Lack Of Reactivity Research Articles

An unexpected IgE anti-receptor binding domain response following natural infection and different types of SARS-CoV-2 vaccines

Humoral response to SARS-CoV-2 has been studied, predominantly the classical IgG and its subclasses. Although IgE antibodies are typically specific to allergens or parasites, a few reports describe their production in response to SARS-CoV-2 and other viruses. Here, we investigated IgE specific to receptor binding domain (RBD) of SARS-CoV-2 in a Brazilian cohort following natural infection and vaccination. Samples from 59 volunteers were assessed after infection (COVID-19), primary immunization with vectored (ChAdOx1) or inactivated (CoronaVac) vaccines, and booster immunization with mRNA (BNT162b2) vaccine. Natural COVID-19 induced IgE, but vaccination increased its levels. Subjects vaccinated with two doses of ChAdOx1 exhibited a more robust response than those immunized with two doses of CoronaVac; however, after boosting with BNT162b2, all groups presented similar IgE levels. IgE showed intermediate-to-high avidity, especially after the booster vaccine. We also found IgG4 antibodies, mainly after the booster, and they moderately correlated with IgE. ELISA results were confirmed by control assays, using IgG depletion by protein G and lack of reactivity with heterologous antigen. In our cohort, no clinical data could be associated with the IgE response. We advocate for further research on IgE and its role in viral immunity, extending beyond allergies and parasitic infections.

Non-clinical evaluation of NT-175, an autologous T cell product engineered to express an HLA-A*02:01-restricted TCR targeting TP53 R175H and resistant to TGF-b inhibition.

2560 Background: Adoptive transfer of T-cell receptor (TCR)-engineered T-cells to target shared cancer neoantigens is a promising new immunotherapy approach for patients harboring mutations in tumor suppressor genes such as TP53. TP53 is the most commonly mutated gene across all cancer types, with the R175H mutation being the most prevalent across different indications. NT-175 is an autologous engineered T-cell product expressing an HLA-A*02:01-restricted TCR that specifically targets the TP53 R175H mutation. NT-175 is additionally engineered to lack TGF-β receptor II (TGFBR2) expression, rendering T-cells insensitive to TGF-b-mediated inhibition in the tumor microenvironment. Methods: For manufacturing of NT-175, CD4 and CD8 T-cells are enriched from leukapheresis material, activated in vitro and gene-edited to knock-out both endogenous TGFBR2 and TCR β constant 1/2 (TRBC1/2) and knock-in an HLA-A*02:01-restricted TP53 R175H neoantigen-specific TCR at the TCR α constant (TRAC) locus using CRISPR-Cas9 technology. NT-175 product functionality was evaluated in vivo models and in vitro. T-cell reactivity was assessed by measuring cytotoxicity, proliferation, and cytokine production. The benefit of TGFBR2 knock-out (KO) in the presence of TGF-b was evaluated by measuring phosphorylation of SMAD2/3 proteins, the impact on cell viability and serial killing of target cells. For determination of NT-175 product safety, cross-reactivity and HLA-specificity assessments were carried out. A comprehensive analysis of potential off-target editing by CRISPR/Cas9 was performed to assess potential risk of genotoxicity in clinical grade NT-175. Results: High reactivity of the NT-175 TCR against TP53 R175H and HLA-A*02:01 expressing target cells was observed. T-cell activation and functionality was highly specific, as demonstrated by a lack of reactivity against TP53 WT, minimal cross-reactivity against antigens with up to 4 mismatches to the minimal TP53 R175H encoding epitope recognized by the NT-175 TCR, and lack of T-cell activation in the absence of HLA-A*02:01. In the presence of TGF-b, TGFBR2 KO TCR-edited T-cells displayed inhibition of SMAD2/3 phosphorylation, increased cell viability and increased cytotoxicity and proliferation in serial stimulation assays. In vivo, NT-175 T-cells were able to induce tumor clearance in two independent models. Low frequency chromosomal translocation events (<0.1%) between on-target and off-target Cas9 cleavage sites were detectable in NT-175 T-cells. However importantly, these did not result in autonomous cytokine-independent growth. Conclusions: Non-clinical studies revealed a favorable safety and efficacy profile for NT-175 and supported further clinical development of a TGF-β-resistant TCR-edited T-cell product for mutant TP53-targeted cancer immunotherapy.

