Computational Modeling Studies Research Articles

Spectroscopic, biochemical and computational studies of bioactive DNA minor groove binders targeting 5′-WGWWCW-3′ motif

Spectroscopic, biochemical, and computational modelling studies have been used to assess the binding capability of a set of minor groove binding (MGB) ligands against the self-complementary DNA sequences 5′-d(CGCACTAGTGCG)-3′ and 5′-d(CGCAGTACTGCG)-3′. The ligands were carefully designed to target the DNA response element, 5′-WGWWCW-3′, the binding site for several nuclear receptors. Basic 1D 1H NMR spectra of the DNA samples prepared with three MGB ligands show subtle variations suggestive of how each ligand associates with the double helical structure of both DNA sequences. The variations among the investigated ligands were reflected in the line shape and intensity of 1D 1H and 31P-{1H} NMR spectra. Rapid visual inspection of these 1D NMR spectra proves to be beneficial in providing valuable insights on MGB binding molecules. The NMR results were consistent with the findings from both UV DNA denaturation and molecular modelling studies. Both the NMR spectroscopic and computational analyses indicate that the investigated ligands bind to the minor grooves as antiparallel side-by-side dimers in a head-to-tail fashion. Moreover, comparisons with results from biochemical studies offered valuable insights into the mechanism of action, and antitumor activity of MGBs in relation to their structures, essential pre-requisites for future optimization of MGBs as therapeutic agents.

Impact of interventions to reduce nosocomial transmission of SARS-CoV-2 in English NHS Trusts: a computational modelling study

BackgroundPrior to September 2021, 55,000–90,000 hospital inpatients in England were identified as having a potentially nosocomial SARS-CoV-2 infection. This includes cases that were likely missed due to pauci- or asymptomatic infection. Further, high numbers of healthcare workers (HCWs) are thought to have been infected, and there is evidence that some of these cases may also have been nosocomially linked, with both HCW to HCW and patient to HCW transmission being reported. From the start of the SARS-CoV-2 pandemic interventions in hospitals such as testing patients on admission and universal mask wearing were introduced to stop spread within and between patient and HCW populations, the effectiveness of which are largely unknown.Materials/methodsUsing an individual-based model of within-hospital transmission, we estimated the contribution of individual interventions (together and in combination) to the effectiveness of the overall package of interventions implemented in English hospitals during the COVID-19 pandemic. A panel of experts in infection prevention and control informed intervention choice and helped ensure the model reflected implementation in practice. Model parameters and associated uncertainty were derived using national and local data, literature review and formal elicitation of expert opinion. We simulated scenarios to explore how many nosocomial infections might have been seen in patients and HCWs if interventions had not been implemented. We simulated the time period from March-2020 to July-2022 encompassing different strains and multiple doses of vaccination.ResultsModelling results suggest that in a scenario without inpatient testing, infection prevention and control measures, and reductions in occupancy and visitors, the number of patients developing a nosocomial SARS-CoV-2 infection could have been twice as high over the course of the pandemic, and over 600,000 HCWs could have been infected in the first wave alone. Isolation of symptomatic HCWs and universal masking by HCWs were the most effective interventions for preventing infections in both patient and HCW populations. Model findings suggest that collectively the interventions introduced over the SARS-CoV-2 pandemic in England averted 400,000 (240,000 – 500,000) infections in inpatients and 410,000 (370,000 – 450,000) HCW infections.ConclusionsInterventions to reduce the spread of nosocomial infections have varying impact, but the package of interventions implemented in England significantly reduced nosocomial transmission to both patients and HCWs over the SARS-CoV-2 pandemic.

13. Increases in Aversive Arousal Promote Increased Craving and Greater Aversive Pruning During Planning in Amphetamine Use Disorders: An Experimental Computational Modelling Study

13. Increases in Aversive Arousal Promote Increased Craving and Greater Aversive Pruning During Planning in Amphetamine Use Disorders: An Experimental Computational Modelling Study

Paper Spray Mass Spectrometry with On-Paper Electrokinetic Manipulations: Part-Per-Trillion Detection of Per/Polyfluoroalkyl Substances in Water and Opioids in Urine.

