Alternative Modes Research Articles

Bioinspired Pyrano[2,3-f]chromen-8-ones: Ring C-Opened Analogues of Calanolide A: Synthesis and Anti-HIV-1 Evaluation.

We have designed and synthesized a series of bioinspired pyrano[2,3-f]coumarin-based Calanolide A analogs with anti-HIV activity. The design of these new calanolide analogs involved incorporating nitrogen heterocycles or aromatic groups in lieu of ring C, effectively mimicking and preserving their bioactive properties. Three directions for the synthesis were explored: reaction of 5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one with (i) 1,2,4-triazines, (ii) sulfonylation followed by Suzuki cross-coupling with (het)aryl boronic acids, and (iii) aminomethylation by Mannich reaction. Antiviral assay of the synthesized compounds showed that compound 4 has moderate activity against HIV-1 on enzymes and poor activity on the cell model. A molecular docking study demonstrates a good correlation between in silico and in vitro HIV-1 reverse transcriptase (RT) activity of the compounds when docked to the nonnucleoside RT inhibitor binding site, and alternative binding modes of the considered analogs of Calanolide A were established.

An exploration of students’ use of digital resources for self-study in anatomy: a survey study

BackgroundThe development of technology has provided new ways for active engagement and for visualizing structures in anatomy education including digital resources that may be used outside of the classroom. To support students’ learning, there is a need to better understand students’ experiences of using digital resources. This study aimed to identify which resources students use, their preferences, the purpose of using them, and barriers to adopting tools for self-study of anatomy.MethodsA mixed -methods approach combining qualitative and quantitative data was used to collect and analyse data. Two consecutive cohorts of first-semester medical students (n = 278) were invited to complete an anonymized survey. The survey consisted of itemized questions, free-text space for comments, and one open-ended question. Descriptive statistics were used for demographics and itemized answers. Comments and free-text answers were analysed qualitatively using abductive inference.ResultsOne hundred and twenty-seven students completed the survey (response rate 45%). Most students (46%) reported that they spend more than 30 h/per week on self-study. They used a variety of digital resources for different purposes. Most students used digital resources to prepare for examinations, when they encountered difficulties and after going through a section. Students reported that they would use digital resources to a greater extent if they were offered an introduction, if resources were more accessible, and if they could interact with a tutor. The free-text responses revealed that digital resources helped students understand anatomy, allowed them to make active choices, provided tools for repetition and memorization, accelerated and simplified the learning process, and complemented other learning resources.ConclusionsDigital resources may support the understanding of anatomy by offering alternative modes of learning and providing a valuable complement to other learning resources. Educators should consider how digital resources are introduced and offer support and feedback.

Lived Experiences of People with and without Disabilities across the Lifespan on Autonomous Shuttles

As an emerging, alternative mode of transportation, an in-depth understanding of autonomous shuttle (AS) experiences among all age groups, with and without disabilities, may impact acceptance and adoption of the AS, shape industry guidelines, and impact public policy. Therefore, this study analyzed qualitative data from older (n = 104), younger, and middle-aged (n = 106) adults and people with disabilities (n = 42). The data were obtained by asking participants four open-ended questions from an Autonomous Vehicle User Perception Survey. The result revealed seven themes (Safety, Ease of Use, Cost, Availability, Aging, AS Information, and Experience with AS) for older, younger, and middle-aged adults and six themes (all of the previously mentioned except for Aging) for people with disabilities. Frequency counts indicated priority attention, among all groups, to Safety and Ease of Use. This study provides valuable information pertaining to the experiences, concerns, and motivations of all potential users across age groups and disabilities—and may inform policymakers and industry partners to address their needs more adequately. These findings may contribute to improving and enhancing AS programming, design, and deployment in a safer, accessible, affordable, and tailored way.

