Reconciling periodic rhythms of large-scale biological networks by optimal control

Periodic rhythms are ubiquitous phenomena that illuminate the underlying mechanism of cyclic activities in biological systems, which can be represented by cyclic attractors of the related biological network. Disorders of periodic rhythms are detrimental to the natural behaviours of living organisms. Previous studies have shown that the state transition from one to another attractor can be accomplished by regulating external signals. However, most of these studies until now have mainly focused on point attractors while ignoring cyclic ones. The aim of this study is to investigate an approach for reconciling abnormal periodic rhythms, such as diminished circadian amplitude and phase delay, to the regular rhythms of complex biological networks. For this purpose, we formulate and solve a mixed-integer nonlinear dynamic optimization problem simultaneously to identify regulation variables and to determine optimal control strategies for state transition and adjustment of periodic rhythms. Numerical experiments are implemented in three examples including a chaotic system, a mammalian circadian rhythm system and a gastric cancer gene regulatory network. The results show that regulating a small number of biochemical molecules in the network is sufficient to successfully drive the system to the target cyclic attractor by implementing an optimal control strategy

Quantum well intermixing for the fabrication of InGaAsN/GaAs lasers with pulsed anodic oxidation

Quantum well (QW) intermixing was carried out by post-growth rapid thermal annealing in InGaAsN/GaAs QW laser structures grown by solid-source molecular-beam epitaxy. The intensity and width of the photoluminescence peak showed a dependence on annealing temperature and time, and the maximum intensity and minimum linewidth were obtained after the wafer was annealed at 670 °C for 60 s. The peak luminescence energy blueshifted with increasing annealing time, although it plateaued at an annealing time that corresponded to that yielding the maximum luminescence intensity. The diffusion coefficient for indium was determined from a comparison between experimental data and modeling, but showed that QW intermixing alone was not sufficient to account for the relatively large blueshift after annealing. Defects related to the incorporation of nitrogen in the QW layer were responsible for the low photoluminescence efficiency in the as-grown samples and were annealed out during rapid thermal annealing. During annealing, nitrogen interstitials moved to vacancy sites within the QW and thus suppressed QW intermixing. After annealing wafers under conditions giving the maximum luminescence intensity, lasers were fabricated with pulsed anodic oxidation. © 2004 American Institute of Physics.published_or_final_versio

The value of restatement to fraud prediction

A financial report restatement reflects errors in the previous financial statement, and thus it increases investors’ doubt about the credibility of the financial statement. The primary objective of this paper is to examine whether restatement announcements imply increased fraud risks in Chinese firms in the context that up to one quarter of listed companies have restated their financial reports in China, and explore the implications of the content, severity and reasons for restatements with respect to fraud. In this paper, firms with financial restatements prove to be more likely to be labeled as fraudulent by regulators in China. Second, the following results also are revealed: (1) financial statements, except balance sheet restatements, provide insights into the revelation of fraudulent behaviors, (2) the severity of restatements is positively correlated with future fraud disclosures, and (3) restatements due to negligence are positively correlated with future fraud occurrences. These results imply that restatement announcements and their different characteristics provide important information for detecting financial statement fraud

Boosting the thermoelectric performance of p-type heavily Cu-doped polycrystalline SnSe via inducing intensive crystal imperfections and defect phonon scattering

In this study, we, for the first time, report a high Cu solubility of 11.8% in single crystal SnSe microbelts synthesized via a facile solvothermal route. The pellets sintered from these heavily Cu-doped microbelts show a high power factor of 5.57 μW cm−1 K−2 and low thermal conductivity of 0.32 W m−1 K−1 at 823 K, contributing to a high peak ZT of ∼1.41. Through a combination of detailed structural and chemical characterizations, we found that with increasing the Cu doping level, the morphology of the synthesized Sn1−xCuxSe (x is from 0 to 0.118) transfers from rectangular microplate to microbelt. The high electrical transport performance comes from the obtained Cu+ doped state, and the intensive crystal imperfections such as dislocations, lattice distortions, and strains, play key roles in keeping low thermal conductivity. This study fills in the gaps of the existing knowledge concerning the doping mechanisms of Cu in SnSe systems, and provides a new strategy to achieve high thermoelectric performance in SnSe-based thermoelectric materials

An ex vivo culture model of kidney podocyte injury reveals mechanosensitive, synaptopodin-templating, sarcomere-like structures

