Classical Affine Research Articles

Thermal proteome profiling efficiently identifies ribosome destabilizing oxazolidinones

Identifying the targets of bioactive small molecules is a challenging endeavor for which no general solution currently exists. Classical affinity purification experiments suffer from the need to functionalise a bioactive compound and link it to a solid support, which may interfere with target binding. A modern mass spectrometry-based proteomics technique that has partially circumvented this problem is thermal proteome profiling (TPP), which determines the effect of an unmodified small molecule on the thermal stability of the whole proteome simultaneously. Here, we use TPP to identify the mode-of-action of a newly-discovered autophagy inhibitor based on oxazolidinones often employed as chiral auxiliaries. Surprisingly, a significant portion of all ribosomal proteins were found to be destabilized by the inhibitor, highlighting the utility of this technology for determining a challenging mode-of-action.

Outer-Convex Dominating Set in the Corona of Graphs as Encryption Key Generator

In this paper, we present a new type of symmetric encryption by converting the classical monoalphabetic affine cipher into a polyalphabetic cipher. The proposed encryption utilizes the properties of outer-convex dominating set in the corona of graphs to generate random keys from the shared keyword to every character of the message. The new encryption eliminates the weaknesses of affine cipher, thus increasing the level of confidence for exchanging messages.

Destabilizing single chain major histocompatibility complex class I protein for repurposed enterokinase proteolysis

The lack of a high throughput assay for screening stabilizing peptides prior to building a library of peptide-major histocompatibility complex class I (pMHC-I) molecules has motivated the continual use of in silico tools without biophysical characterization. Here, based on de novo protein fragmentation, the EASY MHC-I (EZ MHC-I) assay favors peptide antigen screening to an unheralded hands-on time of seconds per peptide due to the empty single chain MHC-I protein instability. Unlike tedious traditional labeling- and antibody-based MHC-I assays, repurposed enterokinase directly fragments the unstable single MHC-I chain protein unless rescued by a stabilizing peptide under luminal condition. Herein, the principle behind EZ MHC-I assay not only characterizes the overlooked stability as a known better indicator of immunogenicity than classical affinity but also the novel use of enterokinase from the duodenum to target destabilized MHC-I protein not bearing the standard Asp-Asp-Asp-Asp-Lys motif, which may protend to other protein instability-based assays.

An affine scaling method using a class of differential barrier functions: primal approach

In this paper we propose a family of affine scaling interior point algorithms, called galpv4, using a primal approach, based on a large class of differential barrier functions. We show that these algorithms are in fact an extension and generalization of the classical affine scaling algorithm based on the well-known log barrier function. After carrying out a complete convergence analysis, we select some of these algorithms for comparison with the classical affine scaling algorithm, performed with the help of the familiar Netlib test set.

Commuting involution graphs in classical affine Weyl groups

In this paper we investigate commuting involution graphs in classical affine Weyl groups. Let W be a classical Weyl group of rank n, with its corresponding affine Weyl group. Our main result is that if X is a conjugacy class of involutions in then the commuting involution graph is either disconnected or has diameter at most n + 2. This bound is known to hold for types and so the main work of this paper is to prove the theorem for types and

Crellastatin A, a PARP-1 Inhibitor Discovered by Complementary Proteomic Approaches.

Crellastatin A, a cytotoxic sulfated bis-steroid isolated from the Vanuatu Island marine sponge Crella sp., was selected as an interesting probe for a comprehensive proteomic analysis directed at the characterization of its protein interactors. Given its peculiar structural features, A was submitted to a mass spectrometry-based drug affinity responsive target stability (DARTS) assay combined with (targeted-limited proteolysis-multiple reaction monitoring (t-LiP MRM), rather than a classical affinity purification strategy. Poly-ADP-ribose-polymerase-1 (PARP-1) emerged as the main crellastatin A cellular partner. This result was confirmed by both biochemical and in silico analyses. Further in vitro biological assays highlighted an interesting crellastatin A inhibitory activity on PARP-1.

