Structure-based design and analysis of MAO-B inhibitors for Parkinson’s disease: using in silico approaches

Parkinson’s disease (PD) is a degenerative disorder of the CNS, characterized by cerebral depletion of dopamine (DA), hence one of the approaches to delay the depletion of DA is to inhibit its oxidative deamination. Monoamine oxidases (MAO) carry out the oxidative deamination of monoamines like DA. These are intracellular enzymes, located on the outer mitochondrial membrane. MAO-A and MAO-B are the two subtypes of which MAO-B is the most predominant enzyme and is commonly found in the brain. Inhibition of the MAO-B enzyme boosts the effect of both endogenous and exogenous DA. In this study, we have carried out crystal structure analysis and structure-based design of MAO-B inhibitors. We also performed molecular dynamics, flexible docking, induced-fit docking and ADME prediction of the newly designed compounds.     

Synthesis and evaluation of chromone derivatives as inhibitors of monoamine oxidase

Molecular Diversity - Based on reports that chromone compounds are good potency inhibitors of monoamine oxidase (MAO), the present study evaluates the effect of substitution with flexible side...     

积分球光源分布温度对宽波段光学遥感器绝对辐射定标的影响及其校正

实测了积分球输出光谱辐亮度分布曲线,并得到积分球光源的分布温度。从理论上分析了积分球光源分布温度影响宽波段光学遥感器绝对辐射定标精度的原因和机理,并仿真计算了包括积分球和太阳在内的几种不同分布温度光源定标某宽波段光学遥感器时得到的定标系数。仿真结果表明,不同分布温度间的定标系数最大差别大于2%。在此基础上提出了积分球光源分布温度影响绝对辐射定标系数的校正方法,为提高宽波段遥感器的辐射定标精度和遥感图像辐射校正提供了思路和依据。     

Pharmacophore mapping of flavone derivatives for aromatase inhibition

Aromatase, which catalyses the final step in the steroidogenesis pathway of estrogen, has been target for the design of inhibitor in the treatment of hormone dependent breast cancer for postmenopausal women. The extensive SAR studies performed in the last 30 years to search for potent, selective and less toxic compounds, have led to the development of second and third generation of non-steroidal aromatase inhibitors (AI). Besides the development of synthetic compounds, several naturally occurring and synthetic flavonoids, which are ubiquitous natural phenolic compounds and mediate the host of biological activities, are found to demonstrate inhibitory effects on aromatase. The present study explores the pharmacophores, i.e., the structural requirements of flavones (Fig. 1) for inhibition of aromatase activity, using quantitative structure activity relationship (QSAR) and space modeling approaches. The classical QSAR studies generate the model (R (2) = 0.924, Q (2) = 0.895, s = 0.233) that shows the importance of aromatic rings A and C, along with substitutional requirements in meta and para positions of ring C for the activity. 3D QSAR of Comparative Molecular Field Analysis (CoMFA, R (2) = 0.996, [Formula: see text]) and Comparative Molecular Similarity Analysis (CoMSIA, R (2) = 0.992, [Formula: see text]) studies show contour maps of steric and hydrophobic properties and contribution of acceptor and donor of the molecule, suggesting the presence of steric hindrance due to ring C and R'-substituent, bulky hydrophobic substitution in ring A, along with acceptors at positions 11, and alpha and gamma of imidazole ring, and donor in ring C favor the inhibitory activity. Further space modeling (CATALYST) study (R = 0.941, Delta( cost ) = 96.96, rmsd = 0.876) adjudge the presence of hydrogen bond acceptor (keto functional group), hydrophobic (ring A) and aromatic rings (steric hindrance) along with critical distance among features are important for the inhibitory activity.     

Extraction of natural products using supercritical fluids and pressurized liquids assisted by ultrasound: Current status and trends

Natural products are a source of a wide range of chemical compounds, from pigments to bioactive compounds, which can be extracted and used in different applications. Due to consumer awareness, the interest in natural compounds significantly increased in the last decades, prompting the search for more efficient and environmentally friendly extraction techniques and methods. Pressurized liquids and fluids (sub and supercritical) are being explored to extract natural compounds within the green process concept. The combination of these techniques with ultrasound has emerged as an alternative to intensify the extraction process efficiently. In this context, this work presents a comprehensive review and current insights into the use of high-pressure systems, specifically supercritical fluid extraction and pressurized liquid extraction assisted by ultrasound, as emerging technologies for extracting bioactive compounds from natural products. The extraction mechanisms, applications, and the influence of operational parameters in the process are addressed, in addition to an analysis of the main challenges to be overcome for widespread application.     

