Kinetic behavior of the general modifier mechanism of Botts and Morales with non-equilibrium binding

In this paper, we perform a complete analysis of the kinetic behavior of the general modifier mechanism of Botts and Morales in both equilibrium steady states and non-equilibrium steady states (NESS). Enlightened by the non-equilibrium theory of Markov chains, we introduce the net flux into discussion and acquire an expression of product rate in NESS, which has clear biophysical significance. Up till now, it is a general belief that being an activator or an inhibitor is an intrinsic property of the modifier. However, we reveal that this traditional point of view is based on the equilibrium assumption. A modifier may no longer be an overall activator or inhibitor when the reaction system is not in equilibrium. Based on the regulation of enzyme activity by the modifier concentration, we classify the kinetic behavior of the modifier into three categories, which are named hyperbolic behavior, bell-shaped behavior, and switching behavior, respectively. We show that the switching phenomenon, in which a modifier may convert between an activator and an inhibitor when the modifier concentration varies, occurs only in NESS. Effects of drugs on the Pgp ATPase activity, where drugs may convert from activators to inhibitors with the increase of the drug concentration, are taken as a typical example to demonstrate the occurrence of the switching phenomenon.Comment: 19 pages, 10 figure

Analysis on Safety of Removing the Closure Segment in a Prestressed Concrete Cable-stayed Bridge

AbstractAiming at failure of closure segment in a prestressed concrete cable-stayed bridge, a strengthening technology, namely replacing the closure segment, was firstly put forward. But removing the old closure segment was a process of release of internal force and had great risk. So the structural safety possibly induced by removing must be analyzed and confirmed. Based on FEM and summary of engineering experience, the construction stages for removing the old closure segment were simulated, and then some analysis relevant to safety, including thermal effect, dynamic characteristics and global stability of the whole bridge structure, were systematically presented. According to these analysis results, corresponding prevention and control measures were provided to ensure construction safety. Studies showed that, variation range of its structural state between before and after removing is not obvious, and its dynamic characteristics changed little after removing. In addition, structural instability could not be induced by removing, but for the sake of improving construction safety reliability, necessary safety prevention and control measures were indispensable. Analysis on safety of removing the old closure segment constituted the important part of the strengthening technology of replacing the closure segment, and became the theoretical basis of removing partial structural members for existing bridges

SemanticCAP: Chromatin Accessibility Prediction Enhanced by Features Learning from a Language Model

A large number of inorganic and organic compounds are able to bind DNA and form complexes, among which drug-related molecules are important. Chromatin accessibility changes not only directly affects drug-DNA interactions, but also promote or inhibit the expression of critical genes associated with drug resistance by affecting the DNA binding capacity of TFs and transcriptional regulators. However, Biological experimental techniques for measuring it are expensive and time consuming. In recent years, several kinds of computational methods have been proposed to identify accessible regions of the genome. Existing computational models mostly ignore the contextual information of bases in gene sequences. To address these issues, we proposed a new solution named SemanticCAP. It introduces a gene language model which models the context of gene sequences, thus being able to provide an effective representation of a certain site in gene sequences. Basically, we merge the features provided by the gene language model into our chromatin accessibility model. During the process, we designed some methods to make feature fusion smoother. Compared with other systems under public benchmarks, our model proved to have better performance

Hawking radiation from (2+1)-dimensional BTZ black holes

Motivated by the Robinson-Wilczek's recent viewpoint that Hawking radiation can be treated as a compensating energy momentum tensor flux required to cancel gravitational anomaly at the horizon of a Schwarzschild-type black hole, we investigate Hawking radiation from the rotating $(2+1)$-dimensional BTZ black hole and the charged $(2+1)$-dimensional BTZ black hole, via cancellation of gauge and gravitational anomalies at the horizon. To restore gauge invariance and general coordinate covariance at the quantum level, one must introduce the corresponding gauge current and energy momentum tensor fluxes to cancel gauge and gravitational anomalies at the horizon. The results show that the values of these compensating fluxes are exactly equal to those of $(1+1)$-dimensional blackbody radiation at the Hawking temperature.Comment: 15 pages; references updated and added; to appear in Phys. Lett.

