Favorable Regions Research Articles

In silico investigation of a novel anti-EGFR scFv-IL-24 fusion protein induces apoptosis in malignant cells.

Epidermal growth factor receptor (EGFR), a member of the HER receptor family, is over expressed in various cancer cells. Using tumor-specific antibodies to deliver cytotoxic agents directly to the tumor cells is an effective treatment strategy. Targeted therapy by fusing anti-EGFR scFv with tumor-specific cytokines promises the emergence of a new era. We designed a novel immuno-apoptotic fusion protein, anti-EGFR scFv-IL-24, consisting of a specific cancer cell targeting antibody and recombinant cytokine IL-24 to explore its anti-cancerous potential. Amino acid sequences of both anti-EGFR scFv and IL-24 were fused using a specific rigid linker. In silico characterization of the designed fusion protein like to predict the primary, secondary, physiochemical properties, quality, and structural validation using online bioinformatic tools. The newly designed fusion protein consists of 402 amino acids that showed good quality with a predicted value of 76.7% having 81.5% residues in the most favored region as predicted by ERRAT2 and Ramachandran plot analysis. Docking and simulation studies were performed using HDOCK and Desmond module of Schrodinger. All the parameters of quality, validity, interaction analysis, and stability suggested that the fused molecule is fully operational and functional. The results of the study support that the anti-EGFR scFv-IL-24 fused protein could be proved as a novel candidate to combat cancer.

Insights on in-silico approaches for identifying potential bioactive inhibitors for TNF-α and IL-6 proteins associated with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic immunocompromised disorder that primarily affects joints thereby leading to synovial inflammation, pain, stiffness, stress, and affecting the quality of life. The present study aimed to determine and identify bioactive compounds that can be developed as potential inhibitors to target human TNF-α and IL-6 proteins associated with RA. The present study also aimed to determine physiochemical properties and toxicity of compounds by ADMET, identify binding pockets via CASTp server, stereochemical quality of protein by PROCHECK, MMGB/SA analysis by fastDRH and molecular dynamics (WebGro). The findings of the present study revealed staurosporine was the most effective compound against TNF-α with the highest binding affinity of −10.8 kcal/mol. Similarly, withanoside L showed the highest binding affinity of −8.2 kcal/mol when docked against IL-6. In the present study, rutin, withanoside II, and withanoside IV did not follow Lipinski’s rule of five whereas staurosporine, somnifericin, and withanolide L followed RO5. In the present study, the top binding pocket of TNF-α had highest area (SA) of 2743.25 Å2 and volume (SA) 4514.06 Å3 whereas IL-6 had highest area (SA) of 63.54 Å2 and volume (SA) of 38.58 Å3 respectively. In this study, Ramachandran plot analysis revealed that 90.2% and 95.2% residues for TNF-α and IL-6 proteins occupied the most favored region. In the present study, TNF-α rutin complex and IL-6 rutin complex showed the highest PB1 score of 13.69 kcal/mol and 12.30 kcal/mol respectively. WebGro server estimated molecular dynamic properties (RMSD, Rg, SASA, RMSF and hydrogen bonds) of the proteins. Bio2Byte tools predicted the biophysical behaviour of the proteins. The findings of the present study revealed that staurosporine and withanolide L could be developed as potential inhibitors of TNF- α and IL-6, however further in-vitro and in-vivo studies are required to validate these results.

Proteome based analysis of circulating SARS-CoV-2 variants: approach to a universal vaccine candidate.

The discovery of the first infectious variant in Wuhan, China, in December 2019, has posed concerns over global health due to the spread of COVID-19 and subsequent variants. While the majority of patients experience flu-like symptoms such as cold and fever, a small percentage, particularly those with compromised immune systems, progress from mild illness to fatality. COVID-19 is caused by a RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approach involved utilizing immunoinformatic to identify vaccine candidates with multiple epitopes and ligand-binding regions in reported SARS-CoV-2 variants. Through analysis of the spike glycoprotein, we identified dominant epitopes for T-cells and B-cells, resulting in a vaccine construct containing two helper T-cell epitopes, six cytotoxic T-cell epitopes, and four linear B-cell epitopes. Prior to conjugation with adjuvants and linkers, all epitopes were evaluated for antigenicity, toxicity, and allergenicity. Additionally, we assessed the vaccine Toll-Like Receptors complex (2, 3, and 4). The vaccine construct demonstrated antigenicity, non-toxicity, and non-allergenicity, thereby enabling the host to generate antibodies with favorable physicochemical characteristics. Furthermore, the 3D structure of the B-cell construct exhibited a ProSA-web z-score plot with a value of -1.71, indicating the reliability of the designed structure. The Ramachandran plot analysis revealed that 99.6% of the amino acid residues in the vaccine subunit were located in the high favored observation region, further establishing its strong candidacy as a vaccination option.