We developed a simple, paper-based device that enables sensitive detection by mass spectrometry (MS) without solid phase extraction or other sample preparation. Using glass fiber filter papers within a 3D printed holder, the device employs electrokinetic manipulations to stack, separate, and desalt charged molecules on paper prior to spray into the MS. Due to counter-balanced electroosmotic flow and electrophoresis, charged analytes stack on the paper and desalting occurs in minutes. One end of the paper strip was cut into a sharp point and positioned near the inlet of a MS. The stacked analyte bands move toward the paper tip with the EOF where they are ionized by paper spray. The device was applied to analysis of PFAS in tap water with sub part-per-trillion detection limits in less than ten minutes with no sample pretreatment. Analysis of opioids in urine also occurs in minutes. The crucial parameters to enable stacking, separation, and MS ionization of both positively and negatively charged analytes were determined and optimized. Experimental and computational modeling studies confirm the electrokinetic stacking and analyte transport mechanisms. On-paper separations were carried out by stacking analyte bands at different locations depending on their electrophoretic mobility, achieving baseline separation in some cases.

432 Ligament Engagement and In-Situ Force During Multiplanar Loading of the Medial Knee Ligaments

OBJECTIVES/GOALS: Load sharing across the arc of knee flexion of the medial knee ligaments (MKLs) is not well understood. The goal of this research is to characterize ligament engagement and in-situ force within the deep and superficial medial collateral ligament (dMCL, sMCL) and the posterior oblique ligament (POL) in response to externally applied multiplanar loads. METHODS/STUDY POPULATION: Ten human cadaveric knees, 5 male and 5 female, age 32±7 (25-42) [mean±SD (range min-max)] years, were mounted to a force sensor and a 6-degree-of-freedom robotic arm. Knee kinematics, before and after serial dissection of the sMCL, dMCL, and POL, were recorded from 0-30 degrees during applied isolated external rotation, valgus angulation, and anterior tibial moments, and the force (Newtons, N) borne by each structure was measured via the principle of superposition. Loads in the dMCL, sMCL, and POL will be compared across each knee and at each flexion angle with paired t-tests and repeated-measures analysis of variance with Tukey post hoc testing. Ten knees will provide >99% power to detect differences of 5N ± 3% at p=0.05, which is considered the threshold for clinically meaningful force differences. RESULTS/ANTICIPATED RESULTS: Our anticipated results include characterization of the means and standard deviations of the in-situ forces within the dMCL, sMCL, and POL in response to externally applied valgus angulation, tibial external rotation, and anterior-directed tibial loading at 0, 15, and 30 degrees of knee flexion. Our statistical analysis will determine if there are clinically meaningful differences (5N ± 3%) in the loads within each ligament at different knee flexion angles and will also provide data regarding differential relative ligament engagement for each applied force scenario, which is an indication of the percentage of contribution that each structure contributes to knee stability during application of forces and torques to the knee. DISCUSSION/SIGNIFICANCE: Data on ligament engagement and in-situ forces will help clinicians better diagnose potentially injured ligaments when they observe pathological knee laxity in an injured patient. Our results will also inform future computer modeling studies on injury mechanisms, individual anatomical variability, and surgical planning.

A potential link between aromatics-induced oviposition repellency behaviors and specific odorant receptor of Aedes albopictus.

The Asian tiger mosquito, Aedes albopictus, is a competent vector for the spread of several viral arboviruses including dengue, chikungunya, and Zika. Several vital mosquito behaviors linked to survival and reproduction are primarily dependent on a sophisticated olfactory system for semiochemical perception. However, a limited number of studies has hampered our understanding of the relationship between the A. albopictus acute olfactory system and the complex chemical world. Here, we performed a qRT-PCR assay on antennae from A. albopictus of differing sex, age and physiological states, and found that AalbOr10 was enriched in blood-fed female mosquitoes. We then undertook single sensillum recording to de-orphan AalbOr10 using a panel of physiologically and behaviorally relevant odorants in a Drosophila 'empty neuron' system. The results indicated that AalbOr10 was activated by seven aromatic compounds, all of which hampered egg-laying in blood-fed mosquitoes. Furthermore, using a post-RNA interference oviposition assay, we found that reducing the transcript level of AalbOr10 affected repellent activity mediated by 2-ethylphenol at low concentrations (10-4 vol/vol). Computational modeling and molecular docking studies suggested that hydrogen bonds to Y68 and Y150 mediated the interaction of 2-ethylphenol with AalbOr10. We reveal a potential link between aromatics-induced oviposition repellency behaviors and a specific odorant receptor in A. albopictus. Our findings provide a foundation for identifying active semiochemicals for the monitoring or controlling of mosquito populations. © 2024 Society of Chemical Industry.

