Generational Shift Research Articles

DDRE-27. METABOLIC SWITCHING AS A MECHANISM OF DRUG RESISTANCE AGAINST NAMPT INHIBITION IN GLIOMAS

Abstract BACKGROUND Gliomas exhibit significant heterogeneity in treatment response and characteristically deploy resistance mechanisms that render conventional therapies ineffective. Recently, novel agents have been developed that target regulators of differential energy pathways specifically utilized by gliomas. We previously reported on the targeting of Nicotinamide Phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the NAD+ salvage pathway and its essential role in glioma cell energy metabolism. Here, we determined the mechanisms by which glioma cells bypass blockade of energy metabolism and develop resistance to NAMPT inhibitors. METHODS Using isogenic parental and drug-resistant patient-derived glioma stem-like cells (GSCs), we examined adaptive changes after NAMPT inhibition in glycolysis, mitochondrial function (oxidative state, basal respiration rate, spare respiratory capacity, maximum respiration capacity and proton leak) and metabolite levels using Agilent Seahorse assay and targeted metabolomics. Cross reactivity across various NAMPT inhibitors was measured using Cell Titer Glo assay. RESULTS GSCs exposed for an extended period to sub-lethal doses of FK866, a potent NAMPT inhibitor, acquired drug resistance to the agent which were also cross-resistant to other NAMPT inhibitors. Drug-resistant GSCs showed a decrease in extracellular acidification rate and oxygen consumption rate compared to isogenic parental lines. Further, metabolomic analysis showed a high accumulation of glutamate, creatine and histidine metabolites in these cells. These results indicate a shift in metabolism of drug-resistant GSCs from carbon metabolism to nitrogen metabolism. CONCLUSIONS GSCs resistant to the NAMPT inhibitor, FK866 showed cross resistance to other NAMPT inhibitors indicating specificity of this effect. The resistance mechanism involves a shift of preferential energy generation from glycolysis to amino acid metabolism which allows the cells to use alternative methods to generate NAD. Additional results from ongoing studies to delineate the mechanisms of metabolic switch in the drug resistance lines will be presented that will help develop strategies to combat resistance to NAMPT inhibitors.

Opportunities and Challenges to Improve a Public Research Program in Plant Breeding and Enhance Underutilized Plant Genetic Resources in the Tropics.

The American tropics are hotspots of wild and domesticated plant biodiversity, which is still underutilized by breeding programs despite being conserved at regional gene banks. The improvement of those programs depends on long-term public funds and the maintenance of specialized staff. Unfortunately, financial ups and downs complicate staff connectivity and their research impact. Between 2000 and 2010, Agrosavia (Corporación Colombiana de Investigación Agropecuaria) dramatically decreased its public financial support. In 2017, we surveyed all 52 researchers from Agrosavia involved in plant breeding and plant genetic resource programs to examine the effect of decimating funds in the last ten years. We hypothesized that the staff dedicated to plant breeding still suffer a strong fragmentation and low connectivity. As we expected, the social network among researchers is weak. The top ten central leaders are predominantly males with an M.Sc. degree but have significant experience in the area. The staff has experience in 31 tropical crops, and 17 are on the list of underutilized species. Moreover, although 26 of these crops are in the national germplasm bank, this has not been the primary source for their breeding programs. We proposed five principles to improve connectivity among teams and research impact: (1) The promotion of internal discussion about gender gaps and generation shifts to design indicators to monitor and decrease this disparity over time. (2) The construction of long-term initiatives and synergies with the Colombian government to support the local production of food security crops independent of market trends. (3) Better collaboration between the National Plant Germplasm Bank and plant breeding researchers. (4) A concerted priority list of species (especially those neglected or underutilized) and external institutions to better focus the collaborative efforts in research using public funds. (5) Better spaces for the design of projects among researchers and training programs in new technologies. These principles could also apply in other tropical countries with public plant breeding research programs facing similar challenges.