A Model for the Lithospheric Architecture of the Central Andes and the Localization of Giant Porphyry Copper Deposit Clusters

Abstract In the central Andes, giant porphyry copper deposits of similar ages group into discrete geographic clusters that are regularly spaced and aligned within orogen-parallel belts. This clustering highlights how exceptional geologic processes affected localized regions of the lithosphere during mineralization and that the spatial and temporal distribution of giant porphyry deposits is nonrandom. Development of favorable regions of lithosphere for significant metal concentration are linked to the overlap of structural pathways that focus fluid and magma flow from the mantle to upper crust during high-horizontal-compressive-strain events. These structural pathways are notoriously difficult to identify in the field due to their often-subtle surficial manifestations and continental scale. Field mapping at multiple scales in northwest Argentina and southern Peru, as well as regional structural traverses throughout the central Andes, indicates the presence of regional-scale structural corridors 5 to 25 km wide and hundreds of km long that consist of myriad fault planes. The variable width and diffuse surface expression of these corridors is interpreted to reflect the upward propagation of underlying zones of basement weakness through younger supracrustal sequences in the overriding plate. Such structural corridors are (1) apparent at multiple scales of investigation, (2) long-lived, (3) preferentially reactivated though time, and (4) evident in geophysical data sets. This structural architecture formed in response to the interplay of pre-Cenozoic tectonics and the orientation of inherited structural weaknesses. These fault systems persist in the upper crust as steep zones of enhanced permeability that can preferentially reactivate as pathways for ascending hydrous magmas and fluids during major deformation events. Linear orogen-parallel structural belts cogenetic with the magmatic arc provide the first-order control to giant porphyry copper deposit distribution. The second-order control is the intersection of orogen-oblique structural corridors with the orogen-parallel belts, localizing deposit clusters at these intersections. Such regions are inferred to have been zones of deep permeability, with vertical translithospheric pathways activated during high-strain tectonic events that affected the intra-arc stress field.

Quantification of time-dependent deterioration in mechanical property and ballistic performance through Cunniff Number of poly (p-phenylene terephthalamide) fibers under UV irradiation

Poly (p-phenylene terephthalamide) fibers, a crucial constituent of soft body armor, experience significant deterioration in mechanical and ballistic performance due to UV exposure. However, photo-degradation by UV radiation involves complex chemical reactions and the difficulty in estimating the extent of damage that restricts the development of the predictive aging models or kinetics in such fibrous materials. Hence in this work, the photo-degradation kinetics of poly (p-phenylene terephthalamide) or KF-fibers is quantified by correlating the degradation behavior of different properties with time, thereby assessing the useful performance span of the UV-aged (UV-KF) fibers. The experimental trends indicate three stages of deterioration of any property (modulus, extension at break, Cunniff Number and crystallinity), i.e., an exponential decline followed by an increase over a short duration and finally, a steady and continuous drop. The suitable performance period of UV-aged fibers is estimated based on the initial two stages and presented as ‘favorable property region’ or ‘FPR-zone.’ Changes in V50 ballistic limit, theoretically derived from Cunniff Number, are also estimated, which show a good agreement with the literature data. It reveals that the energy absorption capacity of UV-KF fibers corresponds to initial two years as a span of considerable ballistic protection before continuing to function at 50% of its original protection level for lower aging temperatures. Besides, the apparent activation energy for all the studied properties is correlated to the microstructural and physico-chemical aspects. It indicates that relative changes in molar mass by bond scission/rearrangement and alterations in crystallinity are proportionally related to the degree of variation in modulus and extension at break, thus affecting the wave-velocities in terms of Cunniff Number. The proposed degradation model further can be extended to determine the rate of degradation and lifetime of various ballistic materials under other environmental conditions.

The Effect of Environmental Disasters on Endocrine Status, Hematology Parameters, Body Composition, and Physical Performance in Young Soccer Players: A Case Study of the Aral Sea Region.