Review of experimental studies on the properties of the ozone-safe refrigerant R1234yf and their mathematical modeling using equations of state

In this review, a set of 44 experimental studies on the thermophysical properties of the promising ozone-safe refrigerant R1234yf are considered. Based on the experimental data, the following properties are found to be necessary when using the refrigerant: saturation pressure, saturated vapor density, p–v–t dependence, isobaric heat capacity, isochoric heat capacity, isobaric heat capacity of an ideal gas, sound velocity, dynamic viscosity, kinematic viscosity, surface tension, and thermal conductivity. In addition, the published measurement errors are specified. Furthermore, a list of computational modeling studies on the thermodynamic properties of the refrigerant R1234yf with an indication of the type of equation of state used is presented. The contributions of Russian scientists to the development of this field are also described. This review increases the efficiency of the information search on the properties of R1234yf and their modeling. Finally, conclusions are drawn regarding the completeness of the information based on experiments and the extent of possibilities of the current modeling methods for the properties of the refrigerant under consideration.

Predicting sex differences in the effects of diuretics in renal epithelial transport during angiotensin II-induced hypertension.

Chronic angiotensin II (ANG II) infusion is an experimental model that induces hypertension in rodents. The natriuresis, diuresis, and blood pressure responses differ between males and females. This is perhaps not unexpected, given the rodent kidney, which plays a key role in blood pressure regulation, exhibits marked sex differences. Under normotensive conditions, compared with males, the female rat nephron exhibits lower Na+/H+ exchanger 3 (NHE3) activity along the proximal tubule but higher Na+ transporter activities along the distal segments. ANG II infusion-induced hypertension induces a pressure natriuretic response that reduces NHE3 activity and shifts Na+ transport capacity downstream. The goals of this study were to apply a computational model of epithelial transport along a rat nephron 1) to understand how a 14-day ANG II infusion impacts segmental electrolyte transport in male and female rat nephrons and 2) to identify and explain any sex differences in the effects of loop diuretics, thiazide diuretics, and K+-sparing diuretics. Model simulations suggest that the NHE3 downregulation in the proximal tubule is a major contributor to natriuresis and diuresis in hypertension, with the effects stronger in males. All three diuretics are predicted to induce stronger natriuretic and diuretic effects under hypertension compared with normotension, with relative increases in sodium excretion higher in hypertensive females than in males. The stronger natriuretic responses can be explained by the downstream shift of Na+ transport load in hypertension and by the larger distal transport load in females, both of which limit the ability of the distal segments to further elevate their Na+ transport.NEW & NOTEWORTHY Sex differences in the prevalence of hypertension are found in human and animal models. The kidney, which regulates blood pressure, exhibits sex differences in morphology, hemodynamics, and membrane transporter distributions. This computational modeling study provides insights into how the sexually dimorphic responses to a 14-day angiotensin II infusion differentially impact segmental electrolyte transport in rats. Simulations of diuretic administration explain how the natriuretic and diuretic effects differ between normotension and hypertension and between the sexes.

Biological motion perception in the theoretical framework of perceptual decision-making: An event-related potential study

Biological motion perception plays a critical role in various decisions in daily life. Failure to decide accordingly in such a perceptual task could have life-threatening consequences. Neurophysiology and computational modeling studies suggest two processes mediating perceptual decision-making. One of these signals is associated with the accumulation of sensory evidence and the other with response selection. Recent EEG studies with humans have introduced an event-related potential called Centroparietal Positive Potential (CPP) as a neural marker aligned with the sensory evidence accumulation while effectively distinguishing it from motor-related lateralized readiness potential (LRP). The present study aims to investigate the neural mechanisms of biological motion perception in the framework of perceptual decision-making, which has been overlooked before. More specifically, we examine whether CPP would track the coherence of the biological motion stimuli and could be distinguished from the LRP signal. We recorded EEG from human participants while they performed a direction discrimination task of a point-light walker stimulus embedded in various levels of noise. Our behavioral findings revealed shorter reaction times and reduced miss rates as the coherence of the stimuli increased. In addition, CPP tracked the coherence of the biological motion stimuli with a tendency to reach a common level during the response, albeit with a later onset than the previously reported results in random-dot motion paradigms. Furthermore, CPP was distinguished from the LRP signal based on its temporal profile. Overall, our results suggest that the mechanisms underlying perceptual decision-making generalize to more complex and socially significant stimuli like biological motion.