Metrical theorems on systems of affine forms

In this paper we discuss metric theory associated with the affine (inhomogeneous) linear forms in the so called doubly metric settings within the classical and the mixed setups. We consider the system of affine forms given by q↦qX+α, where q∈Zm (viewed as a row vector), X is an m×n real matrix and α∈Rn. The classical setting refers to the dist(qX+α,Zm) to measure the closeness of the integer values of the system (X,α) to integers. The absolute value setting is obtained by replacing dist(qX+α,Zm) with dist(qX+α,0); and the more general mixed settings are obtained by replacing dist(qX+α,Zm) with dist(qX+α,Λ), where Λ is a subgroup of Zm.We prove the Khintchine–Groshev and Jarník type theorems for the mixed affine forms and Jarník type theorem for the classical affine forms. We further prove that the sets of badly approximable affine forms, in both the classical and mixed settings, are hyperplane winning. The latter result, for the classical setting, answers a question raised by Kleinbock (1999).

Drug-Target Residence Time Affects in Vivo Target Occupancy through Multiple Pathways.

The drug discovery and development process is greatly hampered by difficulties in translating in vitro potency to in vivo efficacy. Recent studies suggest that the long-neglected drug-target residence time parameter complements classical drug affinity parameters (KI, Kd, IC50, or EC50) and is a better predictor of in vivo efficacy. Compounds with a long drug-target residence time are often more efficacious in vivo. The impact, however, of the drug-target residence time on in vivo efficacy remains controversial due to difficulties in experimentally determining the in vivo target occupancy during drug treatment. To tackle this problem, an in vivo displacement assay was developed using soluble epoxide hydrolase as a biological model. In this report, we experimentally demonstrated that drug-target residence time affects the duration of in vivo drug-target binding. In addition, the drug-target residence time plays an important role in modulating the rate of drug metabolism which also affects the efficacy of the drug.

Affine Volterra processes

We introduce affine Volterra processes, defined as solutions of certain stochastic convolution equations with affine coefficients. Classical affine diffusions constitute a special case, but affine Volterra processes are neither semimartingales, nor Markov processes in general. We provide explicit exponential-affine representations of the Fourier–Laplace functional in terms of the solution of an associated system of deterministic integral equations of convolution type, extending well-known formulas for classical affine diffusions. For specific state spaces, we prove existence, uniqueness, and invariance properties of solutions of the corresponding stochastic convolution equations. Our arguments avoid infinite-dimensional stochastic analysis as well as stochastic integration with respect to non-semimartingales, relying instead on tools from the theory of finite-dimensional deterministic convolution equations. Our findings generalize and clarify recent results in the literature on rough volatility models in finance.

Micro Axial Turbine Hill Charts: Affinity Laws, Experiments and CFD Simulations for Different Diameters

Water supply systems are one of the main hydraulic systems with significant potential for the installation of micro-hydropower devices. Although there are already some mini-hydropower applications in water supply systems, it is still a huge potential that continues to be under-exploited. The arrangement based on an axial turbine, such as an inline tubular propeller, with different diameters and rotational speeds suitable to exploit the existing potential in the water sector, is fully tested. The turbine with the nominal diameter of 85 mm was analysed through experimental campaigns and numerical models for a large range of heads and flow measurements to access its performance. A good correlation between the physical model and the numerical results were obtained, with mean values of deviation less than 5% regarding flow, mechanical power and efficiency. These results were extrapolated to other similar turbine with 170 mm, using affinity laws to investigate the power extraction performance. Both geometries were also numerically investigated using computational fluid dynamics (CFD) models and comparisons were made between the affinity model and experimental results. The results identified differences when compared with the classical affinity curves. Therefore, new formulations based on affinity equations were proposed for the analyzed axial turbine with different diameters without imposing a constant turbine efficiency since actually it does not keep constant as CFD calibrated model proved. Compared to experimental test efficiencies for different rotational speeds, the new proposed affinity laws provided a maximum error of 12% for both diameters.

The quantum thermodynamic force responsible for quantum state transformation and the flow and backflow of information

Why do quantum evolutions occur and why do they stop at certain points? In classical thermodynamics affinity was introduced to predict in which direction an irreversible process proceeds. In this paper the quantum mechanical counterpart of the classical affinity is found. It is shown that the quantum version of affinity can predict in which direction a process evolves. A new version of the second law of thermodynamics is derived through quantum affinity for energy-incoherent state interconversion under thermal operations. we will also see that the quantum affinity can be a good candidate to be responsible, as a force, for driving the flow and backflow of information in Markovian and non-Markovian evolutions. Finally we show that the rate of quantum coherence can be interpreted as the pure quantum mechanical contribution of the total thermodynamic force and flow. Thus it is seen that, from a thermodynamic point of view, any interaction from the outside with the system or any measurement on the system may be represented by a quantum affinity.