Non-clinical evaluation of NT-112, an autologous T cell product engineered to express an HLA-C*08:02-restricted TCR targeting KRAS G12D and resistant to TGF-b inhibition.

e14533 Background: Adoptive transfer of T-cell receptor (TCR)-engineered T-cells to target shared cancer neoantigens is a promising new immunotherapy approach for patients harboring mutations in oncogenes such as KRAS. Activating mutations in KRAS are among the most prevalent oncogenic driver mutations in human cancers, with KRAS G12D being the most frequent KRAS mutation in colorectal carcinoma and pancreatic cancer. NT-112 is an autologous engineered T-cell product expressing an HLA-C*08:02-restricted TCR that specifically targets the KRAS G12D mutation. NT-112 is additionally engineered to lack TGF-β receptor II (TGFBR2) expression, rendering T-cells insensitive to TGF-b-mediated inhibition in the tumor microenvironment. Methods: For manufacturing of NT-112, CD4 and CD8 T-cells are enriched from leukapheresis material, activated in vitro and gene-edited to knock-out both endogenous TGFBR2 and TCR β constant 1/2 (TRBC1/2) and knock-in an HLA-C*08:02-restricted KRS G12D neoantigen-specific TCR at the TCR α constant (TRAC) locus using CRISPR-Cas9 technology. NT-112 product functionality was evaluated in both in vivo models and in vitro co-culture experiments with a panel of cell lines including those endogenously expressing the KRAS G12D mutation. T-cell reactivity was assessed by measuring cytotoxicity, proliferation, and cytokine production. For determination of NT-112 product safety, cross-reactivity and allo-reactivity assessments were carried out. A comprehensive analysis of potential off-target editing by CRISPR/Cas9 was performed to assess potential risk of genotoxicity in clinical grade NT-112. Results: High reactivity of the NT-112 TCR against KRAS G12D and HLA-C*08:02-expressing target cells was observed. T-cell activation and functionality was highly specific, as demonstrated by a lack of reactivity against KRAS WT, minimal cross-reactivity in Alanine and Glycine scans, and lack of T-cell activation in the absence of HLA-C*08:02. In vivo, NT-112 T-cells were able to induce tumor clearance in two independent models. Low frequency chromosomal translocation events (<0.1%) between on-target and off-target Cas9 cleavage sites were detectable in NT-112 T-cells. However importantly, these did not result in autonomous cytokine-independent growth. Conclusions: Non-clinical studies revealed a favorable safety and efficacy profile for NT-112 and supported further clinical development of a TGF-β-resistant TCR-edited T-cell product for mutant KRAS-targeted cancer immunotherapy.

Catatonia and melancholia interface: exploring a new paradigm for evaluation and treatment. A case series and literature review.

Catatonia has been increasingly associated with mood disorders and is recognized as a specifier in the DSM-5 and DSM-5-TR. The DSM-5-TR recognizes melancholia as a specifier for depressive episodes in major depressive disorder and bipolar disorder. It is characterized by severe anhedonia, lack of reactivity, excessive or delusional guilt, and significant vegetative symptoms. As the conceptualization of melancholia expanded beyond its mood components to include psychomotor disturbances, its overlap with psychomotor symptoms or catatonia becomes evident. This overlap was also described in Kahlbaum's original literature, where he describes the transition between states of melancholia, mania, and catatonia. Case summary of six patients with major depressive disorder or depressed phase of bipolar disorder who were admitted for severe depression, anhedonia, intense anxiety, psychomotor agitation or retardation, indecisiveness, perseveration, and vegetative symptoms such as poor sleep, appetite, and significant weight loss. All patients demonstrated rapid and complete resolution of their mood and psychomotor symptoms, indecisiveness, perseveration, as well as psychosis shortly after administration of lorazepam, with recurrence of the above symptoms upon lorazepam discontinuation and resolution upon resumption, in an on-and-off manner. The present study argues for a closer relationship between melancholia and catatonia based on our case series, historical review, overlap in phenomenology, and response to treatment. We propose provisional [Mahgoub] criteria for patients with severe depression and melancholia. The role of GABA agonists, such as lorazepam, can be explored as an option for patients with treatment-resistant depression who meet these criteria for melancholia. Absence of a standardized, systematic assessment tool and a small sample size.

