A line search filter approach for the system of nonlinear equations

AbstractSome constrained optimization approaches have been recently proposed for the system of nonlinear equations (SNE). Filter approach with line search technique is employed to attack the system of nonlinear equations in this paper. The system of nonlinear equations is transformed into a constrained nonlinear programming problem at each step, which is then solved by line search strategy. Furthermore, at each step, some equations are treated as constraints while the others act as objective functions, and filter strategy is then utilized. In essence, constrained optimization methods combined with filter technique are utilized to cope with the system of nonlinear equations

Observation of Non-Hermitian Skin Effect in Thermal Diffusion

The paradigm shift of the Hermitian systems into the non-Hermitian regime profoundly modifies the inherent topological property, leading to various unprecedented effects such as the non-Hermitian skin effect (NHSE). In the past decade, the NHSE effect has been demonstrated in quantum, optical and acoustic systems. Besides in those non-Hermitian wave systems, the NHSE in diffusive systems has not yet been explicitly demonstrated, despite recent abundant advances in the study of topological thermal diffusion. Here we first design a thermal diffusion lattice based on a modified Su-Schrieffer-Heeger model which enables the observation of diffusive NHSE. In the proposed model, the periodic heat exchange rate among adjacent unit cells and the asymmetric temperature field coupling inside unit cells can be judiciously realized by appropriate configurations of structural parameters of unit cells. The transient concentration feature of temperature field on the boundary regardless of initial excitation conditions can be clearly observed, indicating the occurrence of transient thermal skin effect. Nonetheless, we experimentally demonstrated the NHSE and verified the remarkable robustness against various defects. Our work provides a platform for exploration of non-Hermitian physics in the diffusive systems, which has important applications in efficient heat collection, highly sensitive thermal sensing and others.Comment: 23 pages, 5 figure

Antitumor Agents. 284. New Desmosdumotin B Analogues with Bicyclic B-Ring as Cytotoxic and Antitubulin Agents

We previously reported that the biological activity of analogues of desmosdumotin B (1) was dramatically changed depending on the B-ring system. A naphthalene B-ring analogue 3 exerted potent in vitro activity against a diverse panel of human tumor cell lines with GI50 values of 0.8–2.1 μM. In contrast, 1-analogues with a phenyl B-ring showed unique selective activity against P-glycoprotein (P-gp) overexpressing multidrug resistance cell line. We have now prepared and evaluated 1-analogues with bicyclic or tricyclic aromatic B-ring systems as in vitro inhibitors of human cancer cell line proliferation. Among all synthesized derivatives, 21 with a benzo[b]thiophenyl B-ring was highly active, with GI50 values of 0.06–0.16 μM, and this activity was not influenced by overexpression of P-gp. Furthermore, 21 inhibited tubulin assembly in vitro with an IC 50 value of 2.0 μM and colchicine binding by 78% as well as cellular microtubule polymerization and spindle formation

Umbilical cord blood: A promising source for allogeneic CAR-T cells

Chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed and refractory acute lymphoblastic leukemia (R/R ALL). However, autologous CAR-T cells derived from patients with B-ALL often show poor amplification ability, exhaustion, and anergy. To overcome these limitations, allogeneic CAR-T cells may be used as effective substitutes; however, which source would be the best substitute is unclear. In this study, we compared the immunophenotype and antitumor efficacy of anti-CD19 CAR-T cells derived from healthy donor cord blood (CB), healthy donor peripheral blood (PB), and PB of B-ALL patients [PB (patient)] in vitro and NOD-Prkdcem26cd52Il2rgem26Cd22/Nju (NCG)-immunodeficient mice, respectively. The results revealed that CAR-T cells derived from healthy donor CB and PB showed a higher proportion of naive T cells and longer tumor suppression in tumor-bearing mice than those of PB (patient). PB (patient) CAR-T cells had a higher proportion of regulatory T cells (Treg cells) and released high levels of interluekin-10 (IL-10), which also suggest a poor prognosis. Thus, CAR-T cells derived from healthy donors have better antitumor efficacy than CAR-T cells derived from PB (patient), and CB may be a good source of allogeneic CAR-T cells

Antitumor Agents. 280. Multidrug Resistance-Selective Desmosdumotin B Analogues

6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR–selective flavonoid with significant in vitro anticancer activity against a multi-drug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2-analogues were synthesized and evaluated to determine the effect of B-ring modifications on MDR-selectivity. Analogues with a B-ring Me (3) or Et (4) group had substantially increased MDR–selectivity. Three new disubstituted analogues, 35, 37 and 49, also had high collateral sensitivity (CS) indices of 273, 250 and 100, respectively. Furthermore, 2–4 also displayed MDR-selectivity in an MDR hepatoma-cell system. While 2–4 showed either no or very weak inhibition of cellular P-glycoprotein (P-gp) activity, they either activated or inhibited the actions of the first generation P-gp inhibitors verapamil or cyclosporin, respectively

