Computational Modeling Studies Research Articles

Determination of the grid impedance in power consumption modes with harmonics

The paper investigates the harmonic impedance determination of the power supply system of a mining enterprise. This parameter is important when calculating modes with voltage distortions, since the determined parameters of harmonic currents and voltages significantly depend on its value, which allow the most accurate modeling of processes in the presence of distortions in voltage and current. The power supply system of subsurface mining is considered, which is characterized by a significant branching of the electrical network and the presence of powerful nonlinear loads leading to a decrease in the power quality at a production site. The modernization of the mining process, the integration of automated electrical drive systems, renewable energy sources, energy-saving technologies lead to an increase in the energy efficiency of production, but also to a decrease in the power quality, in particular, to an increase in the level of voltage harmonics. The problem of determining the grid harmonic impedance is solved in order to improve the quality of design and operation of power supply systems for mining enterprises, taking into account the peculiarities of their workload in the extraction of solid minerals by underground method. The paper considers the possibility of determining the grid impedance based on the measurement of non-characteristic harmonics generated by a special nonlinear load. A thyristor power controller based on phase regulation of the output voltage is considered as such a load. Simulation computer modeling and experimental studies on a laboratory test bench are used to confirm the proposed method. The recommendations for selecting load parameters and measuring device connection nodes have been developed.

Repurposing FDA-approved drugs to inhibit IL-33 mediated mast cell function

Abstract IL-33 is an IL-1-family cytokine that is released from fibroblasts, epithelial, endothelial, and some immune cells in response to tissue damage or inflammatory signals. IL-33 activates mast cells, innate leukocytes that play a key role in asthma. IL-33 induces production of inflammatory cytokines that worsen allergic diseases like asthma. It is essential to better understand IL-33 function and how to suppress it. Computer modeling studies using the SYBYL and GOLD algorithms to screen 3035 FDA-approved drugs for interactions with the IL-33 receptor, ST2, at the IL-33 binding site revealed several potential ST2 antagonists. In this study, we show that mouse bone marrow derived mast cells (BMMCs) treated with the antiviral drug lopinavir had diminished IL-33 responsiveness. Specifically, lopinavir (15mM) significantly reduced IL-33-mediated IL-6 and IL-13 secretion. Lopinavir effects noted when the drug was given simultaneously with IL-33 and were maximal when given 1 hour prior to IL-33 and suppression. These rapid effects suggest a direct drug-receptor interaction. We treated BMMCs with drug for up to 24 hours to assess for alternative mechanisms such as ST2 down-regulation, which was not noted. Other candidate drugs included clindamycin, which had no effect on IL-33-mediated cytokine production, and ritonavir and cobcistat, which increased cytokine secretion. Our data demonstrate that lopinavir can inhibit IL-33 mediated mast cell function, likely as an off-target effect of the drug. These data support further investigation of lopinavir and suggest the utility of repurposing FDA-approved drugs in allergy and asthma treatment.

Repurposing the inhibitors of MMP-9 and SGLT-2 against ubiquitin specific protease 30 in Parkinson’s disease: computational modelling studies

Ubiquitin specific protease 30 (USP30) has been attributed to mitochondrial dysfunction and impediment of mitophagy in Parkinson’s disease (PD). This happens once ubiquitin that supposed to bind with deformed mitochondria at the insistence of Parkin, it’s been recruited by USP30 via the distal ubiquitin binding domain. This is a challenge when PINK1 and Parkin loss their functions due to mutation. Although, there are reports on USP30s’ inhibitors but no study on the repurposing of inhibitors approved against MMP-9 and SGLT-2 as potential inhibitors of USP30 in PD. Thus, the highlight therein, is to repurpose approved inhibitors of MMP-9 and SGLT-2 against USP30 in PD using extensive computational modelling framework. 3D structures of Ligands and USP30 were obtained from PubChem and protein database (PDB) servers respectively, and were subjected to molecular docking, ADMET evaluation, DFT calculation, molecular dynamics simulation (MDS) and free energy calculations. Out of the 18 drugs, 2 drugs showed good binding affinity to the distal ubiquitin binding domain, moderate pharmacokinetic properties and good stability. The findings showed canagliflozin and empagliflozin as potential inhibitors of USP30. Thus, we present these drugs as repurposing candidates for the treatment of PD. However, the findings in this current study needs to be validated experimentally. Communicated by Ramaswamy H. Sarma

