes to include, opening the door to possible attacks. For example, a malicious proposer can omit votes from targeted committee members, resulting in lost profits and, ultimately, their departure from the system. This paper presents Iniva, an inclusive and incentive-compatible vote aggregation scheme that prevents such vote omission attacks. Iniva relies on a tree overlay with carefully selected fallback paths, making it robust against process failures without needing reconfiguration or additional redundancy. Our analysis shows that Iniva significantly reduces the chance to omit individual votes while ensuring that omitting many votes incurs a significant cost. In addition, our experimental results show that Iniva enjoys robustness, scalability, and reasonable throughput.Comment: Committee-based blockchains, Vote omission attack, Vote inclusion, Signature aggregation, Incentive-compatibl

An Extensible Framework for Implementing and Validating Byzantine Fault-tolerant Protocols

HotStuff is a Byzantine fault-tolerant state machine replication protocol that incurs linear communication costs to achieve consensus. This linear scalability promoted the protocol to be adopted as the consensus mechanism in permissioned blockchains. This paper discusses the architecture, testing, and evaluation of our extensible framework to implement HotStuff and its variants. The framework already contains three HotStuff variants and other interchangeable components for cryptographic operations and leader selection. Inspired by the Twins approach, we also provide a testing framework for validating protocol implementations by inducing Byzantine behaviors. Test generation is protocol-agnostic; new protocols can execute the test suite with little-to-no modifications. We report relevant insights on how we benefited from Twins for validation and test-driven development. Leveraging our deployment tool, we evaluated our implementation in various configurations.acceptedVersio

Curcumin loaded pH-sensitive hybrid lipid/block copolymer nanosized drug delivery systems

Curcumin is a perspective drug candidate with pleiotropic antineoplastic activity, whose exceptionally low aqueous solubility and poor pharmacokinetic properties have hampered its development beyond the preclinical level. A possible approach to overcome these limitations is the encapsulation of curcumin into nano-carriers, incl. liposomes. The present contribution is focused on feasibility of using hybrid pH-sensitive liposomes, whereby curcumin is entrapped as a free drug and as a water soluble inclusion complex with PEGylated tert-butylcalix[4]arene, which allows the drug to occupy both the phospholipid membranes and the aqueous core of liposomes. The inclusion complexes were encapsulated in dipalmithoylphosphathydilcholine:cholesterol liposomes, whose membranes were grafted with a poly(isoprene-b-acrylic acid) diblock copolymer to confer pH-sensitivity. The liposomes were characterized by DLS, ζ-potential measurements, cryo-TEM, curcumin encapsulation efficacy, loading capacity, and in vitro release as a function of pH. Free and formulated curcumin were further investigated for cytotoxicity, apoptosis-induction and caspase-8, and 9 activation in chemosensitive HL-60 and its resistant sublines HL-60/Dox and HL-60/CDDP. Formulated curcumin was superior cytotoxic and apoptogenic agent vs. the free drug. The mechanistic assay demonstrated that the potent proapoptotic effects of pH-sensitive liposomal curcumin presumably mediated via recruitment of both extrinsic and intrinsic apoptotic pathways in both HL-60 and HL-60/CDDP cells

Defective Molecular Timer in the Absence of Nucleotides Leads to Inefficient Caspase Activation

In the intrinsic death pathway, cytochrome C (CC) released from mitochondria to the cytosol triggers Apaf-1 apoptosome formation and subsequent caspase activation. This process can be recapitulated using recombinant Apaf-1 and CC in the presence of nucleotides ATP or dATP [(d)ATP] or using fresh cytosol and CC without the need of exogenous nucleotides. Surprisingly, we found that stored cytosols failed to support CC-initiated caspase activation. Storage of cytosols at different temperatures led to the loss of all (deoxy)nucleotides including (d)ATP. Addition of (d)ATP to such stored cytosols partially restored CC-initiated caspase activation. Nevertheless, CC could not induce complete caspase-9/3 activation in stored cytosols, even with the addition of (d)ATP, despite robust Apaf-1 oligomerization. The Apaf-1 apoptosome, which functions as a proteolytic-based molecular timer appeared to be defective as auto-processing of recruited procaspase-9 was inhibited. Far Western analysis revealed that procaspase-9 directly interacted with Apaf-1 and this interaction was reduced in the presence of physiological levels of ATP. Co-incubation of recombinant Apaf-1 and procaspase-9 prior to CC and ATP addition inhibited CC-induced caspase activity. These findings suggest that in the absence of nucleotide such as ATP, direct association of procaspase-9 with Apaf-1 leads to defective molecular timer, and thus, inhibits apoptosome-mediated caspase activation. Altogether, our results provide novel insight on nucleotide regulation of apoptosome

Screening for Active Small Molecules in Mitochondrial Complex I Deficient Patient's Fibroblasts, Reveals AICAR as the Most Beneficial Compound

Congenital deficiency of the mitochondrial respiratory chain complex I (CI) is a common defect of oxidative phosphorylation (OXPHOS). Despite major advances in the biochemical and molecular diagnostics and the deciphering of CI structure, function assembly and pathomechanism, there is currently no satisfactory cure for patients with mitochondrial complex I defects. Small molecules provide one feasible therapeutic option, however their use has not been systematically evaluated using a standardized experimental system. In order to evaluate potentially therapeutic compounds, we set up a relatively simple system measuring different parameters using only a small amount of patient's fibroblasts, in glucose free medium, where growth is highly OXPOS dependent. Ten different compounds were screened using fibroblasts derived from seven CI patients, harboring different mutations

A NOVEL POWER QUALITY IMPROVEMENT TECHNIQUE FED INDUCTION MACHINE DRIVE USING SINGLE LEG SAPF

To avoid problems on neighbors’ facilities and to keep a good electric power quality service. The harmonic currents on the electrical grid degrade the voltages waveform. The Shunt Active Power Filters are nowadays a good solution, since they can solve harmonic current problems, and also compensate the power factor. Shunt Active Power Filters have various advantages over Passive ones, since they don’t need to be configured to a specific harmonic, but, all harmonics can be simultaneously compensated