A review of computational modeling and deep brain stimulation: applications to Parkinson's disease

Biophysical computational models are complementary to experiments and theories, providing powerful tools for the study of neurological diseases. The focus of this review is the dynamic modeling and control strategies of Parkinson's disease (PD). In previous studies, the development of parkinsonian network dynamics modeling has made great progress. Modeling mainly focuses on the cortex-thalamus-basal ganglia (CTBG) circuit and its sub-circuits, which helps to explore the dynamic behavior of the parkinsonian network, such as synchronization. Deep brain stimulation (DBS) is an effective strategy for the treatment of PD. At present, many studies are based on the side effects of the DBS. However, the translation from modeling results to clinical disease mitigation therapy still faces huge challenges. Here, we introduce the progress of DBS improvement. Its specific purpose is to develop novel DBS treatment methods, optimize the treatment effect of DBS for each patient, and focus on the study in closed-loop DBS. Our goal is to review the inspiration and insights gained by combining the system theory with these computational models to analyze neurodynamics and optimize DBS treatment.     

THE DETERMINATION OF THE COMPUTATIONAL DEGREES OF FREEDOM OF BAR SYSTEMS1)

为了简化和统一结构力学教材中杆件体系计算自由度$W$的算法,本文提出了“直接法”。该方法以相邻节点间的杆件和结点为分析对象,对于含$m$根杆件、$g$ 个单刚结点和$h$个单铰结点的平面杆件体系,直接法给出计算自由度公式$W=3m-(3g+2h$)。相比于已有方法,直接法研究对象清晰,数学运算统一,适合于编程计算,便于初学者准确而快速计算复杂体系的$W$;也为结构超静定次数的确定提供了一种简单有效的数值算法。     

Anti-Staphylococcal Activity of the Auranofin Analogue Bearing Acetylcysteine in Place of the Thiosugar: An Experimental and Theoretical Investigation

Auranofin (AF, hereafter) is an orally administered chrysotherapeutic agent approved for the treatment of rheumatoid arthritis that is being repurposed for various indications including bacterial infections. Its likely mode of action involves the impairment of the TrxR system through the binding of the pharmacophoric cation [AuPEt₃]⁺. Accordingly, a reliable strategy to expand the medicinal profile of AF is the replacement of the thiosugar moiety with different ligands. Herein, we aimed to prepare the AF analogue bearing the acetylcysteine ligand (AF-AcCys, hereafter) and characterize its anti-staphylococcal activity. Biological studies revealed that AF-AcCys retains an antibacterial effect superimposable with that of AF against Staphylococcus aureus, whereas it is about 20 times less effective against Staphylococcus epidermidis. Bioinorganic studies confirmed that upon incubation with human serum albumin, AF-AcCys, similarly to AF, induced protein metalation through the [AuPEt₃]⁺ fragment. Additionally, AF-AcCys appeared capable of binding the dodecapeptide Ac-SGGDILQSGCUG-NH₂, corresponding to the tryptic C-terminal fragment (488–499) of hTrxR. To shed light on the pharmacological differences between AF and AF-AcCys, we carried out a comparative experimental stability study and a theoretical estimation of bond dissociation energies, unveiling the higher strength of the Au–S bond in AF-AcCys. From the results, it emerged that the lower lipophilicity of AF-AcCys with respect to AF could be a key feature for its different antibacterial activity. The differences and similarities between AF and AF-AcCys are discussed, alongside the opportunities and consequences that chemical structure modifications imply.     

Stereoisomeric Tris-BINOL-Menthol Bulky Monophosphites: Synthesis,Characterisation and Application in Rhodium-Catalysed Hydroformylation

Four stereoisomeric monoether derivatives, based on axially chiral (R)- or (S)-BINOL bearing a chiral (+)- or (−)-neomenthyloxy group were synthesised and fully characterised by NMR spectroscopy and X-ray crystallography. The respective tris-monophosphites were thereof prepared and fully characterised. The coordination ability of the new bulky phosphites with Rh(CO)₂(acac), was attested by ³¹P NMR, which presented a doublet in the range of δ = 120 ppm, with a ¹J(¹⁰³Rh-³¹P) coupling constant of 290 Hz. The new tris-binaphthyl phosphite ligands were further characterised by DFT computational methods, which allowed us to calculate an electronic (CEP) parameter of 2083.2 cm⁻¹ and an extremely large cone angle of 345°, decreasing to 265° upon coordination with a metal atom. Furthermore, the monophosphites were applied as ligands in rhodium-catalysed hydroformylation of styrene, leading to complete conversions in 4 h, 100% chemoselectivity for aldehydes and up to 98% iso-regioselectivity. The Rh(I)/phosphite catalytic system was also highly active and selective in the hydroformylation of disubstituted olefins, including (E)-prop-1-en-1-ylbenzene and prop-1-en-2-ylbenzene.     

