RETAIL OPERATIONS, CONSUMER STOCKPILING, AND LOGISTICS IT RESOURCES

This dissertation examines research questions within two streams: (1) consumer behavior and retail operations and (2) Information Technology (IT) and operational performance. Specifically, the first two essays study the impacts of consumer stockpiling behavior on retail operations management using natural experiment methodology. The third essay explores the interaction of logistics IT resources, organizational factors, and operational performance. The first essay examines how environmental stress affects consumer stockpiling behavior using the 2008–2009 financial crisis as a natural experiment. Although overall consumption falls due to budgetary constraints, the essay shows that environmental stress increases consumers’ propensity to stockpile during promotional periods. As consumers exhibit a higher stockpiling propensity, retailers are subject to an increased demand variation between regular and promotional periods, exposing themselves to a higher stockout risk. Moreover, the increase in demand variation is compounded if retailers adopt a randomly-priced promotion strategy. Consequently, a high-low promotion strategy coupled with greater stockpiling propensity requires more safety stock inventory during times of environmental stress due to economic downturns. The second essay explores how retail operations performance varies in the face of consumer stockpiling behavior utilizing hurricanes as a natural experiment. The essay shows that supply-side characteristics (retail network and product variety), demand-side characteristics (hurricane experience and household income), and disaster-side characteristics (hazard proximity and hazard intensity) significantly affect consumer stockpiling propensity as the hurricane approaches. Further, increased consumer stockpiling propensity has an immediate and persistent impact on retail operations, such as higher product availability before hurricanes and lower product availability after hurricanes. Note that this impact depends on store formats. This study suggests retailers need to carefully monitor factors affecting consumer stockpiling behavior during natural disasters. This would allow retailers to better manage their inventories and increase their ability to fulfill consumer demand. The third essay studies the interaction of logistics IT resources, organizational factors, and operating performance. The previous typology of logistics IT resources is extended into four mid-level constructs: operations-focused IT, decision-focused IT, service-focused IT, and IT development capability. The results show that operations-focused IT, decision-focused IT, and IT development capability is more related to superior operating performance than service-focused IT. Moreover, it is shown that organizational factors, such as firm size, firm age, and firm ownership, may enhance or suppress the effects of logistics IT resources on operational performance. In general, logistics firms should carefully manage IT resources according to their particular organizational environment in order to achieve competitive advantage. The findings for the first two essays contribute to retail operations theory by proposing and testing novel questions about the impact of the presence of consumer stockpiling behavior on retail operations management using natural experiment methodology. The findings for the third essay contribute to business logistics theory by proposing a typology for logistics IT resources and testing hypotheses regarding the impact of logistics IT resources on logistics firms’ operational performance

Adversarial Meta Sampling for Multilingual Low-Resource Speech Recognition

Low-resource automatic speech recognition (ASR) is challenging, as the low-resource target language data cannot well train an ASR model. To solve this issue, meta-learning formulates ASR for each source language into many small ASR tasks and meta-learns a model initialization on all tasks from different source languages to access fast adaptation on unseen target languages. However, for different source languages, the quantity and difficulty vary greatly because of their different data scales and diverse phonological systems, which leads to task-quantity and task-difficulty imbalance issues and thus a failure of multilingual meta-learning ASR (MML-ASR). In this work, we solve this problem by developing a novel adversarial meta sampling (AMS) approach to improve MML-ASR. When sampling tasks in MML-ASR, AMS adaptively determines the task sampling probability for each source language. Specifically, for each source language, if the query loss is large, it means that its tasks are not well sampled to train ASR model in terms of its quantity and difficulty and thus should be sampled more frequently for extra learning. Inspired by this fact, we feed the historical task query loss of all source language domain into a network to learn a task sampling policy for adversarially increasing the current query loss of MML-ASR. Thus, the learnt task sampling policy can master the learning situation of each language and thus predicts good task sampling probability for each language for more effective learning. Finally, experiment results on two multilingual datasets show significant performance improvement when applying our AMS on MML-ASR, and also demonstrate the applicability of AMS to other low-resource speech tasks and transfer learning ASR approaches.Comment: accepted in AAAI202

Fibroblast Growth Factor-10 (FGF-10) Mobilizes Lung-resident Mesenchymal Stem Cells and Protects Against Acute Lung Injury.