Energy efficiency overestimated by classic affinity laws: relation between volumetric flow rate and static pressure of an axial mine fan adjusted by a variable frequency driver

ABSTRACTA significant problem with operating a coal mine fan is finding ways to save energy while still maintaining the required air supply to working faces. The authors developed and tested the performance of a K45-4-№9/18.5 kW axial mine fan adjusted by a variable frequency driver set to different fractions of a typical national electric grid frequency of 50 Hz. Its volumetric flow-rate and static pressure (Q-H) data were fitted with fifth-order polynomial equations using least-squares regression. The extremes of the Q-H curves descend with decreasing frequency and differ significantly from the predictions of classic affinity laws (CAL) in fluid dynamics. The air-flow power predicted by CAL theory deviates from the baseline of the fifth-order polynomial extremes by a maximum of 48%. Interestingly, the deviation between theoretical and experimental values increases with decreasing power frequency. These results are evidence of the theoretical overestimation of energy efficiency of an AMF adjusted by a VFD.

A Lysine-Targeted Affinity Label for Serine-β-Lactamase Also Covalently Modifies New Delhi Metallo-β-lactamase-1 (NDM-1).

The divergent sequences, protein structures, and catalytic mechanisms of serine- and metallo-β-lactamases hamper the development of wide-spectrum β-lactamase inhibitors that can block both types of enzymes. The O-aryloxycarbonyl hydroxamate inactivators of Enterobacter cloacae P99 class C serine-β-lactamase are unusual covalent inhibitors in that they target both active-site Ser and Lys residues, resulting in a cross-link consisting of only two atoms. Many clinically relevant metallo-β-lactamases have an analogous active-site Lys residue used to bind β-lactam substrates, suggesting a common site to target with covalent inhibitors. Here, we demonstrate that an O-aryloxycarbonyl hydroxamate inactivator of serine-β-lactamases can also serve as a classical affinity label for New Delhi metallo-β-lactamase-1 (NDM-1). Rapid dilution assays, site-directed mutagenesis, and global kinetic fitting are used to map covalent modification at Lys211 and determine KI (140 μM) and kinact (0.045 min-1) values. Mass spectrometry of the intact protein and the use of ultraviolet photodissociation for extensive fragmentation confirm stoichiometric covalent labeling that occurs specifically at Lys211. A 2.0 Å resolution X-ray crystal structure of inactivated NDM-1 reveals that the covalent adduct is bound at the substrate-binding site but is not directly coordinated to the active-site zinc cluster. These results indicate that Lys-targeted affinity labels might be a successful strategy for developing compounds that can inactivate both serine- and metallo-β-lactamases.

Variational community partition with novel network structure centrality prior

In this paper, we proposed a novel two-stage optimization method for network community partition, which is based on inherent network structure information. The introduced optimization approach utilizes the new network centrality measure of both links and vertices to construct the key affinity description of the given network, where the direct similarities between graph nodes or nodal features are not available to obtain the classical affinity matrix. Indeed, such calculated network centrality information presents the essential structure of network, hence, the proper measure for detecting network communities, which also introduces a `confidence' criterion for referencing new labeled benchmark nodes. For the resulted challenging combinatorial optimization problem of graph clustering, the proposed optimization method iteratively employs an efficient convex optimization algorithm which is developed based under a new variational perspective of primal and dual. Experiments over both artificial and real-world network datasets demonstrate that the proposed optimization strategy of community detection significantly improves result accuracy and outperforms the state-of-the-art algorithms in terms of accuracy and reliability.

