Downstream Aspects Research Articles

Some of the Understudied Dimensions of Ritual

Ritual: How Seemingly Senseless Acts Make Life Worth Living by Dimitris Xygalatas offers a popularized accounting of an adaptationist view of ritual. By highlighting the author’s own work on the topic, the text itself primarily addresses questions of public rituals’ often extreme costs and its relationship to cooperation. This emphasis, though, comes at the expense of other interesting and/or downstream aspects of ritual that, in my view, deserve more attention. In this commentary, I address a handful of the most relevant to the target text, namely: 1) religious vs. secular rituals; 2) the spatio-temporal distribution of ritual; 3) ritual frequency and timing; 4) the demographic structuring of ritual; 5) ritual’s complicated relationship to control and chance; and 6) ritual as a significant generator of meaningful models about the world.

Competitiveness Improvement Strategies of Msme Blora Batik: Analytic Network Process Approach

Purpose: This study aims to develop strategic priorities for increasing the competitiveness of Batik SMEs in Blora Regency Theoretical Framework: Previous research in the field of company competitive advantage argued what approach is suitable to be used by MSME to grow sustainably. Sustainability of a company 's competitive advantage is influenced by the potential of existing resources (Grant, 1991). Design/Methodology/Approach: This research was conducted in Blora Regency, Central Java, which is one of the regions in Indonesia that is rich in culture and local wisdom. Like other areas in Central Java, Blora has batik as a traditional craft which is quite popular. Until now, the Blora Regency Government continues to develop the sustainability of Blora batik through empowerment programs. The data analysis method used in this research is the Analytic Network Process (ANP) which is a mathematical theory that allows decision making to deal with interrelated factors (dependence) and mathematical feedback. Findings: The findings in this study indicate that Batik Blora is a business unit that has the potential to develop and be competitive with various advantages. As a product that elevates regional advantages, it is necessary to increase business aspects that include upstream to downstream aspects so that the competitiveness of Blora batik can continue to increase. Research, Practical & Social Implications: The most prioritized aspect in increasing the competitiveness of Blora batik is the aspect of the business cycle which emphasizes increasing innovation and diversification as well as increasing business productivity. Originality/Value: This research is a research that focuses on the development strategy of Batik MSMEs with the ANP approach which has never been done before.

Competitiveness Improvement Strategies of Msme Blora Batik: Analytic Network Process Approach

Purpose: This study aims to develop strategic priorities for increasing the competitiveness of Batik SMEs in Blora Regency Theoretical Framework: Previous research in the field of company competitive advantage argued what approach is suitable to be used by MSME to grow sustainably. Sustainability of a company 's competitive advantage is influenced by the potential of existing resources (Grant, 1991). Design/Methodology/Approach: This research was conducted in Blora Regency, Central Java, which is one of the regions in Indonesia that is rich in culture and local wisdom. Like other areas in Central Java, Blora has batik as a traditional craft which is quite popular. Until now, the Blora Regency Government continues to develop the sustainability of Blora batik through empowerment programs. The data analysis method used in this research is the Analytic Network Process (ANP) which is a mathematical theory that allows decision making to deal with interrelated factors (dependence) and mathematical feedback. Findings: The findings in this study indicate that Batik Blora is a business unit that has the potential to develop and be competitive with various advantages. As a product that elevates regional advantages, it is necessary to increase business aspects that include upstream to downstream aspects so that the competitiveness of Blora batik can continue to increase. Research, Practical & Social Implications: The most prioritized aspect in increasing the competitiveness of Blora batik is the aspect of the business cycle which emphasizes increasing innovation and diversification as well as increasing business productivity. Originality/Value: This research is a research that focuses on the development strategy of Batik MSMEs with the ANP approach which has never been done before.

Hemophagocytic lymphohistiocytosis: A disorder of T cell activation, immune regulation, and distinctive immunopathology.