Anionic species from multivalent metal salts are differentially retained during aqueous ionic gelation of sodium alginate and could fine-tune the hydrogel properties

The role of anionic counterions of divalent metal salts in alginate gelation and hydrogel properties has been thoroughly investigated. Three anions were selected from the Hofmeister series, namely sulphate, acetate and chloride, paired in all permutations and combinations with divalent metal cations like calcium, zinc and copper. Spectroscopic analysis revealed the presence of anions and their interaction with the respective metal cations in the hydrogel. The data showed that the gelation time and other hydrogel properties were largely controlled by cations. However, subtle yet significant variations in viscoelasticity, water uptake, drug release and cytocompatibility properties were anion dependent in each cationic group. Computational modelling based study showed that metal-anion-alginate configurations were energetically more stable than the metal-alginate models. The in vitro and in silico studies concluded that acetate anions preceded chlorides in the drug release, swelling and cytocompatibility fronts, followed by sulphate anions in each cationic group. Overall, the data confirmed that anions are an integral part of the metal-alginate complex. Furthermore, anions offer a novel option to further fine-tune the properties of alginate hydrogels for myriads of applications. In addition, full exploration of this novel avenue would enhance the usability of alginate polymers in the pharmaceutical, environmental, biomedical and food industries.

Tool-pin profile effects on thermal and material flow in friction stir butt welding of AA2219-T87 plates: computational fluid dynamics model development and study

Tool-pin profile effects on thermal and material flow in friction stir butt welding of AA2219-T87 plates: computational fluid dynamics model development and study

Proactive esophageal cooling during laser cardiac ablation: A computer modeling study.

Laser ablation is increasingly used to treat atrial fibrillation (AF). However, atrioesophageal injury remains a potentially serious complication. While proactive esophageal cooling (PEC) reduces esophageal injury during radiofrequency ablation, the effects of PEC during laser ablation have not previously been determined. We aimed to evaluate the protective effects of PEC during laser ablation of AF by means of a theoretical study based on computer modeling. Three-dimensional mathematical models were built for 20 different cases including a fragment of atrial wall (myocardium), epicardial fat (adipose tissue), connective tissue, and esophageal wall. The esophagus was considered with and without PEC. Laser-tissue interaction was modeled using Beer-Lambert's law, Pennes' Bioheat equation was used to compute the resultant heating, and the Arrhenius equation was used to estimate the fraction of tissue damage (FOD), assuming a threshold of 63% to assess induced necrosis. We modeled laser irradiation power of 8.5 W over 20 s. Thermal simulations extended up to 250 s to account for thermal latency. PEC significantly altered the temperature distribution around the cooling device, resulting in lower temperatures (around 22°C less in the esophagus and 9°C in the atrial wall) compared to the case without PEC. This thermal reduction translated into the absence of transmural lesions in the esophagus. The esophagus was thermally damaged only in the cases without PEC and with a distance equal to or shorter than 3.5 mm between the esophagus and endocardium (inner boundary of the atrial wall). Furthermore, PEC demonstrated minimal impact on the lesion created across the atrial wall, either in terms of maximum temperature or FOD. PEC reduces the potential for esophageal injury without degrading the intended cardiac lesions for a variety of different tissue thicknesses. Thermal latency may influence lesion formation during laser ablation and may play a part in any collateral damage.