Reactivity of Superbasic Carbanions Generated via Reductive Radical-Polar Crossover in the Context of Photoredox Catalysis.

Photocatalytic reactions involving a reductive radical-polar crossover (RRPCO) generate intermediates with carbanionic reactivity. Many of these proposed intermediates resemble highly reactive organometallic compounds. However, conditions of their formation are generally not tolerated by their isolated organometallic versions and often a different reactivity is observed. Our investigations on their nature and reactivity under commonly used photocatalytic conditions demonstrate that these intermediates are indeed best described as free, superbasic carbanions capable of deprotonating common polar solvents usually assumed to be inert such as acetonitrile, dimethylformamide, and dimethylsulfoxide. Their basicity not only towards solvents but also towards electrophiles, such as aldehydes, ketones, and esters, is comparable to the reactivity of isolated carbanions in the gas-phase. Previously unsuccessful transformations thought to result from a lack of reactivity are explained by their high reactivity towards the solvent and weakly acidic protons of reaction partners. An intuitive explanation for the mode of action of photocatalytically generated carbanions is provided, which enables methods to verify reaction mechanisms proposed to involve an RRPCO step and to identify the reasons for the limitations of current methods.

Thermodynamic Insights into Phosphonate Binding in Metal-Azolate Frameworks.

Organophosphorus chemicals, including chemical warfare agents (CWAs) and insecticides, are acutely toxic materials that warrant capture and degradation. Metal-organic frameworks (MOFs) have emerged as a class of tunable, porous, crystalline materials capable of hydrolytically cleaving, and thus detoxifying, several organophosphorus nerve agents and their simulants. One such MOF is M-MFU-4l (M = metal), a bioinspired azolate framework whose metal node is composed of a variety of divalent first-row transition metals. While Cu-MFU-4l and Zn-MFU-4l are shown to rapidly degrade CWA simulants, Ni-MFU-4l and Co-MFU-4l display drastically lower activities. The lack of reactivity was hypothesized to arise from the strong binding of the phosphate product to the node, which deactivates the catalyst by preventing turnover. No such study has provided detailed insight into this mechanism. Here, we leverage isothermal titration calorimetry (ITC) to monitor the binding of an organophosphorus compound with the M-MFU-4l series to construct a complete thermodynamic profile (Ka, ΔH, ΔS, ΔG) of this interaction. This study further establishes ITC as a viable technique to probe small differences in thermodynamics that result in stark differences in material properties, which may allow for better design of first-row transition metal MOF catalysts for organophosphorus hydrolysis.

Development of a lateral flow assay for rapid and accurate detection of chicken anemia virus

