Sirtuins as Important Factors in Pathological States and the Role of Their Molecular Activity Modulators

Sirtuins (SIRTs), enzymes from the family of NAD⁺-dependent histone deacetylases, play an important role in the functioning of the body at the cellular level and participate in many biochemical processes. The multi-directionality of SIRTs encourages scientists to undertake research aimed at understanding the mechanisms of their action and the influence that SIRTs have on the organism. At the same time, new substances are constantly being sought that can modulate the action of SIRTs. Extensive research on the expression of SIRTs in various pathological conditions suggests that regulation of their activity may have positive results in supporting the treatment of certain metabolic, neurodegenerative or cancer diseases or this connected with oxidative stress. Due to such a wide spectrum of activity, SIRTs may also be a prognostic markers of selected pathological conditions and prove helpful in assessing their progression, especially by modulating their activity. The article presents and discusses the activating or inhibiting impact of individual SIRTs modulators. The review also gathered selected currently available information on the expression of SIRTs in individual disease cases as well as the biological role that SIRTs play in the human organism, also in connection with oxidative stress condition, taking into account the progress of knowledge about SIRTs over the years, with particular reference to the latest research results.     

Prediction of mode I fracture toughness of rock using linear multiple regression and gene expression programming

Prediction of mode I fracture toughness (K_IC) of rock is of significant importance in rock engineering analyses. In this study, linear multiple regression (LMR) and gene expression programming (GEP) methods were used to provide a reliable relationship to determine mode I fracture toughness of rock. The presented model was developed based on 60 datasets taken from the previous literature. To predict fracture parameters, three mechanical parameters of rock mass including uniaxial compressive strength (UCS), Brazilian tensile strength (BTS), and elastic modulus (E) have been selected as the input parameters. A cluster of data was collected and divided into two random groups of training and testing datasets. Then, different statistical linear and artificial intelligence based nonlinear analyses were conducted on the training data to provide a reliable prediction model of K_IC. These two predictive methods were then evaluated based on the testing data. To evaluate the efficiency of the proposed models for predicting the mode I fracture toughness of rock, various statistical indices including coefficient of determination (R²), root mean square error (RMSE), and mean absolute error (MAE) were utilized herein. In the case of testing datasets, the values of R², RMSE, and MAE for the GEP model were 0.87, 0.188, and 0.156, respectively, while they were 0.74, 0.473, and 0.223, respectively, for the LMR model. The results indicated that the selected GEP model delivered superior performance with a higher R² value and lower errors.     

Influence of SiC microstructure on its corrosion behavior in molten FLiNaK salt

The influence of the microstructure on the corrosion rate of three monolithic SiC samples in FLiNaK salt at 900 °C for 250 h was studied. The SiC samples, labeled as SiC-1, SiC-2, and SiC-3, had corrosion rates of 0.137, 0.020, and 0.043 mg/cm²h, respectively. Compared with grain size and the presence of special grain boundaries (i.e., Σ3), the content of high-angle grain boundaries (HAGBs) appeared to have the strongest influence on the corrosion rate of SiC in FLiNaK salt, since the corrosion rate increased six times as the concentration of high-angle grain boundaries increased from 19 to 32% for SiC-2 and SiC-1, respectively. These results stress the importance of controlling the content of HAGBs during the production process of SiC.     

Omics Analysis of Blood-Responsive Regulon in Bordetella pertussis Identifies a Novel Essential T3SS Substrate

Bacterial pathogens sense specific cues associated with different host niches and integrate these signals to appropriately adjust the global gene expression. Bordetella pertussis is a Gram-negative, strictly human pathogen of the respiratory tract and the etiological agent of whooping cough (pertussis). Though B. pertussis does not cause invasive infections, previous results indicated that this reemerging pathogen responds to blood exposure. Here, omics RNA-seq and LC–MS/MS techniques were applied to determine the blood-responsive regulon of B. pertussis. These analyses revealed that direct contact with blood rewired global gene expression profiles in B. pertussis as the expression of almost 20% of all genes was significantly modulated. However, upon loss of contact with blood, the majority of blood-specific effects vanished, with the exception of several genes encoding the T3SS-secreted substrates. For the first time, the T3SS regulator BtrA was identified in culture supernatants of B. pertussis. Furthermore, proteomic analysis identified BP2259 protein as a novel secreted T3SS substrate, which is required for T3SS functionality. Collectively, presented data indicate that contact with blood represents an important cue for B. pertussis cells.     

Adaptive robust boundary control of shaft vibrations under perturbations with unknown upper bounds

This paper presents robust and adaptive boundary control designs to stabilize the two‐dimensional vibration of hybrid shaft model. The hybrid shaft is mathematically represented by a set of partial differential equations, governing the shaft vibrations, coupled to ordinary differential equations, describing rigid body spinning and dynamic boundary conditions. The control objective is to stabilize the transverse vibrations of the perturbed shaft while regulating the spinning rate. To achieve this, the paper first establishes robust boundary control laws that fulfil the control objective in the presence of modeling uncertainties and external disturbances operating over the shaft domain and boundary. Lyapunov‐based analyses show that the proposed robust control exponentially stabilizes the shaft with vanishing distributive perturbations, while assuring ultimately bounded vibrations in the case of nonvanishing perturbations. Then, adaptive control philosophy is utilized to achieve redesigned robust controllers that only use online adaptation of control gains without acquiring the knowledge of bounds on perturbations, as well as dynamic parameters. An advantage of this design is avoiding an overconservative robust control law, which may induce poor stability and chattering in tackling system perturbations with unknown upper bounds. Simulations through finite element method illustrate the results. Copyright © 2014 John Wiley & Sons, Ltd.     