The Aral Sea region (Uzbekistan) is infamous because of the ecological disaster characterized by the disappearance of the Aral Sea due to excessive uncontrolled water intake for agriculture needs. A new desert occurrence, soil and climate aridization led to pesticide and toxic metals environment pollution. The impact of environmental conditions in some areas of Uzbekistan on the health of soccer players is not as noticeable as, for example, the effectiveness of training, so it is not widely discussed in scientific papers. The aim of the present study was to study the features of endocrine status, hematology parameters (e.g., red blood cells (RBC) and hemoglobin (Hb)), and their influence on body composition and physical fitness performance in local young soccer players of the Aral Sea region as the territory of ecological disaster. The study involved 60 male soccer players aged from 18 to 22 years. Participants were divided into two groups: the experimental group (EG), which consisted of 30 soccer players living on the territory of the Aral ecological disaster region, and the control group (CG), which included 30 soccer players, natives of the ecologically favorable region of Uzbekistan. All volunteers had anthropometric measurements, concentrations of insulin-like growth factor-1 (IGF-1), total testosterone (TT), estradiol (E2), cortisol (C), RBC, and Hb count. Moreover, Yo-Yo Intermittent Recovery Test Level 1 (YYIRT1) and professional skills tests such as dribbling shuttle test (DSt) and goal accuracy test (GAt) were assessed. When comparing the CG group to the EG group, it was observed that the EG group exhibited statistically significantly reduced levels of TT and E2 (p < 0.05). No significant statistical difference was observed between the two groups in terms of IGF-1 and C (p > 0.05). Regarding hematological parameters, Hb, Ht, and mean corpuscular volume (MCV) were found to be significantly lower in the EG compared with the CG (p < 0.05). Moreover, the distance covered in the YYIR1 test was found to be significantly lower in soccer players within the EG compared with the CG (p < 0.05). Additionally, it was determined that there was no significant difference between the groups in terms of DSt and GAt values (p > 0.05). Lastly, significant differences were observed between the EG and CG in terms of anthropometric characteristics (diameters, skinfold, and somatotype profile) (p < 0.05). The present study showed that the changes in evaluated characteristics might result from the complex influence of endocrine-disrupting chemicals, the content of which is high in the environment of the Aral Sea region. The results obtained may help monitor the health of athletes living in an environmentally unfriendly environment.

Computational Modeling, High-Level Soluble Expression and In Vitro Cytotoxicity Assessment of Recombinant Pseudomonas aeruginosa Azurin: A Promising Anti-Cancer Therapeutic Candidate.

Azurin is a natural protein produced by Pseudomonas aeruginosa that exhibits potential anti-tumor, anti-HIV, and anti-parasitic properties. The current study aimed to investigate the potential of azurin protein against breast cancer using both in silico and in vitro analyses. The amino acid sequence of Azurin was used to predict its secondary and tertiary structures, along with its physicochemical properties, using online software. The resulting structure was validated and confirmed using Ramachandran plots and ERRAT2. The mature azurin protein comprises 128 amino acids, and the top-ranked structure obtained from I-TASSER was shown to have a molecular weight of 14 kDa and a quality factor of 100% by ERRAT2, with 87.4% of residues in the favored region of the Ramachandran plot. Docking and simulation studies of azurin protein were conducted using HDOCK and Desmond servers, respectively. The resulting analysis revealed that Azurin docked against p53 and EphB2 receptors demonstrated maximum binding affinity, indicating its potential to cause apoptosis. The recombinant azurin gene was successfully cloned and expressed in a BL21 (DE3) strain using a pET20b expression vector under the control of the pelB ladder, followed by IPTG induction. The azurin protein was purified to high levels using affinity chromatography, yielding 70 mg/L. In vitro cytotoxicity assay was performed using MCF-7 cells, revealing the significant cytotoxicity of the azurin protein to be 105 µg/mL. These findings highlight the potential of azurin protein as an anticancer drug candidate.