Significant challenges to poultry health are posed by chicken anemia virus (CAV), which induces immunosuppression and causes increased susceptibility to secondary infections. The effective management and containment of CAV within poultry stocks require precise and prompt diagnosis. However, a deficiency persists in the availability of low-cost, rapid, and portable CAV detection devices. In this study, an immunochromatographic lateral-flow test strip-based assay was developed for CAV detection using in-house generated monoclonal antibodies (MABs) against CAV viral protein 1 (VP1). The recombinant truncated VP1 protein (Δ60VP1), with amino acid residues 1 to 60 of the native protein deleted, was produced via a prokaryotic expression system and utilized for immunizing BALB/c mice. Subsequently, high-affinity MABs against Δ60VP1 were generated and screened using conventional hybridoma technology combined with serial dilution assays. Two MABs, MAB1, and MAB3, both binding to distinct epitopes of Δ60VP1, were selected for the development of a lateral-flow assay. Sensitivity analysis demonstrated that the Δ60VP1 antigen could be detected by our homemade lateral-flow assay at concentrations as low as 625 ng/mL, and this sensitivity was maintained for at least 6 mo. The assay exhibited high specificity, as evidenced by its lack of reactivity with surrogate recombinant proteins and the absence of cross-reactivity with other chicken viruses and viral antigens. Comparative analysis with quantitative PCR data demonstrated substantial agreement, with a Kappa coefficient of 0.66, utilizing a sample set comprising 305 clinical chicken serum samples. In conclusion, the first lateral-flow assay for CAV detection was developed in this study, utilizing 2 specific anti-VP1 MABs. It is characterized by simplicity, rapidity, sensitivity, and specificity.

Assessing ecotoxicity, synergic and antagonistic actions of commonly used components of polymerization mixture in molecularly imprinted polymers preparation process

Increasingly, the challenge is the optimal process of developing a suitable MIP-type sorptive material (taking into account its final form and application area), which is mainly related to the efficiency/effectiveness of the polymerization process. The lack of reaction or its low efficiency generates additional waste and puts it into the environmental cycle. The main aim of the performed research was the estimation of ecotoxicity, and effect of joint action of commonly used components of polymerization mixture applied in MIPs preparation process. The general purpose of this work is to apply bioluminescent bacteria in order to find any potential interactions taking place in two and three-component polymerization mixtures containing selected MIP polymerization components. According to calculated EC50 values for all tested compounds, the toxicity of MIP components to the bioluminescent bacterium Vibrio fischeri can be arranged in decreasing order as follows: DVB > DCM > EDGMA > MAA > TMSPMA > APTES > MMA > TEOS > TMPTA > AA > ACN. Based on obtained results, it was concluded that EGDMA has a strong influence on the antagonistic interactions among mixture components. An overestimation of the toxicity value was noticed for only eight mixtures, where one of the component was DVB, EGDMA, or TEOS.

Computational and Experimental Confirmation of the Diradical Character of para-Quinonedimethide.

The ground-state structure of the parent para-quinonedimethide (p-QDM) molecule is generally represented in its closed shell form, i.e., as a cyclic, nonaromatic, through-conjugated/cross-conjugated hybrid comprising four C═C bonds. Nonetheless, p-QDM has been theorized to contain a contribution from its open-shell aromatic singlet diradical form. VBSCF calculations identify an open-shell contribution of 29% to the structure, while CASPT2(16,16)/def2-TZVP and ωB97XD/aug-cc-pVTZ calculations predict that dimerization proceeds along an open-shell singlet diradical pathway with a low (77 kJ/mol) barrier toward dimerization, which occurs by way of C-C bond formation between the exocyclic methylene carbons. A similar low (98 kJ/mol) barrier exists toward the reaction between a p-QDM molecule and the radical trap TEMPO. These predictions are verified experimentally through the isolation of bis-TEMPO-trapped p-QDM, its C-C coupled dimer, and by demonstrating that a mixture of p-QDM and TEMPO can initiate the radical polymerization of n-butyl acrylate at ambient temperature. In contrast to p-QDM, tetracyanoquinone (TCNQ) neither dimerizes nor reacts with TEMPO, despite having a similar diradical character to p-QDM. This lack of reactivity is consistent with both a higher kinetic barrier and a thermodynamically unfavorable process, which is ascribed to destabilizing steric clashes and polar effects.

The cell walls of different Chara species are characterized by branched galactans rich in 3-O-methylgalactose and absence of AGPs.