Chronic kidney diseases are widespread and incurable. The biophysical mechanisms underlying them are unclear, in part because material systems for reconstituting the microenvironment of relevant kidney cells are limited. A critical question is how kidney podocytes (glomerular epithelial cells) regenerate foot processes of the filtration apparatus following injury. Recently identified sarcomere-like structures (SLSs) with periodically spaced myosin IIA and synaptopodin appear in injured podocytes in vivo. We hypothesized that SLSs template synaptopodin in the initial stages of recovery in response to microenvironmental stimuli and tested this hypothesis by developing an ex vivo culture system that allows control of the podocyte microenvironment. Results supported our hypothesis. SLSs in podocytes that migrated from isolated kidney glomeruli presented periodic synaptopodin-positive clusters that nucleated peripheral, foot process-like extensions. SLSs were mechanoresponsive to actomyosin inhibitors and substrate stiffness. Results suggest SLSs as mechanobiological mediators of podocyte recovery and as potential targets for therapeutic intervention

Assembling a Natural Small Molecule into a Supramolecular Network with High Structural Order and Dynamic Functions

Programming the hierarchical self-assembly of small molecules has been a fundamental topic of great significance in biological systems and artificial supramolecular systems. Precise and highly programmed self-assembly can produce supramolecular architectures with distinct structural features. However, it still remains a challenge how to precisely control the self-assembly pathway in a desirable way by introducing abundant structural information into a limited molecular backbone. Here we disclose a strategy that directs the hierarchical self-assembly of sodium thioctate, a small molecule of biological origin, into a highly ordered supramolecular layered network. By combining the unique dynamic covalent ring-opening-polymerization of sodium thioctate and an evaporation-induced interfacial confinement effect, we precisely direct the dynamic supramolecular self-assembly of this simple small molecule in a scheduled hierarchical pathway, resulting in a layered structure with long-range order at both macroscopic and molecular scales, which is revealed by small-angle and wide-angle X-ray scattering technologies. The resulting supramolecular layers are found to be able to bind water molecules as structural water, which works as an interlayer lubricant to modulate the material properties, such as mechanical performance, self-healing capability, and actuating function. Analogous to many reversibly self-assembled biological systems, the highly dynamic polymeric network can be degraded into monomers and reformed by a water-mediated route, exhibiting full recyclability in a facile, mild, and environmentally friendly way. This approach for assembling commercial small molecules into structurally complex materials paves the way for low-cost functional supramolecular materials based on synthetically simple procedures

Rescue of mesangial cells from high glucoseinduced over-proliferation and extracellular matrix secretion by hydrogen sulfide

Abstract Background. Hydrogen sulfide (H 2 S) is considered as the third gasotransmitter after nitric oxide and carbon monoxide. This gas molecule participates in the regulation of renal function. Diabetic nephropathy (DN) is one of the major chronic complications of diabetes. The present study aimed to explore the changes in H 2 S metabolism in the early stage of DN and the effects of H 2 S on cultured rat renal glomerular mesangial cells (MCs). Methods. Cultured rat MCs and streptozotocin (STZ)-induced diabetic rats were used in this study. Expression levels of cystathionine γ-lyase (CSE), transforming growth factor-β1 (TGF-β1) and collagen IV in rat renal cortex and in cultured MCs were determined by quantitative real-time PCR and western blot. Reactive oxygen species (ROS) released from rat MCs was assessed by fluorescent probe assays. MCs proliferation was analyzed by 5′-bromo-2′-deoxyuridine incorporation assay. Results. H 2 S levels in the plasma and renal cortex and the levels of CSE messenger RNA (mRNA) and protein in renal cortex were significantly reduced, while the levels of TGF-β1 and collagen IV increased 3 weeks after STZ injection. Administration of NaHS, a H 2 S donor, reversed the increases in TGF-β1 and collagen IV in diabetic rats. By contrast, NaHS did not alter the TGF-β1 and collagen IV levels in non-diabetic rats. But NaHS lowered the CSE mRNA level in renal cortex. Exposure to high glucose promoted ROS generation and cell proliferation, up-regulated the expression of TGF-β1 and collagen IV but decreased the CSE expression in cultured MCs. Treatment of cultured MCs with NaHS reversed the effect of high glucose. NaHS did not change ROS generation, cell proliferation, TGF-β1 and collagen IV expression in the cells cultured with normal glucose. Reduction of endogenous H 2 S generation by DLpropargylglycine, a CSE inhibitor, produced similar cellular effects as high glucose, including increases in cell proliferation, TGF-β1 and collagen IV expressions and ROS generation. Conclusion. Suppressed CSE-catalyzed endogenous H 2 S production in the kidney by hyperglycemia may play an important role in the pathogenesis of DN