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关键词： Differential games   Incomplete information   Hamilton-Jacobi-Isaacs equation   Signal  

摘要： In this paper, we investigate the existence of value for a two-person zero-sum differential game with symmetric incomplete information and with signal revealing. Before the game begins, the initial state of the dynamic is chosen randomly among a finite number of points in R-n, while both players have only a probabilistic knowledge of the chosen initial state. During the game, if the system reaches a fixed closed target set K, the current state of the system at the hitting time is revealed to both players. We prove in this paper that this game has a value and its value function is the unique bounded continuous viscosity solution of a suitable Hamilton-Jacobi-Isaacs equation.

关键词： Maiorana-McFarland bent functions   Vectorial Boolean functions   Autocorrelation   Differential-linear uniformity   Finite fields  

摘要： The differential-linear connectivity table (DLCT) of a vectorial Boolean function was recently introduced by Bar-On et al. at EUROCRYPT'19, whose value at a point is related to the autocorrelation value of its component functions. Further, in INDOCRYPT'19, we proposed a new construction method for vectorial Boolean functions with very low differentiallinear uniformity using Maiorana-McFarland bent functions. The difficulty of that construction method was to identify the permutations and the sub-functions that satisfy the conditions to attain good cryptographic properties. In this paper we discover novel techniques to construct such sub-functions to generate vectorial Boolean functions with substantially improved cryptographic properties. Our proposed methods are based on ideas from combinatorics as well as finite fields. In particular, we construct the sub-functions to generate (4t, t - 1)-function, t >= 5, in a different manner than our Indocrypt'19 paper. Further our new methods help in obtaining sub-functions to generate balanced (4t + 2, t - 1)function and (2k, k)-function with very good nonlinearity and very low differential-linear uniformity, that were never demonstrated earlier. (c) 2021 Elsevier Inc. All rights reserved.

关键词： pancreatic ductal adenocarcinoma   polyamine metabolism   tumor microenvironment   immune suppression   polyamine blockade therapy   survival   macrophage   CD86   DFMO   polyamine transport inhibitor  

摘要： Simple Summary Pancreatic cancer has a five-year survival rate of less than 8% and is the fourth leading cause of cancer death in the United States. Existing therapeutics have failed to improve pancreatic ductal adenocarcinoma (PDAC) patient outcomes. There has been success with other tumor types in targeting aberrant polyamine upregulation as a therapeutic strategy. The present study identified dysregulation of polyamine pathways to be evident in human PDAC progression. Additionally, reduced survival of pancreatic cancer patients was associated with increased expression of specific polyamine-related genes. Polyamine blockade therapy significantly increased overall survival of pancreatic tumor-bearing mice, along with macrophage presence (F4/80) and significantly increased T-cell co-stimulatory marker (CD86) in the tumor microenvironment. Based on these findings, we hypothesized that a polyamine blockade therapy could potentially prime the tumor microenvironment to be more susceptible to existing therapeutics. Future studies which test polyamine blockade therapy with existing therapeutics could increase the molecular tools available to treat PDAC. Pancreatic cancer is the fourth leading cause of cancer death. Existing therapies only moderately improve pancreatic ductal adenocarcinoma (PDAC) patient prognosis. The present study investigates the importance of the polyamine metabolism in the pancreatic tumor microenvironment. Relative mRNA expression analysis identified differential expression of polyamine biosynthesis, homeostasis, and transport mediators in both pancreatic epithelial and stromal cells from low-grade pancreatic intraepithelial neoplasia (PanIN-1) or primary PDAC patient samples. We found dysregulated mRNA levels that encode for proteins associated with the polyamine pathway of PDAC tumors compared to early lesions. Next, bioinformatic databases were used to assess expression of select genes involved in polyamine metabolism and their impact on patient

关键词： Photovoltaic model   Parameter estimation   PV cell   Improved differential evolution   Temperature variation  

摘要： With renewable energy currently making the headlines, photovoltaic technology has shown significant potential as one of the best energy sources. It thus becomes necessary to predict the performance of photovoltaic systems by modeling it accurately and optimally. We propose a new hybrid algorithm for extracting PV cell parameters to improve their performance and efficiency when subjected to temperature variations. A metaheuristic approach is combined with an analytical approach to improve the accuracy and robustness. We call this approach improved differential evolution (IDE). The performance of the proposed method is evaluated for selected cell data. For validation, several analyses and comparisons are made with other methods, and the results illustrate the accuracy and precision of IDE. The proposed technique can estimate the parameters in an optimal way at any temperature, together with high convergence speed and a short simulation time.

