Linear Progression Research Articles

Abstract 2392: Transcriptome analysis from a linear melanoma progression model reveals lncRNAs involved with malignancy, EMT and metastasis

Abstract In the human genome, it is estimated that more than 90% of all transcripts are transcribed into non-coding RNAs (ncRNA), classified as small (such as miRNAs) and long (lncRNA). It has been demonstrated that ncRNAs have an important role in biological processes, such as proliferation, differentiation and cellular migration. Changes in their expression have been associated to several diseases, including cancer. Melanoma is one of the most aggressive types of cancer, with high probability of metastasis and showing an unfavorable response to therapies. Our lab has developed a melanoma progression model, which was established by exposing nontumorigenic melanocytes to sustained stressed conditions (cycles of adhesion blockage), sequentially generating 4 cell lines (melan-a, nontumorigenic melanocytes; 4C, premalignant melanocytes; 4C11-, non-metastatic melanoma cells; 4C11+, metastatic melanoma cells) in which different cell lines represent distinct stages of the progression. Previous data comparing the RNA sequencing results from all 4 cell lines identified a total of 3662 genes, coding and non-coding, which displayed differentiated expression (DE) levels when comparing two or more cell lines. Out of them, 492 were DE lncRNAs. We categorized them into three distinct signatures: malignancy, epithelial mesenchymal transition (EMT), or metastasis, according to their expression profile. We analyzed the neighboring genes from those lncRNAs, as it is well described that lncRNA might regulate the gene expression of its neighbors in cis. We identified the lncRNA Dlx4os, with 6 neighbor genes correlated to EMT signature and overall survival of melanoma patients using two different melanoma cohorts (TCGA and Leeds). Among them, the Dlx4 gene, which expression correlates to poor prognosis, shares the same promoter site on opposite strands in chromosome 11 with Dlx4os. We also identified HOTAIR, a well described lncRNA, altered in the EMT signature. We silenced HOTAIR, Dlx4os and Dlx4 on 4C and 4C11- cell lines through RNA interference. We studied their impact on EMT-related genes and observed a change in RNA and protein expression levels, indicating that they might play a role on EMT. Dlx4os also altered cell migration in vitro and tumorigenesis in vivo. We aim to identify lncRNAs that have specific roles in melanoma progression and understand their mode of action. The results could be used as the basis for new prognostics techniques, diagnostic and melanoma therapy, as it may contribute to a better understanding of the role of lncRNAs on the melanoma genesis and progression. Citation Format: Ana L. Ayub, Diogo Pessoa, Lenial A. Sejour, Ioannis Vlachos, Jérémie Nsengimana, Julia Newton-Bishop, Eduardo M. Reis, Frank J. Slack, Miriam G. Jasiulionis. Transcriptome analysis from a linear melanoma progression model reveals lncRNAs involved with malignancy, EMT and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2392.

Linear and Branching Progression of Chronic Lymphocytic Leukemia (CLL) Under PI3K Inhibition (PI3Ki)

