Cells produce an extracellular matrix (ECM) with a stereotypic organization that is important for tissue function. The insect cuticle is a layered ECM that mainly consists of the polysaccharide ...chitin and associated proteins adopting a quasi‐crystalline structure. Our understanding of the molecular mechanisms deployed during construction of the highly ordered protein–chitin ECM so far is limited. In this study, we report on the role of the chitin deacetylase 1 (LmCDA1) in the organization of the protein–chitin ECM in the migratory locust Locusta migratoria, and LmCDA1 localizes predominantly to the apical tier of the protein–chitin ECM, but it is also found in lower regions. Reduction of LmCDA1 function correlates with lower amounts of chitin and impedes conversion of chitin to chitosan by deacetylation. Establishment of the quasi‐crystalline architecture of the protein–chitin ECM is, however, independent of LmCDA1 activity, but it is dependent on another chitin deacetylase, LmCDA2, which has no detectable effects on chitin deacetylation and, as shown previously, no influence on chitin content. Our data reveal that LmCDA1 and LmCDA2 act in parallel and independently from each other in defining the dimensions of the cuticle. Both enzymes are non‐uniformly distributed within the protein–chitin matrix, suggesting a site‐autonomous function.
Summary
Cancer immunotherapy unleashing the power of host immunity on eliminating cancer cells represents a critical advance in cancer treatment; however, effective anti‐tumor responses are largely ...dampened by the immunosuppressive tumor microenvironment (TME). Emerging studies have revealed that physiological features in the TME, including glucose deprivation, hypoxia and low pH, established by the metabolically dysregulated cancer cells restrict anti‐tumor immunity by impeding the metabolic fitness of tumor‐infiltrating cytotoxic CD8+ T cells and natural killer (NK) cells. Furthermore, infiltrating immunomodulatory cells with different metabolic preferences also facilitate the establishment of the immunosuppressive TME. Therefore, deciphering the metabolic cross‐talk between immune cells and cancer cells in the TME and elucidating the impact of this process during tumorigenesis are needed to harness anti‐tumor immunity more effectively. Herein, we summarize the immunosuppressive features of TME and how these features impair anti‐tumor immunity. Moreover, we postulate how immune cells may be involved in shaping the metabolic features of cancer cells and discuss how we might improve the anti‐tumor functions of tumor‐specific T cells by rewiring their metabolic regulations.
In this review, we summarize how metabolic conflicts in the tumor microenvironment dampen host anti‐tumor immunity, and also discuss the probable contributions of immunoediting to the establishment of immunosuppressive tumor microenvironment with metabolic modulations for infiltrating immune cells.
•A dense skeleton of UHPC can be obtained with a relatively low binder amount.•To get the highest mechanical properties, an optimal amount of nano-silica is calculated.•The combined effect of SP and ...nano-silica additions on the hydration of UHPC is analyzed.•The mechanism of the microstructure development of UHPC is analyzed.
This paper presents the effect of nano-silica on the hydration and microstructure development of Ultra-High Performance Concrete (UHPC) with a low binder amount. The design of UHPC is based on the modified Andreasen and Andersen particle packing model. The results reveal that by utilizing this packing model, a dense and homogeneous skeleton of UHPC can be obtained with a relatively low binder amount (about 440kg/m3). Moreover, due to the high amount of superplasticizer utilized to produce UHPC in this study, the dormant period of the cement hydration is extended. However, due to the nucleation effect of nano-silica, the retardation effect from superplasticizer can be significantly compensated. Additionally, with the addition of nano-silica, the viscosity of UHPC significantly increases, which causes that more air is entrapped in the fresh mixtures and the porosity of the hardened concrete correspondingly increases. In contrary, due to the nucleation effect of nano-silica, the hydration of cement can be promoted and more C–S–H gel can be generated. Hence, it can be concluded that there is an optimal nano-silica amount for the production of UHPC with the lowest porosity, at which the positive effect of the nucleation and the negative influence of the entrapped air can be well balanced.
The this paper, we introduce a pair of Sobolev spaces with special Jacobi–Gegenbauer weights, in which the general boundary-value problem for a class of ordinary integro-differential equations ...characterized by the positivity of the difference of orders of the inner and outer differential operators is well-posed in the Hadamard sense. Based on this result, we justify the general polynomial projection method for solving the corresponding problem. An application of general results to the proof of the convergence of the polynomial Galerkin method for solving the Cauchy problem in the Sobolev weighted space is given. The convergence rate of the method is characterized in terms of the best polynomial approximations of an exact solution, which automatically responds to the smoothness properties of the coefficients of the equation.