Learner-teacher targeted bullying in South African high schools

ABSTRACT Studies about workplace bullying recognise that teaching is becoming a high-risk profession. Despite the global concern about teacher-targeted bullying by learners, a dearth of studies remain regarding the bullying of teachers. This study aims at contributing towards the limited corpus of knowledge on the preponderance of the phenomenon within the South African schooling contexts. A phenomenological research design qualitative method was employed. Nine teachers in grade 12 class completed semi-structured interviews about the bullying of teachers by learners. Findings evince that teachers are bullied in diverse ways. Findings further reveal that generational shift in learner behavioural pattern, learner drug addiction and school violence, too much learner-centred approach policy by the government, poor parental school involvement and inadequate resources in schools are contributory factors for teachers being bullied. The study exposes the resultant effect of bullying on teachers as severe; responsible for stress, emotional distress, isolation, teacher burnout and sometimes attrition from practice. The findings are discussed in the literature. It is concluded that bullying of teachers poses a serious challenge in South African schools; hence, it must be urgently addressed by whatever pragmatic policy to pre-empt domestic violence faced by teachers.

Moving toward health equity: A journey

Moving toward health equity: A journey

Ultrasonic time reversal on defects in carbon fibre reinforced polymer using chirp-coded ultrasound in complex media

Various nonlinear methods have been investigated in recent years offering improvements of over conventional B-mode in medical imaging and non-destructive testing (NDT) [1]. The most common include harmonic and overtone generation, inter-modulation product generation and resonant frequency shift, also known as Nonlinear Elastic Wave Spectroscopy (NEWS) methods. Furthermore, new optimized excitations such as Nonlinear Time Reversal (TR) based methods are needed and, thanks to the analysis of symmetry properties of cross-correlation generated functions, a wide range of innovation are classified within TR-NEWS methods [2]. This work proposes to unite the frequency-modulated constant-wave scatterer localization with TR-NEWS principles to enable the localization of scatterers distant from the transducers and the analysis of their nonclassical nonlinearity which often can be caused by microdamage or cracking. In this paper, using the found frequency of the defect, the delayed TR–NEWS can be leveraged to periodically excite the damaged region with the focused ultrasound. Resonance excitation results show potential for enhancing the wave motion more than a simple focused waves [3]. Thanks to the complexity of the acoustical propagation in a complex medium, the physical interpretation of the cross-correlation function used during the TR-NEWS analysis can be easily understood in terms of the acoustic energy focused in space and in time.

일본의 배외주의에 맞선 재일작가 이용덕(李龍德)의 문학

This paper considers the representation of discrimination and hatred in Lee Yong􋹲 deok's debut novel, “Call me when you want to die”(2014), and thinks about the problem of ‘Hate Speech’ in the recent work “Before You Stab Me with a bamboo spear”(2020). His works criticize the extreme exclusionism of Japan including Zaitokukai(在特会) antagonizing Zainichi Koreans. Lee Yong􋹲deok is a Zainich Korean writer who found the reason for his literature against the exclusionism of Japan. In particular, it is worth noting that “Before You Stab Me With A Bamboo” focuses more on showing various thoughts and different ways of responding to the exclusionism of Japan, rather than on the conflict and confrontation between the Japanese and the Zainichi Koreans. In addition to the main characters who fought against exclusionists or pursued the establishment of ideal community in Korea, there are many characters who show different lives of Zainichi Koreans living in an age of discrimination and hatred. Lee Yong􋹲deok’s literature shows a generational shift in Zainichi Korean literature by creating an independent and active narrative against the extreme and widespread exclusionism of Japan.

Reducing human health impacts from power sector emissions with redispatch and energy storage

Emissions from the power sector significantly contribute to ambient air pollution and its associated adverse human health impacts. In this study, we explore how to cost-effectively reduce health impacts due to fine particulate matter (PM2.5) attributable to power plant emissions by internalizing real-time health costs in plant dispatch decisions and re-optimizing the unit commitment and economic dispatch in light of these impacts. We show that internalizing the time- and location-varying health damage costs into power system operational decisions can reduce 61%–97% of adverse health impacts through decreases in coal generation and strategic shifts in the location and timing of pollutant releases. We also find that adding energy storage to the grid can mitigate health impacts by reducing wind power curtailment. Our findings demonstrate the need to consider temporal and spatial heterogeneity when determining the social cost of emissions.