542. Alterations in Reward Sensitivity and Pavlovian Biases are Associated With Smoking Cessation Outcomes: A Computational Modeling and fMRI Study

542. Alterations in Reward Sensitivity and Pavlovian Biases are Associated With Smoking Cessation Outcomes: A Computational Modeling and fMRI Study

Visual attention modulates the transition from fine-grained, serial processing to coarser-grained, more parallel processing: A computational modeling study

During reading acquisition, beginning readers transition from serial to more parallel processing. The acquisition of word specific knowledge through orthographic learning is critical for this transition. However, the processes by which orthographic representations are acquired and fine-tuned as learning progresses are not well understood. Our aim was to explore the role of visual attention in this transition through computational modeling. We used the BRAID-Learn model, a Bayesian model of visual word recognition, to simulate the orthographic learning of 700 4-to 10-letter English known words and novel words, presented 5 times each to the model. The visual attention quantity available for letter identification was manipulated in the simulations to assess its influence on the learning process. We measured the overall processing time and number of attentional fixations simulated by the model across exposures and their impact on two markers of serial processing, the lexicality and length effects, depending on visual attention quantity. Results showed that the two lexicality and length effects were modulated by visual attention quantity. The quantity of visual attention available for processing further modulated novel word orthographic learning and the evolution of the length effect on processing time and number of attentional fixations across repeated exposures to novel words. The simulated patterns are consistent with behavioral data and the developmental trajectories reported during reading acquisition. Overall, the model predicts that the efficacy of orthographic learning depends on visual attention quantity and that visual attention may be critical to explain the transition from serial to more parallel processing.

Many Roles of Carbohydrates: A Computational Spotlight on the Coronavirus S Protein Binding.

Glycosylation is one of the post-translational modifications with more than 50% of human proteins being glycosylated. The exact nature and chemical composition of glycans are inaccessible to X-ray or cryo-electron microscopy imaging techniques. Therefore, computational modeling studies and molecular dynamics must be used as a "computational microscope". The spike (S) protein of SARS-CoV-2 is heavily glycosylated, and a few glycans play a more functional role "beyond shielding". In this mini-review, we discuss computational investigations of the roles of specific S-protein and ACE2 glycans in the overall ACE2-S protein binding. We highlight different functions of specific glycans demonstrated in myriad computational models and simulations in the context of the SARS-CoV-2 virus binding to the receptor. We also discuss interactions between glycocalyx and the S protein, which may be utilized to design prophylactic polysaccharide-based therapeutics targeting the S protein. In addition, we underline the recent emergence of coronavirus variants and their impact on the S protein and its glycans.

An Experimental and Computational Modeling Study on Additively Manufactured Micro‐Architectured Ti–24Nb–4Zr–8Sn Hollow‐Strut Lattice Structures

Herein, the design, manufacturing, and mechanical testing of hollow‐strut lattice structures of the metastable β‐titanium alloy Ti–24Nb–4Zr–8Sn (Ti2448) are performed. Due to the absence of studies in the literature, this study focusses on two important aspects: 1) the designing of micro‐architectured lattice structures and 2) metastable β‐titanium alloy. Face‐centered cubic (FCC) and body‐centered cubic (BCC) hollow‐strut lattices are designed by computer‐aided design and manufactured by laser powder bed fusion. The microstructure of the hollow lattices shows plates of α″‐martensite phase within the β phase. The FCC hollow lattice structure shows higher tensile strength compared to the BCC hollow lattice structure, while the load‐bearing capability of the FCC hollow lattice structure is lower than that of the BCC hollow lattice structure. At lower strains, the tensile force‐displacement curve of the hollow lattice structure matches the simulated tensile force‐displacement curve. At higher strains, a large deviation in the force‐displacement curve is observed in the hollow lattices.

Equivalence of quantum and classical third order response for weakly anharmonic coupled oscillators.