Streptophyte algae are the closest relatives to land plants; their latest common ancestor performed the most drastic adaptation in plant evolution around 500 million years ago: the conquest of land. Besides other adaptations, this step required changes in cell wall composition. Current knowledge on the cell walls of streptophyte algae and especially on the presence of arabinogalactan-proteins (AGPs), important signalling molecules in all land plants, is limited. To get deeper insights into the cell walls of streptophyte algae, especially in Charophyceae, we performed sequential cell wall extractions of four Chara species. The three species Chara globularis, Chara subspinosa and Chara tomentosa revealed comparable cell wall compositions, with pectins, xylans and xyloglucans, whereas Chara aspera stood out with higher amounts of uronic acids in the pectic fractions and lack of reactivity with antibodies binding to xylan- and xyloglucan epitopes. Search for AGPs in the four Chara species and in Nitellopsis obtusa revealed the presence of galactans with pyranosidic galactose in 1,3-, 1,6- and 1,3,6-linkage, which are typical galactan motifs in land plant AGPs. A unique feature of these branched galactans was high portions of 3-O-methylgalactose. Only Nitellopsis contained substantial amounts of arabinose A bioinformatic search for prolyl-4-hydroxylases, involved in the biosynthesis of AGPs, revealed one possible functional sequence in the genome of Chara braunii, but no hydroxyproline could be detected in the four Chara species or in Nitellopsis obtusa. We conclude that AGPs that is typical for land plants are absent, at least in these members of the Charophyceae.

Too civil to care? How online hate speech against different social groups affects bystander intervention

A large share of online users has already witnessed online hate speech. Because targets tend to interpret such bystanders’ lack of reaction as agreement with the hate speech, bystander intervention in online hate speech is crucial as it can help alleviate negative consequences. Despite evidence regarding online bystander intervention, however, whether bystanders evaluate online hate speech targeting different social groups as equally uncivil and, thereby, equally worthy of intervention remains largely unclear. Thus, we conducted an online experiment systematically varying the type of online hate speech as homophobia, racism, and misogyny. The results demonstrate that, although all three forms were perceived as uncivil, homophobic hate speech was perceived to be less uncivil than hate speech against women. Consequently, misogynist hate speech, compared to homophobic hate speech, increased feelings of personal responsibility and, in turn, boosted willingness to confront.

Inflation tolerance ranges in the New Keynesian model

A number of central banks in advanced countries use ranges, or bands, around their inflation target to formulate their monetary policy strategy. The adoption of such ranges has been proposed by some policymakers in the context of the Fed and the ECB reviews of their strategies. Using a standard New Keynesian macroeconomic model, we analyze the consequences of tolerance range policies, characterized by a stronger reaction of the central bank to inflation when inflation lies outside the range, than when it is close to the target, i.e. the central value of the band. We show that (i) a tolerance band should not be a zone of inaction: the lack of reaction may trigger substantial unwarranted volatility and lead to multiple equilibria; (ii) the trade-off between the reaction needed outside the range versus inside appears unfavorable: a very strong reaction, when inflation is far from the target, is required to compensate for a moderately lower reaction within tolerance band; (iii) these results, obtained within the framework of a stylized model, are robust to many alterations, in particular allowing for the zero lower bound.

Role of supramolecular steric compression during photoinduced intramolecular hydrogen abstraction reactions of ketones and thioketones

Excited state behavior of molecules is influenced by the environment in which they are present. The influence of solvents on reactions is understood in terms of the bulk properties of the solvent such as polarity, polarizability, hydrogen bonding, solvophobic interactions etc. Under these conditions, the ‘space’ surrounding the guest does not play any role in influencing the fate of an excited molecule. The current study focusses on understanding the factors that control the excited state reactivity of molecules within a confined space. In this context organic capsules assembled from two molecules of octa acid serves as the host and aryl alkyl ketones and aryl alkyl thioketones as reactive guests. One obvious prediction has been when the product is larger in size than the host capsule it would not be formed within the confined space although this may be the predominant product in solution. The authors demonstrate below that even if the product fits well within the capsule it may not be formed if the intermediate structures that connects the reactant to product does not fit within the capsule. The above hidden factor that controls photoproduct distribution has been investigated employing several aryl alkyl ketones that undergo γ-hydrogen abstraction as guests. In some of the examples investigated here, the Yang cyclization product, cyclobutanol, is suppressed within OA capsule even though it fits well within the capsule. Another factor that has come to light is ‘time’. Aryl alkyl thioketones that react from short lived second excited state (S2) fail to undergo δ-hydrogen abstraction within OA capsule although this is the only photoreaction in solution. MD simulations of the thioketones suggest that within the capsule the relevant hydrogens are not within the ideal geometry required for abstraction. Lack of reactivity is attributed to the insufficient time for the excited molecule to achieve the required conformation within the narrow space. Longer lived aryl alkyl ketones had no such problems in adopting a conformation required for hydrogen abstraction. Obviously, time becomes critical when the space is narrow. The results reported here brings out that one could consider ‘free space’ and ‘time’ as valuable tools to control product distribution while performing photochemistry in supramolecular assemblies.