Hemophagocytic lymphohistiocytosis (HLH) is a disorder that has been recognized since the middle of the last century. In recent decades, increasing understanding of the genetic roots and pathophysiology of HLH has led to improved diagnosis and treatment of this once universally fatal disorder. HLH is best conceptualized as a maladaptive state of excessive T cell activation driving life-threatening myeloid cell activation, largely via interferon-gamma (IFN-γ). In familial forms of HLH (F-HLH), inherited defects of lymphocyte cytotoxic biology underlie excessive T cell activation, demonstrating the importance of the perforin/granzyme pathway as a negative feedback loop limiting acute T cell activation in response to environmental factors. HLH occurring in other contexts and without apparent inherited genetic predisposition remains poorly understood, though it may share some downstream aspects of pathophysiology including excessive IFN-γ action and activation of innate immune effectors. Iatrogenic forms of HLH occurring after immune-activating therapies for cancer are providing new insights into the potential toxicities of inadequately controlled T cell activation. Diagnosing HLH increasingly relies on context-specific measures of T cell activation, IFN-γ activity, and inflammation. Treatment of HLH largely relies on cytotoxic chemotherapy, though targeted therapies against T cells, IFN-γ, and other cytokines are increasingly utilized.

Disaster Management of Flood and Retaintion Techniques

Abstract: The most frequent and destructive type of natural disaster, floods annually have an impact on the lives of tens of millions of people all over the world. Climate change and increased climate variability were predicted to result in more frequent and intense floods in the past. Growing demands for channels are being made in order to reduce severe rural flooding by effecting a significant amount of additional storm runoff. This investigation intends to assess how well a deep channel device proposed for Kolhapur’s historic centre will reduce flooding. In order to lessen the devastating effects of floods and regularly make the area more flood-proof, we will lower the flood force at the downstream aspect by providing a suitable channel of a specified sort of size.

Targeting social connection in the context of Trauma: Functional outcomes and mechanisms of change

The current study presents and preliminarily tests a brief, theory driven intervention designed to target social connectivity as a transdiagnostic mechanism of health. We tested four hypotheses to examine whether and how explicitly targeting social behavior engagement (activating values-led behaviors towards specific network members) may improve other downstream aspects of social connectivity (i.e., social cognitions measured as loneliness, interpersonal closeness, perceived social support) and functioning (quality of life [QOL] and posttraumatic stress symptoms [PTS]). Methods. Participants included 15 patients (10 veterans, 5 firefighters) who completed the six-session intervention. Demographics: age (M = 46, SD = 17), 87% male, race (80% Caucasian, 20% Hispanic), 60% married/partnered, 47% living alone. Our multi-analytic approach included parametric and non-parametric tests: (a) significance testing and effect sizes to examine whether variables of interest changed, and (b) Granger causality analysis of repeated measures to examine the mechanistic theory of change (does social behavior engagement lead to improved social cognition and functioning?). Results. Statistically significant, medium-large effect size improvements were shown for QOL (Cohens d = 1.05), PTS (d = 1.05), social behavior engagement (d = 0.78), and several social cognitions (loneliness, d = 0.80, interpersonal closeness, d = 0.53). Models accounted for medium-large variance explained in improved QOL (R2 = 0.47, 95% CI [0.00,0.66]) and PTS (R2 = 0.56, 95% CI[0.07,0.72]). The theory of change was supported, with increase in social behaviors preceding improvement in social cognitions (not vice-versa). Conclusions. Improving social connectivity is a mechanism for improving QOL and mental health. Focus on initiating values-driven social behaviors may be an efficient and effective entry point to stimulate change.