World Literature, Neoliberalism, and the Culture of Discontent ed. by Sharae Deckard and Stephen Shapiro

Reviewed by: World Literature, Neoliberalism, and the Culture of Discontent ed. by Sharae Deckard and Stephen Shapiro Shahab Nadimi Deckard, Sharae, and Stephen Shapiro, eds. World Literature, Neoliberalism, and the Culture of Discontent. Palgrave Macmillan, 2019. Pp. 269. CDN$166.24 hardcover. As the term neoliberalism, with its lack of unequivocal definition, is applied across diverse contexts, it has become more and more contested over the last few decades. However, financialization, deregulation of markets, privatization of public services, and wealth accumulation through dispossession remain some of the features associated with this concept. Within this context, World Literature, Neoliberalism, and the Culture of Discontent asks two important questions: are the cultural and ideological implications of neoliberalism experienced only in the US and Europe? How does neoliberalism function in a globalized setting? As editors Sharae Deckard and Stephen Shapiro note, the major goal of this collection is to forge a term that best characterizes the distinctive features of the last few decades that also include contexts beyond the Euro-American capitalist model of neoliberalism. The editors ask the reader to think through a broader framework of the capitalist world system within which neoliberalism is situated. The essays in this collection seek to reexamine the historical formulation of the term, periodize different phases of neoliberalism up to the present, and restore capitalism as the major object of critique to fully understand the shifting temporalities within these phases (4). Eleven chapters explore how neoliberalism is practiced in the core zones, semiperipheries, and peripheries. In their introductory essay, the editors address the difficulties and complexities of defining the term in diverse contexts while trying to provide a full-fledged approach that links different accounts of neoliberalism. They use a comparative framework to discuss these global zones and integrate three methodologies: a world-historical perspective; a world-ecological dimension; and a world-literary/cultural conception. Using the first methodology, the editors begin with “rehistoricizing” the development of neoliberalism within a “long spiral” of world-system perspectives. This method provides a comprehensive historical approach and focuses on the role of regions beyond Europe and North America. More than just undertaking a genealogical method, Deckard and Shapiro succeed in differentiating various phases of neoliberalism within capitalism’s longue durée. Following Duménil and Lévy’s The Crisis of Neoliberalism, the editors further divide the approximately 90-year neoliberal period into two major cycles of 40–50 years with an overlapping minor period in between. The neoliberal period is characterized by “a cluster of different, sequential conjunctural moments, a longer generational shift, and a longer duration of more expansive economic changes and processes” (40). Nested in the late nineteenth century, the first phase of neoliberalism runs from the 1930s through the mid-1960s as a reaction to the economic crisis [End Page 440] of the Great Depression along with the emergence of right-wing politics (Kennedy and Shapiro). Before entering the second major phase, this period saw an overlapping and transitional decade from the mid-1960s to the mid-1970s as a key condition for neoliberalism to attack the working class and become a dominant force. In this period, social welfare protection began to be cut within the capitalist cores (Deckard and Shapiro 41). The second phase, from the late 1970s to 2008–11, began to hollow out the middle classes by forcing them into personal debts. A cluster of mini-cycles runs through this longer period that marks the growth of neoliberal strategies (42). The current phase, also called “late” neoliberalism, may indicate the movement of neoliberalism toward the supremacy of East and South Asia (6). Within their second methodology, the editors examine neoliberalism from a world-ecology perspective. As such, the process of neoliberalization is seen as a dynamic process/phenomenon “that registers the changing global composition of class relations governing the exploitation of peoples and the appropriation of natural resources” (25). Kerstin Oloff’s essay “From ‘Section 936’ to ‘Junk’: Neoliberalism, Ecology, and Puerto Rican Literature” explores the work of novelists such as Rafael Sánchez, Mayra Santos-Febres, Josué Montijo, and Rafael Acevedo from the 1970s onward, offering sharp-witted ways to lay bare “shifting socio-ecological realities...