Biochemical and metabolic characterization of a G6PC2 inhibitor

Three glucose-6-phosphatase catalytic subunits, that hydrolyze glucose-6-phosphate (G6P) to glucose and inorganic phosphate, have been identified, designated G6PC1-3, but only G6PC1 and G6PC2 have been implicated in the regulation of fasting blood glucose (FBG). Elevated FBG has been associated with multiple adverse clinical outcomes, including increased risk for type 2 diabetes and various cancers. Therefore, G6PC1 and G6PC2 inhibitors that lower FBG may be of prophylactic value for the prevention of multiple conditions. The studies described here characterize a G6PC2 inhibitor, designated VU0945627, previously identified as Compound 3. We show that VU0945627 preferentially inhibits human G6PC2 versus human G6PC1 but activates human G6PC3. VU0945627 is a mixed G6PC2 inhibitor, increasing the Km but reducing the Vmax for G6P hydrolysis. PyRx virtual docking to an AlphaFold2-derived G6PC2 structural model suggests VU0945627 binds two sites in human G6PC2. Mutation of residues in these sites reduces the inhibitory effect of VU0945627. VU0945627 does not inhibit mouse G6PC2 despite its 84% sequence identity with human G6PC2. Mutagenesis studies suggest this lack of inhibition of mouse G6PC2 is due, in part, to a change in residue 318 from histidine in human G6PC2 to proline in mouse G6PC2. Surprisingly, VU0945627 still inhibited glucose cycling in the mouse islet-derived βTC-3 cell line. Studies using intact mouse liver microsomes and PyRx docking suggest that this observation can be explained by an ability of VU0945627 to also inhibit the G6P transporter SLC37A4. These data will inform future computational modeling studies designed to identify G6PC isoform-specific inhibitors.

Muscle Morphology Does Not Solely Determine Knee Flexion Weakness After Anterior Cruciate Ligament Reconstruction with a Semitendinosus Tendon Graft: A Combined Experimental and Computational Modeling Study.

The distal semitendinosus tendon is commonly harvested for anterior cruciate ligament reconstruction, inducing substantial morbidity at the knee. The aim of this study was to probe how morphological changes of the semitendinosus muscle after harvest of its distal tendon for anterior cruciate ligament reconstruction affects knee flexion strength and whether the knee flexor synergists can compensate for the knee flexion weakness. Ten participants 8-18months after anterior cruciate ligament reconstruction with an ipsilateral distal semitendinosus tendon autograft performed isometric knee flexion strength testing (15°, 45°, 60°, and 90°; 0° = knee extension) positioned prone on an isokinetic dynamometer. Morphological parameters extracted from magnetic resonance images were used to inform a musculoskeletal model. Knee flexion moments estimated by the model were then compared with those measured experimentally at each knee angle position. A statistically significant between-leg difference in experimentally-measured maximal isometric strength was found at 60° and 90°, but not 15° or 45°, of knee flexion. The musculoskeletal model matched the between-leg differences observed in experimental knee flexion moments at 15° and 45° but did not well estimate between-leg differences with a more flexed knee, particularly at 90°. Further, the knee flexor synergists could not physiologically compensate for weakness in deep knee flexion. These results suggest additional factors other than knee flexor muscle morphology play a role in knee flexion weakness following anterior cruciate ligament reconstruction with a distal semitendinosus tendon graft and thus more work at neural and microscopic levels is required for informing treatment and rehabilitation in this demographic.

Does-dual mobility still offer improved stability in smaller cup sizes? A computer modelling comparison of stability with 22-mm versus 28-mm inner heads in dual-mobility versus single-bearing constructs.

Dislocation remains 1 of the leading causes of revision after primary total hip arthroplasty (THA) and there is clear evidence the dual-mobility (DM) is used more frequently to minimise this. But in smaller cups, whether the use of DM with smaller 22-mm heads imparts any increased stability compared to standard bearing is unknown; especially when those smaller cups now allow for large single-bearing (SB) heads. 3 primary cup sizes (48 mm, 50 mm, 52 mm) were chosen a priori for modelling. Head sizes trialled for the standard bearing (SB) constructs group were 28-0 mm, 32-0 mm and 36-0 mm against neutral polyethylene liners. In the modular sub-hemispheric DM constructs the inner head sizes for the DM constructs were altered where appropriate (22-0 mm vs. 28-0 mm). Cup position, stem offset, and stem size were standardised. Both DM constructs outperformed all SB constructs because of a statistically significant jump distance increase (p < 0.001). However, there was no difference in range of motion (ROM) or jump distances between the 22-mm and 28-mm DM inner heads.The ROM angle before impingement between the DM (with 22-mm or 28-mm heads) and SB (with different head sizes where appropriate) showed no statistically significant difference. However, DM constructs presented significantly larger jump distances than SB constructs for both provocative dislocation tests across all 3 cup sizes.Of interest, for 50-mm and 52-mm cup sizes (for which this particular DM construct design can accommodate both 22-mm and 28-mm inner heads), there were no differences in ROM or jump distance between 22-mm versus 28-mm inner heads. In this computer-modelling study, DM constructs are advantageous over SB constructs for improving jump distances in clinically provocative positions, but not range of motion angles. Inner head diameter of DM has no effect on stability.

