The Effect of the Elevated Circulating Levels of IL-33 on Metastasis of Colorectal Cancer

In the United States, colorectal cancer is the third leading cause of cancer-related deaths in both men and women1. The pathogenesis of colorectal cancer begins with the development of polyps in the innermost colorectal lining and progresses to the final stage when metastasis occurs2. Metastasis is the spread of cancer cells to other organs, and has been shown to be organ specific rather than a random process. Genes that direct tumor cells to target specific organs have been identified. The primary tumor is thought to secrete molecules that promote the establishment of liver metastasis even before the arrival of cancer cells into this organ. We have previously isolated a highly liver metastatic cell line, CT26-FL3 by in vivo selection of CT26 cells in balb/c mice. Microarray analyses showed that the CT26-FL3 cells expressed 34-fold higher levels of the Interleukin-33 (IL-33) cytokine as compared to the parental and less metastatic CT26 cells. Over-expression of IL-33 was shown to potently promote tumor proliferation and metastasis to the liver5 indicating that IL-33 plays a crucial role in the pathogenesis of colon cancer. In this study, we will use C57Bl/6 mice and the murine colon cancer cell line, MC38, to increase circulating serum levels of IL-33 using a gene therapy approach by in vivo electroporation of a plasmid expressing IL-33, pV1J-IL33. We hypothesized that the increased secretion of IL-33 in MC38 tumor cells will increase cell metastasis to the liver, and that increasing circulating levels of IL-33 in mice bearing MC38 tumors will be sufficient to enhance its ability to metastasize to the liver. Here we report the construction of plasmids expressing IL-33 and verification of the expression of IL-33 from these plasmids in transfected cells by Western Blot analyses. We also discuss the introduction of pV1J-IL-33 into C57Bl/6 mice by quadriceps injections and in vivo electroporation. Lastly, we report ELISA assays on mouse sera after splenic injections of MC38 tumor cells to determine the levels of secreted IL-33 and how long the IL-33 levels stayed up regulated after in vivo electroporation. We concluded that the elevated serum levels of IL-33 increased tumor proliferation and their ability to metastasize to the liver in C57Bl/6 mice

HOW KNOWLEDGE MANAGEMENT INTENTION INFLUENCED BY ORGANIZATIONAL CULTURE AND KNOWLEDGE MANAGEMENT CULTURE

In the current knowledge economy era, knowledge has become an organization’s primary resource due to the fact that an organization is an extension of an information society. Therefore, firms that are able to effectively manage their knowledge resources can expect to reap a wide range of benefits. Due to the diversity of organizational culture (which include results-oriented, tightly controlled, job-oriented, closed system, solidarity, sociability and need for achievement), a significant issue is the way organizational culture impacts on KM intention in the KM process through the mediation of KM culture. Indeed, strong culture has a direct impact on KM culture and KM intention. This paper details our study findings, which indicate that while results-oriented, solidarity, sociability and strong cultures have significant positive effects on an organization’s ability to foster a KM culture in the KM process, a job-oriented culture has a significant negative effect. Moreover, both KM culture and strong culture have positive direct effects on an individual’s intention to manage knowledge. Also discussed in this paper are the implications of the study and its contribution to research and management practice

Career Anchors, National Culture and Leave Intent of MIS Professionals in Taiwan

This study focuses on the career anchors of MIS professionals and adopts the well-established career theory, Schein\u27s Career Anchors, as the fundamental theory in this study. The present paper attempts to investigate the relationship between career anchors and leave intent of MIS professionals in Taiwan. The study adds the cultural construct, Chinese Relationalism, into its research model, in order to comprehend the role of Chinese Relationalism in the context of the career anchor model. Three career anchors: technical competence, autonomy, and entrepreneurship, have direct (negative or positive) and significant impacts on the intents of MIS professionals to leave their employment. This study establishes that Chinese Relationalism impacts on the technical competence, geographical security, identity, lifestyle, and various career anchors of MIS professionals and also moderates the relationships between autonomy, entrepreneurship and the leave intent of MIS professionals in Taiwan

Route Exploration and Synthesis of The Reported Pyridone-Based PDI Inhibitor STK076545

The enzyme protein disulfide isomerase (PDI) is essential for the correct folding of proteins and the activation of certain cell surface receptors, and is a promising target for the treatment of cancer and thrombotic conditions. A previous high-throughput screen identified the commercial compound STK076545 as a promising PDI inhibitor. To confirm its activity and support further biological studies, a resynthesis was pursued of the reported β-keto-amide with an N-alkylated pyridone at the α-position. Numerous conventional approaches were complicated by undesired fragmentations or rearrangements. However, a successful 5-step synthetic route was achieved using an aldol reaction with an α-pyridone allyl ester as a key step. An X-ray crystal structure of the final compound confirmed that the reported structure of STK076545 was achieved, however its lack of PDI activity and inconsistent spectral data suggest that the commercial structure was misassigned

Contexts can be Cheap: Solving Stochastic Contextual Bandits with Linear Bandit Algorithms

In this paper, we address the stochastic contextual linear bandit problem, where a decision maker is provided a context (a random set of actions drawn from a distribution). The expected reward of each action is specified by the inner product of the action and an unknown parameter. The goal is to design an algorithm that learns to play as close as possible to the unknown optimal policy after a number of action plays. This problem is considered more challenging than the linear bandit problem, which can be viewed as a contextual bandit problem with a \emph{fixed} context. Surprisingly, in this paper, we show that the stochastic contextual problem can be solved as if it is a linear bandit problem. In particular, we establish a novel reduction framework that converts every stochastic contextual linear bandit instance to a linear bandit instance, when the context distribution is known. When the context distribution is unknown, we establish an algorithm that reduces the stochastic contextual instance to a sequence of linear bandit instances with small misspecifications and achieves nearly the same worst-case regret bound as the algorithm that solves the misspecified linear bandit instances. As a consequence, our results imply a $O(d\sqrt{T\log T})$ high-probability regret bound for contextual linear bandits, making progress in resolving an open problem in (Li et al., 2019), (Li et al., 2021). Our reduction framework opens up a new way to approach stochastic contextual linear bandit problems, and enables improved regret bounds in a number of instances including the batch setting, contextual bandits with misspecifications, contextual bandits with sparse unknown parameters, and contextual bandits with adversarial corruption

Ancient pigs reveal a near-complete genomic turnover following their introduction to Europe

Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process