Critical current density: Measurements vs. reality

Different experimental techniques are employed to evaluate the critical current density (Jc), namely transport current measurements and two different magnetisation measurements forming quasi-equilibrium and dynamic critical states. Our technique-dependent results for superconducting YBa 2Cu3O7 (YBCO) film and MgB2 bulk samples show an extremely high sensitivity of Jc and associated interpretations, such as irreversibility fields and Kramer plots, which lose meaning without a universal approach. We propose such approach for YBCO films based on their unique pinning features. This approach allows us to accurately recalculate the magnetic-field-dependent Jc obtained by any technique into the Jc behaviour, which would have been measured by any other method without performing the corresponding experiments. We also discovered low-frequency-dependent phenomena, governing flux dynamics, but contradicting the considered ones in the literature. The understanding of these phenomena, relevant to applications with moving superconductors, can clarify their dramatic impact on the electric-field criterion through flux diffusivity and corresponding measurements. © Copyright EPLA, 2013

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.We thank W. Liu and L. Xu from the Huazhen Laboratory Animal Breeding Centre for helping in the collection of monkey tissues, D. Zhu and H. Li from the Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) for technical help, G. Guo and H. Sun from Zhejiang University for providing HCL and MCA gene expression data matrices, G. Dong and C. Liu from BGI Research, and X. Zhang, P. Li and C. Qi from the Guangzhou Institutes of Biomedicine and Health for experimental advice or providing reagents. This work was supported by the Shenzhen Basic Research Project for Excellent Young Scholars (RCYX20200714114644191), Shenzhen Key Laboratory of Single-Cell Omics (ZDSYS20190902093613831), Shenzhen Bay Laboratory (SZBL2019062801012) and Guangdong Provincial Key Laboratory of Genome Read and Write (2017B030301011). In addition, L.L. was supported by the National Natural Science Foundation of China (31900466), Y. Hou was supported by the Natural Science Foundation of Guangdong Province (2018A030313379) and M.A.E. was supported by a Changbai Mountain Scholar award (419020201252), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030502), a Chinese Academy of Sciences–Japan Society for the Promotion of Science joint research project (GJHZ2093), the National Natural Science Foundation of China (92068106, U20A2015) and the Guangdong Basic and Applied Basic Research Foundation (2021B1515120075). M.L. was supported by the National Key Research and Development Program of China (2021YFC2600200).S

Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases

2D Black Phosphorus: from Preparation to Applications for Electrochemical Energy Storage

Black phosphorus (BP) is rediscovered as a 2D layered material. Since its first isolation in 2014, 2D BP has triggered tremendous interest in the fields of condensed matter physics, chemistry, and materials science. Given its unique puckered monolayer geometry, 2D BP displays many unprecedented properties and is being explored for use in numerous applications. The flexibility, large surface area, and good electric conductivity of 2D BP make it a promising electrode material for electrochemical energy storage devices (EESDs). Here, the experimental and theoretical progress of 2D BP is presented on the basis of its preparation methods. The structural and physiochemical properties, air instability, passivation, and EESD applications of 2D BP are discussed systemically. Specifically, the latest research findings on utilizing 2D BP in EESDs, such as lithium‐ion batteries, supercapacitors, and emerging technologies (lithium–sulfur batteries, magnesium‐ion batteries, and sodium‐ion batteries), are summarized. On the basis of the current progress, a few personal perspectives on the existing challenges and future research directions in this developing field are provided

Human Antimicrobial Peptide LL-37 Inhibits Adhesion of Candida albicans by Interacting with Yeast Cell-Wall Carbohydrates

Candida albicans is the major fungal pathogen of humans. Fungal adhesion to host cells is the first step of mucosal infiltration. Antimicrobial peptides play important roles in the initial mucosal defense against C. albicans infection. LL-37 is the only member of the human cathelicidin family of antimicrobial peptides and is commonly expressed in various tissues and cells, including epithelial cells of both the oral cavity and urogenital tract. We found that, at sufficiently low concentrations that do not kill the fungus, LL-37 was still able to reduce C. albicans infectivity by inhibiting C. albicans adhesion to plastic surfaces, oral epidermoid OECM-1 cells, and urinary bladders of female BALB/c mice. Moreover, LL-37-treated C. albicans floating cells that did not adhere to the underlying substratum aggregated as a consequence of LL-37 bound to the cell surfaces. According to the results of a competition assay, the inhibitory effects of LL-37 on cell adhesion and aggregation were mediated by its preferential binding to mannan, the main component of the C. albicans cell wall, and partially by its ability to bind chitin or glucan, which underlie the mannan layer. Therefore, targeting of cell-wall carbohydrates by LL-37 provides a new strategy to prevent C. albicans infection, and LL-37 is a useful, new tool to screen for other C. albicans components involved in adhesion