A Novel Compressive Image Encryption with an Improved 2D Coupled Map Lattice Model

The digital image, as the critical component of information transmission and storage, has been widely used in the fields of big data, cloud and frog computing, Internet of things, and so on. Due to large amounts of private information in the digital image, the image protection is fairly essential, and the designing of the encryption image scheme has become a hot issue in recent years. In this paper, to resolve the shortcoming that the probability density distribution (PDD) of the chaotic sequences generated in the original two-dimensional coupled map lattice (2D CML) model is uneven, we firstly proposed an improved 2D CML model according to adding the offsets for each node after every iteration of the original model, which possesses much better chaotic performance than the original one, and also its chaotic sequences become uniform. Based on the improved 2D CML model, we designed a compressive image encryption scheme. Under the condition of different keys, the uniform chaotic sequences generated by the improved 2D CML model are utilized for compressing, confusing, and diffusing, respectively. Meanwhile, the message authentication code (MAC) is employed for guaranteeing that the encryption image be integration. Finally, theoretical analysis and simulation tests both demonstrate that the proposed image encryption scheme owns outstanding statistical, well encryption performance, and high security. It has great potential for ensuring the digital image security in application.

Spatiotemporal Complexity Analysis for a Space-Time Discrete Generalized Toxic-Phytoplankton-Zooplankton Model with Self-Diffusion and Cross-Diffusion

In this paper, a couple map lattice (CML) model is used to study the spatiotemporal dynamics and Turing patterns for a space-time discrete generalized toxic-phytoplankton-zooplankton system with self-diffusion and cross-diffusion. First, the existence and stability conditions for fixed points are obtained by using linear stability analysis. Second, the conditions for the occurrence of flip bifurcation, Neimark–Sacker bifurcation and Turing bifurcation are obtained by using the center manifold reduction theorem and bifurcation theory. The results show that there exist two nonlinear mechanisms, flip-Turing instability and Neimark–Sacker–Turing instability. Moreover, some numerical simulations are used to illustrate the theoretical results. Interestingly, rich dynamical behaviors, such as periodic points, periodic or quasi-periodic orbits, chaos and interesting patterns (plaques, curls, spirals, circles and other intermediate patterns) are found. The results obtained in the CML model contribute to comprehending the complex pattern formation of spatially extended discrete generalized toxic-phytoplankton-zooplankton system.

Microrna-142 Deficiency Promotes Chronic Myeloid Leukemia (CML) Transformation from Chronic Phase (CP) to Blast Crisis (BC)

