The hydrolysis mechanism of the anticancer ruthenium drugs NAMI-A and ICR investigated by DFT-PCM calculations

(ImH)[trans-RuCl4(DMSO-S)(Im)], (Im = imidazole, DMSO-S = S-bonded dimethylsulfoxide), NAMI-A, is the first anticancer ruthenium compound that successfully completed Phase I clinical trials. NAMI-A shows a remarkable activity against lung metastases of solid tumors, but is not effective in the reduction of primary cancer. The structurally similar (ImH)[trans-RuCl4(Im)(2)], ICR (or KP418), and its indazole analog (KP1019) are promising candidate drugs in the treatment of colorectal cancers, but have no antimetastatic activity. Despite the pharmacological relevance of these compounds, no rationale has been furnished to explain their markedly different activity. While the nature of the chemical species responsible for their antimetastatic/anticancer activity has not been determined, it has been suggested that the difference between reduction potentials of NAMI-A and ICR may be the key to the different biological responses they induce. In this work, Density Functional Theory calculations were performed to investigate the hydrolysis of NAMI-A and ICR in both Ru-III and Ru-II oxidation states, up to the third aquation. In line with experimental findings, our calculations provide a picture of the hydrolysis of NAMI-A and ICR mainly as a stepwise loss of chloride ligands. While dissociation of Im is unlikely under neutral conditions, that of DMSO becomes competitive with the loss of chloride ions as the hydrolysis proceeds. Redox properties of NAMI-A and ICR and of their most relevant hydrolytic intermediates were also studied in order to monitor the effects of biological reductants on the mechanism of action. Our findings may contribute to the identification of the active compounds that interact with biological targets, and to explain the different biological activity of NAMI-A and ICR

A Monte Carlo Simulation Approach to the Reliability Modeling of the Beam Permit System of the Relativistic Heavy Ion Collider (RHIC) at BNL

N/

Disorder and Synchronization in a Josephson Junction Plaquette

We describe the effects of disorder on the coherence properties of a 2 x 2 array of Josephson junctions (a plaquette ). The disorder is introduced through variations in the junction characteristics. We show that the array will remain one-to-one frequency locked despite large amounts of the disorder, and determine analytically the maximum disorder that can be tolerated before a transition to a desynchronized state occurs. Connections with larger N x M arrays are also drawn

Demonstration of Josephson effect submillimeter wave sources with increased power

This is the published version, also available here: http://dx.doi.org/10.1063/1.111904.A submillimeter wave source based on a new design using Josephson junction arrays has been developed and tested. The maximum rf power, delivered to a 68Ω load and detected on chip, was 47 μW at 394 GHz. Significant power was detected at a number of frequencies from 300 to 500 GHz where the power was 10 μW. The observed power at the designed operating frequency near 400 GHz is consistent with all 500 junctions in the series biased array delivering current in phase to the loads. This is in agreement with simulations of smaller arrays of the same design. The linewidth, inferred from the measured resistance at the point of maximum power, with T=4.2 K, is less than 1 MHz. The minimum inferred linewidth near 400 GHz, at somewhat lower power, is about 100 kHz

Socially and biologically inspired computing for self-organizing communications networks

The design and development of future communications networks call for a careful examination of biological and social systems. New technological developments like self-driving cars, wireless sensor networks, drones swarm, Internet of Things, Big Data, and Blockchain are promoting an integration process that will bring together all those technologies in a large-scale heterogeneous network. Most of the challenges related to these new developments cannot be faced using traditional approaches, and require to explore novel paradigms for building computational mechanisms that allow us to deal with the emergent complexity of these new applications. In this article, we show that it is possible to use biologically and socially inspired computing for designing and implementing self-organizing communication systems. We argue that an abstract analysis of biological and social phenomena can be made to develop computational models that provide a suitable conceptual framework for building new networking technologies: biologically inspired computing for achieving efficient and scalable networking under uncertain environments; socially inspired computing for increasing the capacity of a system for solving problems through collective actions. We aim to enhance the state-of-the-art of these approaches and encourage other researchers to use these models in their future work

Quantitative fault tree analysis of the Beam Permit System elements of Relativistic Heavy Ion Collider (RHIC) at BNL DISCLAIMER QUANTITATIVE FAULT TREE ANALYSIS OF THE BEAM PERMIT SYSTEM ELEMENTS OF RELATIVISTIC HEAVY ION COLLIDER (RHIC) AT BNL*

Abstract The RHIC Beam Permit System (BPS) plays a key role in safeguarding against the anomalies developing in the collider during a run. The BPS collects RHIC subsystem statuses to allow the beam entry and its existence in the machine. The building blocks of BPS are Permit Module (PM) and Abort Kicker Module (AKM), which incorporate various electronic boards based on VME specification. This paper presents a quantitative Fault Tree Analysis (FTA) of the PM and AKM, yielding the failure rates of three top failures that are potential enough to cause a significant downtime of the machine. The FTA helps tracing down the top failure of the module to a component level failure (such as an IC or resistor). The fault trees are constructed for all module variants and are probabilistically evaluated using an analytical solution approach. The component failure rates are calculated using manufacturer datasheets and MIL-HDBK-217F. The apportionment of failure modes for components is calculated using FMD-97. The aim of this work is to understand the importance of individual components of the RHIC BPS regarding its reliable operation, and evaluate their impact on the operation of BPS