Generic Reactions Research Articles

Reconstruction of a genome-scale metabolic model and in-silico flux analysis of Aspergillus tubingensis: a non-mycotoxinogenic citric acid-producing fungus

BackgroundAspergillus tubingensis is a citric acid-producing fungus that can utilize sugars in hydrolysate of lignocellulosic biomass such as sugarcane bagasse and, unlike A. niger, does not produce mycotoxins. To date, no attempt has been made to model its metabolism at genome scale.ResultsHere, we utilized the whole-genome sequence (34.96 Mb length) and the measured biomass composition to reconstruct a genome-scale metabolic model (GSMM) of A. tubingensis DJU120 strain. The model, named iMK1652, consists of 1652 genes, 1657 metabolites and 2039 reactions distributed over four cellular compartments. The model has been extensively curated manually. This included removal of dead-end metabolites and generic reactions, addition of secondary metabolite pathways and several transporters. Several mycotoxin synthesis pathways were either absent or incomplete in the genome, providing a genomic basis for the non-toxinogenic nature of this species. The model was further refined based on the experimental phenotypic microarray (Biolog) data. The model closely captured DJU120 fermentative data on glucose, xylose, and phosphate consumption, as well as citric acid and biomass production, showing its applicability to capture citric acid fermentation of lignocellulosic biomass hydrolysate.ConclusionsThe model offers a framework to conduct metabolic systems biology investigations and can act as a scaffold for integrative modelling of A. tubingensis.

Kinetics of Intercluster Reactions between Atomically Precise Noble Metal Clusters [Ag25(DMBT)18]- and [Au25(PET)18]- in Room Temperature Solutions.

The kinetics of intercluster metal atom exchange reactions between solvated [Ag25(DMBT)18]- and [Au25(PET)18]- (DMBT and PET are 2,4-dimethylbenzenethiol and 2-phenylethanethiol, respectively, both C8H10S) were probed by electrospray ionization mass spectrometry and computer-based modeling. Anion mass spectra and collision induced dissociation (CID) measurements show that both cluster monomers and dimers are involved in the reactions. We have modeled the corresponding kinetics assuming a reaction mechanism in which metal atom exchange occurs through transient dimers. Our kinetic model contains three types of generic reactions: dimerization of monomers, metal atom exchange in the transient dimers, and dissociation of the dimers to monomers. There are correspondingly 377 discrete species connected by in total 1302 reactions (i.e., dimerization, dissociation and atom exchange reactions) leading to the entire series of monomeric and dimeric products [AgmAu25-m]- (m = 1-24) and [AgmAu50-m]2- (m = 0-50), respectively. The rate constants of the corresponding reactions were fitted to the experimental data, and good agreement was obtained with exchange rate constants which scale with the probability of finding a silver or gold atom in the respective monomeric subunit of the dimer, i.e., reflecting an entropic driving force for alloying. Allowing the dimerization rate constant to scale with increasing gold composition of the respective reactants improves the agreement further. The rate constants obtained are physically plausible, thus strongly supporting dimer-mediated metal atom exchange in this intercluster reaction system.

A design principle for posttranslational chaotic oscillators.

SummaryChaos behavior has been observed in various cellular and molecular processes. Here, we modeled reversible phosphorylation dynamics to elucidate a design principle for autonomous chaos generation that may arise from generic enzymatic reactions. A comprehensive parameter search demonstrated that the reaction system composed of a set of kinases and phosphatases and two substrates with two modification sites exhibits chaos behavior. All reactions are described according to the Michaelis-Menten reaction scheme without exotic functions being applied to enzymes and substrates. Clustering analysis of parameter sets that can generate chaos behavior revealed the existence of motif structures. These chaos motifs allow the two-substrate species to interact via enzyme availability and constrain the two substrates' dynamic changes in phosphorylation status so that they occur at different timescales. This chaos motif structure is found in several enzymatic reactions, suggesting that chaos behavior may underlie cellular autonomy in a variety of biochemical systems.