Policies and Strategies for Improving the Research and Scientific Publications Quality at State Islamic Religious Colleges in Kalimantan

The quality of research and scientific publications is an essential concern in managing higher education institutions. Therefore, this research aims to examine the policies and strategies for enhancing the quality of research and scientific publications in State Islamic Religious Colleges. This is a qualitative study that gathers data from library and field research. The findings show that each university already has regulations based on provisions from the Ministry of Higher Education, including the Internal Quality Assurance System (SPMI) and External Quality Assurance System (SPME), for managing research quality. Additionally, UIN Antasari Banjarmasin, UIN Samarinda, and IAIN Palangkaraya are improving the quality of research and scientific publications of their lecturers with policies such as allocating 30% of BOPTN funds and implementing the LITAPDIMAS system. However, the outputs and benefits of these policies have not been fully realized due to budget absorption issues that limit the development of a research and publication culture. Therefore, developing such a culture presents a significant challenge that requires a long-term commitment and the participation of all stakeholders. The culture-building process should start from upstream to downstream aspects.

A Novel Metric for Assessing National Strength in Scientific Research: Understanding China's Research Output in Quantum Technology through Collaboration

Abstract Purpose The 5th Plenary Session of the 19th Communist Party of China (CPC) Central Committee clearly states that developing science and technology through self-reliance and self-strengthening provides the strategic underpinning for China's development. Based on this background, this paper explores a metric model for assessing national scientific research strength through collaboration on research papers. Design/methodology/approach We propose a novel metric model for assessing national scientific research strength, which sets two indicators, national scientific self-reliance (SR) and national academic contribution (CT), to reflect “self-reliance” and “self-strengthening” respectively. Taking the research papers in quantum technology as an example, this study analyzes the scientific research strength of various countries around the world, especially China in quantum technology. Findings The results show that the research of quantum technology in China has always been relatively independent with fewer international collaboration papers and located in a more marginal position in cooperation networks. China's academic contribution (CT) to global quantum technology research is increasing and has been greater than that of the United States in 2020. Combining the two indicators, CT and SR, China's research strength in the quantum field closely follows the United States, and the United States is the most powerful with high research autonomy. Research limitations This paper only reflects China's scientific research strength in quantum technology from collaboration on research papers and doesn’t consider the segmentation of quantum technology and the industrial upstream and downstream aspects, which need further study. Practical implications The model is helpful to better understand the national scientific research strength in a certain field from “self-reliance” and “self-strengthening”. Originality/value We propose a novel metric model to measure the national scientific research strength from the perspective of “self-reliance” and “self-strengthening”, which provides a solid basis for the assessment of the strength level of scientific research in countries/regions and institutions.

Progress on Conventional and Advanced Techniques of In Situ Transesterification of Microalgae Lipids for Biodiesel Production

Global warming and the depletion of fossil fuels have spurred many efforts in the quest for finding renewable, alternative sources of fuels, such as biodiesel. Due to its auxiliary functions in areas such as carbon dioxide sequestration and wastewater treatment, the potential of microalgae as a feedstock for biodiesel production has attracted a lot of attention from researchers all over the world. Major improvements have been made from the upstream to the downstream aspects related to microalgae processing. One of the main concerns is the high cost associated with the production of biodiesel from microalgae, which includes drying of the biomass and the subsequent lipid extraction. These two processes can be circumvented by applying direct or in situ transesterification of the wet microalgae biomass, hence substantially reducing the cost. In situ transesterification is considered as a significant improvement to commercially produce biodiesel from microalgae. This review covers the methods used to extract lipids from microalgae and various in situ transesterification methods, focusing on recent developments related to the process. Nevertheless, more studies need to be conducted to further enhance the discussed in situ transesterification methods before implementing them on a commercial scale.