Exogenous iron redistribution between brain and liver after administering <Superscript>57</Superscript>Fe<Subscript>3</Subscript>O<Subscript>4</Subscript> ferrofluid to a rat brain ventricle

The natural excretion of ⁵⁷Fe enriched magnetic nanoparticles from a rat’s brain through its blood–brain barrier is studied. Dextran-coated iron oxide nanoparticles are transcranially injected into the rat’s brain ventricle. The injected nanoparticles undergo biotransformation into iron-containing proteins distributed over the brain tissues, while the exogenous iron transported from the brain to other organs is eliminated from the body over time.     

A large scale double beta and dark matter experiment: GENIUS

The recent results from the HEIDELBERG-MOSCOW experiment have demonstrated the large potential of double beta decay to search for new physics beyond the Standard Model. To increase by a major step the present sensitivity for double beta decay and dark matter search much bigger source strengths and much lower backgrounds are needed than used in experiments under operation at present or under construction. We present here a study of a project proposed recently [1], which would operate one ton of ‘naked’ enriched GErmanium-detectorsinliquid NItrogenas shielding in an Underground Setup (GENIUS). It improves the sensitivity to neutrino masses to 0.01 eV. A ten ton version would probe neutrino masses even down to 10^?3 eV. The first version would allow to test the atmospheric neutrino problem, the second at least part of the solar neutrino problem. Both versions would allow in addition significant contributions to testing several classes of GUT models. These are especially tests of R-parity breaking supersymmetry models, leptoquark masses and mechanism and right-handed W-boson masses comparable to LHC. The second issue of the experiment is the search for dark matter in the universe. The entire MSSM parameter space for prediction of neutralinos as dark matter particles could be covered already in a first step of the full experiment with the same purity requirements, but using only 100 kg of ⁷⁶Ge or even of natural Ge making the experiment competitive to LHC in the search for supersymmetry. The layout ofthe proposed experiment is discussed and the shielding and purity requirements are studied using GEANT Monte Carlo simulations. As a demonstration of the feasibility of the experiment first results of operating a ‘naked’ Ge detector in liquid nitrogen are presented.     

Pattern Classifications Using Grover’s and Ventura’s Algorithms in a Two-qubits System

Carrying out the classification of patterns in a two-qubit system by separately using Grover’s and Ventura’s algorithms on different possible superposition, it has been shown that the exclusion superposition and the phase-invariance superposition are the most suitable search states obtained from two-pattern start-states and one-pattern start-states, respectively, for the simultaneous classifications of patterns. The higher effectiveness of Grover’s algorithm for large search states has been verified but the higher effectiveness of Ventura’s algorithm for smaller data base has been contradicted in two-qubit systems and it has been demonstrated that the unknown patterns (not present in the concerned data-base) are classified more efficiently than the known ones (present in the data-base) in both the algorithms. It has also been demonstrated that different states of Singh-Rajput MES obtained from the corresponding self-single- pattern start states are the most suitable search states for the classification of patterns |00>,|01 >, |10> and |11> respectively on the second iteration of Grover’s method or the first operation of Ventura’s algorithm.     

铝合金微弧氧化过程中电学参量的特性研究

利用自制的数据采集系统研究了恒定电压下铝合金微弧氧化过程中有关电学参量随时间的变化规律.结果表明：通电回路中的阴极和阳极峰值电流随处理时间的变化明显分为5个阶段；陶瓷膜的动态正向电阻和电阻率随处理时间分阶段变化，而动态的反向电阻和电阻率随时间的变化不大.在微弧氧化过程中，各时刻的动态正、反向电阻值不同，一般情况下，动态正向电阻远大于反向电阻.对不同处理时间样品的扫描电子显微镜分析表明，陶瓷膜呈多孔结构并随处理时间分阶段变化. 关键词： 铝合金 微弧氧化 电学参量 陶瓷膜     

Using selective intensity and a HATS to evaluate noise sources in a car working at idle

