Compositional Verification of Interacting Systems Using Event Monads

Large software systems are usually divided into multiple components that interact with each other. How to verify interacting components in a modular way is one of the major problems in formal verification. In many cases, interaction between components can be modeled asynchronously, where events are sent without requiring a response in order to continue with execution of the component. In this paper, we propose a lightweight, event-based framework for verification of components with asynchronous interaction. We define event monads and event systems, and a Hoare logic-style calculus for reasoning about them. The framework is implemented in Isabelle and applied to several case studies, including models for distributed computing, cache-coherence protocols, and verification of partition scheduling in a real-time operating system

Practicing Green Residence Business Model Based on TPB Perspective

Green residence is the future of urban development, it is also an attempt to implement the green business model in the residential business field. The key to the success of a green business model is that a wide range of customers can accept its green value proposition and react to it through their purchase decisions. This study aims to develop a theory of a planned behavior (TPB) research model to predict individuals’ intention to purchase green residence. This study took steel structure residence as an example, which was widely recognized as one emerging type of green residence. The samples were selected in Baotou city of Inner Mongolia, P.R. China. Data analysis was performed using the structural equation modeling (SEM) with data obtained from a survey of 208 respondents using SPSS19.0 and AMOS17.0. The results found that the individuals’ intention to purchase green residence was significantly affected by attitude, subjective norm, and perceived behavioral control. Moreover, the empirical evidence showed that these influences differed between different gender groups. Specifically, women responders had a stronger effect on the path attitude impact on purchase intention than men. These findings can provide implications for practicing the green business model of real estate enterprise

Sphingosine-1-phosphate/S1P Receptors Signaling Modulates Cell Migration in Human Bone Marrow-Derived Mesenchymal Stem Cells

The recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) to damaged tissues and sites of inflammation is an essential step for clinical therapy. However, the signals regulating the motility of these cells are still not fully understood. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, is known to have a variety of biological effects on various cells. Here, we investigated the roles of S1P and S1P receptors (S1PRs) in migration of human BMSCs. We found that S1P exerted a powerful migratory action on human BMSCs. Moreover, by employing RNA interference technology and pharmacological tools, we demonstrated that S1PR1 and S1PR3 are responsible for S1P-induced migration of human BMSCs. In contrast, S1PR2 mediates the inhibition of migration. Additionally, we explored the downstream signaling pathway of the S1P/S1PRs axis and found that activation of S1PR1 or S1PR3 increased migration of human BMSCs through a Gi/extracellular regulated protein kinases 1/2- (ERK1/2-) dependent pathway, whereas activation of S1PR2 decreased migration through the Rho/Rho-associated protein kinase (ROCK) pathway. In conclusion, we reveal that the S1P/S1PRs signaling axis regulates the migration of human BMSCs via a dual-directional mechanism. Thus, selective modulation of S1PR’s activity on human BMSCs may provide an effective approach to immunotherapy or tissue regeneration

SPAG5 upregulation contributes to enhanced c-MYC transcriptional activity via interaction with c-MYC binding protein in triple-negative breast cancer

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that lacks effective therapeutic targets. Sperm-associated antigen 5 (SPAG5) is a mitotic spindle-associated protein that is involved in various biological processes in cervical cancer and bladder urothelial carcinoma. However, the role of SPAG5 in TNBC remains undefined. Methods The expression of SPAG5 was examined in TNBC patients via quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry (IHC). The biological functions of SPAG5 in TNBC and the underlying mechanisms were investigated in vitro and in vivo. Results SPAG5 expression was significantly upregulated in TNBC tissues compared with that in paired adjacent noncancerous tissues (ANTs). High SPAG5 expression was associated with increased lymph node metastasis and high risk of local recurrence. SPAG5 protein expression was significantly associated with poor disease-free survival in TNBC. Gene set enrichment analysis of TNBC data from The Cancer Genome Atlas (TCGA) indicated that high SPAG5 expression was significantly associated with cell cycle and the ATR-BRCA pathway. Functional assays demonstrated that SPAG5 expression promoted tumor growth in vitro and in vivo. In addition, SPAG5-silenced cells were more sensitive to the PARP inhibitor (PARPi) olaparib. Mechanistically, SPAG5 interacted with c-MYC binding protein (MYCBP), thereby increasing MYCBP protein levels and leading to increased c-MYC transcriptional activity, which promoted the expression of the c-MYC target genes: CDC20, CDC25C, BRCA1, BRCA2, and RAD51.Knockdown of MYCBP or c-MYC abolished the SPAG5-induced cell-cycle progression and cell proliferation of TNBC. Conclusions Collectively, our results indict that SPAG5 is an efficient prognostic factor in TNBC, and that SPAG5 knockdown increases the sensitivity of TNBC to the PARPi olaparib. SPAG5 promotes tumor growth and DNA repair by increasing c-MYC transcriptional activity via interaction with MYCBP. The SPAG5/MYCBP/c-MYC axis may represent a potential therapeutic target for TNBC treatment