Characterization of a putative metal-dependent PTP-like phosphatase from Lactobacillus helveticus 2126

To date, there are very limited reports on sequence analysis and structure-based molecular modeling of phosphatases produced by probiotic bacteria. Therefore, a novel protein tyrosine-like phosphatase was characterized from L. helveticus 2126 in this study. The purified bacterial phosphatase was subjected to mass spectrometric analysis, and the identity of constructed sequence was analyzed using peptide mass fingerprint. The 3-D structure of protein was elucidated using homology modeling, while its stability was assessed using Ramachandran plot, VERIFY 3D, and PROCHECK. The bacterium produced an extracellular phosphatase of zone diameter 15 ± 0.8 mm on screening medium within 24 h of incubation. This bacterial phosphatase was highly specific towards sodium phytate as it yielded the lowest Km value of 299.50 ± 4.95 μM compared to other phosphorylated substrates. The activity was effectively stimulated in the presence of zinc, magnesium, and manganese ions thereby showing its PTP-like behavior. The phosphatase showed a molecular mass of 43 kDa, and the corresponding M/Z ratio data yielded 46% query coverage to Bacillus subtilis (3QY7). This showed a 61.1% sequence similarity to Ligilactobacillus ruminis (WP_046923835.1). The final sequence construct based on these bacteria showed a conserved motif “HCHILPGIDD” in their active site. In addition, homology modeling showed a distorted Tim barrel structure with a trinuclear metal center. The final model after energy minimization showed 90.9% of the residues in the favorable region of Ramachandran’s plot. This structural information can be used in genetic engineering for improving the overall stability and catalytic efficiency of probiotic bacterial phosphatases.

Cosmological gravitational particle production of massive spin-2 particles

The phenomenon of cosmological gravitational particle production (CGPP) is expected to occur during the period of inflation and the transition into a hot big bang cosmology. Particles may be produced even if they only couple directly to gravity, and so CGPP provides a natural explanation for the origin of dark matter. In this work we study the gravitational production of massive spin-2 particles assuming two different couplings to matter. We evaluate the full system of mode equations, including the helicity-0 modes, and by solving them numerically we calculate the spectrum and abundance of massive spin-2 particles that results from inflation on a hilltop potential. We conclude that CGPP might provide a viable mechanism for the generation of massive spin-2 particle dark matter during inflation, and we identify the favorable region of parameter space in terms of the spin-2 particle’s mass and the reheating temperature. As a secondary product of our work, we identify the conditions under which such theories admit ghost or gradient instabilities, and we thereby derive a generalization of the Higuchi bound to Friedmann-Robertson-Walker (FRW) spacetimes.

Investigation of the Formation and Further Development of Longitudinal Disturbances and Their Secondary Instability on the Flying Wing Model

Detailed investigation of two-dimensional roughness element influence on the flow behind three-dimensional roughness element was carried out. For the first time studies were conducted on the windward side of the flying wing in the range of free-stream 7,2 – 20 m/s in the favourable gradient region behind roughness elements. Secondary instability mechanisms of disturbances leading to turbulence stage were investigated. It was shown that longitudinal structure forming behind three-dimensional roughness element grows downstream and has its trajectory slightly bend. The longitudinal structure consists of two stationary disturbances different in size. This can be explained by presence of cross flow and secondary disturbances leading to the transition. On the straight wing model, influence of the distributed suction on the stationary disturbance development was investigated and quantitatively determined. It was shown that suction is able to relaminarize the flow and eliminate the separation of the boundary layer.

Computer-aided drug design against schizophrenia by targeting SP4

Schizophrenia (SZ) is a mental disorder and affects ~1% of the worldwide population. It is considered a chronic and severe condition that impacts the thoughts, emotions, and behavior, of the patient often leading to a distortion of reality. Numerous computational techniques such as threading technique, homology modeling technique, and ab initio technique were applied for 3D structure prediction of the selected SZ protein SP4. The 3D predicted structures of SP4 were further evaluated and validated by utilizing Anolea, ProCheck, and Errat evaluation tools. Interestingly, it was observed that the overall quality factor of the selected structure was 77.542%. The predicted structure of SP4 showed 3.97% residues in the outlier region of Ramachandran plot while 96.03% in the allowed and the favored region of the evaluated plot. The study of molecular docking analyses was done to identify the compounds against SZ by targeting SP4. Moreover, the scrutinized compounds showed the least binding energy of -10.1 Kcal/mol. The highest binding affinity was observed among the binding residues (Leu-199, Ala-275, Gly-262, Leu-198, Thr-333, Ser-334, Leu-339, Ala-206, Leu-208, Gly-281, Ile-207, Val-283, Pro-286, and Ala-287). The scrutinized molecules from the selected library may have the ability to regulate the activity of SZ by targeting SP4. The scrutinized molecules can behave as a potential compound and the 3D predicted structure of SP4 is reliable for structural insights and functional analyses.