Walking an unknown street with bounded detour

A polygon with two distinguished vertices, s and g, is called a street if the two boundary chains from s to g are mutually weakly visible. For a mobile robot with on-board vision system we describe a strategy for finding a short path from s to g in a street not known in advance, and prove that the length of the path created does not exceed 1 + π times the length of the shortest path from s to g. Experiments suggest that our strategy is much better than this, as no ratio bigger than 1.8 has yet been observed. This is complemented by a lower bound of 1.41 for the relative detour each strategy can be forced to generate.     

摄动有限体积法重构近似高精度的意义

研讨有限体积(FV)方法重构近似高精度的作用问题.FV方法中积分近似采用中点规则为二阶精度时,重构近似高精度(精度高于二阶)的意义和作用是一个有争议的问题.利用数值摄动技术[1,2]构造了标量输运方程的积分近似为二阶精度、重构近似为任意阶精度的迎风型和中心型摄动有限体积(PFV)格式.迎风PFV格式无条件满足对流有界准则(CBC),中心型PFV格式为正型格式,两者均不会产生数值振荡解.利用PFV格式求解模型方程的数值结果表明:与一阶迎风和二阶中心格式相比,PFV格式精度高、对解的间断分辨率高、稳定性好、雷诺数的适用范围大,数值地"证实"重构近似高精度和PFV格式的实际意义和好处.     

Effect of local variations of the laminar flame speed on the global finger-flame acceleration scenario

Numerous formulations describing the dynamics and morphology of corrugated flames, including the scenarios of flame acceleration, are based on a “geometrical consideration”, where the wrinkled-to-planar flame velocities ratio, S_w /S_L , is evaluated as the scaled flame surface area, while the entire combustion chemistry is immersed into the planar flame speed S_L , which is assumed to be constant. However, S_L may experience noticeable spatial/temporal variations in practice, in particular, due to pressure/temperature variations as well as non-uniform distribution of the equivalence ratio and/or that of combustible or inert dust impurities. The present work initiates the systematic study of the impact of the local S_L -variations on the global flame evolution scenario. The variations are assumed to be imposed externally, in a manner being a free functional of the formulation. Specifically, the linear, parabolic and hyperbolic spatial S_L -distributions are incorporated into the formulations of finger flame acceleration in pipes, and they are compared to the case of constant S_L . Both two-dimensional channels and cylindrical tubes are considered. The conditions promoting or moderating flame acceleration are identified, and the revisited equations for the flame shape, velocity and acceleration rate are obtained for various S_L -distributions. The theoretical findings are validated by the computational simulations of the reacting flow equations, with agreement between the theory and modelling demonstrated.     

A study of properties of adaptive quadratic grids for three-dimensional near-surface field computations

Curved geometries and the corresponding near-surface fields typically require a large number of linear computational elements. High-order numerical solvers have been primarily used with low-order meshes. There is a need for curved, high-order computational elements. Typical near-surface meshes consist of hexahedral and/or prismatic elements. The present work studies the employment of quadratic meshes that are relatively coarse for field simulations. Directionally quadratic high-order elements are proposed for the near-surface field regions. The quadratic meshes are compared with the conventional low-order ones in terms of accuracy and efficiency. The cases considered include closed surface volume calculations, as well as computation of gradients of several analytic fields. A special method of adaptive local quadratic meshes is proposed and evaluated. Truncation error analysis for quadratic grids yields comparison with the conventional linear hexahedral/prismatic meshes, which are subject to typical distortions such as stretching, skewness, and torsion.     

Unravelling the Enigma of Nonoxidative Conversion of Methane on Iron Single-Atom Catalysts

The direct, nonoxidative conversion of methane on a silica-confined single-atom iron catalyst is a landmark discovery in catalysis, but the proposed gas-phase reaction mechanism is still open to discussion. Here, we report a surface reaction mechanism by computational modeling and simulations. The activation of methane occurs at the single iron site, whereas the dissociated methyl disfavors desorption into gas phase under the reactive conditions. In contrast, the dissociated methyl prefers transferring to adjacent carbon sites of the active center (Fe₁©SiC₂), followed by C−C coupling and hydrogen transfer to produce the main product (ethylene) via a key −CH−CH₂ intermediate. We find a quasi Mars–van Krevelen (quasi-MvK) surface reaction mechanism involving extracting and refilling the surface carbon atoms for the nonoxidative conversion of methane on Fe₁©SiO₂ and this surface process is identified to be more plausible than the alternative gas-phase reaction mechanism.     

Robust Atomistic Modeling of Materials,Organometallic, and Biochemical Systems

Modern chemistry seems to be unlimited in molecular size and elemental composition. Metal-organic frameworks or biological macromolecules involve complex architectures and a large variety of elements. Yet, a general and broadly applicable theoretical method to describe the structures and interactions of molecules beyond the 1000-atom size regime semi-quantitatively is not self-evident. For this purpose, a generic force field named GFN-FF is presented, which is completely newly developed to enable fast structure optimizations and molecular-dynamics simulations for basically any chemical structure consisting of elements up to radon. The freely available computer program requires only starting coordinates and elemental composition as input from which, fully automatically, all potential-energy terms are constructed. GFN-FF outperforms other force fields in terms of generality and accuracy, approaching the performance of much more elaborate quantum-mechanical methods in many cases.