Two-dimensional (2D) infrared (IR) spectra are commonly interpreted using a quantum diagrammatic expansion that describes the changes to the density matrix of quantum systems in response to light-matter interactions. Although classical response functions (based on Newtonian dynamics) have shown promise in computational 2D IR modeling studies, a simple diagrammatic description has so far been lacking. Recently, we introduced a diagrammatic representation for the 2D IR response functions of a single, weakly anharmonic oscillator and showed that the classical and quantum 2D IR response functions for this system are identical. Here, we extend this result to systems with an arbitrary number of bilinearly coupled, weakly anharmonic oscillators. As in the single-oscillator case, quantum and classical response functions are found to be identical in the weakly anharmonic limit or, in experimental terms, when the anharmonicity is small relative to the optical linewidth. The final form of the weakly anharmonic response function is surprisingly simple and offers potential computational advantages for application to large, multi-oscillator systems.

Crosslinking Rapidly Cured Epoxy Resin Thermosets: Experimental and Computational Modeling and Simulation Study.

The power of computational modeling and simulation for establishing clear links between materials' intrinsic properties and their atomic structure has more and more increased the demand for reliable and reproducible protocols. Despite this increased demand, no one approach can provide reliable and reproducible outcomes to predict the properties of novel materials, particularly rapidly cured epoxy-resins with additives. This study introduces the first computational modeling and simulation protocol for crosslinking rapidly cured epoxy resin thermosets based on solvate ionic liquid (SIL). The protocol combines several modeling approaches, including quantum mechanics (QMs) and molecular dynamics (MDs). Furthermore, it insightfully provides a wide range of thermo-mechanical, chemical, and mechano-chemical properties, which agree with experimental data.

Energy Saving through Automation of the Lightweight Floor Heating System

The overview of the literature sources showed that over the last decade, the attention to the study of heat transfer processes with the automation and periodic use of underfloor heating systems has increased significantly. The aim of this study was to investigate the heat flux density from the surface of the lightweight floor heating system dependence on different parameters. These parameters are material of the finishing coating, average temperature difference between indoor air and heat carrier, heat carrier temperature and its flow rate, thickness of the thermal insulation layout under the lightweight floor heating system. The article shows results of both experimental and computational modelling studies of the lightweight floor heating system which was operated in different regimes and with different (ceramic tile and laminate) finishing coatings. A new experimental stand has been created in the thermophysical laboratory of the Institute of Engineering Thermophysics of the National Academy of Sciences of Ukraine for the purposes of experimental studies. For the purposes of comparison of different operational regimes as well as the determination of the energy saving through automation of the operation regimes of the lightweight floor heating system, the CFD modelling was conducted. The results showed that such systems have significant potential for automation and heat supply purposes of different premises since they have low thermal inertia due to the absence of the concrete screed monolith. On the other hand, the research showed that use of quantitative regulation of the lightweight floor heating system, by reducing the flow of the heat carrier is more effective in this case than qualitative with change of heat carrier temperature.

Rationalizing the Binding Modes of PET Radiotracers Targeting the Norepinephrine Transporter

A new PET radiotracer 18F-AF78 showing great potential for clinical application has been reported recently. It belongs to a new generation of phenethylguanidine-based norepinephrine transporter (NET)-targeting radiotracers. Although many efforts have been made to develop NET inhibitors as antidepressants, systemic investigations of the structure-activity relationships (SARs) of NET-targeting radiotracers have rarely been performed. Without changing the phenethylguanidine pharmacophore and 3-fluoropropyl moiety that is crucial for easy labeling, six new analogs of 18F-AF78 with different meta-substituents on the benzene-ring were synthesized and evaluated in a competitive cellular uptake assay and in in vivo animal experiments in rats. Computational modeling of these tracers was established to quantitatively rationalize the interaction between the radiotracers and NET. Using non-radiolabeled reference compounds, a competitive cellular uptake assay showed a decrease in NET-transporting affinity from meta-fluorine to iodine (0.42 and 6.51 µM, respectively), with meta-OH being the least active (22.67 µM). Furthermore, in vivo animal studies with radioisotopes showed that heart-to-blood ratios agreed with the cellular experiments, with AF78(F) exhibiting the highest cardiac uptake. This result correlates positively with the electronegativity rather than the atomic radius of the meta-substituent. Computational modeling studies revealed a crucial influence of halogen substituents on the radiotracer-NET interaction, whereby a T-shaped π-π stacking interaction between the benzene-ring of the tracer and the amino acid residues surrounding the NET binding site made major contributions to the different affinities, in accordance with the pharmacological data. The SARs were characterized by in vitro and in vivo evaluation, and computational modeling quantitatively rationalized the interaction between radiotracers and the NET binding site. These findings pave the way for further evaluation in different species and underline the potential of AF78(F) for clinical application, e.g., cardiac innervation imaging or molecular imaging of neuroendocrine tumors.