Design and Synthesis of Diverse Functional Kinked Nanowire Structures for Nanoelectronic Bioprobes

Functional kinked nanowires (KNWs) represent a new class of nanowire building blocks, in which functional devices, for example, nanoscale field-effect transistors (nanoFETs), are encoded in geometrically controlled nanowire superstructures during synthesis. The bottom-up control of both structure and function of KNWs enables construction of spatially isolated point-like nanoelectronic probes that are especially useful for monitoring biological systems where finely tuned feature size and structure are highly desired. Here we present three new types of functional KNWs including (1) the zero-degree KNW structures with two parallel heavily doped arms of U-shaped structures with a nanoFET at the tip of the “U”, (2) series multiplexed functional KNW integrating multi-nanoFETs along the arm and at the tips of V-shaped structures, and (3) parallel multiplexed KNWs integrating nanoFETs at the two tips of W-shaped structures. First, U-shaped KNWs were synthesized with separations as small as 650 nm between the parallel arms and used to fabricate three-dimensional nanoFET probes at least 3 times smaller than previous V-shaped designs. In addition, multiple nanoFETs were encoded during synthesis in one of the arms/tip of V-shaped and distinct arms/tips of W-shaped KNWs. These new multiplexed KNW structures were structurally verified by optical and electron microscopy of dopant-selective etched samples and electrically characterized using scanning gate microscopy and transport measurements. The facile design and bottom-up synthesis of these diverse functional KNWs provides a growing toolbox of building blocks for fabricating highly compact and multiplexed three-dimensional nanoprobes for applications in life sciences, including intracellular and deep tissue/cell recordings.Chemistry and Chemical Biolog

Aging-Related Alterations of Glymphatic Transport in Rat: In vivo Magnetic Resonance Imaging and Kinetic Study

OBJECTIVE: Impaired glymphatic waste clearance function during brain aging leads to the accumulation of metabolic waste and neurotoxic proteins (e.g., amyloid-β, tau) which contribute to neurological disorders. However, how the age-related glymphatic dysfunction exerts its effects on different cerebral regions and affects brain waste clearance remain unclear. METHODS: We investigated alterations of glymphatic transport in the aged rat brain using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and advanced kinetic modeling. Healthy young (3-4 months) and aged (18-20 months) male rats (n = 12/group) underwent the identical MRI protocol, including T2-weighted imaging and 3D T1-weighted imaging with intracisternal administration of contrast agent (Gd-DTPA). Model-derived parameters of infusion rate and clearance rate, characterizing the kinetics of cerebrospinal fluid (CSF) tracer transport via the glymphatic system, were evaluated in multiple representative brain regions. Changes in the CSF-filled cerebral ventricles were measured using contrast-induced time signal curves (TSCs) in conjunction with structural imaging. RESULTS: Compared to the young brain, an overall impairment of glymphatic transport function was detected in the aged brain, evidenced by the decrease in both infusion and clearance rates throughout the brain. Enlarged ventricles in parallel with reduced efficiency in CSF transport through the ventricular regions were present in the aged brain. While the age-related glymphatic dysfunction was widespread, our kinetic quantification demonstrated that its impact differed considerably among cerebral regions with the most severe effect found in olfactory bulb, indicating the heterogeneous and regional preferential alterations of glymphatic function. CONCLUSION: The robust suppression of glymphatic activity in the olfactory bulb, which serves as one of major efflux routes for brain waste clearance, may underlie, in part, age-related neurodegenerative diseases associated with neurotoxic substance accumulation. Our data provide new insight into the cerebral regional vulnerability to brain functional change with aging