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from the BCR-ABL1 fusion gene that encodes a constitutively activated tyrosine kinase (TK). Although TK inhibitors (TKIs) induce disease remission and prolonged survival in CML patients, a subset are resistant and progress from chronic phase (CP) to blast crisis (BC) with poor prognosis. Understanding the molecular mechanisms of transformation from CP to BC is necessary in the development of effective treatments. Here, we used the inducible SCLtTA/BCR-ABL transgenic CP CML model to study the molecular mechanism of disease evolution. Upon tetracycline withdrawal to induce BCR-ABL expression, both the SCLtTA/BCR-ABL homozygous (homo, i.e., SCLtTA+/+BCR-ABL+/+, hereafter called BCR-ABL) and heterozygous (het, i.e., SCLtTA+/-BCR-ABL+/-) mice developed and died of CP CML without developing BC CML, implying that BCR-ABL dosage is insufficient to induce transformation. MicroRNA (miR)-142 is highly expressed in hematopoietic cells with a critical role in normal hematopoiesis. In miR-142 knockout (KO)(miR-142−/−) mice, hematopoietic stem and progenitor cells expanded with a decrease of hematopoietic output. Loss of miR-142 function has been reported in lymphoma, acute lymphocytic leukemia and acute myeloid leukemia. Of note, we also observed lower levels of miR-142 in CD34+CD38- cells from patients with BC CML versus (vs) patients with CP CML. Thus, we hypothesized that miR-142 insufficiency may promote CML transformation from CP to BC. To test our hypothesis, we generated miR-142 KO BCR-ABL (i.e., miR-142−/−BCR-ABL) mice and observed increasing leukemic blasts over time after BCR-ABL induction in the blood and bone marrow (BM), but not in miR-142 wt (miR-142+/+)BCR-ABL controls even when the latter became moribund. MiR-142−/−BCR-ABL mice had larger spleens and significantly shorter survival [median: 26 vs 54 days (d); p<0.0001] than miR-142+/+BCR-ABL controls. Of note, while both homo (miR-142−/−) and het (miR-142+/−) miR-142 KO BCR-ABL mice eventually developed BC CML, the former had a significantly faster progression to BC and shorter survival (median: 26 vs 45 d; p=0.003) than the latter, suggesting miR-142 deficiency alone is sufficient to initiate BC transformation in the CP CML model in a dose-dependent manner. Importantly, all these features were recapitulated in congenic recipient mice transplanted with BM Lin-Sca-1+c-Kit+ cells (LSKs, 2000/mouse) from diseased miR-142−/−BCR-ABL mice, suggesting LSKs were enriched in leukemic stem cells and able to reproduce BC. Of note, in an RNA-seq analysis comparing LSKs from diseased miR-142−/−BCR-ABL (BC) and miR-142+/+ BCR-ABL(CP) mice, 504 genes were found differentially expressed. Gene set enrichment analysis (GSEA) showed only four pathways differentially expressed (upregulated); three [i.e., oxidative phosphorylation, glycolysis and adipogenesis] regulating cell metabolism and the fourth regulating protein secretion. Next, we developed a novel CpG-miR-142 mimic oligonucleotide, hereafter called CpG-M-miR-142, to restore miR-142 levels. Treatment with CpG-M-miR-142 (20mg/kg/day, iv, 4 weeks) on day 2 after BCR-ABL induction significantly prolonged survival of miR-142−/−BCR-ABL mice compared with CpG-scramble (SCR) (75% vs 33% survival rate at day 40 after BCR-ABL induction; median survival: not reached vs 25 d; p=0.03). Since we observed lower miR-142 levels in TKI-resistant vs TKI-sensitive CML patients (p=0.02), we selected LSKs from diseased miR-142−/−BCR-ABL and miR-142+/+BCR-ABL mice and exposed them to TKI nilotinib (NIL; 2µM) or vehicle for 72 hours to evaluate if downregulation of miR-142 was associated with TKI resistance. We observed lower apoptosis and higher cell growth in NIL-treated miR-142−/−BCR-ABL LSKs vs NIL-treated miR-142+/+BCR-ABL LSKs. The decreased sensitivity of miR-142−/−BCR-ABL LSKs to TKI was rescued by treatment with CpG-M-miR-142. CpG-M-miR-142 (2µM) plus NIL significantly increased apoptosis and reduced cell growth in miR-142−/−BCR-ABL LSKs compared with SCR+ NIL. We showed a key role of miR-142 deficiency in the transformation of CP CML to BC CML associated with deregulation of metabolic pathways. Restoring miR-142 expression in vivo with CpG-M-miR-142 significantly decreased the BC transformation rate, prolonged survival of miR-142−/−BCR-ABL mice and may increase sensitivity to TKIs. Disclosures Marcucci: Iaso Bio: Membership on an entity's Board of Directors or advisory committees; Abbvie: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Other: Research Support (Investigation Initiated Clinical Trial); Takeda: Other: Research Support (Investigation Initiated Clinical Trial); Merck: Other: Research Support (Investigation Initiated Clinical Trial).

The Validity and Effectiveness of the Reflective-Metacognitive Learning Model to Improve Students’ Metacognition Ability in Indonesia

Purpose - This study investigated the content and construct validity of the Reflective-Metacognitive Learning (RML) Model, and the effectiveness of the RML Model in comparison with Cognitive-Metacognitive Learning (CML) Model in improving students’ metacognitive knowledge, skills, and awareness after the learning process. Methodology - This experimental study began with developing the RML Model, which covered planning, development and evaluation. A focus group discussion involving four experts in science education was conducted to determine the validity of the RML Model and its supporting devices in terms of content validity and construct validity. An experimental study using a randomized pretest-posttest control group design was then implemented on forty senior high school students to evaluate the effectiveness of the RML Model against the CML Model. Data were analyzed descriptively and statistically. Findings - The results showed that the RML Model was highly valid in terms of content validity and construct validity, Metacognitive knowledge increased to a high degree, while metacognitive skills and awareness increased to a medium degree. Based on the results, it was concluded that the RML Model was valid and more effective than the CML Model in terms of improving students’ metacognitive ability. Significance - The RML Model, which is marked by the reflection of thinking processes as the core, is expected to improve students' metacognitive ability.