Wind farm integrated restructured electricity market analysis using Ant Lion optimizer algorithm

ABSTRACT The optimal market strategy investigation is an enormous task for the system operator in a wind-integrated restructured power system. Bidding makes competition among all the market players in an electricity market and it forces to operate transmission lines near to their thermal limit and as an outcome, congestion may occur in the transmission system. The wind farm can take a vital role in this situation to mitigate transmission congestion by providing some additional powers to the system. To present the imprint of the wind farm in a deregulated power system, the work is formulated in a congested transmission environment considering the maximization of social welfare (SW) as an objective function. A generator shift factor (GSF)-based approach is presented in the work to mitigate the transmission congestion by rescheduling the supplier power. The power transfer distribution factor (PTDF) decides the optimal place of the wind farm (WF) in the system. Ant lion optimizer (ALO) algorithm is used in a modified IEEE 30-bus system to analyze the work. To validate the results obtained from the ALO algorithm, a comparison study is performed in this work with other three meta-heuristic algorithms namely particle swarm optimization (PSO), artificial bee colony (ABC), and moth swarm algorithm (MSA). The comparative results show that the ALO algorithm is much effective than the other three considered algorithms for the presented problem formulations. Four different real-time wind speed data are taken to check the efficiency of the presented approach with considering the intermittent nature of wind speed. It is revealed that the social benefit is raised with increment in wind speed irrespective of optimization techniques.

Broadband (8.5-13.5 µm) intra-pulse difference frequency generation in a LiGaS2 crystal of a 90 fs 744 nm laser pulse after its continuous redshift in air.

Broadband frequency downconversion of a 90 fs 744 nm Ti:sapphire laser pulse into the mid-infrared (IR) was demonstrated via its filamentation-induced self-frequency shift in air and subsequent intra-pulse difference frequency generation in a LiGaS2 crystal. The filamentation of the laser pulse in air provided its continuous spectral broadening to the Stokes wing with spectral humps separated by ∼1000cm-1 that was appropriate for the laser pulse difference frequency conversion into the mid-IR. The difference frequency emission spectrum spanned from 8.5 to 13.5 µm at the e-2 level. The transform limited pulse duration of the mid-IR pulse was 47 fs, which corresponded to a 1.3-cycle laser pulse. Energy conversion efficiency was up to 10-4 and 5⋅10-4 without and with chirp compensation, respectively.

Mind the Robot! Variation in Attributions of Mind to a Wide Set of Real and Fictional Robots

The rapid rise of computing power has prompted the desire to develop more social, human-like robots. Quantitatively comparing different computing systems on their ability to simulate human qualities has been a major technical challenge. A recent framework put forth by Gray et al. (Science 315(5812):619, 2007. https://doi.org/10.1126/science.1134475) provides promise as a new means for comparing robots. While the framework has been validated for assessing individual robots with different descriptions, or different behaviours, the framework has not been applied to a wider landscape of robots and machines situated amongst other characters. The present study sought to investigate attributions of mind towards a wide range of real and fictional robots. We asked participants to rate the agency (the ability “to do”) and experience (the ability “to feel”) of 24 characters made up of humans, robots, inanimate objects, and animals. Although robots were collectively rated lower than humans on agency and experience, there was significant variation among robots—even when fictional robots were omitted. The results of this investigation suggest that building robots that are perceived to feel is a fruitful avenue for future development as people are more open to perceiving aspects of mind in a wider range of robots than previously established. Our results also indicate that age is a critical factor in people’s attributions of mind to robots, suggesting that there may be a generational shift towards greater acceptance of robots’ ability to both do and feel.

6G - a generation too far? [News - analysis

Now that 5G has arrived with an advertising onslaught from operators like EE, what else could there be for the telecom industry to work on but 6G? Due out around the end of this decade, 6G would keep wireless communications on much the same timescale set since 3G first appeared. But questions are now being asked as to whether these generational shifts are working out the way the industry intended. One of the early aims for 5G was to bring cellular wireless to industrial applications that could not use its predecessors. Although 4G made some attempts to cut the round-trip latency for delivering packets over the air, 5G was designed to cut that to a millisecond or so. In principle, this makes it possible to coordinate robots without having to cable them up, assuming you do not try to have the control systems for those robots running in a data centre overseas. In practice, the wireless operators are, as with 3G and 4G, pushing new phones to consumers and, by all accounts, are not doing that badly at it. Both 3G and 4G suffered from false starts and so took a while to get out of the gate. 5G was somewhat luckier and may have had a boost from the pandemic and the shift to remote working, and living. At the recent 6G World Symposium, Andreas Müller, general chair of the 5G Alliance for Connected Industries and Automation and head of corporate-sector communication and network technology at Bosch's corporate research centre, said there is still some work to do on the standard to get it ready for factories. “The problem for industrials is that a lot for them only comes with Releases 16 and 17,” he said. The 3GPP group's Release 16 or 5G Phase 2 was finalised last summer, two years after the initial Release 15; Release 17 is due to become a finalised standard next year.