关键词： Inflammatory breast cancer   Locally advanced breast cancer   Tumor-infiltrating lymphocytes   pCR   PD-L1   CD20   Immuno-oncology   Patient outcomes  

摘要： Purpose This study evaluated epidemiologic and immune factors associated with pathologic complete response (pCR), breast cancer-specific survival (BCSS) and disease-free survival (DFS) outcomes in inflammatory (IBC) and locally advanced breast cancer (LABC) patients. Methods Tumor-infiltrating lymphocytes (TILs) and CD20(+) B-cell frequencies (CD20(+)), and PD-L1 expression on tumor (PD-L1(+)carcinoma cells) and immune (PD-L1(+)TILs) cells were analyzed by immunohistochemistry along with clinicopathologic factors as modifiers of pCR and outcomes in 221 IBC and 162 LABC patients. Analysis included Kaplan-Meier curves and Cox proportional hazard models. Results IBC and LABC display similar levels of TILs, CD20(+), and combined CD20(+) and PD-L1(+)TILs (CD20(+)PD-L1(+)TILs), while LABC contained more PD-L1(+)TILs and PD-L1(+) carcinoma cells. Absence of lymphovascular involvement, high TILs, PD-L1(+) carcinoma cells, and combined CD20(+) and PD-L1(+) carcinoma cells correlated with pCR in IBC and LABC patients. High PD-L1(+)TILs correlated with pCR only in LABC;less lymph node involvement at diagnosis, CD20(+) and CD20(+)PD-L1(+)TILs correlated with pCR only in IBC (P < 0.04, all comparisons). Achievement of pCR in IBC and LABC patients correlated with BCSS and DFS (P < 0.02). In multivariate analyses, pCR remained an independent prognostic factor of improved DFS in IBC and LABC patients, but of BCSS in only LABC. CD20(+)PD-L1(+)TILs remained an independent prognostic factor of improved DFS and BCSS only in IBC. Conclusion CD20(+)PD-L1(+)TILs are an independent prognostic biomarker of improved outcomes in IBC, but not LABC. Selecting IBC patients by CD20 and PD-L1 status could stratify patients and potentially identify those in whom activating CD20 agents and anti-PD-1/PD-L1 therapy could be explored.

关键词： follicular lymphoma   chronic lymphocytic leukemia   mutational signatures   activation-induced cytidine deaminase   DNA repair pathways  

摘要： Activation-induced deaminase (AID) is required for somatic hypermutation in immunoglobulin genes, but also induces off-target mutations. Follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL), the most frequent types of indolent B-cell tumors, are exposed to AID activity during lymphomagenesis. We designed a workflow integrating de novo mutational signatures extraction and fitting of COSMIC (Catalogue Of Somatic Mutations In Cancer) signatures, with tridimensional chromatin conformation data (Hi-C). We applied the workflow to exome sequencing data from lymphoma samples. In 33 FL and 30 CLL samples, 42% and 34% of the contextual mutations could be traced to a known AID motif. We demonstrate that both CLL and FL share mutational processes dominated by spontaneous deamination, failures in DNA repair, and AID activity. The processes had equiproportional distribution across active and nonactive chromatin compartments in CLL. In contrast, canonical AID activity and failures in DNA repair pathways in FL were significantly higher within the active chromatin compartment. Analysis of DNA repair genes revealed a higher prevalence of base excision repair gene mutations (p = 0.02) in FL than CLL. These data indicate that AID activity drives the genetic landscapes of FL and CLL. However, the final result of AID-induced mutagenesis differs between these lymphomas depending on chromatin compartmentalization and mutations in DNA repair pathways.

关键词： Chocolate   DSC   Crystals   Polymorphs   Thermal analysis   Melting point  

摘要： Differential scanning calorimetry (DSC) is a method widely used to examine the melting or crystallization profile of cocoa butter and chocolate. The (perceived) ease of use makes the method very appealing not only in academia, but also in the chocolate industry. Our study presents a critical evaluation of the parameters that influence the generated information (i.e., the apparent melting point and specific heat of fusion) on dark chocolates of various cocoa contents and evaluates the suitability of DSC as generic or "universal" analytical method. The tested parameters included sample weight and form, temperature protocol, and heating rate. In general, the melting point of all dark chocolates increased as a function of increasing heating rate. The weight and form of the samples influenced the melting points but not the specific heat of fusion, while the starting temperatures of the thermal analysis did not seem to affect the melting profiles of the chocolates. We observe that a comparison between different studies researching chocolate behavior using DSC is not trivial due to insufficient detail on the procedure followed and conclude that DSC is maybe better suited for inner-study comparisons.

