Peripheral blood mononuclear cells of breast cancer patients can be reprogrammed to enhance anti-HER-2/neu reactivity and overcome myeloid-derived suppressor cells [poster abstract]

Barriers limiting the efficacy of adoptive cellular therapy (ACT) for breast cancer patients include immune suppression mediated by myeloid-derived suppressor cells (MDSC) and a low frequency of tumor-reactive memory T cells (Tm). Recently, we developed an ex vivo protocol to reprogram tumor-reactive murine splenocytes; these cells were found to be resistant to MDSC suppression and protected FVBN202 mice from tumor challenge. Here, we evaluated the clinical applicability of reprogramming tumor-sensitized PBMCs isolated from patients with early stage breast cancer by treatment with bryostatin 1 and ionomycin (B/I) combined with IL-2, IL-7 and IL-15. Our data demonstrate that reprogrammed cells are enriched with Tm cells (n=5; p=0.006), as well as activated CD56+(n=6; p=0.003) and CD161+ (n=4; p=0.02) NKT cells, and demonstrate expansion in total cell numbers (n=16; p=0.003) compared to baseline cells. Reprogrammed PBMCs displayed enhanced HER-2/neu-specific IFN-γ producing immune responses (n=6; p=0.04); non-reprogrammed control PBMC IFN-γ production was not significant (n=6; p=0.4). Furthermore, high-throughput sequencing analysis of the T cell receptor (TcR) Vβ in one patient demonstrated clonal expansion of specific TcR VJ recombination events resulting from cellular reprogramming, suggestive of an enriched frequency of specific tumor antigen-primed T cell clones. Interestingly, reprogrammed T cells were resistant to autologous CD33+ CD11b+ HLA-DRlo/- MDSCs, as determined by further enhanced HER-2/neu-specific IFN-γ secretion in the presence of MDSCs (n=6; p=0.03). Activated CD161+ NKT cells comprising 3% or greater of total reprogrammed cells rendered T cells resistant to MDSCs (n=3; p=0.02). Upregulation of NKG2D expression on CD161+(n=5; p=0.0006) and CD56+ (n=5; p=0.04) NKT cells resulted from cellular reprogramming. Therefore, NKG2D signaling was blocked using anti-NKG2D blocking antibody in our co-culture system, resulting in the abrogation of resistance to MDSCs as determined by blunted IFN-γ secretion (n=3; p=0.04). Finally, the phenotype of MDSCs after co-culture with reprogrammed PBMC was examined; we observed downregulation of CD11b expression (n=3; p=0.02) concomitant with HLA-DR upregulation on MDSCs (n=3; p=0.001); suggestive of induced maturation of MDSCs into Dendritic Cells (DC). The results of our study offer the following strategies to improve ACT of breast cancer: i) inclusion of activated NKT cells in ACT to overcome MDSC suppression by inducing MDSC maturation into DCs, and ii) PBMC reprogramming to enrich the frequency of tumor-reactive Tm cells

Mapping and pyramiding of two major genes for resistance to the brown planthopper (Nilaparvata lugens [Stål]) in the rice cultivar ADR52

The brown planthopper (BPH), Nilaparvata lugens (Stål), is one of the most serious and destructive pests of rice, and can be found throughout the rice-growing areas of Asia. To date, more than 24 major BPH-resistance genes have been reported in several Oryza sativa ssp. indica cultivars and wild relatives. Here, we report the genetic basis of the high level of BPH resistance derived from an Indian rice cultivar, ADR52, which was previously identified as resistant to the whitebacked planthopper (Sogatella furcifera [Horváth]). An F2 population derived from a cross between ADR52 and a susceptible cultivar, Taichung 65 (T65), was used for quantitative trait locus (QTL) analysis. Antibiosis testing showed that multiple loci controlled the high level of BPH resistance in this F2 population. Further linkage analysis using backcross populations resulted in the identification of BPH-resistance (antibiosis) gene loci from ADR52. BPH25 co-segregated with marker S00310 on the distal end of the short arm of chromosome 6, and BPH26 co-segregated with marker RM5479 on the long arm of chromosome 12. To characterize the virulence of the most recently migrated BPH strain in Japan, preliminary near-isogenic lines (pre-NILs) and a preliminary pyramided line (pre-PYL) carrying BPH25 and BPH26 were evaluated. Although both pre-NILs were susceptible to the virulent BPH strain, the pre-PYL exhibited a high level of resistance. The pyramiding of resistance genes is therefore likely to be effective for increasing the durability of resistance against the new virulent BPH strain in Japan

