Interactions of asbestos-activated macrophages with an experimental fibrosarcoma

Supernatants from in vivo asbestos-activated macrophages failed to show any cytostatic activity against a syngeneic fibrosarcoma cell line in vitro. UICC chrysotile-induced peritoneal exudate cells also failed to demonstrate any growth inhibitory effect on the same cells in Winn assays of tumor growth. Mixing UICC crocidolite with inoculated tumor cells resulted in a dose-dependent inhibition of tumor growth; this could, however, be explained by a direct cytostatic effect on the tumor cells of high doses of crocidolite, which was observed in vitro

Plumo: An Ultralight Blockchain Client

Syncing the latest state of a blockchain can be a resource-intensive task, driving (especially mobile) end users towards centralized services offering instant access. To expand full decentralized access to anyone with a mobile phone, we introduce a consensus-agnostic compiler for constructing ultralight clients, providing secure and highly efficient blockchain syncing via a sequence of SNARK-based state transition proofs, and prove its security formally. Instantiating this, we present Plumo, an ultralight client for the Celo blockchain capable of syncing the latest network state summary in just a few seconds even on a low-end mobile phone. In Plumo, each transition proof covers four months of blockchain history and can be produced for just $25 USD of compute. Plumo achieves this level of efficiency thanks to two new SNARK-friendly constructions, which may also be of independent interest: a new BLS-based offline aggregate multisignature scheme in which signers do not have to know the members of their multisignature group in advance, and a new composite algebraic-symmetric cryptographic hash function

A Quantum Random Number Generator Certified by Value Indefiniteness

In this paper we propose a quantum random number generator (QRNG) which utilizes an entangled photon pair in a Bell singlet state, and is certified explicitly by value indefiniteness. While "true randomness" is a mathematical impossibility, the certification by value indefiniteness ensures the quantum random bits are incomputable in the strongest sense. This is the first QRNG setup in which a physical principle (Kochen-Specker value indefiniteness) guarantees that no single quantum bit produced can be classically computed (reproduced and validated), the mathematical form of bitwise physical unpredictability. The effects of various experimental imperfections are discussed in detail, particularly those related to detector efficiencies, context alignment and temporal correlations between bits. The analysis is to a large extent relevant for the construction of any QRNG based on beam-splitters. By measuring the two entangled photons in maximally misaligned contexts and utilizing the fact that two rather than one bitstring are obtained, more efficient and robust unbiasing techniques can be applied. A robust and efficient procedure based on XORing the bitstrings together---essentially using one as a one-time-pad for the other---is proposed to extract random bits in the presence of experimental imperfections, as well as a more efficient modification of the von Neumann procedure for the same task. Some open problems are also discussed.Comment: 25 pages, 3 figure

The heat released during catalytic turnover enhances the diffusion of an enzyme

Recent studies have shown that the diffusivity of enzymes increases in a substrate-dependent manner during catalysis,. Although this observation has been reported and characterized for several different systems–, the precise origin of this phenomenon is unknown. Calorimetric methods are often used to determine enthalpies from enzyme-catalysed reactions and can therefore provide important insight into their reaction mechanisms,. The ensemble averages involved in traditional bulk calorimetry cannot probe the transient effects that the energy exchanged in a reaction may have on the catalyst. Here we obtain single-molecule fluorescence correlation spectroscopy data and analyse them within the framework of a stochastic theory to demonstrate a mechanistic link between the enhanced diffusion of a single enzyme molecule and the heat released in the reaction. We propose that the heat released during catalysis generates an asymmetric pressure wave that results in a differential stress at the protein–solvent interface that transiently displaces the centre-of-mass of the enzyme (chemoacoustic effect). This novel perspective on how enzymes respond to the energy released during catalysis suggests a possible effect of the heat of reaction on the structural integrity and internal degrees of freedom of the enzyme

Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience

Hypo-fractionated radiotherapy and stereotactic body radiotherapy are viable options for treatment of oligometastases. A prodrug of mitomycin-C is under clinical testing as a pegylated liposomal formulation (Promitil) with an improved safety profile over mitomycin-C. Promitil was offered to two patients with oligometastases from colorectal cancer as radiosensitizer. Each derived durable clinical benefit from Promitil administered immediately prior to and following irradiation. Transient toxicity to normal tissues of moderate to severe degree was observed. Promitil appears to have potential clinical value in this setting.HIGHLIGHTS- Delivery of radio-sensitizing drugs with pegylated (long-circulating) liposomes is a pharmacologically rational approach which remains largely clinically untested.- A mitomycin-c prodrug delivered by pegylated liposomes (Promitil) is activated by thiol groups, which are produced in excess by radiation-damaged cells, thus potentiating the radio-sensitizing effect of Promitil.- Two durable clinical responses in patient with colorectal oligometastases to Promitil and radiotherapy suggest that this approach may be of value in cancer chemo-radiotherapy