Fusion-fission-mitophagy cycling and metabolic reprogramming coordinate nerve growth factor (NGF)-dependent neuronal differentiation.

Neuronal differentiation is regulated by nerve growth factor (NGF) and other neurotrophins. We explored the impact of NGF on mitochondrial dynamics and metabolism through time-lapse imaging, metabolomics profiling, and computer modeling studies. We show that NGF may direct differentiation by stimulating fission, thereby causing selective mitochondrial network fragmentation and mitophagy, ultimately leading to increased mitochondrial quality and respiration. Then, we reconstructed the dynamic fusion-fission-mitophagy cycling of mitochondria in a computer model, integrating these processes into a single network mechanism. Both the computational model and the simulations are able to reproduce the proposed mechanism in terms of mitochondrial dynamics, levels of reactive oxygen species (ROS), mitophagy, and mitochondrial quality, thus providing a computational tool for the interpretation of the experimental data and for future studies aiming to detail further the action of NGF on mitochondrial processes. We also show that changes in these mitochondrial processes are intertwined with a metabolic function of NGF in differentiation: NGF directs a profound metabolic rearrangement involving glycolysis, TCA cycle, and the pentose phosphate pathway, altering the redox balance. This metabolic rewiring may ensure: (a) supply of both energy and building blocks for the anabolic processes needed for morphological reorganization, as well as (b) redox homeostasis.

A comparative modeling study of the mitochondrial function of the proximal tubule and thick ascending limb cells in the rat kidney.

To reabsorb >99% of the glomerular filtrate, the metabolic demand of the kidney is high. Interestingly, renal blood flow distribution exhibits marked inhomogeneity, with typical tissue oxygen tension (Po2) of 50-60 mmHg in the well-perfused cortex and 10-20 mmHg in the inner medulla. Cellular fluid composition and acidity also varies substantially. To understand how different renal epithelial cells adapt to their local environment, we have developed and applied computational models of mitochondrial function of proximal convoluted tubule cell (baseline Po2 = 50 mmHg, cytoplasmic pH = 7.20) and medullary thick ascending limb (mTAL) cell (baseline Po2 = 10 mmHg, cytoplasmic pH = 6.85). The models predict key cellular quantities, including ATP generation, P/O (phosphate/oxygen) ratio, proton motive force, electrical potential gradient, oxygen consumption, the redox state of key electron carriers, and ATP consumption. Model simulations predict that close to their respective baseline conditions, the proximal tubule and mTAL mitochondria exhibit qualitatively similar behaviors. Nonetheless, because the mTAL mitochondrion has adapted to a much lower Po2, it can sustain a sufficiently high ATP production at Po2 as low as 4-5 mmHg, whereas the proximal tubule mitochondria would not. Also, because the mTAL cytosol is already acidic under baseline conditions, the proton motive force (pmf) exhibits higher sensitivity to further acidification. Among the different pathways that lead to oxidative phosphorylation impairment, the models predict that both the proximal tubule and mTAL mitochondria are most sensitive to reductions in Complex III activity.NEW & NOTEWORTHY Tissue fluid composition varies substantially within the mammalian kidney. The renal cortex is well perfused and pH neutral, whereas some medullary regions are hypoxic and acidic. How do these environments affect the mitochondrial function of proximal convoluted tubule and medullary thick ascending limb cells, which reside in the cortex and medulla, respectively? This computational modeling study demonstrates that these mitochondria can adapt to their contrasting environments and exhibit different sensitivities to perturbations to local environments.