Introduction: B-cell receptor (BCR) signaling is a critical pathway in chronic lymphocytic leukemia (CLL). BTK or PI3K antagonists can abolish BCR-derived signals. Idelalisib inhibits the delta isoform of PI3K and has been already approved for patients with CLL, whereas duvelisib inhibits both the delta and gamma isoforms of PI3K and is currently being evaluated in clinical trials. Despite their remarkable efficacy, a proportion of patients develop progressive disease after initial response to the drug, sometimes in the form of transformation to high-grade lymphoma. Several mechanisms of resistance have been described in patients taking the BTK inhibitor ibrutinib, including BTK or phospholipase C gamma-2 mutations. There is, however, little information regarding the mechanisms of resistance to PI3Ki.In our institution, out of 12 patients who received PI3Ki as salvage therapy, 6 patients had their medication stopped due to progressive disease, 3 with transformed disease and 1 with accelerated CLL. In this study, we comprehensively evaluated the genomic aberrations of these last 4 patients with the aim of unraveling the molecular mechanisms of disease progression in this patient population.Patients and methods: DNA (tumor and germline) was extracted from peripheral blood/lymphoid tissue samples drawn before and after progression under PI3Ki. One case showed a CLL with increased proliferation (accelerated CLL), two cases showed transformation to a diffuse large B-cell lymphoma (DLBCL), and one to a plasmablastic lymphoma (PBL). Somatic copy number alterations (CNA) were identified using genome-wide copy number arrays. Whole-exome sequencing (WES) or whole-genome sequencing (WGS) was performed as previously described (Puente et al. Nature 2015).Results: All patients had relapsed after rituximab, fludarabine and cyclophosphamide (RFC) first-line therapy, and rituximab plus bendamustine second-line therapy with the exception of one patient, who received RFC twice. All had significant lymphadenopathy before PI3Ki initiation, initially responded to PI3Ki, and then experienced progression 103, 151, 329 and 752 days after treatment initiation. IGH rearrangement analysis revealed that the relapsed tumor was clonally related to the original CLL in all cases. Pre-PI3Ki samples from all patients harbored high-risk genomic aberrations by FISH/SNP arrays, including del(11q) in 3 patients and del(17p) in 1 patient. In 3 patients, all abnormalities identified before PI3Ki were maintained at progression, but several other alterations (1, 14, and 2 lesions, respectively) were acquired, consistent with a linear pattern of evolution. In the PBL transformation, some initial alterations were maintained (8q gain, 17p and 19p losses), some were not found (4q, and 19q gains, 2q loss), and 54 new alterations emerged at relapse, suggesting that the resistant clone arose from an early branch during CLL evolution. Together, 3 out of 4 patients (all except the patient with accelerated CLL) have alterations involving ARID1A (1 patient with a point mutation, and 2 patients with selective losses) . Other acquired aberrations in these patients were CDKN2A losses (2 patients), TP53 disruption (2 patients), MYC activating mutation (1 patient), 1 frameshift mutation in USP28 (1 patients), 2p16 gain (1 patient) and NFKBIE mutation (1 patient).Conclusion: Overall, CLL progression after PI3Ki may follow different pathways including linear progression with increasing proliferation and transformation to DLBCL through different mechanisms (TP53, CDKN2A, NFKBIE inactivation, MYC activation or ARID1A inactivation among others) and branching transformation to PBL that may represent an alternative pathway to escape from BCR-dependent activation. DisclosuresDelgado:Abbvie, Jansen, Gilead, Roche: Consultancy, Speakers Bureau. Lopez-Guillermo:Roche: Consultancy, Other: Research grant; Celgene: Consultancy; Gilead: Consultancy; Janssen: Consultancy; Novartis: Consultancy.

Clinical-dermoscopic similarities between atypical nevi and early stage melanoma.

Atypical (Clark) nevi are benign tumors that may be considered precursors of melanoma. Many studies acknowledge a linear progression from typical to atypical nevi that eventually transform into melanoma. It is often challenging to differentiate a Clark nevus from melanoma, especially in its early stages, due to their clinical, dermoscopic, and histological resemblance. Dermoscopy is a powerful tool in early melanoma diagnosis, but it is a subjective method of examination. Therefore, the use of dermoscopic algorithms and checklists can overcome this issue. In the case of a difficult diagnosis, since both dermoscopy and histopathological exam are subjective methods of examination, modern molecular biology techniques can be used to distinguish between benign and malignant tumors. This study aimed to test the accuracy of specific clinical and dermoscopic criteria in order to distinguish between benign and malignant tumors, with a secondary objective to provide an overview of the clinical and dermoscopic features of atypical nevi and melanoma. In the present study, dermoscopic algorithms did not necessarily help distinguish benign and malignant tumors but demonstrated that nevi and melanoma have similar characteristics.