“The mother is a child, too”: neoliberal segmentarity, reproductive futurism, and relationality in Enlightened

ABSTRACT This article examines Mike White and Laura Dern’s HBO series Enlightened (2011–13) in relation to questions of segmentarity, motherhood, feminism, reproductive futurism, and neoliberal capitalism. Rather than looking at the series’ central whistleblower narrative, this article instead examines a secondary plot charting the protagonist’s affective investment in the plight of a Mexican immigrant and her two American children. Drawing on a Deleuzo-Guattarian framework, the article argues that Enlightened foregrounds the important connections between segmentarity and our contemporary neoliberal era, particularly in the context of current political debates surrounding immigration in the United States. The article also examines the ways in which Enlightened teases out the nationalist and neoliberal biases inherent in Lee Edelman’s formulation of reproductive futurism, and briefly draws on Safe (Todd Haynes, 1995), forging key comparisons between the film and Enlightened in relation to their shared interest in New Age spirituality, capitalism, maternity, and ecology. Through the lens of Deleuze and Guattari’s thinking on segmentarity and becoming, the article argues that Enlightened posits alternative modes of community, mothering, and futurity.

Inferring trip purposes and mode substitution effect of rental e-scooters in London

The lack of information on trip purpose and alternative mode in micromobility service usage data remains a major analytical challenge. Conventional survey method is subject to significant sampling and stated preference biases. To overcome this challenge, this paper presents a new inference method through a case study of rental e-scooters in London. The inference method features a rule-based algorithm for matching observed rental e-scooter trips with filtered trip samples in the English National Travel Survey (NTS) series. Probability distribution of trip purposes and alternative modes are then retrieved from NTS. Inference results are validated using official data. Discrepancies, sources of biases and correction measures are investigated. Based on the inferred mode substitution pattern, we estimate greenhouse gas emissions reduction of selected rental e-scooter trips in London (36–103 g CO2e per mile). It is expected that the proposed method is applicable to a wide range of micromobility studies using service usage data.

A unique binding mode of P1' Leu-containing target sequences for Streptococcus pyogenes sortase A results in alternative cleavage.

Sortase enzymes are cysteine transpeptidases that attach environmental sensors, toxins, and other proteins to the cell surface in Gram-positive bacteria. The recognition motif for many sortases is the cell wall sorting signal (CWSS), LPXTG, where X = any amino acid. Recent work from ourselves and others has described recognition of additional amino acids at a number of positions in the CWSS, specifically at the Thr (or P1) and Gly (or P1') positions. In addition, although standard cleavage occurs between these two residues (P1/P1'), we previously observed that the SrtA enzyme from Streptococcus pneumoniae will cleave after the P1' position when its identity is a Leu or Phe. The stereochemical basis of this alternative cleavage is not known, although homologs, e.g., SrtA from Listeria monocytogenes or Staphylococcus aureus do not show alternative cleavage to a significant extent. Here, we use protein biochemistry, structural biology, and computational biochemistry to predict an alternative binding mode that facilitates alternative cleavage. We use Streptococcus pyogenes SrtA (spySrtA) as our model enzyme, first confirming that it shows similar standard/alternative cleavage ratios for LPATL, LPATF, and LPATY sequences. Molecular dynamics simulations suggest that when P1' is Leu, this amino acid binds in the canonical S1 pocket, pushing the P1 Thr towards solvent. The P4 Leu (L̲PATL) binds as it does in standard binding, resulting in a puckered binding conformation. We use P1 Glu-containing peptides to support our hypotheses, and present the complex structure of spySrtA-LPALA to confirm favorable accommodation of Leu in the S1 pocket. Overall, we structurally characterize an alternative binding mode for spySrtA and specific target sequences, expanding the potential protein engineering possibilities in sortase-mediated ligation applications.

Costate-Supplement ADP for Model-Free Optimal Control of Discrete-Time Nonlinear Systems.

