In the modern era of multi-core systems, the main aim is to utilize the cores properly.This utilization can be done by concurrent programming. But developing a flawless and well-organized concurrent program is difficult. Software Transactional Memory Systems (STMs) are a convenient programming interface which assist the programmer to access the shared memory concurrently without worrying about consistency issues such as priority-inversion, deadlock, livelock, etc. Another important feature that STMs facilitate is compositionality of concurrent programs with great ease. It composes different concurrent operations in a single atomic unit by encapsulating them in a transaction.Many STMs available in the literature execute read/write primitive operations on memory buffers. We represent them as Read-Write STMs or RWSTMs. Whereas, there exist some STMs (transactional boosting and its variants) which work on higher level operations such as insert, delete, lookup, etc. on a hash-table. We refer these STMs as Object Based STMs or OSTMs. The literature of databases and RWSTMs say that maintaining multiple versions 1 A preliminary version of this paper appeared in 20th International Symposium on Stabilization, Safety, and Security of Distributed Systems (SSS 2018) and awarded with the Best Student Paper Award. A poster version of this work received Best Poster Award in NETYS 2018. 2 Author sequence follows the lexical order of last names. All the authors can be contacted at the addresses given above. Archit Somani's phone number: +91 -7095044601. ensures greater concurrency. This motivates us to maintain multiple version at higher level with object semantics and achieves greater concurrency. So, this paper proposes the notion of Optimized Multi-version Object Based STMs or OPT-MVOSTMs which encapsulates the idea of multiple versions in OSTMs to harness the greater concurrency efficiently. For efficient memory utilization, we develop two variations of OPT-MVOSTMs. First, OPT-MVOSTM with garbage collection (or OPT-MVOSTM-GC) which uses unbounded versions but performs garbage collection scheme to delete the unwanted versions. Second, finite version OPT-MVOSTM (or OPT-KOSTM) which maintains at most K versions by replacing the oldest version when (K + 1) th version is created by the current transaction. We propose the OPT-MVOSTMs for hash-table and list objects as OPT-HT-MVOSTM and OPT-list-MVOSTM respectively. For memory utilization, we propose two variants of both the algorithms as OPT-HT-MVOSTM-GC, OPT-HT-KOSTM and OPT-list-MVOSTM-GC, OPT-list-KOSTM respectively. OPT-HT-KOSTM performs best among its variants and outperforms state-of-the-art hash-table based STMs (HT-OSTM, ESTM, RWSTM, HT-MVTO, HT-KSTM) by a factor of 3.62, 3.95, 3.44, 2.75, 1.85 for workload W1 (90% lookup, 8% insert and 2% delete), 1. 44, 2.36, 4.45, 9.84, 7.42 for workload W2 (50% lookup, 25% insert and 25% delete), and 2. 11, 4.05, 7.84, 12.94, 10.70 for workload W3 (10% lookup, 45% insert and 45% delete) respectively. Similarly, OPT-list-KOSTM performs ...
Nitric oxide is a small messenger molecule utilized by nature in cell signalling and the non-specific immune response. At present, nitric oxide releasing prodrugs cannot be efficiently targeted towards a specific body compartment, which restricts their therapeutic applications. To address this limitation, we have designed two photolabile nitric oxide releasing prodrugs, tert-butyl S-nitrosothiol and tert-dodecane S-nitrosothiol, which are based on the S-nitrosothiol functionality. By modulating the prodrugs' hydrophobicity, we postulated that we could increase their stability within the cell by preventing their interaction with hydrophilic thiols and metal ions; processes that are known to inactivate this prodrug class. Our data demonstrate that these prodrugs have improved nitric oxide release kinetics compared to currently available S-nitrosothiols, as they are highly stable in vitro in the absence of irradiation (t 1 ⁄ 2 > 3 h), while their rate of decomposition can be regulated by controlling the intensity or duration of the photostimulus. Nitric oxide release can readily be achieved using non-laser based light sources, which enabled us to characterize photoactivation as a trigger mechanism for nitric oxide release in A549 lung carcinoma cells. Here we confirmed that irradiation induced highly significant increases in cytotoxicity within a therapeutic drug range (1-100 lM), and the utility of this photoactivation switch opens up avenues for exploring the applications of these prodrugs for chemical biology studies and chemotherapy.Key words: chemical biology, drug design, molecular modeling, nitric oxide, S-nitrosothiol Abbreviations: DTPA, diethylenetriaminepentaacetic acid; MbO 2 , oxy-myoglobin; met-Mb, met-myoglobin; MTT, 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; NO, nitric oxide (nitrogen monoxide); PDT, photodynamic therapy; PI, propidium iodide; SNT, Snitrosothiol; tBuSNO, tert-butyl S-nitrosothiol; tDodSNO, tert-dodecane S-nitrosothiol. Nitric oxide (NO) is a signalling molecule that regulates multiple physiological and pathological processes. NO and downstream nitrogen oxides, collectively termed Reactive Nitrogen Species (RNS), display limited molecular recognition and engage in reactions with many different cellular components (1,2). Due to this lack of specificity, the cellular effects of RNS are determined by the concentration and duration of the NO signal. At low concentrations, NO signals through activation of guanylate cyclase, while at higher levels RNS can act as cellular toxins through nitrosation and nitration reactions, which cause damage to cell membranes and DNA (3). Additionally NO binding can directly alter the function of metalloproteins (4) and sequester iron from iron-sulphur proteins (5).The main drawback to the in vivo use of NO donor drugs is that they do not display organ or tissue specificity. Therefore it is exceedingly challenging to selectively deliver NO to a target compartment, with non-specific NO release causing changes to vascular dynamics that ...
Enhanced bifunctional catalytic activities are shown by monobasic tridentate Cu(ii) Schiff-base complexes.
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