Operations management has the tradition of coming from and going back to real‐life applications. It deals with the management of the process of matching supply with demand. The emerging business ...process in a sharing economy or an innovative marketplace calls for active management at the operational level. We take a neoclassical perspective by drawing inspiration from the classic models in operations management and economics. We aim at building connections and identifying differences between those traditional models and the new applications in sharing economy and innovative marketplaces. We also point out potential future research directions.
Microbial nucleic acids are major signatures of invading pathogens, and their recognition by various host pattern recognition receptors (PRRs) represents the first step toward an efficient innate ...immune response to clear the pathogens. The nucleic acid-sensing PRRs are localized at the plasma membrane, the cytosol, and or various cellular organelles. Sensing of nucleic acids and signaling by PRRs involve recruitment of distinct signaling components, and PRRs are intensively regulated by cellular organelle trafficking. PRR-mediated innate immune responses are also heavily regulated by posttranslational modifications, including phosphorylation, polyubiquitination, sumoylation, and glutamylation. In this review, we focus on our current understanding of recognition of microbial nucleic acid by PRRs, particularly on their regulation by organelle trafficking and posttranslational modifications. We also discuss how sensing of self nucleic acids and dysregulation of PRR-mediated signaling lead to serious human diseases.
Sensing of viral RNA by the cytosolic receptors RIG-I and melanoma differentiation-associated gene 5 (MDA5) leads to innate antiviral response. How RIG-I and MDA5 are dynamically regulated in innate ...antiviral response is not well understood. Here, we show that TRIM38 positively regulates MDA5- and RIG-I-mediated induction of downstream genes and acts as a SUMO E3 ligase for their dynamic sumoylation at K43/K865 and K96/K888, respectively, before and after viral infection. The sumoylation of MDA5 and RIG-I suppresses their K48-linked polyubiquitination and degradation in uninfected or early-infected cells. Sumoylation of the caspase recruitment domains of MDA5 and RIG-I is also required for their dephosphorylation by PP1 and activation upon viral infection. At the late phase of viral infection, both MDA5 and RIG-I are desumoylated by SENP2, resulting in their K48-linked polyubiquitination and degradation. These findings suggest that dynamic sumoylation and desumoylation of MDA5 and RIG-I modulate efficient innate immunity to RNA virus and its timely termination.
Anti-PD-1/PD-L1 immunotherapy has achieved impressive therapeutic outcomes in patients with multiple cancer types. However, the underlined molecular mechanism(s) for moderate response rate (15-25%) ...or resistance to PD-1/PD-L1 blockade remains not completely understood. Here, we report that inhibiting the deubiquitinase, USP8, significantly enhances the efficacy of anti-PD-1/PD-L1 immunotherapy through reshaping an inflamed tumor microenvironment (TME). Mechanistically, USP8 inhibition increases PD-L1 protein abundance through elevating the TRAF6-mediated K63-linked ubiquitination of PD-L1 to antagonize K48-linked ubiquitination and degradation of PD-L1. In addition, USP8 inhibition also triggers innate immune response and MHC-I expression largely through activating the NF-κB signaling. Based on these mechanisms, USP8 inhibitor combination with PD-1/PD-L1 blockade significantly activates the infiltrated CD8
T cells to suppress tumor growth and improves the survival benefit in several murine tumor models. Thus, our study reveals a potential combined therapeutic strategy to utilize a USP8 inhibitor and PD-1/PD-L1 blockade for enhancing anti-tumor efficacy.
Abstract When assessed using the difference between urban and rural air temperatures, the urban heat island (UHI) is most prominent during the nighttime. Typically, nocturnal UHI intensity is ...maintained throughout the night. The UHI intensity over Dallas–Fort Worth (DFW), Texas, however, experienced frequent “collapses” (sudden decreases) around midnight during August 2011, while the region was experiencing an intense heat wave. Observational and modeling studies were conducted to understand this unique phenomenon. Sea-breeze passage was found to be ultimately responsible for the collapses of the nocturnal UHI. Sea-breeze circulation developed along the coast of the Gulf of Mexico during the daytime. During the nighttime, the sea-breeze circulation was advected inland (as far as ~400 km) by the low-level jet-enhanced southerly flow, maintaining the characteristics of sea-breeze fronts, including the enhanced wind shear and vertical mixing. Ahead of the front, surface radiative cooling enhanced the near-surface temperature inversion in rural areas through the night with calm winds. During the frontal passage (around midnight at DFW), the enhanced vertical mixing at the leading edge of the fronts brought warmer air to the surface, leading to rural surface warming events. In contrast, urban effects led to a nearly neutral urban boundary layer. The enhanced mechanical mixing associated with sea-breeze fronts, therefore, did not increase urban surface temperature. The different responses to the sea-breeze frontal passages between rural (warming) and urban areas (no warming) led to the collapse of the UHI. The inland penetration of sea-breeze fronts at such large distances from the coast and their effects on UHI have not been documented in the literature.