A mathematical approach of the entropic index applied to chemical systems

AbstractThis article deals with the mathematical efforts for developing an entropic performance index, taking into account both the different entropy concepts for establishing it, including Communication Theory, and its practical application. To illustrate the performance of the index developed, two different approaches were applied to a reactive system that consists of multiple generic reactions. The reactive system was optimized using the strategy of generating the minimum entropy rate and then the index was applied to check the progress of the process. The index increased from 0.2146 to 0.549, thus indicating a better result and, consequently, more favourable operating conditions. Additionally, a more refined procedure was carried out, which generated a maximum value for the index of 0.6174. To reveal the efficiency of this index, classic indicators based on trade‐offs between conversion and yield were also used to optimize the reactive system, which resulted in an index value of 0.6129. A detailed comparative analysis showed a convergence of the optimal regions, given by the classical method and that established by the entropy index. However, the optimal operating points are different, which can be explained by the interactions between the components considered by the entropic index. The conclusion to be drawn is that the results based on the entropy index describe the real system more appropriately, and therefore its performance is superior.

Evaluating active investing with generic trading reactions

AbstractWe evaluate the performance of rules using past information to generate daily trading signals. Assuming generic trading reactions to buy and sell signals, we derive an analytic excess return that isolates commissions, interests, the impact of trading timing, and that of the benchmark's choice. The result is useful in dealing with data snooping through leverage and benchmark tweaking. We illustrate the empirical implications by examining trend‐following performance across Dow Jones Industrial Average (1927–2016) and an international sample of major equity indexes and blue‐chip stocks (1980–2016). The results show substantial, fading, non‐persistent and highly methodology‐sensitive excess returns.

Intensification of Catalytic Processes through the Pellet Structuring: Steady-State Properties of a Bifunctional Catalyst Pellet Applied to Generic Chemical Reactions and the Direct Synthesis of DME

Structuring of different types of catalytic active centers at a single-pellet level appears to be a promising and powerful tool for integration and intensification of multistep solid-catalyzed chemical reactions. However, the enhancement in the product yield and selectivity strongly depends on the proper choice of the distribution of different catalysts within the pellet. To demonstrate potential benefits from properly designed catalyst pellet, numerical studies were conducted with the aid of the mathematical model of a single spherical bifunctional catalyst pellet. The analysis was performed both for a system of two generic chemical reactions and for a real process, i.e., direct synthesis of dimethyl ether (DME) from synthesis gas via methanol. Evaluation of the pellet performance was done for three arrangements of the catalytic active sites within the pellet, i.e., a uniform distribution of two types of catalytic active centers in the entire volume of the pellet, and two core–shell structures. It was demonstrated that, especially for the larger pellets typical for fixed-bed applications, the product yield might be significantly improved by selecting proper catalyst arrangements within the pellet.

Computational Modeling of Electrochemical Systems: Activation-Control vs. Mass-Transport-Control Analysis

The computational modeling of two generic heterogeneous reactions within an electrochemical cell formed by two planar electrodes in contact with an aqueous electrolyte was carried out with the FlexPDE 6 software. Both Red-Ox reactions were initially given identical kinetic and mass transport parameters to corroborate the functionality of the model. The derived steady-state current/overpotential curves, under mass transport control, were compared to the analytical model for Nernstian reactions (1). A very good match was found. The diffusion coefficients and standard reaction-rate-constants were afterwards varied. Inspecting the current/overpotential curve shape helped to rapidly identify the reaction-rate control-mechanism: either mass transport or activation. However, if the current density at each given potential is recorded before a steady-state value is attained, the correct identification of the reaction-rate control-mechanism may be hindered.

Stress-Induced Evolutionary Innovation: A Mechanism for the Origin of Cell Types.

Understanding the evolutionary role of environmentally induced phenotypic variation (i.e., plasticity) is an important issue in developmental evolution. A major physiological response to environmental change is cellular stress, which is counteracted by generic stress reactions detoxifying the cell. A model, stress-induced evolutionary innovation (SIEI), whereby ancestral stress reactions and their corresponding pathways can be transformed into novel structural components of body plans, such as new cell types, is described. Previous findings suggest that the cell differentiation cascade of a cell type critical to pregnancy in humans, the decidual stromal cell, evolved from a cellular stress reaction. It is hypothesized that the stress reaction in these cells was elicited ancestrally via inflammation caused by embryo attachment. The present study proposes that SIEI is a distinct form of plasticity-based evolutionary change leading to the origin of novel structures rather than adaptive transformation of pre-existing characters.