Predicting Potential Challenges of Regional Hydrogen Cooperation Through a Case Study of the European Union

Climate disasters will become more common if carbon emissions continue unabated. In response, the United Nations (UN) has called for countries to achieve net-zero carbon emissions by 2050. For many countries, adopting hydrogen energy through imports and regional cooperation is critical to achieving this goal. This study will look at the potential benefits and challenges of regional hydrogen cooperation through a case study of regional hydrogen cooperation in the European Union (EU). The main argument is that the challenges confronting the EU are likely to be encountered elsewhere. The EU provides a particularly favourable environment for regional cooperation. If these challenges were encountered in a favourable environment, they would likely be encountered in less favourable regions as well. The main implication is that other regional cooperations will likely face challenges such as domestic opposition, weak international cooperation in hydrogen R&amp;D, overly lenient carbon emissions accounting, and exacerbated regional inequality.

Learning under concept drift and non-stationary noise: Introduction of the concept of persistence

Learning from noisy data is a challenging task especially when the system under consideration has a non-stationary nature. The source of the noise is often assumed to be stationary, however the severity or characteristics of noise may also be time-varying, which causes multiple sources of drift in the collected data. This study introduces a novel adaptive learning rate approach to improve learning when the observations from a non-stationary system is altered by an also non-stationary source of noise. As an example to this approach, we propose Persistence Aware Robust Learner (PeARL), an online learning method that utilizes a novel concept called persistence, which is a local noisiness estimation metric to measure the correspondence of a signal to discrete white noise. Making use of this metric, PeARL is able to adaptively adjust the learning rate for each observation during learning to reduce the effect of noise. With this level of control on the learning rate, noisy instances have less disruptive effect on the maintained estimate. We experimentally evaluate PeARL on (a) systematically generated synthetic data and (b) real-world data, including accelerometer readings collected from people (HASC2010corpus) and current measurements from electric motors collected within the scope of EU-funded research project iRel40. The experiments reveal a favorable region of noise rate, in which the proposed method achieves up to 40% reduction in mean absolute error (MAE).

On the Stability and Behavioral Diversity of Single and Collective Bernoulli Balls.

The ability to express diverse behaviors is a key requirement for most biological systems. Underpinning behavioral diversity in the natural world is the embodied interaction between the brain, body, and environment. Dynamical systems form the basis of embodied agents, and can express complex behavioral modalities without any conventional computation. While significant study has focused on designing dynamical systems agents with complex behaviors, for example, passive walking, there is still a limited understanding about how to drive diversity in the behavior of such systems. In this article, we present a novel hardware platform for studying the emergence of individual and collective behavioral diversity in a dynamical system. The platform is based on the so-called Bernoulli ball, an elegant fluid dynamics phenomenon in which spherical objects self-stabilize and hover in an airflow. We demonstrate how behavioral diversity can be induced in the case of a single hovering ball via modulation of the environment. We then show how more diverse behaviors are triggered by having multiple hovering balls in the same airflow. We discuss this in the context of embodied intelligence and open-ended evolution, suggesting that the system exhibits a rudimentary form of evolutionary dynamics in which balls compete for favorable regions of the environment and exhibit intrinsic "alive" and "dead" states based on their positions in or outside of the airflow.

P-Mode Oscillations in Highly Gravitationally Stratified Magnetic Solar Atmospheres

The aim of the study reported in this paper is to gain understanding of solar global oscillations and the propagation characteristics of p-mode oscillations in the highly gravitationally stratified magnetic solar atmosphere. The paper presents the results of 3D (3-dimensional) numerical magnetohydrodynamic (MHD) simulations of a model solar atmosphere with a uniform, vertical and cylindrically symmetric magnetic field. We use simulation drivers which result in oscillations mimicking the behaviour of p-mode oscillations. The paper reports the variation of the energy flux and oscillation frequency of the magnetosonic modes and examines their dependence on the magnetic field strength. We report results for the temporal analysis of observational data for the quiet Sun and for a region containing a small sunspot (solar pore). We compare the temporal analysis of results from observations of these ubiquitous intensity oscillations with numerical simulations of potential signatures of global oscillations of the solar atmosphere. We conclude that magnetic regions of the solar atmosphere are favourable regions for the propagation of a small leakage of energy by slow magnetosonic modes. The results also exhibit a variation in the frequency of the oscillations at different heights in the low-to-mid solar atmosphere and for different values of the magnetic field. The numerically obtained periodic behaviour and variation in frequency, even in this simplified model atmosphere, is consistent with the observational data. We find frequencies and frequency variations that are similar to measurements obtained from the intensity time series of images taken by the Solar Dynamics Observatory.