In this article, an adaptive dynamic programming (ADP) scheme utilizing a costate function is proposed for optimal control of unknown discrete-time nonlinear systems. The state-action data are obtained by interacting with the environment under the iterative scheme without any model information. In contrast with the traditional ADP scheme, the collected data in the proposed algorithm are generated with different policies, which improves data utilization in the learning process. In order to approximate the cost function more accurately and to achieve a better policy improvement direction in the case of insufficient data, a separate costate network is introduced to approximate the costate function under the actor-critic framework, and the costate is utilized as supplement information to estimate the cost function more precisely. Furthermore, convergence properties of the proposed algorithm are analyzed to demonstrate that the costate function plays a positive role in the convergence process of the cost function based on the alternate iteration mode of the costate function and cost function under a mild assumption. The uniformly ultimately bounded (UUB) property of all the variables is proven by using the Lyapunov approach. Finally, two numerical examples are presented to demonstrate the effectiveness and computation efficiency of the proposed method.

Different Level of Tolerance to Herbicides is Displayed by Triticum aestivum L. Cultivars Depending on Herbicide Category and Mode of Application

Abstract Herbicides (HBs) are an integral part of modern agricultural practice globally as one of the most suitable methods for chemical weed control. Hence, they may inadvertently damage crops through similar mechanisms well-functioning at weeds. Tolerance to three categories of treatments (tribenuron-methyl, 2,4 D and their combination), and the impact of the mode of application (pre-treatment of seeds or spraying on plants) was assessed through morphometric analysis (total plant length, root length, stem length, lengths of the first three leaves, relative water content-RWC), and pigment content analysis for some wheat (Triticum aestivum L.) cultivars in use in Albania. Results speak of a cultivar specific tolerance to each HB category, discriminating “Dajti” as the most resistant cultivar, and suggesting that the stress imposed to plants by the combination of HBs can produce significant differences in pigment content. The mode of treatment, on the other side showed that glyphosate pre-treatment of seeds led to inhibition of germination, and plants germinated from seed pre-treatment with in 2,4-D displayed significant modification of plant morphology, and germination rate, and had limited impact on RWC. On contrary, few statistically significant changes in morphometric traits and pigments content were evidenced when plants were treated with 2,4-D or glyphosate after the germination. In conclusion, the combination of HBs produced significant changes in plant pigments content compared to the impact of each HB alone, and the pre-treatment of seeds lead either to inhibition or delayed germination. Based on the above we recommend avoiding these practices, and suggest further exploration of alternative HB combinations and modes of treatment before large scale applications.

Self-adaptive gas flow and phase change behaviors during hydrate exploitation by alternate injection of N2 and CO2

Since hydrate resources play a part of the stratigraphic framework structure in sediments, establishing a safe and economic method for hydrates exploitation remains the primary challenge to this day. Among the proposed methods, the spontaneous displacement of CH4 from hydrate cages by CO2 seems to be a perfect mechanism to address gas production and CO2 storage, especially in today's strong demand for carbon reduction and replacing clean energy. After extensive lab researches, in the past decade, injecting a mixture of CO2 and small molecule gas has become a key means to enhance displacement efficiency and has great potential for application. However, there is a lack of in-depth research on gas flow in the reservoir, while the injected gas always passes through low-saturated hydrate areas with high permeability and then occurs gas channel in a short term, finally resulting in the decreases in gas production efficiency and produced gas quality. Therefore, we explored a new injection-production mode of alternate injection of N2 and CO2 in order to fully coordinate the advantages of N2 in enhanced hydrate decomposition and CO2 in solid storage and heat compensation. These alternate “taking” and “storing” processes perfectly repair the problem of the gas channel, achieving self-regulation effect of CH4 recovery and CO2 storage. The 3-D experimental results show that compared to the mixed gas injection, CH4 recovery is increased by >50% and CO2 storage is increased by >70%. Additionally, this alternate injection mode presented a better performance in CH4 concentration of produced gas and showed outstanding N2 utilization efficiency. Further, we analyzed its self-adaptive gas flow mechanism and proposed an application model of “one injection and multiple production”. We look forward to this study accelerating the application of CO2-CH4 replacement technology.

