A multiperiod network reconfiguration to meet the requirement of hourly hosting capacity under a minimal required number of switching operations, taking into consideration the uncertainty of ...renewable generation, is formulated as a nonlinear, nondifferentiable integer optimization problem with nonlinear equality and inequality constraints. A four-stage solution methodology, including an assessment stage, a time-partitioning stage, an optimization stage, and an evaluation stage, is developed to solve the constrained large-scale nonlinear integer optimization problem. A fuzzy C-means clustering algorithm is applied to partition the time period to facilitate the design of a minimum-number switching solution. A hybrid particle swarm optimization algorithm is developed to find an optimal network topology for each partitioned time period. The IEEE 123-bus case and a 1001-node system, three-phase and unbalanced, are used to evaluate the proposed method with promising results.
Terpenes are the largest class of small‐molecule natural products on earth, and the most abundant by mass. Here, we summarize recent developments in elucidating the structure and function of the ...proteins involved in their biosynthesis. There are six main building blocks or modules (α, β, γ, δ, ε, and ζ) that make up the structures of these enzymes: the αα and αδ head‐to‐tail trans‐prenyl transferases that produce trans‐isoprenoid diphosphates from C5 precursors; the ε head‐to‐head prenyl transferases that convert these diphosphates into the tri‐ and tetraterpene precursors of sterols, hopanoids, and carotenoids; the βγ di‐ and triterpene synthases; the ζ head‐to‐tail cis‐prenyl transferases that produce the cis‐isoprenoid diphosphates involved in bacterial cell wall biosynthesis; and finally the α, αβ, and αβγ terpene synthases that produce plant terpenes, with many of these modular enzymes having originated from ancestral α and β domain proteins. We also review progress in determining the structure and function of the two 4Fe‐4S reductases involved in formation of the C5 diphosphates in many bacteria, where again, highly modular structures are found.
Natural building blocks: Recent progress has been achieved in determining the structure, function, and inhibition of the enzymes responsible for the formation of terpenes and isoprenoids. Most of these enzymes contain combinations of α‐, β‐, γ‐, δ‐, ε‐, and/or ζ‐domain structures that in many cases are fused to form modular proteins. Gene fusion, exon loss, and recombination are thought to play major roles in the genesis of these enzymes.
Cancer immunotherapies targeting adaptive immune checkpoints have substantially improved patient outcomes across multiple metastatic and treatment-refractory cancer types. However, emerging studies ...have demonstrated that innate immune checkpoints, which interfere with the detection and clearance of malignant cells through phagocytosis and suppress innate immune sensing, also have a key role in tumour-mediated immune escape and might, therefore, be potential targets for cancer immunotherapy. Indeed, preclinical studies and early clinical data have established the promise of targeting phagocytosis checkpoints, such as the CD47-signal-regulatory protein α (SIRPα) axis, either alone or in combination with other cancer therapies. In this Review, we highlight the current understanding of how cancer cells evade the immune system by disrupting phagocytic clearance and the effect of phagocytosis checkpoint blockade on induction of antitumour immune responses. Given the role of innate immune cells in priming adaptive immune responses, an improved understanding of the tumour-intrinsic processes that inhibit essential immune surveillance processes, such as phagocytosis and innate immune sensing, could pave the way for the development of highly effective combination immunotherapy strategies that modulate both innate and adaptive antitumour immune responses.
Highlights • The TME can dampen or enhance the efficacy of immunotherapy. • Immunotherapy targets both the TME and tumor cells. • Manipulating the TME can improve current immunotherapies.
•Leader sense of humor was negatively related to workplace loneliness climate.•Workplace loneliness climate was negatively related to team performance.•The impact of leader sense of humor was ...conditioned by team bureaucratic practices.•The impact of leader sense of humor relied on its style.
Extending research on loneliness at work to the team level, we integrate leader humor and team bureaucratic practices literature to predict how and when team performance is enhanced by combatting workplace loneliness climate. We tested our theoretical model across two studies. In Study 1, we found that leader sense of humor resulted in lower workplace loneliness climate and, thus, in better team performance. Furthermore, leader sense of humor was negatively related to workplace loneliness climate only under low team bureaucratic practices. Study 2 replicated and extended Study 1 by testing the critical role of leader humor styles. Results illustrated that affiliative humor strengthened, while aggressive humor weakened, the negative effect of leader sense of humor on workplace loneliness climate. These findings present a comprehensive approach to broadening knowledge about leader humor and loneliness at work in teams, and they are insightful to practitioners who aim to build effective teams.