Preliminary Impact Assessment of Carbon Border Adjustment Mechanism on Russian Economy

The principal objective of the European Commission with the proposal of Carbon Border Adjustment Mechanism (CBAM) is to impose a levy on imports in particular energy-concentrated European sectors which are relative to carbon content of imported goods. The integration of carbon tax is very likely to result, that CBAM will have significant impact on international trade among European Union and Russia within the ACEFIS (aluminium, cement, electricity, fertilizers, iron, steel) industries. Therefore, the key question that authors of article addressed was the extent to which the CBAM policy trade instrument could affect Russian economy. The classification of the preliminary impact assessment in this article relies on the case-study concept with empirical data. The most significant impact could be represented on the Russian exports of iron and steel, whereas, the carbon levies would represent—€ 655 million in 2020 and € 398 million for fertilizers. The preliminary analysis clearly highlights that integration of CBAM can arise additional costs of imports from Russia within ACEFIS industries by more than € 1.1 billion. The levies from integration of CBAM could result in additional costs either on the side of exporters (Russia) in the form of loss in market share, or on the side of importers (European Union) in the form of shift of demand from ACEFIS goods or shift towards suppliers from most favourable regions. The ambition to create carbon neutral world is promising; however, decrease of the degree of carbon extensive industries will require a lot of additional investments.

Investigating the activation of passive metals by a combined in-situ AFM and Raman spectroscopy system: a focus on titanium

Understanding the main steps involved in the activation of passive metals is an extremely important subject in the mechanical and energy industry and generally in surface science. The titanium-H2SO4 system is particularly useful for this purpose, as the metal can either passivate or corrode depending on potential. Although several studies tried to hypothesise the surface state of the electrode, there is no general consensus about the surface state of Ti in the active–passive transition region. Here by combining in-situ atomic force microscopy (AFM) and Raman spectroscopy, operating in an electrochemical cell, we show that the cathodic electrification of Ti electrodes causes the dissolution of the upper TiO2 portion of the passive film leaving the electrode covered by only a thin layer of titanium monoxide. Fast anodic reactions involved the acidification of the solution and accumulation of sulphur containing anions. This produces a local increase of the solution turbidity, allowing to distinguish favourable regions for the precipitation of TiOSO4·2H2O. These results give a clear answer to the long-stated question of the physical origin behind the formation of negative polarization resistances, sometimes occurring in corroding systems, and a rationale about the proton-induced degradation of passive surfaces in presence of sulphur containing species.

Comparative modeling and enzymatic affinity of novel haloacid dehalogenase from Bacillus megaterium strain BHS1 isolated from alkaline Blue Lake in Turkey

This study presents the initial structural model of L-haloacid dehalogenase (DehLBHS1) from Bacillus megaterium BHS1, an alkalotolerant bacterium known for its ability to degrade halogenated environmental pollutants. The model provides insights into the structural features of DehLBHS1 and expands our understanding of the enzymatic mechanisms involved in the degradation of these hazardous pollutants. Key amino acid residues (Arg40, Phe59, Asn118, Asn176, and Trp178) in DehLBHS1 were identified to play critical roles in catalysis and molecular recognition of haloalkanoic acid, essential for efficient binding and transformation of haloalkanoic acid molecules. DehLBHS1 was modeled using I-TASSER, yielding a best TM-score of 0.986 and an RMSD of 0.53 Å. Validation of the model using PROCHECK revealed that 89.2% of the residues were located in the most favored region, providing confidence in its structural accuracy. Molecular docking simulations showed that the non-simulated DehLBHS1 preferred 2,2DCP over other substrates, forming one hydrogen bond with Arg40 and exhibiting a minimum energy of −2.5 kJ/mol. The simulated DehLBHS1 exhibited a minimum energy of −4.3 kJ/mol and formed four hydrogen bonds with Arg40, Asn176, Asp9, and Tyr11, further confirming the preference for 2,2DCP. Molecular dynamics simulations supported this preference, based on various metrics, including RMSD, RMSF, gyration, hydrogen bonding, and molecular distance. MM-PBSA calculations showed that the DehLBHS1-2,2-DCP complex had a markedly lower binding energy (−21.363 ± 1.26 kcal/mol) than the DehLBHS1-3CP complex (-14.327 ± 1.738 kcal/mol). This finding has important implications for the substrate specificity and catalytic function of DehLBHS1, particularly in the bioremediation of 2,2-DCP in contaminated alkaline environments. These results provide a detailed view of the molecular interactions between the enzyme and its substrate and may aid in the development of more efficient biocatalytic strategies for the degradation of halogenated compounds. Communicated by Ramaswamy H. Sarma