Consumer responses to corporate social irresponsibility: The role of moral emotions, evaluations, and social cognitions

AbstractWe investigate the mediating roles of moral emotions and attitudes between perceptions of corporate irresponsible actions, on the one hand, and consumer responses, on the other hand, and further examine their contingencies based on consumer social cognitions. Our findings show that, for corporate transgressions, multiple social cognitions (moral identity, relational and collective self‐concepts, and affective empathy) moderate the elicitation of negative moral emotions (contempt and anger) and overall evaluations (attitudes), which, in turn, lead to negative responses toward the company (negative word of mouth, complaint behaviors, and boycotting). Our study adds to extant research on corporate social irresponsibility by examining three generic reactions people have toward corporate social irresponsibility and demonstrating important boundary conditions. In addition, hypotheses are tested on a sample of adult consumers. Implications for communication by firms are considered.

Hidden messenger from quantum geometry: Towards information conservation in quantum gravity

The back reactions of Hawking radiation allow nontrivial correlations between consecutive Hawking quanta, which gives a possible way of resolving the paradox of black hole information loss known as the hidden messenger method. In a recent work of Ma et al. [ arXiv:1711.10704 ], this method is enhanced by a general derivation using small deviations of the states of Hawking quanta off canonical typicality. In this paper, we use this typicality argument to study the effects of generic back reactions on the quantum geometries described by spin network states, and discuss the viability of entropy conservation in loop quantum gravity. We find that such back reactions lead to small area deformations of quantum geometries including those of quantum black holes. This shows that the hidden-messenger method is still viable in loop quantum gravity, which is a first step towards resolving the paradox of black hole information loss in quantum gravity.

RetroTransformDB: A Dataset of Generic Transforms for Retrosynthetic Analysis

Presently, software tools for retrosynthetic analysis are widely used by organic, medicinal, and computational chemists. Rule-based systems extensively use collections of retro-reactions (transforms). While there are many public datasets with reactions in synthetic direction (usually non-generic reactions), there are no publicly-available databases with generic reactions in computer-readable format which can be used for the purposes of retrosynthetic analysis. Here we present RetroTransformDB—a dataset of transforms, compiled and coded in SMIRKS line notation by us. The collection is comprised of more than 100 records, with each one including the reaction name, SMIRKS linear notation, the functional group to be obtained, and the transform type classification. All SMIRKS transforms were tested syntactically, semantically, and from a chemical point of view in different software platforms. The overall dataset design and the retrosynthetic fitness were analyzed and curated by organic chemistry experts. The RetroTransformDB dataset may be used by open-source and commercial software packages, as well as chemoinformatics tools.

Parallel adaptations and common host cell responses enabling feeding of obligate and facultative plant parasitic nematodes.

Parallel adaptations enabling the use of plant cells as the primary food source have occurred multiple times in distinct nematode clades. The hallmark of all extant obligate and facultative plant-feeding nematodes is the presence of an oral stylet, which is required for penetration of plant cell walls, delivery of pharyngeal gland secretions into host cells and selective uptake of plant assimilates. Plant parasites from different clades, and even within a single clade, display a large diversity in feeding behaviours ranging from short feeding cycles on single cells to prolonged feeding on highly sophisticated host cell complexes. Despite these differences, feeding of nematodes frequently (but certainly not always) induces common responses in host cells (e.g. endopolyploidization and cellular hypertrophy). It is thought that these host cell responses are brought about by the interplay of effectors and other biological active compounds in stylet secretions of feeding nematodes, but this has only been studied for the most advanced sedentary plant parasites. In fact, these responses are thought to be fundamental for prolonged feeding of sedentary plant parasites on host cells. However, as we discuss in this review, some of these common plant responses to independent lineages of plant parasitic nematodes might also be generic reactions to cell stress and as such their onset may not require specific inputs from plant parasitic nematodes. Sedentary plant parasitic nematodes may utilize effectors and their ability to synthesize other biologically active compounds to tailor these common responses for prolonged feeding on host cells.

What Drives Trend-Following Profits?

We document the nature of substantial yet transient trend-following profits in equity indexes and stocks. The analysis benefits from a novel framework for evaluating active trading, with generic reactions to buy/sell signals and explicit trading costs. We show that trend-following profits rely on favorable price characteristics rather than a genuine forecasting ability. The price sensitivity of trend signals greatly complements the mean and variance of buy-and-hold returns in explaining the time series variation in buy and sell excess returns. Trend-following’s success revolves suspiciously around price declines and is oversensitive to the “benchmark – length of evaluation period” joint choice.