Environmentally-Friendly Pesticidal Activities of Callicarpa and Karomia Essential Oils from Vietnam and Their Microemulsions.

There is an ongoing interest to identify alternative pesticidal agents to avoid the chronic problems associated with synthetic pesticides. Essential oils have shown promise as botanical pest control agents. In the present study, the essential oils of four members of the Lamiaceae (Callicarpa candicans, C. erioclona, C. macrophylla, and Karomia fragrans; Vietnamese names: Nàng nàng, Tu châu lông mem, Tu châu lá to and Cà diện, respectively), obtained from wild populations in Vietnam, have been obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry. The essential oils were formulated into microemulsions and the essential oils and their microemulsions were screened for mosquito larvicidal activity against Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and for molluscicidal activity against Pomacea canaliculata. Atractylone and (E)-caryophyllene dominated the volatiles of C. candicans (CCEO) and C. erioclona (CEEO), while the major component in C. macrophylla (CMEO) and K. fragrans (KFEO) was (E)-caryophyllene. The essential oils and microemulsions of both C. candicans and C. erioclona exhibited excellent larvicidal activity against all three mosquito species (Ae. aegypti, Ae. albopictus, and Cx. quinquefasciatus) with LC50 values <10 μg/mL. Additionally, the larvicidal activity of the microemulsions were significantly improved compared with their free essential oils, especially for C. candicans and C. erioclona. All four essential oils and their microemulsions showed excellent molluscicidal activity with LC50 <10 μg/mL. In most cases, the essential oils and microemulsions showed greater pesticidal activity against target organisms than the non-target freshwater fish, Oreochromis niloticus. The in silico studies on physicochemical and ADMET properties of the major components in the studied essential oils were also investigated and most of the compounds possessed a favorable ADMET profile. Computational modeling studies of the studied compounds demonstrated a favorable binding interaction with the mosquito odorant-binding protein target and support atractylone, β-selinene, and caryophyllene oxide as potential inhibitors. Based on the observed pesticidal activities of the essential oils and their microemulsions, the Callicarpa species and K. fragrans should be considered for potential cultivation and further exploration as botanical pesticidal agents.

Reduction in defibrillation threshold by modifications to the subcutaneous implantable-cardioverter defibrillator coil

The subcutaneous implantable cardioverter defibrillator (S-ICD) is approved as an alternative to the traditional transvenous ICD (T-ICD). The S-ICD has higher average defibrillation threshold (DFT) than the T-ICD, related primarily to greater distance from shocking coil to ventricular myocardium with the S-ICD. The S-ICD therefore utilizes a larger device capable of generating an 80J shock, compared to 35-40J maximal shock output typical for T-ICDs, and defibrillation efficacy testing is generally recommended for the S-ICD 1 Wilkoff B, Fauchier L, Stiles M, et al. 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. Heart Rhythm 2016;13;e50-86. Google Scholar . We previously published computer modeling of predictors of defibrillation efficacy with the S-ICD, which determined that minimal fat underlying the S-ICD coil and generator (reducing shock impedance), and posterior generator position (better directing the shock vector across the ventricles), are predictors of lower DFT 2 Heist E. Belalcazar A. Stahl W. et al. Determinants of Subcutaneous Implantable Cardioverter-Defibrillator Efficacy. J Am Coll Cardiol EP. 2017; 3: 405-414 Google Scholar . Those findings formed the basis for the PRAETORIAN score, which is utilized in clinical S-ICD implantation to reduce DFT 3 Quast A.-F.B.E. Baalman S.W.E. Brouwer T.F. et al. A novel tool to evaluate the implant position and predict defibrillation success of the subcutaneous implantable cardioverter-defibrillator: The PRAETORIAN score. Heart Rhythm. 2018; 16: 403-410 Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar . A previously published computer modeling study examined the impact of dual S-ICD electrodes and electrode arrays, as well as variations in generator and lead location; results demonstrated reduced DFT with some configurations compared to the standard S-ICD 4 Jolley M. Stinstra J. Tate J. et al. Finite Element Modeling of Subcutaneous Implantable Defibrillator Electrodes in an Adult Torso. Heart Rhythm. 2010; 7: 692-698 Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar . In this current study, we performed computer modeling to determine whether design modifications to the S-ICD coil could result in reductions to S-ICD DFT.