Comparative evaluation of different statistical tools for the prediction of uniaxial compressive strength of rocks

In this study, uniaxial compressive strength (UCS), unit weight (UW), Brazilian tensile strength (BTS), Schmidt hardness (SHH), Shore hardness (SSH), point load index (Is₅₀) and P-wave velocity (V_p) properties were determined. To predict the UCS, simple regression (SRA), multiple regression (MRA), artificial neural network (ANN), adaptive neuro-fuzzy inference system (ANFIS) and genetic expression programming (GEP) have been utilized. The obtained UCS values were compared with the actual UCS values with the help of various graphs. Datasets were modeled using different methods and compared with each other. In the study where the performance indice PI_at was used to determine the best performing method, MRA method is the most successful method with a small difference. It is concluded that the mean PI_at equal to 2.46 for testing dataset suggests the superiority of the MRA, while these values are 2.44, 2.33, and 2.22 for GEP, ANFIS, and ANN techniques, respectively. The results pointed out that the MRA can be used for predicting UCS of rocks with higher capacity in comparison with others. According to the performance index assessment, the weakest model among the nine model is P7, while the most successful models are P2, P9, and P8, respectively.     

A novel quasi-oppositional harmony search algorithm and fuzzy logic controller for frequency stabilization of an isolated hybrid power system

The intermittent wind power in isolated hybrid distributed generation (IHDG) may cause serious problems associated with frequency (f) and power (P) fluctuation. Energy storage devices such as battery, super capacitor, and superconducting magnetic energy storage (SMES) may be used to reduce these fluctuations associated with f and P. This paper presents a study of IHDG power system for improving both f and P deviation profiles with the help of SMES. The studied IHDG power system is consisted of wind turbine generator and diesel engine generator. Both f and P control problems of the studied power system model are addressed in presence or absence of SMES. Fuzzy logic based proportional–integral–derivative (PID) controller with SMES is used for the purpose of minimization of f and P deviations. The different tunable parameters of the PID controller and those of the SMES are tuned by a novel quasi-oppositional harmony search algorithm. Performance study of the IHDG power system model is carried out under different perturbation conditions. The results demonstrate minimum f and P deviations may be achieved by using the proposed fuzzy logic based PID controller along with SMES.     

Engineering grain boundary anisotropy to elucidate grain growth behavior in alumina

Current grain growth models have evolved to account for the relationship between grain boundary energy/mobility anisotropy and the five degrees of grain boundary character. However, the role of grain boundary networks on overall growth kinetics remains poorly understood. To experimentally investigate this problem, a highly textured Al₂O₃ was fabricated by colloidal casting in a strong magnetic field to engineer a unique spatial distribution of grain boundary character. Microstructural evolution was quantified and compared to an untextured sample. From this comparison, a prevalence of (0001)/(0001) terminated grain boundaries with anisotropic networks were identified in the textured sample. These boundaries and their networks were found to be driving grain growth at a faster rate than predicted by models. These findings will allow better modelling of grain growth in real systems by experimentally exploring the impact thereon of grain boundary plane anisotropy and relative energy/mobility differences between neighboring boundaries.     

赤红球菌组氨酸激酶的融合表达和功能分析

对赤红球菌的组氨酸激酶基因进行密码子优化，将优化后的组氨酸激酶基因（rhks）构建重组表达质粒pGEX-4T-2-rhks。将此质粒导入到大肠杆菌BL21（DE3）中进行异源表达。在25 ℃和1 mmol/L异丙基-β-D-硫代吡喃半乳糖苷诱导条件下，组氨酸激酶融合蛋白（GST-RHK）获得成功表达，并具有催化活性。经谷胱甘肽琼脂糖亲和层析纯化，获得电泳纯的GST-RHK，其中纯化倍数为3.1，得率为19.5%。该蛋白大小约为72.75 kDa，Km、Vmax和Kcat值分别为20.92 μmol/L、0.17 μmol/（L·min）和1.4 min－1。野生型赤红球菌、组氨酸激酶基因增强株sdrhkE和组氨酸激酶基因敲减株sdrhkD在分别含有苯酚、甲苯、氯苯、异辛烷4 种有机溶剂的培养基中培养，菌株sdrhkD的生长情况都优于野生型赤红球菌，菌株sdrhkE的生长情况都低于野生型赤红球菌。本研究为进一步揭示赤红球菌SD3中组氨酸激酶涉及的信号转导途径与赤红球菌有机溶剂耐受性的关联机制提供一定参考依据。