Visualizing Probability Distributions Across Bivariate Cyclic Temporal Granularities

Deconstructing a time index into time granularities can assist in exploration and automated analysis of large temporal datasets. This article describes classes of time deconstructions using linear and cyclic time granularities. Linear granularities respect the linear progression of time such as hours, days, weeks and months. Cyclic granularities can be circular such as hour-of-the-day, quasi-circular such as day-of-the-month, and aperiodic such as public holidays. The hierarchical structure of granularities creates a nested ordering: hour-of-the-day and second-of-the-minute are single-order-up. Hour-of-the-week is multiple-order-up, because it passes over day-of-the-week. Methods are provided for creating all possible granularities for a time index. A recommendation algorithm provides an indication whether a pair of granularities can be meaningfully examined together (a “harmony”), or when they cannot (a “clash”). Time granularities can be used to create data visualizations to explore for periodicities, associations and anomalies. The granularities form categorical variables (ordered or unordered) which induce groupings of the observations. Assuming a numeric response variable, the resulting graphics are then displays of distributions compared across combinations of categorical variables. The methods implemented in the open source R package gravitas are consistent with a tidy workflow, with probability distributions examined using the range of graphics available in ggplot2. Supplementary files for this article are available online.

Complex Interplay of Genes Underlies Invasiveness in Fibrosarcoma Progression Model.

Sarcomas are a heterogeneous group of mesenchymal tumours, with a great variability in their clinical behaviour. While our knowledge of sarcoma initiation has advanced rapidly in recent years, relatively little is known about mechanisms of sarcoma progression. JUN-murine fibrosarcoma progression series consists of four sarcoma cell lines, JUN-1, JUN-2, JUN-2fos-3, and JUN-3. JUN-1 and -2 were established from a single tumour initiated in a H2K/v-jun transgenic mouse, JUN-3 originates from a different tumour in the same animal, and JUN-2fos-3 results from a targeted in vitro transformation of the JUN-2 cell line. The JUN-1, -2, and -3 cell lines represent a linear progression from the least transformed JUN-2 to the most transformed JUN-3, with regard to all the transformation characteristics studied, while the JUN-2fos-3 cell line exhibits a unique transformation mode, with little deregulation of cell growth and proliferation, but pronounced motility and invasiveness. The invasive sarcoma sublines JUN-2fos-3 and JUN-3 show complex metabolic profiles, with activation of both mitochondrial oxidative phosphorylation and glycolysis and a significant increase in spared respiratory capacity. The specific transcriptomic profile of invasive sublines features very complex biological relationships across the identified genes and proteins, with accentuated autocrine control of motility and angiogenesis. Pharmacologic inhibition of one of the autocrine motility factors identified, Ccl8, significantly diminished both motility and invasiveness of the highly transformed fibrosarcoma cell. This progression series could be greatly valuable for deciphering crucial aspects of sarcoma progression and defining new prognostic markers and potential therapeutic targets.

The Changing Visions of Chymistry at Seventeenth-Century Jena: The Two Brendels, Rolfinck, Wedel, and Others

The University of Jena was an important locus for chymistry teaching in Germany throughout the seventeenth century. Zacharias Brendel the Elder and the Younger, Werner Rolfinck, and Georg Wolfgang Wedel were four of the Jena professors who offered courses of chymistry during this time. These four held notably divergent views on the purpose, character, and legitimate content of chymistry, as well as of its proper place within the university. The distinctions among them prove especially clear in their widely differing assessments of metallic transmutation and of other longstanding chymical traditions and pursuits. Significantly, their sequential views do not form any linear progression over time. Instead, they illustrate the continuing disagreements and negotiations about chymistry, its role, and its identity as a discipline. The situation at Jena enriches our understanding of chymistry’s seventeenth-century “didactic tradition” and documents the internal diversity of the subject and of its professors and practitioners.