The Effects of Negative Periocular Pressure on Biomechanics of the Optic Nerve Head and Cornea: A Computational Modeling Study.

The purpose of this study was to evaluate the effects of negative periocular pressure (NPP), and concomitant intraocular pressure (IOP) lowering, on the biomechanics of the optic nerve head (ONH) and cornea. We developed a validated finite element (FE) model of the eye to compute tissue biomechanical strains induced in response to NPP delivered using the Multi-Pressure Dial (MPD) system. The model was informed by clinical measurements of IOP lowering and was based on published tissue properties. We also conducted sensitivity analyses by changing pressure loads and tissue properties. Application of -7.9mmHg NPP decreased strain magnitudes in the ONH by c. 50% whereas increasing corneal strain magnitudes by c. 25%. Comparatively, a similar increase in corneal strain was predicted to occur due to an increase in IOP of 4mmHg. Sensitivity studies indicated that NPP lowers strain in the ONH by reducing IOP and that these effects persisted over a range of tissue stiffnesses and spatial distributions of NPP. NPP is predicted to considerably decrease ONH strain magnitudes. It also increases corneal strain but to an extent expected to be clinically insignificant. Thus, using NPP to lower IOP and hence decrease ONH mechanical strain is likely biomechanically beneficial for patients with glaucoma. This study provides the first description of how NPP affects ONH biomechanics and explains the underlying mechanism of ONH strain reduction. It complements current empirical knowledge about the MPD system and guides future studies of NPP as a treatment for glaucoma.

In Vitro Assessment Methods for Antidiabetic Peptides from Legumes: A Review.

Almost 65% of the human protein supply in the world originates from plants, with legumes being one of the highest contributors, comprising between 20 and 40% of the protein supply. Bioactive peptides from various food sources including legumes have been reported to show efficacy in modulating starch digestion and glucose absorption. This paper will provide a comprehensive review on recent in vitro studies that have been performed on leguminous antidiabetic peptides, focusing on the α-amylase inhibitor, α-glucosidase inhibitor, and dipeptidyl peptidase-IV (DPP-IV) inhibitor. Variations in legume cultivars and methods affect the release of peptides. Different methods have been used, such as in sample preparation, including fermentation (t, T), germination (t), and pre-cooking; in protein extraction, alkaline extraction, isoelectric precipitation, phosphate buffer extraction, and water extraction; in protein hydrolysis enzyme types and combination, enzyme substrate ratio, pH, and time; and in enzyme inhibitory assays, positive control type and concentration, inhibitor or peptide concentration, and the unit of inhibitory activity. The categorization of the relative scale of inhibitory activities among legume samples becomes difficult because of these method differences. Peptide sequences in samples were identified by means of HPLC/MS. Software and online tools were used in bioactivity prediction and computational modelling. The identification of the types and locations of chemical interactions between the inhibitor peptides and enzymes and the type of enzyme inhibition were achieved through computational modelling and enzyme kinetic studies.

Computational design of prospective molecular targets for Burkholderia cepacia complex by molecular docking and dynamic simulation studies.