Ritual complexity in a past community revealed by ancient DNA analysis of pre-colonial terracotta items from Northern Ghana

The pre-colonial 6th–14th century terracotta forms of Koma Land, Northern Ghana, contain cavities which may have been intended to hold liquids. These have been linked to traditional African libation, but the specific nature of their contents is unclear. We used generic polymerase chain reactions that would amplify DNA from a range of plant and fungal species in order to identify remains of libations applied to fourteen terracotta items. We anticipated difficulties in distinguishing genuine ancient DNA sequences from those resulting from contaminating material, and therefore also carried out a series of control experiments to assess the extent to which the samples had become contaminated with exogenous DNA during burial, excavation and downstream analysis. Taking account of the results of the control experiments, as well as the difficulties in assigning matches between ancient DNA sequences and database entries, we provide evidence for the use of three different types of plant – plantain/banana, pine and grasses – in libations associated with the terracotta items. We also identified DNA from Coniochaeta yeast within the mouth cavity of one figurine, suggesting that this structure was burnt prior to deposition.

Multistep Reaction Based De Novo Drug Design: Generating Synthetically Feasible Design Ideas.

We describe a "multistep reaction driven" evolutionary algorithm approach to de novo molecular design. Structures generated by the approach include a proposed synthesis path intended to aid the chemist in assessing the synthetic feasibility of the ideas that are generated. The methodology is independent of how the design ideas are scored, allowing multicriteria drug design to address multiple issues including activity at one or more pharmacological targets, selectivity, physical and ADME properties, and off target liabilities; the methods are compatible with common computer-aided drug discovery "scoring" methodologies such as 2D- and 3D-ligand similarity, docking, desirability functions based on physiochemical properties, and/or predictions from 2D/3D QSAR or machine learning models and combinations thereof to be used to guide design. We have performed experiments to assess the extent to which known drug space can be covered by our approach. Using a library of 88 generic reactions and a database of ∼20 000 reactants, we find that our methods can identify "close" analogs for ∼50% of the known small molecule drugs with molecular weight less than 300. To assess the quality of the in silico generated synthetic pathways, synthesis chemists were asked to rate the viability of synthesis pathways: both "real" and in silico generated. In silico reaction schemes generated by our methods were rated as very plausible with scores similar to known literature synthesis schemes.

Characterising Complex Enzyme Reaction Data

The relationship between enzyme-catalysed reactions and the Enzyme Commission (EC) number, the widely accepted classification scheme used to characterise enzyme activity, is complex and with the rapid increase in our knowledge of the reactions catalysed by enzymes needs revisiting. We present a manual and computational analysis to investigate this complexity and found that almost one-third of all known EC numbers are linked to more than one reaction in the secondary reaction databases (e.g., KEGG). Although this complexity is often resolved by defining generic, alternative and partial reactions, we have also found individual EC numbers with more than one reaction catalysing different types of bond changes. This analysis adds a new dimension to our understanding of enzyme function and might be useful for the accurate annotation of the function of enzymes and to study the changes in enzyme function during evolution.

Geometry-induced protein pattern formation

Protein patterns are known to adapt to cell shape and serve as spatial templates that choreograph downstream processes like cell polarity or cell division. However, how can pattern-forming proteins sense and respond to the geometry of a cell, and what mechanistic principles underlie pattern formation? Current models invoke mechanisms based on dynamic instabilities arising from nonlinear interactions between proteins but neglect the influence of the spatial geometry itself. Here, we show that patterns can emerge as a direct result of adaptation to cell geometry, in the absence of dynamical instability. We present a generic reaction module that allows protein densities robustly to adapt to the symmetry of the spatial geometry. The key component is an NTPase protein that cycles between nucleotide-dependent membrane-bound and cytosolic states. For elongated cells, we find that the protein dynamics generically leads to a bipolar pattern, which vanishes as the geometry becomes spherically symmetrical. We show that such a reaction module facilitates universal adaptation to cell geometry by sensing the local ratio of membrane area to cytosolic volume. This sensing mechanism is controlled by the membrane affinities of the different states. We apply the theory to explain AtMinD bipolar patterns in [Formula: see text] EcMinDE Escherichia coli. Due to its generic nature, the mechanism could also serve as a hitherto-unrecognized spatial template in many other bacterial systems. Moreover, the robustness of the mechanism enables self-organized optimization of protein patterns by evolutionary processes. Finally, the proposed module can be used to establish geometry-sensitive protein gradients in synthetic biological systems.

