A decomposition algorithm for two-stage stochastic programs with nonconvex recourse

In this paper, we have studied a decomposition method for solving a class of nonconvex two-stage stochastic programs, where both the objective and constraints of the second-stage problem are nonlinearly parameterized by the first-stage variable. Due to the failure of the Clarke regularity of the resulting nonconvex recourse function, classical decomposition approaches such as Benders decomposition and (augmented) Lagrangian-based algorithms cannot be directly generalized to solve such models. By exploring an implicitly convex-concave structure of the recourse function, we introduce a novel decomposition framework based on the so-called partial Moreau envelope. The algorithm successively generates strongly convex quadratic approximations of the recourse function based on the solutions of the second-stage convex subproblems and adds them to the first-stage master problem. Convergence under both fixed scenarios and interior samplings is established. Numerical experiments are conducted to demonstrate the effectiveness of the proposed algorithm

Shrinkage Clustering: A Fast and Size-Constrained Algorithm for Biomedical Applications

Motivation: Many common clustering algorithms require a two-step process that limits their efficiency. The algorithms need to be performed repetitively and need to be implemented together with a model selection criterion, in order to determine both the number of clusters present in the data and the corresponding cluster memberships. As biomedical datasets increase in size and prevalence, there is a growing need for new methods that are more convenient to implement and are more computationally efficient. In addition, it is often essential to obtain clusters of sufficient sample size to make the clustering result meaningful and interpretable for subsequent analysis. Results: We introduce Shrinkage Clustering, a novel clustering algorithm based on matrix factorization that simultaneously finds the optimal number of clusters while partitioning the data. We report its performances across multiple simulated and actual datasets, and demonstrate its strength in accuracy and speed in application to subtyping cancer and brain tissues. In addition, the algorithm offers a straightforward solution to clustering with cluster size constraints. Given its ease of implementation, computing efficiency and extensible structure, we believe Shrinkage Clustering can be applied broadly to solve biomedical clustering tasks especially when dealing with large datasets

Application of Zebrafish Models in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic, recurrent, and remitting inflammatory disease with unclear etiology. As a clinically frequent disease, it can affect individuals throughout their lives, with multiple complications. Unfortunately, traditional murine models are not efficient for the further study of IBD. Thus, effective and convenient animal models are needed. Zebrafish have been used as model organisms to investigate IBD because of their suggested highly genetic similarity to humans and their superiority as laboratory models. The zebrafish model has been used to study the composition of intestinal microbiota, novel genes, and therapeutic approaches. The pathogenesis of IBD is still unclear and many risk factors remain unidentified. In this review, we compare traditional murine models and zebrafish models in terms of advantages, pathogenesis, and drug discovery screening for IBD. We also review the progress and deficiencies of the zebrafish model for scientific applications

Image-guided interstitial brachytherapy for recurrent cervical cancer after radiotherapy: A single institution experience

PurposeThe aim of this study is to evaluate the efficacy and toxicity of image-guided high-dose rate (HDR) interstitial brachytherapy (ISBT) for the reirradiation of cervical cancer within a previously irradiated area.Methods and materialsTwenty-three consecutive patients with cervical cancer were reirradiated with curative intent using brachytherapy (BT) with or without external beam irradiation. The median biologically equivalent dose in 2-Gy fractions (EQD2) for reirradiation was 64.0 Gy (range: 31.3–95.1 Gy), and the median cumulative EQD2 (for primary treatment and reirradiation) was 152.4 Gy (range: 97.8–200.9 Gy). The average clinical target volume was 82.9 cm3 (range: 26.9–208.3 cm3), and the median treatment-free interval (TFI) was 13 months (range: 3–93 months).ResultsThe median follow-up time was 19 months (range: 2–59 months). The complete response rate after reirradiation was 56.5%. The 1-, 2- 3-, and 4-year post-relapse survival (PRS) rates were 65.2%, 43.5%, 33.8%, and 27.1%, respectively. The median reirradiation EQD2 D2cc of rectum and bladder was 39.5 Gy (range = 14.6–96.2 Gy) and 52.1 Gy (range = 29.1–114.2 Gy). The median cumulative EQD2 D2cc of rectum and bladder was 115.0 Gy (range = 84.4–189.3 Gy) and 130.5 Gy (range = 95.5–173.5 Gy). During follow-up, nine (39.1%) patients had experienced grade 3 or 4 late toxicities. Grade ≥3 rectal toxicity occurred in three patients (13.0%). Grade ≥3 urinary toxicity occurred in five patients (21.7%). One patient (4.3%) had both grade ≥3 urinary and rectal toxicity. Tumor volume, TFI, tumor invasion organ number, and local control were significant prognostic factors adversely affecting OS.ConclusionsFor recurrent cervical cancer after radiotherapy, reirradiation of HDR-ISBT is feasible, even if the local tumor invasion is large, with a good chance of survival and acceptable side effects

Tumour suppressor ING1b maintains genomic stability upon replication stress

The lesion bypass pathway, which is regulated by monoubiquitination of proliferating cell nuclear antigen (PCNA), is essential for resolving replication stalling due to DNA lesions. This process is important for preventing genomic instability and cancer development. Previously, it was shown that cells deficient in tumour suppressor p33ING1 (ING1b) are hypersensitive to DNA damaging agents via unknown mechanism. In this study, we demonstrated a novel tumour suppressive function of ING1b in preserving genomic stability upon replication stress through regulating PCNA monoubiquitination. We found that ING1b knockdown cells are more sensitive to UV due to defects in recovering from UV-induced replication blockage, leading to enhanced genomic instability. We revealed that ING1b is required for the E3 ligase Rad18-mediated PCNA monoubiquitination in lesion bypass. Interestingly, ING1b-mediated PCNA monoubiquitination is associated with the regulation of histone H4 acetylation. Results indicate that chromatin remodelling contributes to the stabilization of stalled replication fork and to the regulation of PCNA monoubiquitination during lesion bypass