The study aimed to screen prospective molecular targets of BCC and potential natural lead candidates as effective binders by computational modeling, molecular docking, and dynamic (MD) simulation studies. Based on the virulent functions, tRNA 5-methylaminomethyl-2-thiouridine biosynthesis bifunctional protein (mnmC) and pyrimidine/purine nucleoside phosphorylase (ppnP) were selected as the prospective molecular targets. In the absence of experimental data, the three-dimensional (3D) structures of these targets were computationally predicted. After a thorough literature survey and database search, the drug-likeness, and pharmacokinetic properties of 70 natural molecules were computationally predicted and the effectual binding of the best lead molecules against both the targets was predicted by molecular docking. The stabilities of the best-docked complexes were validated by MD simulation and the binding energy calculations were carried out by MM-GBSA approaches. The present study revealed that the hypothetical models of mnmC and ppnP showed stereochemical accuracy. The study also showed that among 70 natural compounds subjected to computational screening, Honokiol (3',5-Di(prop-2-en-1-yl) [1,1'-biphenyl]-2,4'-diol) present in Magnolia showed ideal drug-likeness, pharmacokinetic features and showed effectual binding with mnmC and ppnP (binding energies -7.3kcal/mol and -6.6kcal/mol, respectively). The MD simulation and GBSA calculation studies showed that the ligand-protein complexes stabilized throughout tMD simulation. The present study suggests that Honokiol can be used as a potential lead molecule against mnmC and ppnP targets of BCC and this study provides insight into further experimental validation for alternative lead development against drug resistant BCC.

Discussion of “Submerged Flow over Barrage Weirs: A Computational Fluid Dynamics Model Study” by Tirtha Roy Biswas, Pankaj Singh, and Dhrubajyoti Sen

Discussion of “Submerged Flow over Barrage Weirs: A Computational Fluid Dynamics Model Study” by Tirtha Roy Biswas, Pankaj Singh, and Dhrubajyoti Sen

Silibinin Overcomes EMT-Driven Lung Cancer Resistance to New-Generation ALK Inhibitors.

Epithelial-to-mesenchymal transition (EMT) may drive the escape of ALK-rearranged non-small-cell lung cancer (NSCLC) tumors from ALK-tyrosine kinase inhibitors (TKIs). We investigated whether first-generation ALK-TKI therapy-induced EMT promotes cross-resistance to new-generation ALK-TKIs and whether this could be circumvented by the flavonolignan silibinin, an EMT inhibitor. ALK-rearranged NSCLC cells acquiring a bona fide EMT phenotype upon chronic exposure to the first-generation ALK-TKI crizotinib exhibited increased resistance to second-generation brigatinib and were fully refractory to third-generation lorlatinib. Such cross-resistance to new-generation ALK-TKIs, which was partially recapitulated upon chronic TGFβ stimulation, was less pronounced in ALK-rearranged NSCLC cells solely acquiring a partial/hybrid E/M transition state. Silibinin overcame EMT-induced resistance to brigatinib and lorlatinib and restored their efficacy involving the transforming growth factor-beta (TGFβ)/SMAD signaling pathway. Silibinin deactivated TGFβ-regulated SMAD2/3 phosphorylation and suppressed the transcriptional activation of genes under the control of SMAD binding elements. Computational modeling studies and kinase binding assays predicted a targeted inhibitory binding of silibinin to the ATP-binding pocket of TGFβ type-1 receptor 1 (TGFBR1) and TGFBR2 but solely at the two-digit micromolar range. A secretome profiling confirmed the ability of silibinin to normalize the augmented release of TGFβ into the extracellular fluid of ALK-TKIs-resistant NSCLC cells and reduce constitutive and inducible SMAD2/3 phosphorylation occurring in the presence of ALK-TKIs. In summary, the ab initio plasticity along the EMT spectrum may explain the propensity of ALK-rearranged NSCLC cells to acquire resistance to new-generation ALK-TKIs, a phenomenon that could be abrogated by the silibinin-driven attenuation of the TGFβ/SMAD signaling axis in mesenchymal ALK-rearranged NSCLC cells.