FGF-10 can prevent or reduce lung specific inflammation due to traumatic or infectious lung injury. However, the exact mechanisms are poorly characterized. Additionally, the effect of FGF-10 on lung-resident mesenchymal stem cells (LR-MSCs) has not been studied. To better characterize the effect of FGF-10 on LR-MSCs, FGF-10 was intratracheally delivered into the lungs of rats. Three days after instillation, bronchoalveolar lavage was performed and plastic-adherent cells were cultured, characterized and then delivered therapeutically to rats after LPS intratracheal instillation. Immunophenotyping analysis of FGF-10 mobilized and cultured cells revealed expression of the MSC markers CD29, CD73, CD90, and CD105, and the absence of the hematopoietic lineage markers CD34 and CD45. Multipotency of these cells was demonstrated by their capacity to differentiate into osteocytes, adipocytes, and chondrocytes. Delivery of LR-MSCs into the lungs after LPS injury reduced the inflammatory response as evidenced by decreased wet-to-dry ratio, reduced neutrophil and leukocyte recruitment and decreased inflammatory cytokines compared to control rats. Lastly, direct delivery of FGF-10 in the lungs of rats led to an increase of LR-MSCs in the treated lungs, suggesting that the protective effect of FGF-10 might be mediated, in part, by the mobilization of LR-MSCs in lungs

A virus-like particle of the hepatitis B virus preS antigen elicits robust neutralizing antibodies and T cell responses in mice

The preS antigen of hepatitis B virus (HBV) corresponds to the N-terminal polypeptide in the large (L) antigen in addition to the small (S) antigen. The virus-like particle (VLP) of the S antigen is widely used as a vaccine to protect the population from HBV infection. The presence of the S antigen and its antibodies in patient blood has been used as markers to monitor hepatitis B. However, there is very limited knowledge about the preS antigen. We generated a preS VLP that is formed by a chimeric protein between preS and hemagglutinin (HA), and the matrix protein M1 of influenza virus. The HBV preS antigen is displayed on the surface of preS VLP. Asn112 and Ser98 of preS in VLP were found to be glycosylated and O-glycosylation of Ser98 has not been reported previously. The preS VLP shows a significantly higher immunogenicity than recombinant preS, eliciting robust anti-preS neutralizing antibodies. In addition, preS VLP is also capable of stimulating preS-specific CD8+ and CD4+ T cell responses in Balb/c mice and HBV transgenic mice. Furthermore, preS VLP immunization provided protection against hydrodynamic transfection of HBV DNA in mice. The data clearly suggest that this novel preS VLP could elicit robust immune responses to the HBV antigen, and can be potentially developed into prophylactic and therapeutic vaccines

IconQA: A New Benchmark for Abstract Diagram Understanding and Visual Language Reasoning

Current visual question answering (VQA) tasks mainly consider answering human-annotated questions for natural images. However, aside from natural images, abstract diagrams with semantic richness are still understudied in visual understanding and reasoning research. In this work, we introduce a new challenge of Icon Question Answering (IconQA) with the goal of answering a question in an icon image context. We release IconQA, a large-scale dataset that consists of 107,439 questions and three sub-tasks: multi-image-choice, multi-text-choice, and filling-in-the-blank. The IconQA dataset is inspired by real-world diagram word problems that highlight the importance of abstract diagram understanding and comprehensive cognitive reasoning. Thus, IconQA requires not only perception skills like object recognition and text understanding, but also diverse cognitive reasoning skills, such as geometric reasoning, commonsense reasoning, and arithmetic reasoning. To facilitate potential IconQA models to learn semantic representations for icon images, we further release an icon dataset Icon645 which contains 645,687 colored icons on 377 classes. We conduct extensive user studies and blind experiments and reproduce a wide range of advanced VQA methods to benchmark the IconQA task. Also, we develop a strong IconQA baseline Patch-TRM that applies a pyramid cross-modal Transformer with input diagram embeddings pre-trained on the icon dataset. IconQA and Icon645 are available at https://iconqa.github.io.Comment: Corrected typos. Accepted to NeurIPS 2021, 27 pages, 18 figures. Data and code are available at https://iconqa.github.i

In vivo evaluation of additively manufactured multi-layered scaffold for the repair of large osteochondral defects

The repair of osteochondral defects is one of the major clinical challenges in orthopaedics. Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defects. However, less success has been achieved for the regeneration of large defects, which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the tissue. In this study, we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion techniques. The developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen “sandwich” composite system. The microstructure and mechanical properties of the scaffold were examined, and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle model. The 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen–HAp scaffold, and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage, as demonstrated by hyaline-like cartilage formation. The histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control group. Chondrogenic genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control group. The findings showed the safety and efficacy of the cell-free “translation-ready” osteochondral scaffold, which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects

Post-marketing safety surveillance of dalfampridine for multiple sclerosis using FDA adverse event reporting system

Objective: To investigate and analyze the post-marketing adverse event (AE) data of multiple sclerosis (MS) therapeutic drug dalfampridine using the US Food and Drug Administration Adverse Event Reporting System (FAERS) for its clinical safety application.Methods: Use OpenVigil2.1 platform to obtain AE data of dalfampridine from FAERS from February 2010 to September 2022. Match “adverse drug reaction” with preferred term (PT) and system organ class (SOC) according to the Medical Dictionary for Regulatory Activities (MedDRA), then merge the same PT and delete non-AE PT. Positive signals were identified by the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) methods. When AE signals met the criteria of those three methods, they were identified as positive signals.Results: A total of 44,092 dalfampridine-related AE reports were obtained, and 335 AE signals were identified, including 11,889 AE reports. AEs were more common in females and in the 45–65 age group, which is consistent with the epidemiological characteristics of MS. The 335 AE signals involved 21 SOCs, including investigations, infections and infestations, eye disorders, etc. Among the top 20 PTs in signal strength, 10 were associated with abnormal lymphocyte percentage and count, and 5 were associated with abnormal urine tests, some of which were not described in the instruction, such as spinal cord injury cauda equina, haemoglobin urine present, urinary sediment abnormal and so on. The most frequently reported AE signals were urinary tract infection, dizziness, condition aggravated. In addition, 23 AE signals with death outcomes were identified, with an incidence of less than 0.1%.Conclusion: Data mining of FAERS was conducted to analyze the AEs of dalfampridine, and new AE signals were found. This study provides a reference for the safe use of dalfampridine in the treatment of MS

Celastrol targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent cytotoxicity in tumor cells

<p>Abstract</p> <p>Background</p> <p>Celastrol is an active ingredient of the traditional Chinese medicinal plant <it>Tripterygium Wilfordii</it>, which exhibits significant antitumor activity in different cancer models <it>in vitro </it>and <it>in vivo</it>; however, the lack of information on the target and mechanism of action of this compound have impeded its clinical application. In this study, we sought to determine the mode of action of celastrol by focusing on the processes that mediate its anticancer activity.</p> <p>Methods</p> <p>The downregulation of heat shock protein 90 (HSP90) client proteins, phosphorylation of c-Jun NH2-terminal kinase (JNK), and cleavage of PARP, caspase 9 and caspase 3 were detected by western blotting. The accumulation of reactive oxygen species (ROS) was analyzed by flow cytometry and fluorescence microscopy. Cell cycle progression, mitochondrial membrane potential (MMP) and apoptosis were determined by flow cytometry. Absorption spectroscopy was used to determine the activity of mitochondrial respiratory chain (MRC) complexes.</p> <p>Results</p> <p>Celastrol induced ROS accumulation, G2-M phase blockage, apoptosis and necrosis in H1299 and HepG2 cells in a dose-dependent manner. N-acetylcysteine (NAC), an antioxidative agent, inhibited celastrol-induced ROS accumulation and cytotoxicity. JNK phosphorylation induced by celastrol was suppressed by NAC and JNK inhibitor SP600125 (SP). Moreover, SP significantly inhibited celastrol-induced loss of MMP, cleavage of PARP, caspase 9 and caspase 3, mitochondrial translocation of Bad, cytoplasmic release of cytochrome c, and cell death. However, SP did not inhibit celastrol-induced ROS accumulation. Celastrol downregulated HSP90 client proteins but did not disrupt the interaction between HSP90 and cdc37. NAC completely inhibited celastrol-induced decrease of HSP90 client proteins, catalase and thioredoxin. The activity of MRC complex I was completely inhibited in H1299 cells treated with 6 μM celastrol in the absence and presence of NAC. Moreover, the inhibition of MRC complex I activity preceded ROS accumulation in H1299 cells after celastrol treatment.</p> <p>Conclusion</p> <p>We identified ROS as the key intermediate for celastrol-induced cytotoxicity. JNK was activated by celastrol-induced ROS accumulation and then initiated mitochondrial-mediated apoptosis. Celastrol induced the downregulation of HSP90 client proteins through ROS accumulation and facilitated ROS accumulation by inhibiting MRC complex I activity. These results identify a novel target for celastrol-induced anticancer activity and define its mode of action.</p