How Perceptions of the English Language Have Changed in Kazakhstan: A Narrative Analysis

Abstract This study provides an overview of how perceptions of the English language in Kazakhstan have altered over time due to political, economic, social and technological changes. The sociocultural framework includes language commodification and critical pedagogy concerning Indigenous languages; the methodological approach is narrative analysis combined with Bakhtin’s theory of dialogism. Three generational shifts were identified, each reflective of sociocultural changes that have occurred as Kazakhstan has transitioned from Soviet republic to modern Indigenous nation: from the Soviet Era/Soviet Man; to Independent Kazakhstan/Patriots and Outsiders; to Modern Kazakhstan/Young Cosmopolitans. The ongoing popularity of English may eventually threaten the Kazakh language.

Energy Monitoring and Control Using New Linearized Power Flow Technique.(Dept.E)

The paper presents a proposed technique with linearized formula for computing the transmission line power flow in terms of injected power due to any change in power system loading conditions. The formula relates the line power flows to both loads and power generation directly for a transmission network configuration. Being in an integral form, new power flows on the lines can be obtained directly without running a complete load flow programs when the total system generation changes. This formula is a fairly general one as it is suitable for various energy monitoring and control applications such as generation shifts to alleviate the line overloads, the generation redispatch for an incremental change in loading conditions and the on-line load shedding programs as well as the fast contingency analysis.

City Diplomacy: Another Generational Shift?

Abstract City diplomacy has a long history and has witnessed a clear sprawl over the last century. Successive “generations” of city diplomacy approaches have emerged over this period, with a heyday of networked urban governance in the last two decades. The covid-19 pandemic crisis presents a key opportunity to contemplate the direction of city diplomacy amid global systemic disruptions, raising questions about the effectiveness of differing diplomatic styles across cities but also the prospect of a new generational shift. This essay traces the history of generations in city diplomacy, examines prospects for novel ways of understanding city diplomacy, and contemplates how the pandemic’s impact heralds not the demise of internationalization in urban governance but an era in which city diplomacy is even more crucial amid fundamental limitations.

Secular Writers’ Engagement with Religious Tradition in 20th Century Iran: From Undermining to Deconstructing; A Generational Paradigm Shift

The present article is an attempt to conceptually discuss the development of modern secular approaches to religious tradition in contemporary Iran through the lenses of literary works. Throughout the paper, secularism has been understood as in the notion of “changes in the conditions of belief”, proposed by Charles Taylor. With José Casanova’s reading of Taylor’s conception, secularism becomes equivalent to a gradual construction of new and contextually specific images of the self and society, different from European narrative of religious decline. Accordingly, this article revisits the category of the Iranian ‘secular’ writer by looking into the trajectory of the Iranian literature field and its shifting relation to religion, itself influenced by the change in how secularism is understood within the field, during the 20th century. The paper argues that the 1979 revolution and its aftermath led to a paradigm shift in the writers’ conception of secular engagement with the religious tradition when compared with the first and second generation of writers. The first generation of Iranian secular writers mostly undermined the religious tradition as outdated rituals, and the second generation made a return to it as an authentic part of the Iranian identity under the local and global socio-political influences. The third generation went beyond such rejection/embrace narratives, came to see the religious tradition as a constructed cultural legacy, and engaged in re-reading and deconstructing that legacy in new secular ways.