关键词： Chronic pain   Functional abdominal pain   Cognitive behavioral therapy   Pain education   Internet-delivered   Pediatric   Treatment moderators   Patient subgroup   Precision medicine  

摘要： Inconsistent results of psychological treatments for pediatric functional abdominal pain (FAP) may be due to heterogeneity of patients' pain-related psychological characteristics. This randomized controlled trial tested whether statistically derived patient subgroups (high pain dysfunctional [HPD], high pain adaptive [HPA], and low pain adaptive [LPA]) moderated response to cognitive behavior therapy (CBT) for adolescents with FAP and their parents (n = 278 dyads;patients were 66% female, mean [SD] age was 14.62 [1.88] years, and parents were 95% female). Randomization to Internet-delivered CBT vs Internet-delivered pain education (EDU) was stratified by patient subgroup. Follow-up assessments of gastrointestinal (GI) symptoms (primary outcome), abdominal pain, and pain interference were at midtreatment, posttreatment, 6 months, and 12 months. Data were analysed using linear mixed effects models. Significant treatment x subgroup x time interaction effects showed that patient subgroup significantly moderated the effect of treatment on GI symptoms (t[853 = -2.93, P = 0.003) and abdominal pain (t(844) = -2.14, P = 0.03) across the treatment period. Among HPD youth, those in CBT had significantly greater GI symptom reduction than those in EDU through posttreatment. By contrast, among HPA and LPA youth, symptom improvement did not differ by treatment condition. Furthermore, among all patients assigned to CBT, HPD youth demonstrated significantly greater reductions in GI symptoms compared with HPA and LPA youth and greater reductions in abdominal pain compared with LPA youth. All subgroups maintained symptom reductions throughout the follow-up period. Results suggest that subgrouping FAP patients may inform treatment allocation and optimize treatment response.

关键词： PD-L1   HNSCC   head and neck   cell cycle inhibition   blockade   progression   palbociclib   aphidicolin   nocodazole   CDK4   CDK6 inhibitor   epithelial   mesenchymal differentiation status  

摘要： The expression of PD-L1 by tumor cells is mainly associated with its immunosuppressive effect. In fact, PD-1/PD-L1 immune checkpoint inhibitors demonstrated remarkable effects in advanced cancer patients including HNSCC. In this context, irradiation is currently being investigated as a synergistic treatment modality to immunotherapy. However, the majority of HNSCC patients still show little improvement or even hyperprogression. Interestingly, there is increasing evidence for additional cell-intrinsic functions of PD-L1 in tumor cells. In previous studies, we showed that PD-L1 has a strong influence on proliferation, migration, invasion, and survival after irradiation. We demonstrated that cellular expression and localization of PD-L1 differed depending on sensitivity to irradiation. Here, we show that PD-L1 is also differentially expressed during cell cycle progression of HNSCC. Furthermore, cellular localization of PD-L1 also changes depending on a particular cell cycle phase. Moreover, distinct observations occurred depending on the general differentiation status. Overall, the function of PD-L1 cannot be generalized. Rather, it depends on the differentiation status and microenvironment. PD-L1 expression and localization are variable, depending on different factors. These findings may provide insight into why differential response to PD-1/PD-L1 antibody therapy can occur. Detailed understanding of cell-intrinsic PD-L1 functions will further allow antibody-based immunotherapy to be optimized.

关键词： Piezoelectric ceramic   Piezocomposite   Weighted differential evolution   Transducer   Optimization  

摘要： Piezoelectric transducers are designed for wide applications of underwater sonar, energy harvesting, biomedical and nondestructive testing in terms of higher sensitivity and broad bandwidth. Multilayer transducers have well-known advantages of higher sensitivity and thus can be optimized by varying layer thicknesses of active material. The present study deals with mathematical optimization of multilayer transducers exploiting weighted differential evolution (WDE) based computational heuristics for optimized piezoelectric transducer design while satisfying the constraint of constant total thickness. Fitness evaluation is carried out on the basis of one dimensional model (ODM) for simple multilayer, multilayer with bondlines and transducer with bondlines and matching for piezoelectric materials including PZT5h, PMN-PT and piezocomposite with PMN-PT for different loading media. WDE exploited along with ODM for the transducer models has demonstrated the efficacy, reliability and applicability of the proposed scheme. Comparative study of the proposed WDE-ODM with its counterparts including simulated annealing, genetic algorithms, and particle swarm optimization, reveal better performance in terms of accuracy, complexity and convergence metrics for different number of layers for simple transducers. Applicability of WDE-ODM on piezoelectric structures with bondlines, and matching layers has also been accessed and validated. (C) 2021 Elsevier B.V. All rights reserved.