Robust State Machine Passivity-based Control Applied to Fuel Cell Hybrid Source

The disadvantages of fuel cell systems, such as their high cost, lack of reactivity, and inability to collect energy when the fuel cell vehicle is braking, can be overcome by hybridization with storage devices such the battery or the supercapacitors, which is capable of doing so. The energy management system is regarded as an important technique for the hybrid system. Its primary function is to autonomously identify the appropriate quantity of energy that will be supplied by the hybrid source to meet the demand in terms of the load's energy requirements. The primary purpose in this work is the design and validation of an energy management technique based on the state machine and the passivity-based control to manage and control the energy flow of a hybrid fuel cell vehicle's power source, with a fuel cell system serving as the primary source of power and batteries and supercapacitors serving as the secondary sources of power. The results of MATLAB simulations show that the proposed strategy works as expected and the control system has robust dynamic features. Consequently, the passivity-based control makes possible to globally control the hybrid system which has been presented by a state space model in order to reach a set of stable equilibria. Whereas, the state machine is efficient in terms of performance, easy to implement, and provides ideal balance between the amount of energy that is generated and the amount that is consumed.

A Renewed Focus on Surface Chemistry for Advanced Logic-Node Epitaxial Growth Processes

Increased CMOS logic and memory scaling has forced chip architectures into 3D design spaces such as finFET, GAA, nanosheet, etc. These applications require epitaxial structures to be grown in complicated and restrictive geometries which are composed of an increasingly different range of materials. Epi growth selectivity to conventional dielectric materials such as SiO2 and SiNx as well as less conventional materials like SiOxN1-x, Al2O3, and SiOCN must be maintained as usual. However changing demands on epi doping levels and thermal budgets places a large burden on conventional selectivity approaches, which most-often rely on higher HCl partial pressures or HCl etch-back steps. Cl2 etch-back processes have also been used in limited cases as an alternative to HCl, but apart from that, new selective epi growth technology has become somewhat stagnant.The 3D nature of advanced logic architectures means that epi must also be grown on multiple crystal surface orientations like the (100), (110), and (111). For epitaxial growth processes, which by-definition are highly sensitive to the starting surface structure, this represents unique challenges to epitaxial engineers. New approaches to achieve orientation selective growth is now also paramount. Each surface orientation can have different growth rates, etch rates, and dopant incorporation efficiencies which can result in undesirable morphology, defects, and inhomogeneous chemical compositions. Depending on the application the growth rate may need to be maximized on one surface and minimized on another, for example to facilitate “bottom-up” growth from the (100) surface. In other instances, the growth rates may need to be matched as closely as possible, for example to achieve symmetric “diamond-shaped” epi-growth on a Si fin.These issues are at a fundamental level related to surface chemical interactions and finding new solutions will require a molecular-level understanding. In this work we present a fundamental chemical view of these challenges using both theoretical (density functional theory) calculations and in-situ surface analytical results. We analyze the reactive sites on dielectric surfaces and how various deposition precursors interact with these sites. Based on these results we will discuss alternative and/or novel routes to achieving selective epitaxial growth. We apply similar methods to analyzing the structure and reactivity of the Si (100), (110), and (111) surfaces and how deposition precursor molecules react on each surface. Our results reveal why changing Si surface orientations can result in such varied reactivity and ultimately in differing growth and etching rates. We similarly use these results to suggest methods for controlling facet/plane selective epitaxy and/or etching. Central to both dielectric and facet selectivity is precursor engineering, which entails designing new molecules to customize their reactivity (or lack of reactivity) toward specific dielectric surfaces or surface orientations. Figure 1

