Epigenetic Enzyme Mutations: Role in Tumorigenesis and Molecular Inhibitors

Epigenetic modifications, such as DNA methylation and histone modification, result in heritable changes in gene expression without changing the DNA sequence. Epigenetic regulatory enzymes such as DNA methyltransferases, histone methyltransferases, and histone deacetylases are involved in epigenetic modification. Studies have shown that the dysregulation caused by changes in the amino acid sequence of these enzymes is closely correlated with tumor onset and progression. In addition, certain amino acid changes in the metabolic enzyme isocitrate dehydrogenase (IDH) are linked to altered epigenetic modifications in tumors. Some small molecule inhibitors targeting these aberrant enzymes have shown promising anti-cancer efficacy in preclinical and clinical trials. For example, the small molecule inhibitor ivosidenib, which targets IDH1 with a mutation at R132, has been approved by the FDA for the clinical treatment of acute myeloid leukemia. In this review, we summarize the recurrent “hotspot” mutations in these enzymes in various tumors and their role in tumorigenesis. We also describe candidate inhibitors of the mutant enzymes which show potential therapeutic value. In addition, we introduce some previously unreported mutation sites in these enzymes, which may be related to tumor development and provide opportunities for future study

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

Antirollover Experimental Method for a Liquid Tank Semitrailer

The liquid tank semitrailer has higher centroid and poor stability, and the vehicle is prone to rollover when turning or changing lanes at high speed. Thus, many companies have developed active antirollover systems in recent years. But the systems’ antirollover capabilities are different. However, there are no specific test conditions and test standards for antirollover systems. Taking this as a starting point, first, an automotive intelligent security cloud terminal and a multiaxis sensor are selected for the test data acquisition, and a remote data acquisition system based on a mobile signal is established. Second, a vehicle road test scheme with a free choice of route is designed. Set the rollover trigger conditions, obtain the test data through the database, and classify the data into dangerous scenarios. Third, the typical scenarios with rollover risk are obtained by data fitting. Finally, the typical antirollover system test conditions of the liquid tank semitrailer are obtained by optimizing and analysing the typical scenarios through the simulation software. The results show that the J-steering test with a turning radius of 45 m in both clockwise and counterclockwise directions can be used as an accurate typical test condition of the antirollover system of liquid tank semitrailers

Laser Self-Mixing Interferometer Based on Multiple Reflections and Phase-Modulation Technique

An improved method combining multiple reflections with the phase-modulation technique (MR-PM) is proposed to construct a self-mixing interferometer with high accuracy. The phase modulation is performed by using an electro-optic modulator that is placed in the external cavity. To broaden the harmonic components spectrum of the self-mixing signal, the multiple-reflection technique is employed. By extracting orthogonal signals from the spectrum, phase demodulation is implemented to realize displacement reconstruction. The principle and signal processing approach are described in detail. A series of simulations and experiments indicate that the measurement accuracy of the system can be effectively improved with the increase in reflection times. The vibration with an amplitude of 44 nm has been proved to be measurable with a reconstruction error less than 3 nm. Due to the advantages of high accuracy and broad measurement range, the proposed method will play a significant role in the field of non-contact nanometer vibration measurement

Effects of Ce-rich RE on microstructure and mechanical properties of as-cast Mg-8Li-3Al-2Zn-0.5Nd alloy with duplex structure

The effects of Ce-rich RE on the microstructure and mechanical properties of as-cast Mg-8Li-3Al-2Zn-0.5Nd-xRE (x = 0, 1, 2, 3 wt%) alloys were investigated. The results indicated that the as-cast Mg-8Li-3Al-2Zn-0.5Nd alloy mainly consisted of α-Mg, β-Li, AlLi, MgLi2Al and Al2Nd phases. With the addition of Ce-rich RE in the alloy, Al3RE and Al2RE phases generated and gradually grew into net-like or block-like structure. With the addition of RE, Al-RE phases generated by consuming Al element and, thus, less Al element was dissolved in the matrix and less AlLi phase formed. Furthermore, less AlLi phase means that more Li element released to cause the increase of β-Li phase and refine the α-Mg phase. Under the influence of these factors, adding more RE led to higher elongation and lower tensile strength and hardness. With the addition of Ce-rich RE, the yield strength and ultimate tensile strength of the as-cast Mg-8Li-3Al-2Zn-0.5Nd alloy gradually decreased from 180 to 152 MPa and from 215 to 193 MPa, respectively, while the elongation was remarkably improved from 21.1% to 40.2%. Keywords: Mg-Li alloy, Rare earth, Ce, Microstructure, Mechanical propert

Observation of curling effects in tubular and planar graphene-like structures by pyrolysis of ferrocene/dichlorobenzene mixtures

© 2018 Elsevier Ltd In this work, we investigate the morphological and structural properties of carbon nanostructures fabricated by means of chemical vapor deposition (CVD) methods in the presence of controlled quantities of Cl-containing precursor and ferrocene. We report the observation of a structural transition from tubular-like carbon nanotube (CNT) morphology into planar few-layers graphite in experiments involving the pyrolysis of ferrocene and dichlorobenzene mixtures. An unusual intermediate curling-like mechanism in the walls of the as-grown CNTs is found when intermediate quantities of dichlorobenzene are used. This unusual phenomenon vanishes for high quantities of dichlorobenzene, where the nucleation of planar few-layers graphene-like structures directly connected to micrometer-scale Fe3C particles is found. Such morphological variation is investigated by means of both scanning electron microscopy (SEM) and transmission electron microscopy (TEM), whereas the structural variation of the obtained structures is analyzed through X-ray diffraction and Raman spectroscopy techniques