A combustion model for multi-component fuels using a physical surrogate group chemistry representation (PSGCR)

A combustion model to simulate the oxidation of multi-component fuels has been developed and applied to model autoignition combustion processes. The model is called the Physical Surrogate Group Chemistry Representation (PSGCR) method, which combines a multi-component fuel model to describe the physical properties of the fuel with reduced reaction mechanisms to represent the chemistry of the fuel components. A group of physical surrogate (PS) components are used to describe the fuel’s physical properties, such as the distillation profile, specific gravity, lower heating value and hydrogen-to-carbon (H/C) ratio. The oxidation processes of the fuel are modeled using skeletal reaction mechanisms for a group of chemical surrogate (CS) components that employ generic reactions as well as detailed reaction kinetics. The generic reactions were built to model unavailable reaction pathways from physical surrogates to the base CS components or their intermediate species. The model includes the 6 major chemical classes of typical hydrocarbon fuels, i.e., n-paraffins, iso-paraffins, olefins, naphthenes, aromatics and oxygenates, and 65 representative hydrocarbon components are included in a data base for the physical surrogate components and 43 chemical surrogate components are considered for the group chemistry representation. Six types of generic reaction sets are proposed to model the oxidation of 15 physical surrogate components that are called extended-CS (chemical surrogate) components. The present generic reactions are modeled such that the major characteristics of the oxidation process of the fuel components are included in a consistent manner.The final version of the PSGCR reaction mechanism consists of 264 species and 1292 reactions. Validation of the reaction mechanisms was performed by comparing predicted ignition delay times with experimental measurements and/or predictions from comprehensive mechanisms available in the literature. The model was also validated against HCCI experimental data of the FACE fuels. Then the model was applied to simulate practical diesel fuel (F76) spray combustion in a constant volume chamber, and the predicted ignition delay times of the surrogate model fuel were compared with measured values. The results show that the present PSGCR method captures the combustion characteristics of complex multi-component fuels, giving reliable performance for combustion predictions, as well as computational efficiency improvements for multi-dimensional CFD simulations through the use of reduced mechanisms.

Differential expression of serum/plasma proteins in various infectious diseases: Specific or nonspecific signatures

Apart from direct detection of the infecting organisms or biomarker of the pathogen itself, surrogate host markers are also useful for sensitive and early diagnosis of pathogenic infections. Early detection of pathogenic infections, discrimination among closely related diseases with overlapping clinical manifestations, and monitoring of disease progression can be achieved by analyzing blood biomarkers. Therefore, over the last decade large numbers of proteomics studies have been conducted to identify differentially expressed human serum/plasma proteins in different infectious diseases with the intent of discovering novel potential diagnostic/prognostic biomarkers. However, in‐depth review of the literature indicates that many reported biomarkers are altered in the same way in multiple infectious diseases, regardless of the type of infection. This might be a consequence of generic acute phase reactions, while the uniquely modulated candidates in different pathogenic infections could be indicators of some specific responses. In this review article, we will provide a comprehensive analysis of differentially expressed serum/plasma proteins in various infectious diseases and categorize the protein markers associated with generic or specific responses. The challenges associated with the discovery, validation, and translational phases of serum/plasma biomarker establishment are also discussed.

Stereoselective Capture of N-Acyliminium Ions Generated from α-Hydroxy-N-acylcarbamides: Direct Synthesis of Uracils from Barbituric Acids Enabled by SmI2 Reduction

Lewis acid promoted cleavage of α-amino alcohols derived from barbituric acids via chemoselective Sm(II)-mediated electron transfer affords a wide range of C6-substituted 5,6-dihydrouracils. The reaction involves the first generation of N-acyliminium ions directly from the versatile barbituric acids and proceeds with excellent stereoselectivity. The products are shown to be active in generic transition metal catalyzed reactions, thus providing a modular and highly practical sequence to the biologically significant uracil derivatives.