Off‐setting climate change through formation flying of aircraft, a feasibility study reliant on high fidelity gas‐phase chemical kinetic data

AbstractApplication of formation flights to civil aviation is gaining interest, primarily due to the fuel burn reduction achieved by flying through another aircraft's wake. However, it is emerging that there are additional, less‐recognized climate benefits via reduction in ozone and contrail warming through this concept. The NOx threshold level is defined as when the loss rate for OH by reaction with NO2 is equal to the loss rates for OH with CO and CH4, beyond which level, ozone formation will decrease. In this study, The NOx threshold level was calculated at different altitudes and found that at cruise altitude (∼10 km), the amount of NO2 required for parity in OH loss with loss due to reaction with CO and CH4 is around 2 ppb. The spatial and temporal NOx threshold levels were estimated by STOCHEM‐Common Representative Intermediate (CRI) global chemical transport model and In‐service Aircraft for Global Observing System (IAGOS) measurement data and found that northern midlatitudes of the atmosphere are the most favorable region existing with the smallest NOx thresholds (0.5 ppb) needed before reduction in ozone formation is likely to occur at cruise altitude of aircraft. Incorporating the major air traffic corridors into the coarse spatial resolution of the chemical transport model overestimated the NOx compensation point, that is, increased photochemical ozone production. Thus, a simple one‐dimensional (1D) aircraft plume dispersion model was developed with higher spatial and temporal resolution for considering aircraft plumes and its chemistry more accurately. The model run shows that the impact of formation flying aircraft emissions on spatially averaged ozone could be halved if the aircraft could maintain separations inside 4 km relative to well separated flights of 10 km or more.

Developing Multi-epitope Antigen Construct from Immunodominant Proteins for Serological Diagnosis of Chlamydia trachomatis: An In Silico Approach

Background: Chlamydiasis is a widespread bacterial infection in the world. Serological tests are expensive, and in addition, intrinsic antigens can cause cross-reactions and make the diagnosis process difficult. Multi-epitope protein antigens are novel and potential diagnostic markers that have the capability of more accurate and cheaper diagnosis. Therefore, in this study, the main goal is to design a new protein vaccine, including multiple epitopes of B cells with dominant immunity from three proteins named MOMP, ompA and Pgp3D from C. trachomatis Methods: The amino acid sequences were obtained from the UniProt database. The areas with the highest antigenicity were identified using the EMBOSS server. Linear B cell epitopes were determined using BCPRED, ABCpred, and Bepipred servers. Epitopes with the highest antigenicity were connected using the EAAAK linker. Results: Two epitopes from MOMP, two from ompA, and one from Pgp3D were selected. These epitopes were connected to each other with the EAAAK linker. Three residues (0.592), 16 residues (0.76), 36 residues (0.578), and 37 residues (0.734) were obtained from the prediction of the spatial structure of the B cell multiple epitopes designed with ElliPro. Model 1 of RaptorX was selected as the best structure. In this model, the ERRAT quality, ProSA-web z-score, and Verify3D were 83.1169, - 5.17 and 84.62% with PASS score, respectively. Moreover, the Ramachandran plot showed that 86.093% of the amino acid residues were located in the favored region. To achieve the highest level of protein expression, the designed multi-epitope reverse-translated with the Genscript server and was cloned in E. coli. The highest level of expression was achieved, and a CAI score of 0.91 was reported. The gene GC content was 51.98%, and the contribution of low-frequency codons was 0%. Conclusion: The results confirmed that the designed construct could identify C. trachomatis with high sensitivity and specificity in serum samples of patients with chlamydiasis. However, further experimental studies are needed for final confirmation.