Video Rental Recommendation System by Using Collaborative Filtering Method

Collaborative filtering works to aggregate ratings or preferences on items; discovers user profiles learning from user’s historic rating record; generates a new recommendation on a basis of inter-pattern comparison. Recommendation system is based on collaborative filtering method. Collaborative filtering based on a prediction for a user should be based on the similarity between the interest profile of that user and those of other users. In this paper, video recommendation system is developed by using Collaborative filtering method. Recommendation system is subdivided into three main parts. First, collect data for movies. Second, search movie by top-ten or by actor or by title or by director. Next, recommend to the user by using recommendation system

Transaction Management Using Serial Validation Approach for Relational Database

Nowadays, accessing the same database from the different applications is natural when one company wants to sell their products not only by itself but also by other partner companies or agencies. The accesses to the database can be transactions from many client applications. It needs to monitor, examine, and control the concurrent accesses so that the overall correctness of the database is maintained. In our case study, we implements data accessed components which uses the serial validation with optimistic concurrency scheme to ensure the serial equivalence of the overlapping client transactions. The use of a multi-tiered architecture to develop the overall system architecture will meet the best architecture design decision to distributed deployment of these components as a separate tire on the web. These components can be connected via their interfaces from any application client and concurrency control is achieved through them

Implementation of Neural Network Based Electricity Load Forecasting

This paper proposed a novel model for short term load forecast (STLF) in the electricity market. The prior electricity demand data are treated as time series. The model is composed of several neural networks whose data are processed using a wavelet technique. The model is created in the form of a simulation program written with MATLAB. The load data are treated as time series data. They are decomposed into several wavelet coefficient series using the wavelet transform technique known as Non-decimated Wavelet Transform (NWT). The reason for using this technique is the belief in the possibility of extracting hidden patterns from the time series data. The wavelet coefficient series are used to train the neural networks (NNs) and used as the inputs to the NNs for electricity load prediction. The Scale Conjugate Gradient (SCG) algorithm is used as the learning algorithm for the NNs. To get the final forecast data, the outputs from the NNs are recombined using the same wavelet technique. The model was evaluated with the electricity load data of Electronic Engineering Department in Mandalay Technological University in Myanmar. The simulation results showed that the model was capable of producing a reasonable forecasting accuracy in STLF

From Ceasefire to Dialogue: The Problem of “All-Inclusiveness” in Myanmar’s Stalled Peace Process

A key principle underpinning Myanmar’s peace process has been the principle of “all-inclusiveness.” Initially, this principle represented a commitment to the inclusion of all ethnic armed organizations (EAOs) in a nation-wide ceasefire agreement (NCA) that would serve as a basis for reconciliation, political dialogue and negotiation over constitutional reform. When President Thein Sein’s transition government (2011–16) began making peace overtures, the principle was widely embraced by EAOs and the military, and ultimately enshrined in the text of the NCA. When Aung San Suu Kyi’s National League for Democracy (NLD) came to power in 2016 and made the peace process its top priority it, too, championed the principle of “all-inclusiveness.” However, as the NLD and the military struggle to convince more EAOs to sign the NCA, it has become apparent that, for all its good intentions, the principle of “all-inclusiveness” has become an obstacle to the peace process. This chapter reviews the peace process to date to examine the problems that have emerged around the concept of “all-inclusiveness.” Drawing on interviews with signatories of the NCA and other key stakeholders,1 the chapter highlights a central challenge confronting the government in its efforts to advance Myanmar’s stalled peace process