Computational modelling and optimization studies of electropentamer for molecular imprinting of DJ-1

Parkinson's disease (PD) is the most prevalent type of incurable movement disorder. Recent research findings propose that the familial PD-associated molecule DJ-1 exists in cerebrospinal fluid (CSF) and that its levels may be altered as Parkinson's disease advances. By using a molecularly imprinted polymer (MIP) as an artificial receptor, it becomes possible to create a functional MIP with predetermined selectivity for various templates, particularly for the DJ-1 biomarker associated with Parkinson's disease. It mostly depends on molecular recognition via interactions between functional monomers and template molecules. So, the computational methods for the appropriate choice of functional monomers for creating molecular imprinting electropolymers (MIEPs) with particular recognition for the detection of DJ-1, a pivotal biomarker involved in PD, are undertaken in this study. Here, molecular docking, molecular dynamics simulations (MD), molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) methods, and quantum mechanical calculation have been applied to investigate the intermolecular interaction between DJ-1 and several functional electropentamers, viz., polypyrrole (PPy), poly(3,4-ethylenedioxythiophene) (PEDOT), poly(o-aminophenol) (POAP), and polythiophene (PTS). In this context, the electropentamers were selected to mimic the imprinted electropolymer system. We analyzed the most stable configurations of the formed complexes involving DJ-1 and electropentamers as a model system for MIEPs. Among these, PEDOT exhibited a more uniform arrangement around DJ-1, engaging in numerous van der Waals, H-bond, electrostatic, and hydrophobic interactions. Hence, it can be regarded as a preferable choice for synthesizing a MIP for DJ-1 recognition. Thus, it will aid in selecting a suitable functional monomer, which is of greater significance in the design and development of selective DJ-1/MIP sensors.

Maximizing aged photovoltaic array power: a computer modelling study

Abstract Photovoltaic (PV) modules age with time for various reasons such as corroded joints and terminals and glass coating defects, and their ageing degrades the PV array power. With the help of the PV array numerical model, this paper explores the effects of PV module ageing on the PV array power, and the power gains and costs of rearranging and recabling aged PV modules in a PV array. The numerical PV array model is first revised to account for module ageing, rearrangement and recabling, with the relevant equations presented herein. The updated numerical model is then used to obtain the array powers for seven different PV arrays. The power results are then analysed in view of the attributes of the seven PV array examples. A guiding method to recommend recabling after rearranging aged modules is then proposed, leading to further significant power gains, while eliminating intra-row mismatches. When certain conditions are met, it was shown that recabling PV modules after rearranging them may lead to further significant power gains, reaching 57% and 98% in two considered PV array examples. Higher gains are possible in other arrays. A cost–benefit analysis weighing annual power gains versus estimated recabling costs is also given for the seven considered PV array examples to guide recabling decisions based on technical and economic merits. In the considered examples, recabling costs can be recovered in &amp;lt;4 years. Compared with the powers of the aged arrays, power gains due to our proposed rearranging and recabling the PV arrays ranged between 73% and 131% in the considered examples—well over the gains reported in the literature. Moreover, the cost of our static module rearrangement and recabling method outshines the costs of dynamic reconfiguration methods recently published in the literature.

Computational Model Study of the Experimentally Suggested Mechanism for Nitrogenase.

The mechanism for N2 activation in the E4 state of nitrogenase was investigated by model calculations. In the experimentally suggested mechanism, the E4 state is obtained after four reductions to the ground state. In a recent theoretical study, results for a different mechanism have been found in excellent agreement with available Electron Paramagnetic Resonance (EPR) experiments for E4. The two hydrides in E4 leave as H2 concertedly with the binding of N2. The mechanism suggested differs from the experimentally suggested one by a requirement for four activation steps prior to catalysis. In the present study, the experimentally suggested mechanism is studied using the same methods as those used in the previous study on the theoretical mechanism. The computed results make it very unlikely that a structure obtained after four reductions from the ground state has two hydrides, and the experimentally suggested mechanism does therefore not agree with the EPR experiments for E4. Another structure with only one hydride is here suggested to be the one that has been observed to bind N2 after only four reductions of the ground state.