The Influence of the Age of the Bone Marrow Microenvironment on Leukaemia Progression

B-cell acute lymphoblastic leukaemia (B-ALL) occurs most commonly in children, while chronic myeloid leukaemia (CML) is more frequent in adults. So far, the myeloid bias of haematopoiesis in elderly people has been considered the main reason for these differences in leukaemia phenotype in different age groups. However, differential contribution of a young versus an old bone marrow (BM) microenvironment (BMM) to leukaemia development may have been underrecognized given the fact that the BMM undergoes constant remodelling during a lifetime. Using a murine transduction/transplantation model of BCR-ABL1+ B-ALL and CML, we recapitulated the human phenotype, whereby young (3-4 weeks old) recipient mice, which received the same number and type of leukaemia-initiating cells as their old (>30 weeks old) counterparts, died significantly earlier of B-ALL, while showing prolonged survival in the CML model. Engraftment of CML-initiating cells in young bone marrow (BM) was decreased and myeloid progenitors in young mice were reduced in the CML model compared to old mice. In contrast, homing of B-ALL-initiating cells to a young BMM was increased, and by in vivo 2-photon microscopy we observed that B-ALL-initiating cells homed to locations closer to bone and vessels and migrated faster in young compared to old mice. In in vitro coculture assays we showed that BCR-ABL1+ B-ALL cells proliferate, migrate and adhere significantly more in the presence of young BM macrophages or in conditioned medium from these macrophages, while CML cells showed stronger adhesion and proliferation in the presence of old BM macrophages. Old macrophages showed hallmarks of ageing such as an increase of reactive oxygen species, increased DNA damage, proliferative defects and mitochondrial alterations compared to young macrophages. In addition, genome-wide profiling of chromatin accessibility using ATAC-seq revealed strong differences between young and old bone marrow-derived macrophages and an enrichment of inflammatory response gene sets, which includes IL-6/Jak/Stat3 signalling, as well as the C-X-C motif chemokine (CXCL) 13. Cxcl13 is a chemoattractant for B cells and we showed its expression to be upregulated in young versus old BM macrophages and to have higher levels in a young versus an old BMM. Inhibition or knockdown of Cxcl13 in BMM-derived macrophages led to a decrease in proliferation of cocultured B-ALL cells and impaired migration of leukaemia cells towards young BMM-derived macrophages. Consistently, deficiency of Cxcr5, the receptor for Cxcl13, on B-ALL-initiating cells prolonged murine survival in our B-ALL model. In support of our murine data, decreased CXCR5 expression was associated with improved outcome in human hyperdiploid B-ALL and revealed a trend towards improved outcome in BCR-ABL1+ B-ALL and other subtypes. Taken together, our study shows that the age of the BMM and, in particular, BM macrophages influence the leukemia phenotype. The CXCL13-CXCR5 axis may act as prognostic marker or an attractive target for the treatment of B-ALL. Disclosures Kumar: Merck: Research Funding; European Patent No. 16187926.7: Other: USE OF FIBRONECTIN OR ILK INHIBITORS FOR USE IN THE TREATMENT OF LEUKEMIA. Stock:Agios: Membership on an entity's Board of Directors or advisory committees; UpToDate: Honoraria; Kite, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Daiichi: Membership on an entity's Board of Directors or advisory committees; Research to Practice: Honoraria. Mullighan:Amgen: Honoraria, Other: speaker, sponsored travel; Loxo Oncology: Research Funding; AbbVie: Research Funding; Illumina: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored travel; Pfizer: Honoraria, Other: speaker, sponsored travel, Research Funding. Lipka:InfectoPharm GmbH: Employment. Krause:Merck KGaA: Research Funding; Patent: Patents & Royalties: European Patents No. 16187926.7-1401, EP18184430.9-.

Decompositions of Marginal Homogeneity Model Using Cumulative Logistic Models for Square Contingency Tables with Ordered Categories

For square contingency tables with ordered categories, Agresti (1984, 2002) considered the marginal cumulative logistic (ML) model, which is an extension of the marginal homogeneity (MH) model. The ML model depends on the probabilities on the main diagonal of the table. This paper (1) proposes the conditional marginal cumulative logistic (CML) model which does not depend on the probabilities on the main diagonal, and (2) decomposes the MH model into the ML (CML) model and the model which indicates the equality of row and column marginal means. Examples are given.