Brain modeling for control: A review

Neurostimulation technologies have seen a recent surge in interest from the neuroscience and controls communities alike due to their proven potential to treat conditions such as epilepsy, Parkinson’s Disease, and depression. The provided stimulation can be of different types, such as electric, magnetic, and optogenetic, and is generally applied to a specific region of the brain in order to drive the local and/or global neural dynamics to a desired state of (in)activity. For most neurostimulation techniques, however, an underlying theoretical understanding of their efficacy is still lacking. From a control-theoretic perspective, it is important to understand how each stimulus modality interacts with the inherent complex network dynamics of the brain in order to assess the controllability of the system and develop neurophysiologically relevant computational models that can be used to design the stimulation profile systematically and in closed loop. In this paper, we review the computational modeling studies of 1) deep brain stimulation, 2) transcranial magnetic stimulation, 3) direct current stimulation, 4) transcranial electrical stimulation, and 5) optogenetics as five of the most popular and commonly used neurostimulation technologies in research and clinical settings. For each technology, we split the reviewed studies into 1) theory-driven biophysical models capturing the low-level physics of the interactions between the stimulation source and neuronal tissue, 2) data-driven stimulus-response models which capture the end-to-end effects of stimulation on various biomarkers of interest, and 3) data-driven dynamical system models that extract the precise dynamics of the brain’s response to neurostimulation from neural data. While our focus is particularly on the latter category due to their greater utility in control design, we review key works in the former two categories as the basis and context in which dynamical system models have been and will be developed. In all cases, we highlight the strength and weaknesses of the reviewed works and conclude the review with discussions on outstanding challenges and critical avenues for future work.

Posteroinferior relevant scapular neck offset in reverse shoulder arthroplasty: key player for motion and friction-type impingement in a computer model.

Range of motion (ROM) and prevention of notching remain a challenge for reverse shoulder arthroplasty (RSA). Both may be affected by the morphology of the scapula. The purpose of this study was to define anteroinferior (a) and posteroinferior (p) relevant scapular neck offset (RSNO) and to examine the hypothesis that pRSNO is significantly smaller than aRSNO, and influences rigid body motion (RBM). Adapting glenosphere implantation strategies may therefore be of value. In this computer model study, we used deidentified computed tomographic scans of 22 patients (11 male and 11 female; mean age: 72.9 years) with massive cuff tears without joint space narrowing. Eight RSA glenoid configurations were tested with a constant neck-shaft angle (145°). Two baseplate types (25 mm; 25 + 3 mm lateralized) and 4 glenospheres (GS) (36 mm; 36 +2 mm of eccentricity; 39 mm; 39 + 3 mm) were used. RSNO was defined as the standardized measurement of the horizontal distance from the inferior extent of the GS to the bony margin of the scapula after baseplate positioning (flush to inferior glenoid extent; neutral position: 0° inclination and 0° version-both software computed). There was a highly significant difference between pRSNO and aRSNO for both genders (P<.001). pRSNO was always smaller than aRSNO. pRSNO was strongly correlated with external rotation (ERO: 0.84) and extension (EXT: 0.74) and moderately correlated with global ROM (GROM: 0.68). There was a moderately strong correlation between aRSNO and internal rotation (IRO: 0.69). pRSNO was strongly correlated with aRSNO, EXT, ERO, IRO, adduction (ADD) and GROM (0.82, 0.72, 0,8, 0.71, 0.82, 0.76) in female patients and with EXT and ERO (0.82, 0.89) in male patients. The median pRSNO allowing for at least 45° ERO and 40° EXT was 14.2 mm for men and 13.8 mm for women. For all patients and models, pRSNO ≥14 mm increased EXT, ERO, and GROM significantly compared with pRSNO <14 mm (P<.001). The combination of lateralization and inferior overhang (eccentricity) led to the most significant increase of pRSNO for each GS size (P<.001). This is one of the first RSA modeling studies evaluating nonarthritic glenoids of both genders. The lateral scapular extent to glenoid relationship is asymmetric. pRSNO is always smaller than aRSNO for both genders and was a critical variable for EXT and ERO, demonstrating additional strong correlation with aRSNO, IRO, ADD, and GROM in female patients. pRSNO ≥14 mm was a safe value to prevent friction-type impingement. Combining increased glenosphere size, lateralization, and inferior overhang gives the best results in this computer-simulated setting.