Semi-supervised Instance Segmentation with a Learned Shape Prior

To date, most instance segmentation approaches are based on supervised learning that requires a considerable amount of annotated object contours as training ground truth. Here, we propose a framework that searches for the target object based on a shape prior. The shape prior model is learned with a variational autoencoder that requires only a very limited amount of training data: In our experiments, a few dozens of object shape patches from the target dataset, as well as purely synthetic shapes, were sufficient to achieve results en par with supervised methods with full access to training data on two out of three cell segmentation datasets. Our method with a synthetic shape prior was superior to pre-trained supervised models with access to limited domain-specific training data on all three datasets. Since the learning of prior models requires shape patches, whether real or synthetic data, we call this framework semi-supervised learning

Iterative Qubits Management for Quantum Index Searching in a Hybrid System

Recent advances in quantum computing systems attract tremendous attention. Commercial companies, such as IBM, Amazon, and IonQ, have started to provide access to noisy intermediate-scale quantum computers. Researchers and entrepreneurs attempt to deploy their applications that aim to achieve a quantum speedup. Grover's algorithm and quantum phase estimation are the foundations of many applications with the potential for such a speedup. While these algorithms, in theory, obtain marvelous performance, deploying them on existing quantum devices is a challenging task. For example, quantum phase estimation requires extra qubits and a large number of controlled operations, which are impractical due to low-qubit and noisy hardware. To fully utilize the limited onboard qubits, we propose IQuCS, which aims at index searching and counting in a quantum-classical hybrid system. IQuCS is based on Grover's algorithm. From the problem size perspective, it analyzes results and tries to filter out unlikely data points iteratively. A reduced data set is fed to the quantum computer in the next iteration. With a reduction in the problem size, IQuCS requires fewer qubits iteratively, which provides the potential for a shared computing environment. We implement IQuCS with Qiskit and conduct intensive experiments. The results demonstrate that it reduces qubits consumption by up to 66.2%

ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a

ΔNp63α, a member of the p53 family of transcription factors, is overexpressed in a number of cancers and plays a role in proliferation, differentiation, migration, and invasion. ΔNp63α has been shown to regulate several microRNAs that are involved in development and cancer. We identified miRNA miR-320a as a positively regulated target of ΔNp63α. Previous studies have shown that miR-320a is downregulated in colorectal cancer and targets the small GTPase Rac1, leading to a reduction in noncanonical WNT signaling and EMT, thereby inhibiting tumor metastasis and invasion. We showed that miR-320a is a direct target of ΔNp63α. Knockdown of ΔNp63α in HaCaT and A431 cells downregulates miR-320a levels and leads to a corresponding elevation in PKCγ transcript and protein levels. Rac1 phosphorylation at Ser71 was increased in the absence of ΔNp63α, whereas overexpression of ΔNp63α reversed S71 phosphorylation of Rac1. Moreover, increased PKCγ levels, Rac1 phosphorylation and cell invasion observed upon knockdown of ΔNp63α was reversed by either overexpressing miR-320a mimic or Rac1 silencing. Finally, silencing PKCγ or treatment with the PKC inhibitor Gö6976 reversed increased Rac1 phosphorylation and cell invasion observed upon silencing ΔNp63α. Taken together, our data suggest that ΔNp63α positively regulates miR-320a, thereby inhibiting PKCγ expression, Rac1 phosphorylation, and cancer invasion.Fil: Aljagthmi, Amjad A.. Wright State University; Estados UnidosFil: Hill, Natasha T.. Wright State University; Estados UnidosFil: Cooke, Mariana. University of Pennsylvania; Estados UnidosFil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados UnidosFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Long, Weiwen. Wright State University; Estados UnidosFil: Kadakia, Madhavi P.. Wright State University; Estados Unido

Homeostatic levels of SRC-2 and SRC-3 promote early human adipogenesis

Individual or joint knockdown of the transcriptional coactivators SRC-2 and SRC-3 inhibits lipid accumulation in adipocytes by decreasing PPARγ activity

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

FBXL16 promotes cell growth and drug resistance in lung adenocarcinomas with KRAS mutation by stabilizing IRS1 and upregulating IRS1/AKT signaling

Lung cancer is the leading cause of cancer‐related deaths worldwide. Lung adenocarcinomas (LUADs) are a major subtype of non‐small‐cell lung cancers (NSCLCs). About 25% of LUADs harbor GTPase KRAS mutations associated with poor prognosis and limited treatment options. While encouraging tumor response to novel covalent inhibitors specifically targeting KRASG12C has been shown in the clinic, either intrinsic resistance exists or acquired therapeutic resistance arises upon treatment. There is an unmet need to identify new therapeutic targets for treating LUADs with activating KRAS mutations, particularly those with resistance to KRASG12C inhibitor(s). In this study, we have revealed that F‐box/LRR‐repeat protein 16 (FBXL16) is selectively upregulated in LUAD with KRAS mutations. It promotes LUAD cell growth and transforms lung epithelial cells. Importantly, FBXL16 depletion greatly enhances sensitivity to the KRASG12C inhibitor (sotorasib) in resistant cells by downregulating phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (PKB; also known as AKT) signaling. Mechanistically, FBXL16 upregulates insulin receptor substrate 1 (IRS1) protein stability, leading to an increase of IGF1/AKT signaling, thereby promoting cell growth and migration. Taken together, our study highlights the potential of FBXL16 as a therapeutic target for treating LUAD with KRAS activating mutations