Maximum aerobic speed as a way to improve social interactions in rugby union

During the last decades, rugby union focused on players’ physical development as the main way of performance optimization. Consequently, a tremendous amount of research attention has been devoted to better understanding the main training parameters, neglecting however to study the effects of physical conditioning on group dynamics. In the present research, a quasi-experimental design in ecological conditions was used to analyze the effects of effort intensity on social interactions, especially during the rest periods of physical training. Semiprofessional rugby union players (N = 61; Mage = 23.78, SD = 7.03 years) participated in this study. They were randomly assigned to four conditions consisting of three 5-min runs. With counterbalancing, the participant sample was divided into four groups. A control group ran at 50% Maximum Aerobic Speed (MAS) while the three experimental groups ran at three different effort intensities (80%, 90%, and 100% MAS) in a counterbalanced order (i.e., linear increase/linear decrease/and quadratic evolution of effort intensity). The results showed a positive relationship between effort intensity and the number of intragroup social interactions during rest periods, this result being accrued at the end of the training session. Interestingly, the results suggested that ending a conditioning session at 100% MAS after a linear progression of effort intensity might influence social identity mobility between different levels of self-abstraction, leading to more cooperation between group members. Overall, this research offers a psychosocial view of training effects that invites academics and coaches to consider effort intensity as a way to develop social bonding in rugby. Lay summary: This study supports the perspective that “working hard” during conditioning influence social interactions between players. As a consequence, our results suggest that conditioning may be a powerful approach to build a feeling of “us-ness” that participates in optimizing group dynamics, and ultimately, performance in rugby. IMPLICATIONS FOR PRACTICE In order to benefit from the positive influence of conditioning on social interactions within a team coach should: • Prefer incremental conditioning ending at the highest intensity, to non-linear training • Encourage emotional expression norms by appointing congratulating behaviors during rest periods and more particularly at the end of the training session • Employ rest zone on the pitch so as to facilitate social bonding between players

Exercise intensity is associated with progression of coronary artery calcification in middle-aged and older athletes: findings from the MARC-2 study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation Background Recent studies have reported increased coronary artery calcification (CAC) in middle-aged male athletes, which is related to the amount and intensity of lifelong exercise. However, previous studies are limited by their cross-sectional study design. Purpose We prospectively assessed progression of CAC and its association to exercise volume and intensity in middle-aged and older athletes. Methods 318 asymptomatic middle-aged and older men were recruited in the Measuring Athlete’s Risk of Cardiovascular events (MARC) study between 2012-2014 and invited for follow-up (MARC-2) between 2019-2020. During both study visits, computed tomography imaging was performed to assess CAC. Exercise characteristics during follow-up were used to calculate exercise volumes (Metabolic equivalent of task [MET]-hours/week), whereas intensities were classified as moderate (3-6 MET), vigorous (6-9 MET) and very vigorous (>9 MET). For linear regression analyses, CAC scores were transformed (Ln delta CAC score + 1) and analyses were adjusted for baseline confounders, CAC at baseline and time between CT scans. Exercise intensities were assessed as proportion of MET-hrs/week and separately included, while adjusting for exercise volume. Results We included 289 men (54.9 ± 6.4 years) for MARC-2, with a follow-up of 6.3 ± 0.5 years. Participants exercised for 41 [25-57] MET-hrs/week, of which the median percentage was 0% [interquartile range 0-19] at moderate, 44% [0-84] at vigorous and 34% [0-80] at very vigorous intensity. At baseline, CAC was present in 151 (52%) men, and increased to 205 (71%) men at follow-up. CAC scores increased from 1 [0-32] to 31 [0-132]. Delta CAC score (26 [0-104]) was not associated with overall exercise volume. However, delta CAC score was negatively associated with vigorous intensity exercise and positively associated with very vigorous intensity exercise (Table). Conclusion Progression of CAC was not associated with overall exercise volume during 6-year follow-up. However, the degree of vigorous intensity exercise was associated with attenuated CAC progression, whereas very vigorous intensity exercise was associated with accelerated CAC progression. Linear regression analyses Progression of CAC (Ln Delta CAC score +1) B (95% CI) P-Value Exercise volume (MET-hours/week) .001 (-.005 - .008) .70 Exercise Intensity Moderate intensity (%) -.002 (-.009 - .005) .65 Vigorous intensity (%) -.005 (-.009 - .000) .03 Very vigorous intensity (%) .005 (.001 - .009) .02