Recent Developments in the Downstream Processing of Phycobiliproteins from Algae: A Review

Algae (both micro and macro) have gained huge attention in the recent past for their high commercial value products. They are the source of various biomolecules of commercial applications ranging from nutraceuticals to fuels. Phycobiliproteins are one such high-value low volume compounds that are mainly obtained from micro and macroalgae. In order to tap the bioresource, a significant amount of work has been carried out for large scale production of algal biomass. However, work on downstream processing aspects of phycobiliproteins (PBPs) from algae is scarce, especially in the case of macroalgae. There are many difficulties in cell wall disruption of both micro and macro algae because of their cell wall structure and compositions. At the same time, there are several challenges in the purification of phycobiliproteins. The current review article focuses on the recent developments in downstream processing of phycobiliproteins (mainly phycocyanins and phycoerythrins) from micro and macroalgae. The current status, recent advancements and potential technologies (that are under development) are summarised in this review article besides providing future directions for the present research area.

Mechanism and Prevention of Ototoxicity Induced by Aminoglycosides.

Aminoglycosides, a class of clinically important drugs, are widely used worldwide against gram-negative bacterial infections. However, there is growing evidence that aminoglycosides can cause hearing loss or balance problems. In this article, we mainly introduce the main mechanism of ototoxicity induced by aminoglycosides. Genetic analysis showed that the susceptibility of aminoglycosides was attributable to mutations in mtDNA, especially A1555G and C1494T mutations in 12S rRNA. In addition, the overexpression of NMDA receptors and the formation of free radicals also play an important role. Understanding the mechanism of ototoxicity induced by aminoglycosides is helpful to develop new therapeutic methods to protect hearing. In this article, the prevention methods of ototoxicity induced by aminoglycosides were introduced from the upstream and downstream aspects.

Strategy and Policy on Dairy Cattle Development in Areas Outside Java Island in Supporting Domestic Fresh Milk Production

<p>Production of domestic fresh milk has not yet meet the national milk demand, so high amount of milk is still imported (88.56%). The distribution of the dairy cattle population is still concentrated in Java Island (98.84%) which already has limited available land resources. The low productivity of dairy cow is due to the decline in the quality of breed, limited feed and capital. The business scale majority is still low, although its institutional aspect has been well established with the existence of cooperatives and the milk processing industry. This paper discusses the strategies and policies for developing dairy cows in areas outside Java which are appropriate from the upstream to the downstream aspects. The development of dairy cows in areas outside Java Island is still slow, even experiencing a population decline in the last 4 years by 66.21% compared to that in Java that has an increase of 22.09%. Barriers include weak human resource factors, lack of availability of feed (forages and concentrates), low milk productivity and quality, and the production market which is the main thing in dairy business has not been developed. There were many obstacles encountered when dairy cow development program in areas outside Java island was established. Therefore, it requires strategies and policies as well as steps that must be carried out on target. There are several things that need to be done, namely selecting the location, procuring the right breed, training the human resources (target breeders), planting forage and making concentrates, and the main thing is institutional development (upstream to downstream), especially institutions for milk production and marketing. Routine assistance by related agencies and other institutions is needed to ensure the sustainability of dairy farming outside Java.</p>

Latent structure of health literacy and its association with health-related management and decision-making in HIV

Objective Determine the latent structure of health literacy in persons living with HIV (PLWH) and its association with health management and decision-making. Method: Participants included 220 PLWH and 123 seronegative participants from Southern California and Alabama who completed a battery of well-validated health literacy measures, along with assessments of health management self-efficacy, health-related decision-making, depression, and basic clinical laboratory measures. Results: Exploratory factor analysis in HIV − participants showed that the shared variance between a battery of health literacy measures, including health word reading, verbal comprehension, numeracy, and self-reported problems was best explained by a single factor. Similarly, a confirmatory factor analysis in PLWH also supported a single factor structure, but for a re-specified four-test solution based on the core performance-based measures of health literacy. In analyses adjusting for demographics, PLWH demonstrated significantly lower health literacy composite scores as compared to their HIV − counterparts. Among PLWH, lower health literacy was independently associated with lower self-efficacy for health management and poorer health-related decision-making. Conclusions: Findings suggest that numeracy, word recognition, and verbal comprehension and reasoning comprise a unitary construct of health literacy that is lower in PLWH as compared to seronegatives and is independently associated with important downstream aspects of health management and decision-making.