We studied the chromosomal composition of micronuclei the peripheral blood T-lymphocytes of women chronically exposed due to their residence in the Techa riverside villages in the Southern Urals ...(cumulative doses to red bone marrow (RBM) ranged from 0.73 to 1.93 Gy, the age range of women was 73 to 82 years). Micronucleus assay with cytochalasin block and multicolor staining of preparations (mFISH method) was used to identify each chromosome. On average, the exposed women had more chromosomes in the micronucleus than those in the comparison group (
p
= 0.001). The probability of micronucleus formation from chromosomes is not equal if we compare the group of exposed women and the comparison group. The biggest number of micronuclei is monocolor; i.e., they are formed from the material of a single chromosome. In 44–55% of cases, monocolor micronuclei are formed by the X chromosome; in 4–7%, by the 16th chromosome. In the groups studied, the 2nd, 4th, 10th, 16th, and X chromosomes occur more frequently in the multicolor micronuclei. The second chromosome occurs statistically significantly more frequently in monocolor micronuclei in exposed women than in those from the comparison group (
p
= 0.001); the 6th, 17th, and 18th chromosomes occur statistically significantly more frequently in multicolor micronuclei (
p
= 0.0036,
p
= 0.023,
p
= 0.02, respectively).
Evaluating Nilotinib Efficacy and Safety in Clinical Trials Newly Diagnosed Patients compares nilotinib and imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase ...(CML-CP). With a minimum follow-up of 3 years, major molecular response, molecular response of BCR-ABL≤ 0.01% expressed on the international scale (BCR-ABL(IS); MR(4)) and BCR-ABL(IS)≤ 0.0032% (MR(4.5)) rates were significantly higher with nilotinib compared with imatinib, and differences in the depth of molecular response between nilotinib and imatinib have increased over time. No new progressions occurred on treatment since the 2-year analysis. Nilotinib was associated with a significantly lower probability of progression to accelerated phase/blast crisis vs imatinib (two (0.7%) progressions on nilotinib 300 mg twice daily, three (1.1%) on nilotinib 400 mg twice daily and 12 (4.2%) on imatinib). When considering progressions occurring after study treatment discontinuation, the advantage of nilotinib over imatinib in preventing progression remained significant (nine (3.2%) progressions on nilotinib 300 mg twice daily, six (2.1%) on nilotinib 400 mg twice daily and 19 (6.7%) on imatinib). Both nilotinib and imatinib were well tolerated, with minimal changes in safety over time. Nilotinib continues to demonstrate superior efficacy in all key response and outcome parameters compared with imatinib for the treatment of patients with newly diagnosed CML-CP.
The smiling emoji has been claimed to be a marker of sarcastic intention among young Chinese users in computer-mediated communication. However, it is not well understood whether people interpret the ...emoji differently based on the characteristics or traits of the sender, as conveyed by occupation stereotypes. We investigated the effect of sender occupation on emoji-based sarcasm interpretation in both unambiguous (Experiment 1) and ambiguous (Experiment 2) contexts. The results showed that contextual incongruity was privileged over sender occupation in cueing sarcastic intention. In unambiguous contexts, sender occupation exerted no significant influence on the interpretation of emoji-based sarcastic statements. In contrast, sender occupation played an important role in the interpretation of emoji-based statements in ambiguous contexts. Specifically, emoji-based ambiguous statements delivered by senders in high‑irony occupations were more likely to be perceived as sarcastic than by those in low-irony occupations. However, sender occupation did not affect the interpretation of the emoji; instead, it biased the judgment of emoji in sarcasm interpretation. In a follow-up experiment (Experiment 3), we investigated the perceived characteristics of both high- and low-irony occupations. The results demonstrated that individuals in high-irony occupations were stereotyped with characteristics, including being humorous, insincere, easy to setting up close relationships, and of a lower social status. Taken together, our study suggests that stereotypical information about the sender could drive the interpretation of potentially sarcastic statements, and the contextual information modulates the effect of sender occupation on sarcasm interpretation.
Abstract
The deployment of self-driving technologies occurs in various industries and economic sectors. Self-driving taxi cabs can be found in city streets, in Russia as well as in other countries. ...The introduction of self-driving technologies in construction, namely, construction machinery, is a promising area that will develop rapidly in the nearest few years. A road grader is the construction machine whose control algorithms resemble those of selfdriving cars the most. One of the first development stages for the self-driving road grader is trajectory plotting.
This article presents the developed trajectory plotting algorithm for the road grader taking into account its design features (minimum turn radius).
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