Noise source ranking is required to make the noise level of a vehicle the lowest possible. That implies knowing the noise sources with the highest contribution to the total noise levels.Through the application of coherence techniques, the selective intensity can be defined as the portion of intensity that is coherent with a reference signal. Therefore, it is an effective way to determine the internal root causes of the emitted noise.In this paper, three experiments based on the selective intensity technique have been defined. The objective is observing the contributions of different noise sources of a vehicle, both outside and inside of it, when it is working at idle, and using as reference signals the two microphones of a HATS.With these experiments, it can be evaluated, on the one hand, the coherence between the intensity in the driver’s seat and external microphones located on both sides of the frontal axle of the car, in the exhaust and in the engine. On the other hand, it is evaluated the coherence between sound intensity in the same external points of the car and different positions of a HATS outside and inside of it; thus, as novelties the relation between the noise emitted by different parts of the vehicle and the noise perceived by the vehicle’s driver and by people located outside could be studied.     

Cheminformatic characterization of natural products from Panama

In this work, we discuss the characterization and diversity analysis of 354 natural products (NPs) from Panama, systematically analyzed for the first time. The in-house database was compared to NPs from Brazil, compounds from Traditional Chinese Medicine, natural and semisynthetic collections used in high-throughput screening, and compounds from ChEMBL. An analysis of the “global diversity” was conducted using molecular properties of pharmaceutical interest, three molecular fingerprints of different design, molecular scaffolds, and molecular complexity. The global diversity was visualized using consensus diversity plots that revealed that the secondary metabolites in the Panamanian flora have a large scaffold diversity as compared to other composite databases and also have several unique scaffolds. The large scaffold diversity is in agreement with the broad range of biological activities that this collection of NPs from Panama has shown. This study also provided further quantitative evidence of the large structural complexity of NPs. The results obtained in this study support that NPs from Panama are promising candidates to identify selective molecules and are suitable sources of compounds for virtual screening campaigns.     

On the weak‐field approximation of nonlinear vacuum electrodynamics of the Plebański class

Plebański's class of nonlinear vacuum electrodynamics is considered, which is for several reasons of interest at the present time. In particular, the question is answered under which circumstances Maxwell's original field equations are recovered approximately and which ‘post‐Maxwellian’ effects could arise. To this end, a weak field approximation method is developed, allowing to calculate ‘post‐Maxwellian’ corrections up to Nth order. In some respect, this is analogue of determining ‘post‐Newtonian’ corrections from relativistic mechanics by a low velocity approximation. As a result, we got a series of linear field equations that can be solved order by order. In this context, the solutions of the lower orders occur as source terms inside the higher order field equations and represent a ‘post‐Maxwellian’ self‐interaction of the electromagnetic field, which increases order by order. It becomes apparent that one has to distinguish between problems with and without external source terms because without sources also high frequency solutions can be approximately described by Maxwell's original equations. The higher order approximations, which describe ‘post‐Maxwellian’ effects, can give rise to experimental tests of Plebańksi's class. Finally, two boundary value problems are discussed to have examples at hand.     

The selective and efficient laser ion source and trap project LIST for on-line production of exotic nuclides

Laser ion sources based on resonant excitation and ionization of atoms are well-established tools for selective and efficient production of radioactive ion beams. A recent trend is the complementary installation of reliable state-of-the-art all solid-state Ti:Sapphire laser systems. To date, 35 elements of the Periodic Table are available at laser ion sources by using these novel laser systems, which complements the overall accessibility to 54 elements including use of traditional dye lasers. Recent progress in the field concerns the identification of suitable optical excitation schemes for Ti:Sapphire laser excitation as well as technical developments of the source in respect to geometry, cavity material as well as by incorporation of an ion guide system in the form of the laser ion source trap LIST.     

An in silico protocol for identifying mTOR inhibitors from natural products

The mammalian target of rapamycin (mTOR) is an anti-cancer target. In this study, we propose an in silico protocol for identifying mTOR inhibitors from the ZINC natural product database. First, a three-dimensional quantitative structure–activity relationship pharmacophore model was built based on known mTOR inhibitors. The model was validated with an external test set, Fischer’s randomization method, a decoy set and pharmacophore mapping conformation testing. The results showed that the model can predict the mTOR inhibition activity of the tested compounds. Virtual screening was performed based on the best pharmacophore model, and the results were then filtered using a molecular docking approach. In addition, molecular mechanics/generalized born surface area analysis was used to refine the selected candidates. The top 20 natural products were selected as potential mTOR inhibitors, and their structural scaffolds could serve as building blocks in designing drug-like molecules for mTOR inhibition.     