Solid-State Electrolyte Fracture in Lithium Metal Batteries

Next generation batteries utilizing solid-state electrolytes to enable use of lithium metal electrodes are of significant interest due to increased energy density and the potential safety enhancements. Despite their high yield strength, high room temperature ionic conductivity, and lack of reactivity with metallic lithium, these ceramic solid electrolytes are still prone to dendrite formation and subsequent cell failure above critical current densities. One experimentally observed dendrite formation and propagation mechanism requires mechanical failure of the electrolyte via fracture. Ceramic solid electrolyte’s do not undergo ductile deformation, leaving fracture as the primary means of stress relaxation. The electrolyte’s propensity to fracture is dependent on its material properties (i.e. fracture toughness), electrode mechanical properties, and the cell operating conditions (e.g. applied current density, stack pressure, temperature). This talk will focus on electrochemical-mechanical coupling (including thermodynamic and kinetic couplings of mechanical forces with electrochemical behavior) and the relationship between the current distribution, developed stresses, and solid-electrolyte fracture initiation at Li protrusions. The effect of current focusing on stress-driven fracture, plastic deformation of lithium, and the influence of mechanical boundary conditions will be described.

Experimentation and optimization of wear behavior on polytetrafluoroethylene composites using response surface methodology and bald eagle search optimization

AbstractIn Industries, polytetrafluoroethylene (PTFE) is used as a solid lubricant due to its excellent toughness, lack of reactivity, high‐thermal stability, and so forth. However, the abrasive resistive behavior is minimal for the virgin PTFE polymer. In this study, the wear and coefficient of friction (COF) of PTFE composite prepared by the combination of 10% halloysite, 10% graphite, and 10% bronze are investigated. The investigations are performed on a pin‐on‐disc test rig and analysis is done by response surface methodology (RSM), especially in Box‐Behnken Design (BBD). The experimentation is performed by varying the sliding distance (Ds), sliding velocity (Vs), and applied load (L). In the analysis of COF, the load is considered as a significant parameter, and sliding distance is an influencing parameter for wear rate. From the experimentation, the proposed PTFE composite promotes COF of 0.0052 and a wear rate of 0.62 × 10−5 mm3/Nm. Such observed wear rate and COF are 2.8 times and 1.5 times better than the pure PTFE. The experimented outcomes are validated using hybrid DBN‐based bald eagle search optimization (DBN‐BESO), and RSM. From the validated results, the proposed hybrid DBN‐BESO prediction process using the Matlab platform promotes closer values to the experimented outcomes. Besides, the parametric optimization is conducted using RSM and BESO approaches with the objective of minimum wear rate and COF. The optimized BESO results are superior to the RSM. BESO‐based optimized wear rate is 0.0317 × 10−5 mm3/Nm and COF is 0.0352.

What's new on septic encephalopathy? Ten things you need to know.

Sepsis associated encephalopathy (SAE) is a frequent complication of sepsis and is associated with a higher risk of short-term mortality and long-term cognitive impairment. The EEG is a sensitive complement of the clinical examination that can also detect and quantify encephalopathy and identify features with prognostic value, such as lack of reactivity. Moreover, despite their effect on outcome is still debated, the EEG is the only tool to detect non-convulsive seizures which can occur in a septic setting. Understanding the pathophysiology of SAE is fundamental to define potential therapeutic targets. Neuroinflammation plays an important role in the development of SAE and many blood and imaging biomarkers have recently shown a promising ability to distinguish SAE form non-SAE patient. In recent years, some interesting mediators of inflammation were successfully targeted in animal models, with a significant reduction in the neuroinflammation and in sepsis-induced cognitive decline. However, the complexity of the host response to sepsis currently limits the use of immunomodulation therapies in humans. Alteration in regulatory systems of cerebral blood flow, namely cerebral autoregulation (CA) and neurovascular coupling, contribute to SAE development. Nowadays, clinicians have access to different tools to assess them at the bedside and CA-based blood pressure protocols should be implemented to optimize cerebral perfusion. Its inauspicious consequences, its complex physiopathology and the lack of efficacious treatment make of SAE a highly active research subject.