Sustainability assessment of bioenergy at different scales: An emergy analysis of biogas power production

The purpose of this work is to present the application of Emergy Analysis to a biogas power plant , with the aim at assessing its integrated sustainability and studying how the emergy indicators of sustainability depend on the boundary selection. The object of the analysis is a biogas power plant fed on agriculture and zootechnical biomass. The complex interaction of the involved subsystems and the exchange of resource flows require powerful integrated analyses as well as the definition of reliable performance indicators. Emergy Analysis has been addressed as specifically useful to integrate the upstream and the downstream aspects along with the potential circularity of resource flows, providing in this way a quantitative estimation of the sustainability performance of the systems. The analysis was applied at two scales: the Reference System (biogas power plant plus the agricultural cultivations) and the Expanded System, which includes also the cattle breeding, whose main purpose is meat and milk production, but which provides the liquid cattle manure for the Reference System operation. The main emergy indicators have been calculated and reported: for the Reference System, the transformity of produced electricity results similar to fossil-based energy production systems; the Emergy Yield Ratio is about 1, showing that the system cannot be considered as an energy source, rather acting like a consumer; the Environmental Loading Ratio is very high, as the local renewable fraction of the resources exploited is very low compared to the non-renewable ones. The expansion of the system analysis allows to study the added value of linking the subsystems agriculture-breeding-energy production, which provide more products and services to the economy than the sole energy. The need of performing sustainability assessment at different scales appears to be presently the main issue in the analyses that should result suitable for the policy-making processes. • A sustainability evaluation is made of a biogas power plant (BPP) by Emergy Analysis. • Two scales are considered: BPP plus agriculture, and BPP plus agriculture and cattle breeding. • Emergy indicators show that the system acts more as a consumer than an energy source. • BPP efficiency is insufficient to make it competitive with fossil fuel-based power generation. • Improvements require to reduce the dependence of agriculture and livestock on fossil fuels.

Optimization of Cassava-Based Non Rice Food Development Using Funds Stimulation of Qardhul-Hasan Transactions

This research activity was done holistically from beginning to end, starting from 3 rd Level of Readiness Technology (TKT + 3) to downstream dominance level. The research objective was to optimize the implementation of Social Engineering Copyright (RS-JGTS) and implementation of TTG-Ts+ in order to realize an independent and sustainable cassava-based food fulfilment center. It used Participatory Action Research (PAR) method to facilitate and motivate the community (producer farmers) to create self-sufficiency food. The strategy to conduct action research was based on O'Brien (2002). The supporting facilities for nutritional analysis in TS + morphology were from the laboratory of life sciences center (LSIH) and simulation analysis. The research results showed that upstream aspects:the implementationof Social Engineering Copyright Cassava Planting Movement Group-(JGTS) in sustainable cassava farming business as a mediumto develop sustainability of cassava raw materials was done with qardhul-hasan transactions facility for costs production through partnership with producers farmers through stimulant fund of qardhul-hasan for production cost with share instalment was done through agreement of cassava; downstream aspect; the implementation of copyright appropriate technology for cassava flour PLUS (TTG Ts +), to realize processed products of dry cassava, cassava flour and mocaf flour. The next was the agreement of cassava-based fast food creation for cassava noodles, onde-onde , and others. The technological readiness (TKT) was at 3-4 level, therefore it need further research in order to increase TKT at a higher level to becomes more optimal.