Numbers do not add up! The pragmatic approach to the framing of medical treatments

AbstractThe risky choice framing effect disclosed that presenting data in a loss scenario lead decision-makers towards risky choices. Conversely, a gain scenario prevents them from taking a risk. Framing effect robustness has been widely confirmed by psychological literature. However, the framing of medical treatments, based on McNeil et al. (1982) paradigm, raised both methodological doubts and contrasting evidence. Our research aimed to investigate the presence and the nature of the framing effect in the McNeil et al. (1982) paradigm. In particular, we thought that the obtained switch of preferences across frames was due to a misleading formulation of the data given in a negative cumulative frequency format. We conducted three studies: (1) we replicated McNeil et al.’s (1982) original study (N=150) with medicine (n=50), statistics (n=50) and lay (n=50) students; (2) we tested (N=180) our hypothesis by comparing a cumulative frequency format with an alternative version, namely a linear progression one; (3) we compared (N=430) the effect of different formats (cumulative frequency, linear progression and interval frequency) on choices. Our results showed that, while the framing effect is present when employing a cumulative frequency format, it disappears when using a linear progression one. Moreover, our results show that decision-makers better understand information when given in a linear progression and an interval frequency format. In the current paper, we argue that the way in which a problem is formulated plays a relevant role in the representation of the decisional task and the decision-making.

Petrogenesis of Basaltic Lavas From the West Pacific Seamount Province: Geochemical and Sr‐Nd‐Pb‐Hf Isotopic Constraints

AbstractIn this study, we report new major and trace element, Sr‐Nd‐Pb‐Hf isotopic compositions and Ar‐Ar ages for basaltic lavas from seven poorly studied seamounts/guyots in the Western Pacific Seamount Province (WPSP). A review of new and published Ar‐Ar ages for seamounts/guyots confirm no linear age progression, as would be expected if these seamounts were produced by the Pacific Plate moving over a stationary mantle plume. These samples exhibit an alkalic character and can be produced by small‐degree partial melting of garnet pyroxenite with CO2. Their isotopic data identify four mantle end‐members (DMM, EMI, EMII, and HIMU) in the WPSP source region. These results confirm previous studies that invoke multiple contemporaneous plumelets in the region and a heterogeneous upper mantle reservoir which has been overprinted by multiple discrete hotspots, which create an anomalous and heterogeneous upper mantle because of mixing/overlapping EMI, EMII, and HIMU tracks, and age progressive volcanism is totally obscured. We propose a model where relict fragments of enriched mantle with distinct isotopic compositions residing in the upper mantle were a product of the formation of the adjacent large oceanic plateaus. These events introduce heterogeneity in the depleted mantle. The infiltration and metasomatism of these relict enriched components by carbonatitic fluids from the low‐velocity zone, create a source that then underwent small degrees of decompressional melting. The partial melts exploited pre‐existing lithospheric faults as an upwelling conduit and the resultant seafloor lava flows have obscured evidence to those pre‐existing lithospheric faults.

Education as an Evolutionary Phenomenon: Huxley, Waddington, and the Foundational Importance of Ethics