Timelike and null geodesics in the Nordström field

The timelike and null geodesics are investigated in the Nordström geometry and it is found that incoming geodesics always encounter a turning point at a finite radial distance. The limits for escape, bound and stable orbits are obtained and they are closer to the source as compared to their counterparts in the Schwarzschild’s field.     

全固态高稳定度纳秒脉冲源的相干合成技术

 单个子源的稳定度指标是多源相干合成技术的关键。文章首先对脉冲源稳定度指标进行了定义，并指出全固态纳秒脉冲源具有较高的稳定度指标，在相干合成中具有潜在优势。对脉冲时基抖动、波形抖动机理进行了深入分析，给出了高稳定度子源设计的关键技术途径，采用过触发、欠容量等具体改善方案，有效提高了子源的时基稳定度和波形稳定度，单个子源脉宽抖动小于等于1%，峰值抖动小于等于1%，单次短时抖动小于等于20 ps，长时漂移小于等于100 ps/min。最终成功实现了256单元的16×16路电路-空间综合合成，研制出30 MW全固态高稳定度多路相干合成纳秒脉冲源，脉冲源16路输出端口最大时基离散度小于30 ps，合成峰值电压抖动小于1%，合成峰值电压效率可达到90%~95%。     

Exploration of structural and physicochemical requirements and search of virtual hits for aminopeptidase N inhibitors

Aminopeptidase N (APN) inhibitors have been reported to be effective in treating of life threatening diseases including cancer. Validated ligand- and structure-based pharmacophore mapping approaches were combined with Bayesian modeling and recursive partitioning to identify structural and physicochemical requirements for highly active APN inhibitors. Based on the assumption that ligand- and structure-based pharmacophore models are complementary, the efficacy of ‘multiple pharmacophore screening’ for filtering true positive virtual hits was investigated. These multiple pharmacophore screening methods were utilized to search novel virtual hits for APN inhibition. The number of hits was refined and reduced by recursive partitioning, drug-likeliness, pharmacokinetic property prediction, and comparative molecular-docking studies. Four compounds were proposed as the potential virtual hits for APN enzyme inhibition.     

Two-dimensional radiative transfer due to curved Dirac delta line sources

In this article, the two-dimensional radiative transport equation is considered for the curved Dirac delta line source. In order to account this source type, Green’s function of the radiative transport equation for the half-plane is derived in parts of the ballistic and diffuse contribution as well as under consideration of the Fresnel reflection at the boundary. The final results are verified with the Monte Carlo method for different collimated beams and several curved sources such as the elliptic and logarithmic spiral line source.     

运动声源快速定位的声达时差法

针对声达时差法只能用于非运动声源定位的问题,本文提出一种运动声源快速定位方法。该方法以声达时差为基本定位原理,基于声源计算位置对多普勒效应进行解耦并进行声信号多普勒效应修正,根据三角定位方法构建声传播空间矩阵,以声源位置偏差度为目标基于单纯形优化搜索算法进行声源位置快速逼近,实现了对匀速直线运动的单声源的定位追踪,提高定位实时性。该方法将声达时差法拓展到运动声源的定位,同时解决了消除多普勒效应带来的计算过程复杂、运算量大的问题,仅用4个传声器就可实现运动声源的快速定位,突破了传统运动声源识别中对大传声器阵列的依赖。仿真实验和实车运动声源识别实验结果证明了该方法的有效性,本研究为短时发声运动声源的识别提供了一种简便、高效的方法。      

Coherent aperture synthesis for incoherent source

We propose a refinement of the method for aperture synthesis for an incoherent source, imparting selectivity and noise immunity to the method. Instead of measuring the phase difference between the signals of the array receivers, we measure the array-averaged phase difference between neighboring receivers by searching for the maximum of the magnitude of the moving array’s response to the source signal during its direction-of-arrival-scanning (phasing). This procedure is carried out after incoherent accumulation. The gain in noise immunity is determined by the gain in the array with the addition of the gain in incoherent accumulation. The size of this gain in the experiment was on the order of 20 dB. The method retains applicability to wideband signals and the possibility of observing other incoherent signals. We demonstrate the possibility of high angular resolution with the synthesized antenna of the source, which does not possess the perfect time coherency of the source and other sources coherent with it. Owing to phase averaging over the array aperture, we obtain an increase in the method’s stability to reverberation. We present results of simulation and applicability of the method in full-scale experiments.