Comparing CO2 emissions impacts of electricity storage across applications and energy systems

Summary Electricity storage systems can support the decarbonization of energy systems. However, the effect of electricity storage use on greenhouse gas emissions is complex because of roundtrip efficiency losses of the storage and its effects on the dispatch of different electricity-generation technologies. The limited literature examining this issue focus on individual electricity storage applications and the geographies where they are applied. Here, we systematically compare the effects of electricity storage on CO2 emissions across four applications in electricity systems resembling seven European countries. Our findings reveal large emission impact differences between applications and countries. Among other findings, we find that when compared with wholesale arbitrage, storing electricity in other applications exhibits much lower effects on CO2 emissions. We also investigate different policy options to reduce CO2 emissions from storing electricity. We find that although a higher carbon price can have a substantial effect on reducing the CO2 emissions from wholesale arbitrage, other applications require alternative approaches.

A centralized hybrid routing model for multicontroller SD‐WANs

AbstractThe increasing complexity of contemporary mobile and application‐centric networks is pushing traditional WAN architectures to its limit. Due to the rise of Cloud‐based services and edge‐computing, the intersite data transfer volume in enterprise networks is rising rapidly. Moreover, enterprises are tending to integrate several communication technologies such as broadband, LTE, MPLS, and so forth for a high‐available dynamic WAN connectivity, which a traditional WAN does not support natively. Additionally, its distributed computing model results in the control‐plane traffic to consume a significant amount of backhaul bandwidth. Software‐defined WAN (SD‐WAN) is a generation shift that adapts the centralized model of SDN to WAN that fills the bottlenecks of its predecessor. It provides over twice the bandwidth having the same backhaul with more manageability, autonomy, and security of the network. In this article, we propose a hybrid routing model for multicontroller SD‐WANs that computes all‐possible routes proactively and serve them on‐demand. The proposed model results in a rapid convergence across the edge devices. The article further discusses the synchronization mechanism among several controllers and a test‐bed implementation to conduct the experiments.

Voice in Human–Agent Interaction

Social robots, conversational agents, voice assistants, and other embodied AI are increasingly a feature of everyday life. What connects these various types of intelligent agents is their ability to interact with people through voice. Voice is becoming an essential modality of embodiment, communication, and interaction between computer-based agents and end-users. This survey presents a meta-synthesis on agent voice in the design and experience of agents from a human-centered perspective: voice-based human–agent interaction (vHAI). Findings emphasize the social role of voice in HAI as well as circumscribe a relationship between agent voice and body, corresponding to human models of social psychology and cognition. Additionally, changes in perceptions of and reactions to agent voice over time reveals a generational shift coinciding with the commercial proliferation of mobile voice assistants. The main contributions of this work are a vHAI classification framework for voice across various agent forms, contexts, and user groups, a critical analysis grounded in key theories, and an identification of future directions for the oncoming wave of vocal machines.

Toward a fundamental understanding of flow-based market coupling for cross-border electricity trading

• Provision of a guide to the main steps and parameters of flow-based market coupling. • Learning goals to help readers understand actions by transmission system operators. • Provision of an open-access model (code and data) based on free-to-use software. • Case studies and sensitivity analyses based on a modified 118-bus IEEE network. • Quantifying effects of generation shift keys, critical lines and security margins. Trading electricity across market zones furthers competitive power prices, security of supply and the integration of renewable energy. In the European Union, flow-based market coupling is the target model to compute correct trading capacities between markets, while approximating physical grid constraints. The methodology relies on predictive, carefully designed parameters to maximize trading opportunities, while keeping congestion management at acceptable levels. This paper explains the fundamentals of flow-based market coupling. It provides an open-access model based on a test network and its data. By providing a guide to the theory and conducting several case studies, the functioning and effects of the most influential parameters are demonstrated. Innovative aspects of this paper are its illustrative nature and its answer to the following research questions: (1) What is the effect of (a) generation shift keys and (b) threshold choice on the selection of critical network elements? (2) What is the effect of (a) generation shift keys, (b) selected critical network elements and (c) security margins on market coupling and congestion management results? It also addresses the effect of higher shares of renewable energy and minimum trading capacities on flow-based market coupling. This analysis shows that (1) the effects of flow reliability margins and selected critical network elements dominate the effect of generation shift keys on flow-based market coupling domains, (2) power systems with an increasing share of renewable energy may necessitate re-adjusted parameters and (3) minimum trading capacities can be guaranteed by redispatch or altering the base case.