MiR-147b-modulated expression of vestigial regulates wing development in the bird cherry-oat aphid Rhopalosiphum padi

BackgroundMost aphids exhibit wing polyphenism in which wingless and winged morphs produce depending on the population density and host plant quality. Although the influence of environmental factors on wing polyphenism of aphids have been extensively investigated, molecular mechanisms underlining morph differentiation (i.e. wing development /degeneration), one downstream aspect of the wing polyphenism, has been poorly understood.ResultsWe examined the expression levels of the twenty genes involved in wing development network, and only vestigial (vg) showed significantly different expression levels in both whole-body and wall-body of third instar nymphs, with 5.4- and 16.14- fold higher expression in winged lines compared to wingless lines, respectively in Rhopalosiphum padi. vg expression was higher in winged lines compared to wingless lines in third, fourth instar nymphs and adults. Larger difference expression was observed in third (21.38-fold) and fourth (20.91-fold) instar nymphs relative to adults (3.12-fold). Suppression of vg using RNAi repressed the wing development of third winged morphs. Furthermore, dual luciferase reporter assay revealed that the miR-147 can target the vg mRNA. Modulation of miR-147b levels by microinjection of its agomir (mimic) decreased vg expression levels and repressed wing development.ConclusionsOur findings suggest that vg is essential for wing development in R. padi and that miR-147b modulates its expression.

A Method for Harmonic Power Tracing by Using Upstream and Downstream Distribution Matrices

In this paper, an algorithm to find the harmonic power flow path for every generator and demand is proposed. In the proposed algorithm, the exact knowledge of harmonic power values is not required to determine the path. Our approach is based on Bialek’s tracing method, which specifies the contribution of each nodal generation/demand in power flow of a particular line. Our approach is faster than Bialek’s method in terms of computation due to the fact that upstream and downstream distribution matrices as well as nodal demand and generation matrices have a much simpler structure. Our method resolves electricity tracing for harmonic problems in both upstream and downstream aspects, resulting in two sets of answers: one for the harmonic power flow path of generator nodes and the other for that of demand nodes. To illustrate our algorithm, a step-by-step solution to a sample case study is provided here using the proposed algorithm. To verify our method, the results of our algorithm for a sample 5-bus power network and the IEEE 14-bus test system are compared to those of Bialek’s method. Finally, the proposed method is applied for harmonic frequency and used to find the path of harmonic power flow in a network.

Inequality in the Indian Water Sector: Challenges and Policy Options

Utilizing illustrative examples based on empirical data, this article attempts to provide an indicative assessment of the growing magnitude of inequality in access to water in India. This assessment was made within an analytical framework that highlights variations across water-using sectors such as rural agriculture and urban, as well as across different sources of water such as groundwater, surface water and others. The dimensions of inequality analysed include: inequality in access to common pool groundwater resources (both inter-generational and intra-generational inequality); inequality caused by monopolistic groundwater markets; inequality in access to common property water from river catchments; inequality in access to subsidized water from public irrigation schemes; and inequality in access to water from municipal water supply systems. The article also discusses the role of major factors which contribute to the inequality in the access to water in different contexts, such as lack of well-defined water use rights, inequality in the ownership of land and other rural assets, spatial and topographical issues such as tail-end and downstream aspects, ineffective water and energy pricing policies, inadequate or poorly designed infrastructure and suboptimal water sector investment. The article concludes by providing feasible policy options and possible implementation principles to reduce inequality in access to water across sectors, sources and regions.

Insights into study design and statistical analyses in translational microbiome studies

Research questions in translational microbiome studies are substantially more complex than their counterparts in basic science. Robust study designs with appropriate statistical analysis frameworks are pivotal to the success of these translational studies. This review considers how study designs can account for heterogeneous phenotypes by adopting representative sampling schemes for recruiting the study population and making careful choices about the control population. Advantages and limitations of 16S profiling and whole-genome sequencing, the two primary techniques for measuring the microbiome, are discussed followed by an overview of bioinformatic processing of high-throughput sequencing data from these measurements. Practical insights into the downstream statistical analyses including data processing and integration, variable transformations, and data exploration are provided. The merits of regularization and ensemble modeling for analyzing microbiome data are discussed along with a recommendation for selecting modeling approaches based on data-driven simulations and objective evaluation. The review builds on several recent discussions of study design issues in microbiome research but with a stronger emphasis on the downstream and often-ignored aspects of statistical analyses that are crucial for bridging the gap between basic science and translation.