This essay sheds light on the “father of epigenetics,” Conrad Hal Waddington’s (1905–1975) tacit critique of one of the most prominent biologists of the twentieth century, Julian Huxley’s (1887–1975) theses concerning the evolutionary meaning and importance of learning and education for the human species. This topic has great significance today when it comes to educators both recognizing and being able to orient themselves in relation to the profound biological and evolutionary aspects of their role and purpose, and in determining their own ethos and modes of activity therein. Here, I highlight Waddington’s stance in relation to Julian Huxley’s thesis that education comprises humanity’s new “psycho-social,” or alternatively, “socio-genetic,” mode of biological inheritance parallel to, yet beyond, the “rawer” biological struggle for existence that most other living organisms are engaged in, namely, that involving natural selection acting on genes or genomes and the exigency of adapting successfully to the environment. According to Huxley, the gradual, yet cumulative, transmission of the knowledge and attainments of one generation to the next, over evolutionary time, via various modes of learning and education, has enabled the human species to have surpassed the capacities of all other organisms on the planet, such that it has become super-dominant. Waddington was in general agreement with Huxley’s thesis regarding the evolutionary significance of humanity’s learning and education here, as well as the latter’s notion that education is an epigenetic phenomenon, namely, comprising a distinct, yet interrelated inheritance system beyond that of genetic inheritance. However, Waddington tacitly disagreed with Huxley’s assertions that in light of such realizations, going forward: (1) humanity should exert the power of its selective agencies so as to take control of the biological processes of all life-forms on the planet; (2) formal education should be reformed into a function of evolutionary humanist ideology, eugenics, and transhumanism; (3) humanity ought to attempt to transcend its current capacities, as though there were a linear progression to some higher stage of biological development that is mechanistically calculable in advance. Waddington’s chief argument against Huxley is that this “socio-genetic” and/or epigenetic system of inheritance has part of its foundation in ethics and in the moral conduct of teacher and learner, and that Huxley’s inert vision of the future of education and of the role and conduct of educators therein are unethical. As such, for Waddington, Huxley’s view can be said to undermine the very inheritance system that has enabled humanity to reach its privileged place, rendering it unsustainable. From a Waddingtonian standpoint, Huxley’s stance is “biologically unwise” in that it undermines the teacher-learner relationship, given that it treats learners mechanistically, namely, as means only to the ends of evolutionary humanist and transhumanist ideology, rather than organismically, meaning as having selective agency and intrinsic worth (a notion that is grounded in the notion that living organisms are bearers of intrinsic purposiveness, as evidenced by the homeostatic, chronobiological, and autopoietic processes belonging to them which enable persistence in the face of entropy). On the contrary, Waddington calls for the cultivation of “biological wisdom” surrounding formal education (e.g., in relation to the aims of such education, its content, its curricula, the behaviour of educators, and the educational activities to be engaged in by learners), that would serve to strengthen the foundations of education qua humanity’s “psycho-social” inheritance system rather than to diminish or undermine it. Last, I associate the Waddingtonian notion of “biological wisdom” with the evolutionary-environmental ethic of “critical pan-selectionism.”

Monthly progression rates of the coral-killing sponge Terpios hoshinota in Sesoko Island, Okinawa, Japan

Terpios hoshinota is a black, encrusting sponge that hosts numerous symbiotic cyanobacteria in its tissues. The sponge often overgrows live scleractinian corals, thereby causing widespread and accelerated coral loss. However, our understanding of how subtropical waters influence the seasonal change in the progression rate of the sponge is poor. To elucidate the progression dynamics over a year, we obtained monthly measurements of linear progression of T. hoshinota (mm month−1) on the branching coral Montipora digitata in the subtropical waters of Sesoko Island, Okinawa, Japan from 2019 to 2020. The progression rate of T. hoshinota varied monthly throughout the year. The progression rates were the highest in summer (July, August, and October) with a mean value of 66 mm month−1, except in September, when strong typhoons came close to Okinawa and the progression rate decreased temporarily. The progression rates were the lowest in February 2020, at 9 mm month−1. The mean annual linear progression rate was estimated to be 28 mm month−1. Therefore, the progression dynamics of T. hoshinota could be linked to their growth mechanisms in relation to the seasonal changes in subtropical waters.

Phylogeny, function and ecology in the deep evolutionary history of the mammalian forelimb.