Multi-mode multi-skill resource-constrained project scheduling problem with differentiated professional capabilities

Motivated by a practical situation in a digital transformation project, this paper considers a resource-constrained project scheduling problem with multiple modes, multiple skill types, and differentiated professional capabilities. In the proposed problem, each project activity has one or more alternative execution modes associated with a trade-off between processing time and resource consumption. In an execution mode, an activity requires a certain number of employees with specific skill types and required professional capabilities. A mixed integer programming model is developed to minimize the total project duration. Since this problem is NP-hard, an efficient immunoglobulin-based artificial immune system (EIAIS) algorithm with a new encoding and decoding scheme and novel components is proposed. The effectiveness of the proposed EIAIS algorithm is tested on randomly generated instances. Computational results show that the proposed EIAIS algorithm has better performance than the existing algorithms.

“Stories one tells in dark times”: Fabulation, fugitivity, and futurity in Olivia Wenzel's 1000 Serpentinen Angst

AbstractThis article engages with aesthetic acts of experimentation in Olivia Wenzel's 1000 Serpentinen Angst. Building on recent scholarship on the politics of aesthetics in Wenzel's text, I argue that these experiments are intertwined with key themes in the book, particularly issues of racialization and of Black (im‐)possibility in present‐day Germany. In this context, my article focuses on a largely overlooked aspect of Wenzel's text, namely its surreal, fantastical, and speculative elements. Drawing on Tavia Nyong'o and Saidiya Hartman's notion of “(critical) fabulation,” I propose that Wenzel's writing mobilizes fantastic, imaginative, and speculative elements to unsettle oppressive realities and realisms in favor of alternative modes of world‐ and future‐making. Inspired by Tina M. Campt's work, I conceptualize these re‐makings as “fugitive” and quotidian strategies, developed in response to a broken world, which still have the potential to generate new infrastructures for relationality and futurity.

Uso misto do solo e a caminhada para fins de transporte em idosos: uma abordagem baseada em diferentes métricas do ambiente construído

Abstract The presence of land use mix (LUM) in a neighborhood has been shown as an important aspect to promote walking as a daily means of transport. However, few studies in the area have applied different measurement strategies to test their effect on alternative modes of travel behavior, such as older adults walking. We applied six LUM measures of land use mix in two neighborhood definitions (500 and 1000m network buffers) and assessed their associations with walking for transport outcomes in adults over age 60 years from the EpiFloripa Aging study, living in the municipality of Florianópolis, Brazil, in 2013/14. Accounting for sociodemographic and environmental variables, adjusted associations found a positive relationship between four LUM and walking. The entropy index and three alternative measures defined by the intensity of commercial and nonresidential uses were positively associated with the walking for transportation, regardless of neighborhood definition. Stronger positive associations were seen when using smaller buffers and measures of the proportion of commercial uses, proportion of nonresidential uses and destination density. The results show that alternative measurements can overcome the entropy index, pointing out the need to adapt LUM measures and neighborhood scale to the geographic context and age group under analysis.

The institutional environment and gig platform transaction cost solutions

Abstract A growing number of labour market participants transact through gig platforms. This choice should reflect a reduction in transaction costs for platform users, compared to costs they meet when using alternative modes of governance. We exploit a unique cross-platform, cross-country data set of gig platform users to test the impact of the institutional environment in one of its dimensions – the strictness of labour market regulation (LMR) – on the ability of gig platforms to reduce users' transaction costs. According to our findings, the regulation indicator of both the user and platform countries influences transaction costs for platform users, even controlling for platform and user characteristics. The platform appears to reduce transaction costs most when users face stricter or weaker LMR, in a U-shaped effect. In the former case, the platform may provide an escape from labour regulations when hiring for tasks, while in the latter case, the platform can economize on the usual transaction costs of private contracting by administrating some types of users' activities.

