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AAA domain containing 3A (ATAD3A) is a nucleus-encoded mitochondrial protein with vital function in communication between endoplasmic reticulum (ER) and mitochondria which is participated in cancer metastasis. Here we show that elevated ATAD3A expression is clinically associated with poor 5-year disease-free survival in patients with colorectal cancer (CRC), especially high-risk CRC patients who received adjuvant chemotherapy. Our results indicated ATAD3A is significantly upregulated to reduce chemotherapy-induced cancer cell death. We found that knockdown of ATAD3A leads to dysregulation in protein processing for inducing ER stress by RNA sequencing (RNA-seq). In response to chemotherapy-induced ER stress, ATAD3A interacts with elevated GRP78 protein to assist protein folding and alleviate ER stress for cancer cell survival. This reduction of ER stress leads to reduce the surface exposure of calreticulin, which is the initiator of immunogenic cell death and antitumor immunity. However, silencing of ATAD3A enhances cell death, triggers the feasibility of chemotherapy-induced ER stress for antitumor immunity, increases infiltration of T lymphocytes and delays tumor regrowth in vitro and in vivo. Clinically, CRC patients with less ATAD3A have high density of CD45+ intratumoral infiltrating lymphocytes (TILs) and memory CD45RO+ TILs. Taken together, our results suggest that pharmacologic targeting to ATAD3A might be a potential therapeutic strategy to enhance antitumor immunity for CRC patients who received adjuvant chemotherapy.

This study aims to conceptualize the effects of perceived retailer service innovativeness (PRSI), perceived service advantage, customer emotional satisfaction, and attitudes to retail patronage intentions. The proposed model is examined by structural equation modelling (SEM) using 1,386 samples from three retail formats in Taiwan. Results suggest that PRSI can be used as a strategic tool to create competitive advantage and customer satisfaction. PRSI is a critical antecedent factor that affects store patronage intentions through material‐based and experience‐based routes. This study affirms that a retailer's ability to offer service innovations, especially free in‐store services, may not immediately increase the financial performance of firms; however, it can change a consumer's attitude towards the store by becoming a critical determinant of success of the retailing system. The research model can be utilized by other retail studies, especially in this era of increased competition when innovation has become a critical strategic tool for differentiation.

Metal dyshomeostasis is central to a number of disorders that result from, inter alia, oxidative stress protein misfolding, and cholesterol dyshomeostasis. In this respect, metal deficiencies are usually readily corrected by treatment with supplements, whereas metal overload can be overcome by the use of metal‐selective chelation therapy. Deferasirox, 4‐[(3Z,5E)‐3,5‐bis(6‐oxo‐1‐cyclohexa‐2,4‐dienylidene)‐1,2,4‐triazolidin‐1‐yl]benzoic acid, Exjade, or ICL670, is used clinically to treat hemosiderosis (iron overload), which often results from multiple blood transfusions. Cyclodextrins are cyclic glucose units that are extensively used in the pharmaceutical industry as formulating agents as well as for encapsulating hydrophobic molecules such as in the treatment of Niemann Pick C or for hypervitaminosis. We have conjugated deferasirox, via an amide coupling reaction, to both 6A‐amino‐6A‐deoxy‐β‐cyclodextrin and 3A‐amino‐3A‐deoxy‐2A(S),3A(R)‐β‐cyclodextrin, at the upper and lower rim respectively creating hybrid molecules with dual properties, capable of both metal chelation and cholesterol encapsulation. Our findings emphasize the importance of the conjugation of β‐cyclodextrin with deferasirox to significantly improve the biological properties and reduce the cytotoxicity of this drug.

Spatial surveillance is critical to health systems, manufacturing industries, and in many other domains. For example, determining hotspots of infectious diseases and detecting defect patterns on semiconductor wafers require sensitive spatial analysis tools. The goal of this paper is to detect spatial clusters with mean shifts. Conventional multivariate analysis methods may ignore spatial structure among data and lead to inefficient inspection. Several likelihood ratio-based scan statistics have been designed for spatial surveillance. However, there is no most powerful test when parameters like shift magnitude and coverage are unknown. This paper proposes a spatial exponentially weighted moving average (spatial-EWMA) approach that can detect the existence and locate the potential centers of shift clusters. The test procedure assigns different weights to the data with different radius levels from the investigated shift center. The efficiency of the spatial-EWMA approach is shown by simulation. Lastly, an example of detecting the counties with high incidence of male thyroid cancer in New Mexico is provided to show the effectiveness of the proposed approach. Copyright © 2013 John Wiley & Sons, Ltd.

Chronic progressive external ophthalmoplegia (CPEO) syndrome is one of the mitochondrial diseases caused by large-scale deletions in mitochondrial DNA (mtDNA) that impair the respiratory function of mitochondria and result in decreased production of ATP in affected tissues. In order to investigate whether CPEO-associated mtDNA mutations (i.e., 4,366-bp and 4,977-bp large-scale deletions) render human cells more vulnerable to apoptosis, we constructed cybrids carrying the deleted mtDNA. Assays for cell viability, DNA fragmentation, cytochrome c release, and caspase 3 activation revealed that UV irradiation at 20 J/m 2 triggered apoptosis in all the cybrids. This treatment also produced elevated intracellular levels of reactive oxygen species (ROS). The rate of UV-induced cell death was more pronounced in the cybrids harboring mtDNA deletions than in the control cybrid with wild-type mtDNA. Subsequently, we evaluated the effect of coenzyme Q 1 0 on the UV-triggered apoptosis. The results showed that after pretreatment of the cybrids with 100 μM coenzyme Q 1 0 the UV-induced cell damage (i.e., ROS production and activation of caspase 3) was significantly reduced. Taken together, these findings suggest that large-scale deletions of mtDNA increased the susceptibility of human cells to the UV-triggered apoptosis and that coenzyme Q 1 0 mitigated the damage; hence, it might potentially serve as a therapeutic agent to treat mitochondrial diseases resulting from mtDNA deletions.