Cyclic GMP-AMP synthase (cGAS) senses double-strand (ds) DNA in the cytosol and then catalyzes synthesis of the second messenger cGAMP, which activates the adaptor MITA/STING to initiate innate ...antiviral response. How cGAS activity is regulated remains enigmatic. Here, we identify ZCCHC3, a CCHC-type zinc-finger protein, as a positive regulator of cytosolic dsDNA- and DNA virus-triggered signaling. We show that ZCCHC3-deficiency inhibits dsDNA- and DNA virus-triggered induction of downstream effector genes, and that ZCCHC3-deficient mice are more susceptible to lethal herpes simplex virus type 1 or vaccinia virus infection. ZCCHC3 directly binds to dsDNA, enhances the binding of cGAS to dsDNA, and is important for cGAS activation following viral infection. Our results suggest that ZCCHC3 is a co-sensor for recognition of dsDNA by cGAS, which is important for efficient innate immune response to cytosolic dsDNA and DNA virus.
Nonlocality is one unique property of quantum mechanics that differs from the classical world. One of its quantifications can be properly described as the maximum global effect caused by locally ...invariant measurements, known as measurement-induced nonlocality (MIN) (2011 Phys. Rev. Lett. 106 120401). Here, we propose quantifying the MIN by the trace norm. We show explicitly that this measure is monotonically decreasing under the action of a completely positive trace-preserving map, which is the general local quantum operation, on the unmeasured party for the bipartite state. This property avoids the undesirable characteristic appearing in the known measure of MIN defined by the Hilbert-Schmidt norm which may be increased or decreased by trivial local reversible operations on the unmeasured party. We obtain analytical formulas of the trace-norm MIN for any -dimensional pure state, two-qubit state, and certain high-dimensional states. As with other quantum correlation measures, the newly defined MIN can be directly applied to various models for physical interpretations.
Recognition of viral RNA by the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) initiates innate antiviral immune response. How the binding of viral RNA to and activation of the RLRs are ...regulated remains enigmatic. In this study, we identified ZCCHC3 as a positive regulator of the RLRs including RIG-I and MDA5. ZCCHC3 deficiency markedly inhibited RNA virus-triggered induction of downstream antiviral genes, and ZCCHC3-deficient mice were more susceptible to RNA virus infection. ZCCHC3 was associated with RIG-I and MDA5 and functions in two distinct processes for regulation of RIG-I and MDA5 activities. ZCCHC3 bound to dsRNA and enhanced the binding of RIG-I and MDA5 to dsRNA. ZCCHC3 also recruited the E3 ubiquitin ligase TRIM25 to the RIG-I and MDA5 complexes to facilitate its K63-linked polyubiquitination and activation. Thus, ZCCHC3 is a co-receptor for RIG-I and MDA5, which is critical for RLR-mediated innate immune response to RNA virus.
•ZCCHC3 mediates viral RNA-triggered innate immune response•ZCCHC3 binds to viral RNA•ZCCHC3 acts as a co-receptor for RIG-I and MDA5•ZCCHC3 mediates polyubiquitination and activation of RIG-I and MDA5 by TRIM25
Recognition of viral RNA by RIG-I-like receptors (RLRs) initiates innate antiviral response. Lian et al. demonstrate that ZCCHC3 is a co-receptor for RLRs, thereby acting as an important modulator of innate antiviral response.
•The existing building could consume up to 7.6 times primary energy compared to rebuilding a new building consumption.•To find a balance between reducing primary energy and reducing environmental ...impact potential, building renovation could be an optimized choice.•The renovated building could meet the current building energy code while preserving at least 80% of the original primary embodied energy.•Avoiding demolishing could result in reduction of overall environmental impact potential by 48%.
A comprehensive case study life-cycle analysis(LCA) was conducted on a four-story National Register historic building with a projected 75-year life span located in Medina, New York. Three adaptive reuse options were compared: historic preservation, renovation, and new construction; six different energy performance targets were constructed and compared as well. The study comprises two parts: a life-cycle energy analysis and a life-cycle environmental impact analysis. In this life-cycle analysis, the building assembly group that consumes the most embodied energy was identified, related suitable renovation options were analyzed, and conclusions were drawn based on the results. The aim of the research was to address the balance between energy and environmental benefits and drawbacks for different adaptive reuse options. Four impact categories (global warming potential, ozone depletion potential, human health particulate potential, and smog potential) were measured and their correlation with primary energy demand was analyzed.
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