Abstract B46: EMT-inducing transcription factors Twist1, Snail1 and Six1 increase metastasis of neighboring tumor cells via induction of Hedgehog-Gli signaling

Abstract Breast cancer is the second leading cause of cancer related deaths in women and more than 90% of these deaths result from metastatic disease rather than from the primary tumor burden. Recent studies have shown that intratumoral heterogeneity exists, and can affect chemotherapeutic and as well as metastatic outcome. To determine if crosstalk between metastatic and non-metastatic breast cancer cells can occur in the earlier stages of metastasis, where an epithelial-to-mesenchymal transition (EMT) is thought to occur in a small population of cells within a tumor, allowing them to metastasize, we examined whether different EMT-inducing pro-metastatic transcription factors (TFs) can influence the EMT status and metastatic properties of cells not expressing these factors (control cells). Twist1 and Snail1 are two EMT-inducing TFs that are known to increase metastasis through cell autonomous mechanisms. Our data demonstrate that these TFs can also non-cell autonomously alter the expression of numerous genes and proteins associated with EMT, as well as increase migration and invasion, when conditioned medium (CM) taken from HMLER-Twist1/Snail1 cells is placed on control cells. We show that the non-cell autonomous effects of Twist1 and Snail1 are in part induced via their ability to up-regulate another known EMT-TF, Six1. Loss of Six1 downstream of these TFs mitigates their ability to non-cell autonomously influence migration and invasion of non-metastatic, non-EMT TF expressing cells, indicating that Six1 is a key player downstream of Twist1 and Snail1. In multiple breast cancer models (including the MCF7 and 4t1 series of cell lines), CM taken from cells that overexpress Six1, when placed on control cells, leads to alterations in expression of EMT-related proteins, as well as increased migration and invasion. This does not occur when CM is taken from Six1 knockdown cells, showing that Six1 can non-cell autonomously cause an EMT in the control non-Six1 expressing cells. Using mouse models, we also demonstrate that highly metastatic, Six1 expressing cells can non-cell autonomously increase the metastatic incidence of weakly metastatic, non-Six1 expressing cells. We find that CM taken from cells expressing Twist1, Snail1, and Six1, when placed on control cells, leads to the induction of hedgehog (Hh) signaling as measured by Gli activity in the control recipient cells. Further, we demonstrate that activation of Hh signaling in control cells (when exposed to CM from metastatic-EMT cells) is critical for the induction of EMT-like characteristics. Interestingly, the mechanism of Gli activation in recipient cells differs depending on the EMT-TF expressed by the cells from which the CM is taken; such that upstream inhibitors of the pathway (cyclopamine and 5E1 monoclonal antibody against Hh ligands) only work in specific contexts, whereas more downstream inhibitors targeting Gli1 (Gant61) inhibit the effects in all contexts. These data suggest that EMT-TFs are able to activate the Gli signaling pathway non-cell autonomously via multiple mechanisms. We observe a strong correlation of Twist1, Snail1, and Six1 with Gli1 in numerous breast cancer datasets, whereas such a correlation is not observed with the ligands of Hh signaling, the more upstream activators of the pathway; an indication that the EMT-TFs may be converging in on increasing Gli activity and hence activating the Hh signaling pathway. Our data demonstrate that EMT-TFs, even if expressed in only a percentage of cells within a primary tumor, can increase metastasis of neighboring cells, and further suggest that inhibitors targeting downstream aspects of the Hedgehog pathway, such as Gli1, may be a novel means to target metastatic progression in heterogeneous breast cancers to increase patient survival. Citation Format: Deepika Neelakantan, Hengo Zhou, Joshua Cabrera, Heide Ford. EMT-inducing transcription factors Twist1, Snail1 and Six1 increase metastasis of neighboring tumor cells via induction of Hedgehog-Gli signaling. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr B46.