Mammals are the only living members of the larger clade Synapsida, which has a fossil record spanning 320 Ma. Despite the fact that much of the ecological diversity of mammals has been considered in the light of limb morphology, the ecological comparability of mammals to their fossil forerunners has not been critically assessed. Because of the wide use of limb morphology in testing ecomorphological hypothesis about extinct tetrapods, we sought: (i) to estimate when in synapsid history, modern mammals become analogues for predicting fossil ecologies; (ii) to document examples of ecomorphological convergence; and (iii) to compare the functional solutions of distinct synapsid radiations. We quantitatively compared the forelimb shapes of the multiple fossil synapsid radiations to a broad sample of extant Mammalia representing a variety of divergent locomotor ecologies. Our results indicate that each synapsid radiation explored different areas of morphospace and arrived at functional solutions that reflected their distinctive ancestral morphologies. This work counters the narrative of non-mammalian synapsid forelimb evolution as a linear progression towards more mammalian morphologies. Instead, a disparate array of early-evolving shapes subsequently contracted towards more mammal-like forms.

Childhood in urban China: A three-generation portrait

This article examines how the experience of childhood has changed in urban China against the backdrop of the wider political, social and economic transformations in the 20th century. Drawing on 95 life history interviews in three urban sites in China, it explores the nature, origins and impact of continuities and changes in childhood experiences across three generations. While expressive intimacy between the only-child generation and their parents increased, the three-generational comparison disputes previous theorizing about the modernization of childhood and the value of children based upon a Euro-American empirical reality. Rather than being trapped in a linear progression model, this article reveals that while the economic value of children as family helpers has dramatically reduced across three generations, the economic prospect of children as old age security goes hand in hand with the emotional value of children, which is shaped by the cultural tradition of filial piety, social welfare context and demographic structure. As a consequence, in contrast with the existing argument of an individualization of childhood in China, this article indicates that the youngest generation – the only-child generation – experienced an increasing regimentalization of childhood, exercised by their parents and driven by both neoliberal market and post-socialist state forces. This article also draws attention to the gender difference in childhood experience across three generations and reveals how the one-child policy has contributed to the increasing value of girls in urban China.

Linguistique sortant du placard

In this paper, I develop a holistic framework for an anti-disciplinary project based in and encompassing the intellectual critiques of colonialism, imperialism, and racism within linguistics in addition to subsuming queer and trans programs of linguistic thought in queering the science of language. This anti-disciplinary project presents a defense of iconoclastic forms of knowledge production that explicitly reject a priori assumptions of the orthodox linguistic canon’s primacy as a body of knowledge and seeks to engage ulterior and auxiliary modes of language science. In rejecting the notion of linear scientific progression – the humanist notion of progress as forward-facing – this project furthermore seeks to move beyond simple critiques, apologetics, and hagiographies and work toward a true repositioning of the field and a productive reimagination of the discipline. To that end, I outline four anti-disciplinary concepts – hetero-cistoriography, transcriptivism, decentralization, and systamatic professionalism – which I argue are productive points of departure from the institution of discipline.

Temporality and the aging self. How subjective time is folding over its linear progression

We were interested in how the retirement transition shapes the structure of time and how these changes, in turn, affect the way people see themselves. Conceptualized as a relation between subjective time and self-concept, we theorized that it can shed more light on the heterogeneity of aging processes at the individual level. We used the narrative method to collect 14 life stories among elders with different retirement tenure. Three distinct time-structuring modes occurring as a response to the retirement transition were identified using the constructivist grounded theory methodology. However, these temporal positions tended to shift in more senior cases, mostly as a response to the contingencies of later life guided by inner functions of reflexivity. Those changes were usually not sudden, eliciting interesting problems of blended temporalities and temporal persistence, which we argue accounts for the duration of these shifts. In conclusion, we develop a conceptual understanding of self-concept in relation to the folding of subjective time and its linear progression in the individual aging process.

1H-NMR Profiling Shows as Specific Constituents Strongly Affect the International EVOO Blends Characteristics: The Case of the Italian Oil.