Religious Freedom, Cybersecurity, and the Stability of Society: Problems and Perspectives from a European Perspective

Although religious freedom significantly affects certain people, the guarantees for its observance also have implications for the quality of social life and the security of the state. Polarization and conflict between religious groups is not only a conflict for new believers, but also contributes to the weakening of the internal state. It seems that one of the elements of such a destabilization of states is the promotion and lack of reaction to the phenomenon of ridiculing religion and its followers in cyberspace. As can be seen from reports on the situation in Poland, there are increasing signs of hostility to religion, stereotyping, and discrimination. The issues can be considered on two levels: individual protection for freedom of speech, and state protection. At the end of this paper, proposals for measures to prevent crimes based on religion or belief are presented.

Petrogenesis of Early Carboniferous Ultramafic–Mafic Volcanic Rocks in the Southern Changning–Menglian Belt, Southeastern Tibetan Plateau: Implications for the Evolution of the Paleo‐Tethyan Ocean

AbstractThe Changning–Menglian Belt represents the main Paleo‐Tethyan Suture in the southeastern Tibetan Plateau, which divides Gondwana‐ and Eurasia‐derived continental fragments from each other. The belt contains ultramafic–mafic volcanic rocks that provide evidence of the tectonic processes which operated during the evolution of the Paleo‐Tethyan Ocean. New geochemical data for Early Carboniferous volcanics in the southern Changning–Menglian Belt show that wehrlites have cumulate and poikilitic textures, and contain low‐Fo (84.2–87.2) olivine, clinopyroxene with low Mg# values (79.4–85.6), and spinel with high Cr# values (67.8–72.4). Estimated equilibrium temperatures obtained using olivine‐spinel Fe‐Mg exchange geothermometry range from 978°C to 1373°C (mean = 1205°C; n = 3). These observations combined with a lack of reaction or melt impregnation textures indicate that these units represent magmatic cumulates rather than having formed as a result of mantle‐melt reactions. Both wehrlites and basalts in the belt have subparallel rare earth element (REE)‐and primitive‐mantle‐normalized multi‐element patterns with slightly positive Nb‐Ta anomalies, but negligible Eu and Zr‐Hf anomalies. The volcanics have similar Sr‐Nd‐Pb isotopic compositions with εNd(t) values of 4.2–4.5 (mean = 4.3; n = 3) and 4.0–4.4 (mean 4.2; n = 4), respectively, and also have similar immobile element ratios, such as Nb/La, Nb/U, Th/La, Zr/Nb, Th/Ta, La/Yb, Nb/Th, Nb/Y, and Zr/Y. These characteristics indicate both units have ocean island basalt (OIB)‐like geochemical affinities, consistent with the fact that the clinopyroxene in the wehrlites is compositionally similar to OIB‐related cumulus clinopyroxene. This suggests that both the wehrlites and basalts were derived from similar parental magmas that underwent generally closed‐system magmatic differentiation dominated by fractionation of the olivine and clinopyroxene. This parental magma was likely generated in an oceanic seamount setting from an OIB‐type mantle source (i.e., asthenospheric mantle) containing garnet‐spinel lherzolite material. Combing this new data with that from oceanic seamount volcano‐sedimentary suites derived from previous research enables the identification of a mature late Paleozoic ocean basin between the passive northeastern Gondwanan margin and the northward‐migrating microcontinent of Lanping–Simao.