Recombinant Adenovirus KGHV500 and CIK Cells Codeliver Anti-p21-Ras scFv for the Treatment of Gastric Cancer with Wild-Type Ras Overexpression

The development of gastric cancer is frequently related to the overexpression of wild-type p21 proteins, but it is rarely related to mutated Ras proteins. We previously constructed a broad-spectrum anti-p21-Ras single-chain variable fragment antibody (scFv), which was carried by the oncolytic adenovirus KGHV500. Here we explored the antitumor effects of this recombinant oncolytic adenovirus carried by cytokine-induced killer (CIK) cells on human gastric SGC7901 cells that overexpress wild-type Ras. The MTT assay, scratch test, Transwell assay, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed in vitro to investigate the proliferation, migration, invasiveness, and cell apoptosis rate, respectively, of the human gastric cell line SGC7901 treated with KGHV500 adenovirus. Then, the tumor-targeting ability and systemic safety of KGHV500 adenovirus delivered by CIK cells were explored in vivo. We found that KGHV500 adenovirus could significantly inhibit proliferation, migration, and invasiveness and promote cell apoptosis in SGC7901 cells in vitro. In vivo studies showed that CIK cells could successfully deliver KGHV500 adenovirus to the tumor site; the two vectors synergistically killed tumor cells, and the treatment was relatively safe for normal tissues. In conclusion, this therapeutic strategy of recombinant adenovirus KGHV500 delivered by CIK cells offers a positive prospect for the targeted therapy of Ras-related cancers. Keywords: oncolytic adenovirus, anti-p21-Ras, scFv, CIK cell, gastric cancer, SGC790

The Childhood Maltreatment Modulates the Impact of Negative Emotional Stimuli on Conflict Resolution

It has been reported that negative emotional stimuli could facilitate conflict resolution. However, it remains unclear about whether and how the impact of negative emotional stimuli on conflict resolution varies depending on childhood maltreatment. To clarify this issue, seventy-nine subjects were required to perform an arrow Eriksen Flanker Task which was presented in the center of emotional pictures. The present study found a significant interaction effect of childhood maltreatment and emotion on executive attention scores in reaction times (RTs) that reflect conflict resolution speed. For subjects in high childhood maltreatment, negative pictures elicited smaller executive attention scores in RTs than neutral and positive pictures, while neutral and positive pictures elicited similar executive attention scores in RTs. By contrast, for subjects in low childhood maltreatment, executive attention scores in RTs were similar across three conditions. These results suggest that the speed of conflict resolution is enhanced in high, instead of low, childhood maltreatment in situations of negative stimuli. This finding extends our understanding of the interaction among emotion, childhood maltreatment and conflict resolution

Two Different Copy Number Variations of the CLCN2 Gene in Chinese Cattle and Their Association with Growth Traits

Copy number variation (CNV) can affect gene function and even individual phenotypic traits by changing the transcription and translation level of related genes, and it also plays an important role in species evolution. Chloride voltage-gated channel 2 (CLCN2) encodes a voltage-gated chloride channel (CLC-2), which has a wide organ distribution and is ubiquitously expressed. Based on previous studies, we hypothesize that CLCN2 could be a candidate gene involved in cell volume regulation, transepithelial transport and cell proliferation. This study aimed to explore CNVs in the CLCN2 gene and investigate its association with growth traits in four Chinese cattle breeds (Yunling cattle, Xianan cattle, Qinchuan cattle and Pinan cattle). We identified there are two copy number variation regions (CNV1: 3600 bp, including exon 2–11; CNV2: 4800 bp, including exon 21–22) of the CLCN2 gene. The statistical analysis showed that the CNV1 mutation in the YL cattle population was significantly associated with cannon circumference (p < 0.01). The CNV2 mutation in the XN cattle population had a significant effect on body slanting length, chest girth and body weight (p < 0.05). In the YL cattle, the association analysis of CLCN2 gene CNV1 and CNV2 combination with cannon circumference was significant (p < 0.01). Our results provide evidence that CNV1 and CNV2 in CLCN2 are associated with growth traits in two different cattle populations and could be used as candidate markers for cattle molecular breeding