Considering the growing number of extra virgin olive oil (EVOO) producers in the world, knowing the influence of olive oils with different geographical origins on the characteristics of the final blend becomes an interesting goal. The present work is focused on commercial organic EVOO blends obtained by mixing multiple oils from different geographical origins. These blends have been studied by 1H-NMR spectroscopy supported by multivariate statistical analysis. Specific characteristics of commercial organic EVOO blends originated by mixing oils from Italy, Tunisia, Portugal, Spain, and Greece were found to be associated with the increasing content of the Italian component. A linear progression of the metabolic profile defined characteristics for the analysed samples—up to a plateau level—was found in relation to the content of the main constituent of the Italian oil, the monocultivar Coratina. The Italian constituent percentage appears to be correlated with the fatty acids (oleic) and the polyphenols (tyrosol, hydroxytyrosol, and derivatives) content as major and minor components respectively. These results, which highlight important economic aspects, also show the utility of 1H-NMR associated with chemometric analysis as a powerful tool in this field. Mixing oils of different national origins, to obtain blends with specific characteristics, could be profitably controlled by this methodology.

Cerebrovascular Reactivity: Purpose, Optimizing Methods, and Limitations to Interpretation - A Personal 20-Year Odyssey of (Re)searching.

The brain is a neurovascular organ. A stimulus-response approach is effective in interrogating the physiology of its vasculature. Ideally, the stimulus is standardized across patients, and in a single patient over time. We developed a standard stimulus and attempted to measure, classify, and interpret the many forms of responses. Over the past 20 years, our work has delivered nuanced insights into normal cerebral vascular physiology, as well as adaptive physiological responses in the presence of disease. The trajectory of our understanding did not follow a logical linear progression; rather, it emerged as a coalescence of new, old, and previously dismissed, ideas that had accumulated over time. In this essay, we review what we believe were our most valuable – and sometimes controversial insights during our two decades-long journey.

자원 제약을 고려한 제안 프로젝트 포트폴리오 문제의 휴리스틱 기법

With regards to the various project to establish information system in the Korean software market, a company intending to win such project considers comprehensively the business detail, expected profits, and probability to win within available resources and comes to determine if to make an offer. Such judgement is one of the most important decision making affecting the overall business management like sales and revenue. Therefore, when the proposed project portfolio is defined as the composition of the project decided to be offered among the ordered projects, Cho, Yoon-Jae(2020) suggests a mathematical model of the problem of maximizing the sum of expected values in constituting the proposed project portfolio and an optimal solution accordingly.<BR> This paper assumes the concept of a project mode to be following: 1) the resources are limited, 2) a linear progression of the probability of the orders to be awarded as the duration of each activity increases, 3) the nature of the proposed project is reflected. Unlike previous studies, this research proposes a heuristic technique as a solution to the composition of the proposed project portfolio. The simulation in this study verifies the effectiveness and efficiency of the proposed algorithm as well.

How to survive a public faming: Understanding "The Spiciest Memelord" via the temporal dynamics of involuntary celebrification

Online public shaming has gained recent popular and academic attention as the tools of networked life are used to enforce societal norms against perceived deviant behavior. However, these acts of non-consensual identity formation do not necessarily need to be negative in nature. Indeed, similar dynamics can occur when an individual’s behavior aligns with societal expectations — a positive incident of involuntary celebrification, which we call “public faming”. These public famings remain understudied within celebrity and microcelebrity studies, despite the fact that more and more ordinary people are being suddenly propelled to short-lived meme fame. This paper seeks to understand the effect on individuals who are non-consensually elevated into the public eye by expanding our understanding of celebrification beyond a simple linear progression from not-famous to microcelebrity to celebrity. As a case study for this new framework, the author performs an autoethnography of her own experience from winning a trivia game show with an Internet-savvy answer, simultaneously giving extremely fleeting mainstream televised fame and viral internet fame. Our new framework of celebrity temporal dynamics allows us to not only understand how a person’s identity can be transformed into a media object subjected to corporations’ and strangers’ manipulations. We also introduce the tool of “radical reciprocity” to help victims of public faming understand potential paths for them to reclaim their narrative.