Refusing Settler Georgics

This essay recovers and seeks to refuse a harmful and enduring eighteenth-century fiction: settler georgic, an imperial mode that North American settlers used to foreclose refusal, naturalize British understandings of cultivation and use, and figure violent dispossession as both inevitable and in the past. Tracing this history helps to show the damage that such logics continue to do as well as the assumptions that govern literary historical methods. I look to the work of Leanne Betasamosake Simpson, whose Noopiming: The Cure for White Ladies (2020) is premised on the refusal of settler narrative, to think through alternate modes of literary history. Read alongside Audra Simpson’s important study of refusal, Mohawk Interruptus (2014), Leanne Simpson’s text opens up possibilities for reading the quieter, everyday refusals that are sometimes overlooked in eighteenth-century archives. This work also suggests the limits of refusal in academic and university contexts, and the ways in which institutional acknowledgements of refusal risk strengthening the settler colonial structures that they claim to refuse.

Learning Experience of Students Using the Learning Management System: User’s Perspective on the Use of Moodle in the University of Jordan

This study aimed to evaluate the effectiveness of Moodle LMS as an alternative delivery mode for education, particularly in the higher education system of Jordan, which has not been evaluated before. The research is based on Moore’s transactional distance learning theory, which considers interactions among students, instructors, and course material, as well as personal characteristics of students. The study included 50 participants who have taken courses on Moodle LMS at the University of Jordan. Both interviews and research surveys were conducted to gather in-depth perceptions and analysis of the participants’ experiences with Moodle LMS. The findings suggest that Moodle LMS was an effective alternative study tool during the COVID-19 pandemic and the user-friendly course design enhanced the user experience of using Moodle LMS. Participants also provided suggestions to optimize the system for better integration in the University of Jordan. Fixing Moodle LMS based on the recommendations of the study participants will significantly improve the learning experience of students. This study contributes to the advancement of the state of the art by evaluating the effectiveness of Moodle LMS in the higher education system of Jordan and providing recommendations for improvement.

Natasha Kellem's Minoritarian Liberalism

Normative liberalism has promoted the freedom of privileged subjects, those entitled to rights – usually white, adult, heteronormative, and bourgeois – at the expense of marginalized groups, such as Black people, children, LGBTQ people, and slum dwellers. In this ethnographic analysis of Rocinha, the largest favela in Rio de Janeiro, Brazil, I explore what happens when liberalism is challenged by people whose lives are impaired by normative understandings of liberty. I call such marginalized visions of freedom “minoritarian liberalism,” a concept that stands in for overlapping, alternative modes of freedom. In this piece, I introduce Natasha Kellem, a charismatic self-declared travesti (a term used in Latin America to indicate a specific form of female gender construction opposite to the sex assigned at birth). Through interconnected experiences, I offer ethnographic evidence of non-normative routes to freedom for those seeking liberties against the backdrop of capitalist exploitation, transphobia, racism, and other patterns of domination.

МОДЕЛИРОВАНИЕ СИСТЕМЫ ЭПИГЕНЕТИЧЕСКОЙ ПАМЯТИ С ТРАНСКРИПЦИОННОЙ РЕПРЕССИЕЙ И МЕТИЛИРОВАНИЕМ ДНК

The in silico model of the epigenetic memory system synthesized in Escherichia coli [Maier et al., 2017, Nat. Comm., 8:15336] was developed. The system includes an artificial memory operon with DNA methyltransferase CcrM from Caulobacter crescentus methylating the promoter of this operon, and an engineered transcriptional repressor gene ZnF that blocks the same promoter in an unmethylated state. The memory operon, which is located on the maintenance plasmid, is controlled by a trigger plasmid carrying a specific arabinose-inducible operon. The artificial trigger operon functions as part of an expanded arabinose regulon. An additional model is used to describe the operation of the latter. The unified model of the memory control system takes into account positive and negative control by the regulatory protein araC, negative feedback self-regulation and negative direct, methylation-sensitive regulation by the ZnF protein, and DNA methylation. The models are built in the language of the formalism of the dynamic theory of molecular genetic control systems. The models were calculated in the SETIES software package to analyze the dynamics of control gene networks, dynamic epigenes and cell ensembles. Computer experiments have shown that the switch has two alternative functional modes, each of which is stable in a series of successive cell divisions. Both modes are characterized in terms of the molecular component dynamics of the artificial memory operon, the trigger operon, and the natural L-arabinose catabolism operon.