New S in town: Sulfonyl hydrazides smoothly undergo sulfenylation with indoles in the presence of 10 mol % I2 to give structurally diverse indole thioethers in moderate to excellent yields with ...extremely high regioselectivity. This study paves the way for the use of sulfonyl hydrazides as unique sulfur electrophiles in chemical synthesis.
Effectively activating macrophages against cancer is promising but challenging. In particular, cancer cells express CD47, a 'don't eat me' signal that interacts with signal regulatory protein alpha ...(SIRPα) on macrophages to prevent phagocytosis. Also, cancer cells secrete stimulating factors, which polarize tumor-associated macrophages from an antitumor M1 phenotype to a tumorigenic M2 phenotype. Here, we report that hybrid cell membrane nanovesicles (known as hNVs) displaying SIRPα variants with significantly increased affinity to CD47 and containing M2-to-M1 repolarization signals can disable both mechanisms. The hNVs block CD47-SIRPα signaling axis while promoting M2-to-M1 repolarization within tumor microenvironment, significantly preventing both local recurrence and distant metastasis in malignant melanoma models. Furthermore, by loading a stimulator of interferon genes (STING) agonist, hNVs lead to potent tumor inhibition in a poorly immunogenic triple negative breast cancer model. hNVs are safe, stable, drug loadable, and suitable for genetic editing. These properties, combined with the capabilities inherited from source cells, make hNVs an attractive immunotherapy.
The cationic nature of heptamethine cyanines gives them the capacity to form aggregates with salts by electrostatic interactions. In this work, NaCl promoted J‐aggregate formation of aza‐coating ...heptamethine cyanines is explored. NaCl can induce the N‐benzyloxycarbonyl Cy‐CO2Bz to assemble into a J‐aggregate having an absorption at 890 nm. Its excellent fluorescence response to NaCl implies that it has great potential for use as a probe for tracing salt stress in plants. Moreover, NaCl also promotes formation of J‐aggregates from the N‐ethyloxycarbonyl Cy‐CO2Et. The aggregate shows an intense absorption at 910 nm compared to the monomer which absorbs at 766 nm. Its J‐aggregated form can serve as a photothermal agent. And the photothermal conversion efficiency is increased from 29.37 % to 57.59 %. This effort leads to the development of two applications of new cyanine J‐aggregates including one for tracing salt stress of plants and the other for promoting photothermal therapy of tumors.
Two J‐aggregates formed by NaCl treatment of aza‐coating hepetamine cyanines act as functional fluorescent probes for monitoring salt stress of plants and promoting photothermal therapy of tumors.
PurposeThe purpose of this research is to examine the relationship between spiritual leadership and employee innovative behavior by testing the mediating role of autonomous motivation and the ...moderating role of employee power distance orientation.Design/methodology/approachThe author predicted an indirect relationship between spiritual leadership and employee innovative behavior via autonomous motivation. Also, the author predicted the positive effect of spiritual leadership on employee innovative behavior will be stronger when employee power distance orientation is high. Hypotheses are tested with data gathered from 174 participants.FindingsResults showed that spiritual leadership was positively related to employee innovative behavior via autonomous motivation. And, the positive relationship between spiritual leadership and autonomous motivation was stronger when employee power distance orientation was high. Furthermore, the indirect effect of autonomous motivation was stronger when employee power distance orientation was high.Research limitations/implicationsThis study provides a new theoretical perspective – self-determination theory – to test how and when spiritual leadership enhances employee innovative behavior by suggesting autonomous motivation as a mediator and employee power distance orientation as a boundary condition.Practical implicationsThe results of this research provide suggestions for leaders to adopt spiritual leadership as well as enhance interactions between them and employees to increase employee innovative behavior.Originality/valueThis study highlights the moderating role of employee power distance orientation and uses self-determination theory to examine how and when spiritual leadership plays a positive role.
Most tumor cells express antigens that can mediate recognition by host CD8(+) T cells. Cancers that are detected clinically must have evaded antitumor immune responses to grow progressively. Recent ...work has suggested two broad categories of tumor escape based on cellular and molecular characteristics of the tumor microenvironment. One major subset shows a T cell-inflamed phenotype consisting of infiltrating T cells, a broad chemokine profile and a type I interferon signature indicative of innate immune activation. These tumors appear to resist immune attack through the dominant inhibitory effects of immune system-suppressive pathways. The other major phenotype lacks this T cell-inflamed phenotype and appears to resist immune attack through immune system exclusion or ignorance. These two major phenotypes of tumor microenvironment may require distinct immunotherapeutic interventions for maximal therapeutic effect.
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