The Impact of PbF2-Based Glasses on Radiation Shielding and Mechanical Concepts: An Extensive Theoretical and Monte Carlo Simulation Study

Journal of Inorganic and Organometallic Polymers and Materials - This work aimed to investigate the impact of Lead-fluoride based glasses via theoretical and simulation techniques on mechanical and...     

Evaluation of Intellectual Property Objects in the Nanoindustry Field

Russian Microelectronics - The recently developed nanomaterials and their production technologies as intellectual property objects (IPOs) are considered. The role of the informational-analytical...     

Alteration of the Route to Menaquinone towards Isochorismate-Derived Metabolites

Chorismate and isochorismate constitute branch-point intermediates in the biosynthesis of many aromatic metabolites in microorganisms and plants. To obtain unnatural compounds, we modified the route to menaquinone in Escherichia coli. We propose a model for the binding of isochorismate to the active site of MenD ((1R,2S, 5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-3-ene-1-carboxylate (SEPHCHC) synthase) that explains the outcome of the native reaction with α-ketoglutarate. We have rationally designed variants of MenD for the conversion of several isochorismate analogues. The double-variant Asn117Arg–Leu478Thr preferentially converts (5S,6S)-5,6-dihydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHD), the hydrolysis product of isochorismate, with a >70-fold higher ratio than that for the wild type. The single-variant Arg107Ile uses (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHA) as substrate with >6-fold conversion compared to wild-type MenD. The novel compounds have been made accessible in vivo (up to 5.3 g L⁻¹). Unexpectedly, as the identified residues such as Arg107 are highly conserved (>94 %), some of the designed variations can be found in wild-type SEPHCHC synthases from other bacteria (Arg107Lys, 0.3 %). This raises the question for the possible natural occurrence of as yet unexplored branches of the shikimate pathway.     

A single-phase algorithm for mining high utility itemsets using compressed tree structures

Mining high utility itemsets (HUIs) from transaction databases considers such factors as the unit profit and quantity of purchased items. Two-phase tree-based algorithms transform a database into compressed tree structures and generate candidate patterns through a recursive pattern-growth procedure. This procedure requires a lot of memory and time to construct conditional pattern trees. To address this issue, this study employs two compressed tree structures, namely, Utility Count Tree and String Utility Tree, to enumerate valid patterns and thus promote fast utility computation. Furthermore, the study presents an algorithm called single-phase utility computation (SPUC) that leverages these two tree structures to mine HUIs in a single phase by incorporating novel pruning strategies. Experiments conducted on both real and synthetic datasets demonstrate the superior performance of SPUC compared with IHUP, UP-Growth, and UP-Growth+ algorithms.     

Calculation and Experimental Determination of the Neutronics Characteristics of the IRT-T Research Reactor

Atomic Energy - The results of calculations and experimental determination of the neutronics characteristics of the IRT-T research reactor are presented. The IRT-T reactor is a pool reactor with...     

基于区块链技术的公益时间银行系统

在现有的时间银行系统中，时间币的发行功能和结算功能完全集中到一个中心节点上。这种极度中心化的功能结构，不仅存在容易发生中心节点单点失效、数据容易被篡改等信息安全问题，还存在着时间币的发行和流通缺乏透明度以及时间币的结算依赖中心化的结算机构等问题。针对这些问题，提出了一种基于区块链技术的解决方法。首先，将时间币的发行功能和结算功能从中心节点上分离出来；然后，利用具有分布式去中心化、集体维护和不可篡改等特性的区块链技术，将分离出来的发行功能逐步去中心化，将分离出来的结算功能去中心化，形成公益时间链（PWTB）；最终，PWTB利用区块链技术以去中心化的方式将时间银行系统由单个节点维护账本变成由集体维护一个分布式的共享账本，使时间币的发行和流通公开透明，时间币的结算不依赖某个中心化的节点。安全分析表明所设计的PWTB能够实现安全的信息传输与存储，以及数据的共享。     

Microtubule Destabilizing Sulfonamides as an Alternative to Taxane-Based Chemotherapy

Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers.     

B Cells with a Senescent-Associated Secretory Phenotype Accumulate in the Adipose Tissue of Individuals with Obesity

Senescent cells accumulate in the adipose tissue (AT) of individuals with obesity and secrete multiple factors that constitute the senescence-associated secretory phenotype (SASP). This paper aimed at the identification of B cells with a SASP phenotype in the AT, as compared to the peripheral blood, of individuals with obesity. Our results show increased expression of SASP markers in AT versus blood B cells, a phenotype associated with a hyper-metabolic profile necessary to support the increased immune activation of AT-derived B cells as compared to blood-derived B cells. This hyper-metabolic profile is needed for the secretion of the pro-inflammatory mediators (cytokines, chemokines, micro-RNAs) that fuel local and systemic inflammation.