On the reducibility of induced representations for classical p-adic groups and related affine Hecke algebras

Let π be an irreducible smooth complex representation of a general linear p-adic group and let σ be an irreducible complex supercuspidal representation of a classical p-adic group of a given type, so that π ⨁ σ is a representation of a standard Levi subgroup of a p-adic classical group of higher rank. We show that the reducibility of the representation of the appropriate p-adic classical group obtained by (normalized) parabolic induction from π ⨁ σ does not depend on σ, if σ is “separated” from the supercuspidal support of π. (Here, “separated” means that, for each factor ρ of a representation in the supercuspidal support of π, the representation parabolically induced from ρ ⨁ σ is irreducible.) This was conjectured by E. Lapid and M. Tadic. (In addition, they proved, using results of C. Jantzen, that this induced representation is always reducible if the supercuspidal support is not separated.) More generally, we study, for a given set I of inertial orbits of supercuspidal representations of p-adic general linear groups, the category CI,σ of smooth complex finitely generated representations of classical p-adic groups of fixed type, but arbitrary rank, and supercuspidal support given by σ and I, and show that this category is equivalent to a category of finitely generated right modules over a direct sum of tensor products of extended affine Hecke algebras of type AB and D and establish functoriality properties, relating categories with disjoint I’s. In this way, we extend results of C. Jantzen who proved a bijection between irreducible representations corresponding to these categories. The proof of the above reducibility result is then based on Hecke algebra arguments, using Kato’s exotic geometry.

Extended affine Lie superalgebras and their affinizations

Extended affine Lie superalgebras are super versions of the defining axioms of extended affine Lie algebras or more generally invariant affine reflection algebras. This class includes finite dimensional basic classical simple Lie superalgebras and affine Lie superalgebras. In this paper, an affinization process is introduced for the class of extended affine Lie superalgebras, and the necessary conditions for an extended affine Lie superalgebra to be invariant under this process are presented. Moreover, new extended affine Lie superalgebras are constructed by means of the affinization process.

Recent advances in proximity-based labeling methods for interactome mapping.

Proximity-based labeling has emerged as a powerful complementary approach to classic affinity purification of multiprotein complexes in the mapping of protein–protein interactions. Ongoing optimization of enzyme tags and delivery methods has improved both temporal and spatial resolution, and the technique has been successfully employed in numerous small-scale (single complex mapping) and large-scale (network mapping) initiatives. When paired with quantitative proteomic approaches, the ability of these assays to provide snapshots of stable and transient interactions over time greatly facilitates the mapping of dynamic interactomes. Furthermore, recent innovations have extended biotin-based proximity labeling techniques such as BioID and APEX beyond classic protein-centric assays (tag a protein to label neighboring proteins) to include RNA-centric (tag an RNA species to label RNA-binding proteins) and DNA-centric (tag a gene locus to label associated protein complexes) assays.

Heavy tails for an alternative stochastic perpetuity model

In this paper we consider a stochastic model of perpetuity-type. In contrast to the classical affine perpetuity model of Kesten (1973) and Goldie (1991) all discount factors in the model are mutually independent. We prove that the tails of the distribution of this model are regularly varying both in the univariate and multivariate cases. Due to the additional randomness in the model the tails are not pure power laws as in the Kesten–Goldie setting but involve a logarithmic term.

On the unification of classical, intuitionistic and affine logics

This article presents aunified logicthat combines classical logic, intuitionistic logic and affine linear logic (restricting contraction but not weakening). We show that this unification can be achieved semantically, syntactically and in the computational interpretation of proofs. It extends our previous work in combining classical and intuitionistic logics. Compared to linear logic, classical fragments of proofs are better isolated from non-classical fragments. We define a phase semantics for this logic that naturally extends the Kripke semantics of intuitionistic logic. We present a sequent calculus with novel structural rules, which entail a more elaborate procedure for cut elimination. Computationally, this system allows affine-linear interpretations of proofs to be combined with classical interpretations, such as the λμ calculus. We show how cut elimination must respect the boundaries between classical and non-classical modes of proof that correspond to delimited control effects.

A Lax type operator for quantum finite W-algebras

For a reductive Lie algebra $$\mathfrak {g}$$ , its nilpotent element f and its faithful finite dimensional representation, we construct a Lax operator L(z) with coefficients in the quantum finite W-algebra $$W(\mathfrak {g},f)$$ . We show that for the classical linear Lie algebras $$\mathfrak {gl}_N$$ , $$\mathfrak {sl}_N$$ , $$\mathfrak {so}_N$$ and $$\mathfrak {sp}_N$$ , the operator L(z) satisfies a generalized Yangian identity. The operator L(z) is a quantum finite analogue of the operator of generalized Adler type which we recently introduced in the classical affine setup. As in the latter case, L(z) is obtained as a generalized quasideterminant.