Uncovering New Conformational States of the Substrate Binding Pocket of LSD1 Potential for Inhibitor Design via Funnel Metadynamics.

Lysine-specific demethylase 1 (LSD1) is a promising therapeutic target for cancer therapy. So far, over 80 crystal structures of LSD1 in different complex states have been deposited in the Protein Data Bank, which are valuable resources for performing structure-based drug design. However, among all of the crystal structures of LSD1, the substrate binding pocket, which is the most efficient druggable site for designing LSD1 inhibitors at present, is very similar no matter whether LSD1 is in the apo or any holo forms, which is inconsistent with its versatile demethylase functions. To investigate whether the substrate binding pocket is rigid or exhibits other representative conformations different from the crystal conformations that are feasible for designing new LSD1 inhibitors, we performed funnel metadynamics simulations to study the conformation dynamics of LSD1 in the binding process of two effective LSD1 inhibitors (CC-90011 and 6X0, CC-90011 undergoing clinical trials). Our results showed that the entrance of the substrate binding pocket is very flexible. Two representative entrance conformations of LSD1 counting against binding with the substrate of histone H3 were detected, which may be used for structure-based LSD1 inhibitor design. Besides, alternative optimal binding modes and prebinding modes for both inhibitors were also detected, which depicted that the key interactions changed along with the binding process. Our results should provide great help for LSD1 inhibitor design.

Analysis of contributing factors in decision to bicycle in developing countries context

Bicycling is a healthy and environmentally beneficial mode of transportation. Despite substantial benefits of bicycling, it is mostly overlooked as a daily form of transportation. Due to urbanization and development in the motorized industry, commuters are attracted to motorized transport modes. The present study was carried out to evaluate the bicycle users' behaviour corresponding to the decision to use a bicycle as a commuter mode and contributing factors in the decision to bicycle in developing countries. To achieve the proposed objectives, an offline face-to-face survey was conducted at a selected stretch in Nagpur city, India. To understand the user's behaviour and attitudes towards bicycling, a Structural Equation Model (SEM) was proposed. The study has revealed that important factors like environmental factors, a lack of existing infrastructure facilities, personal norms, and specific socio-demographic characteristics are responsible for influencing the users' decision to use a bicycle as a commuter mode. From the result, it is concluded that the absence of alternative (motorized) transport modes encourages users to cycle. The lack of cycle infrastructure, the distance, and the purpose of the trip significantly impact the decision to choose a bicycle as a commuter mode. Additionally, it also found that the hot climate and heavy rains demotivate commuters towards cycling. The findings of this study might be useful for transport planners to help them promote sustainable transport modes such as bicycles in the Indian context.

Meritocracy as Authoritarian Co-Optation: Political Selection and Upward Mobility in China

Why does an authoritarian regime adopt meritocracy in its political selection? I argue that meritocracy can be used to co-opt large numbers of ordinary citizens by providing them with an opportunity of socioeconomic advancement instead of income redistribution, as long as the selection process is viewed as inclusive and rule-based. Focusing on the civil service examination in contemporary China, I examine how this meritocratic selection has shaped the relationship between college graduates and the Chinese regime. Exploiting a spatial-cohort variation in applicant eligibility, I find that the exam boosts college graduates’ perceived upward mobility, which in turn weakens their demand for redistribution even in the face of growing inequality. These findings point to an alternative mode of authoritarian co-optation and highlight the role of upward mobility in regime stability.