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We investigate Rindler's frame measurements. From its perspective, we found a geometric/gravitational interpretation of speed of light, mass and uncertainty principle. This can be interpreted as measurements of a black hole universal clock. This lead to an emergence of a timeless state of gravity in a mathematically consistent way. In other words, space my be a frozen time., Comment: 11 pages, 2 figures, reference added

Current debate in the metaphysics of time ordinarily assumes that we should be realists about time. Recently, however, a number of physicists and philosophers of physics have proposed that time will play no role in a completed theory of quantum gravity. This paper defends fictionalism about temporal thought, on the supposition that our world is timeless. We argue that, in the face of timeless physical theories, realism about temporal thought is unsustainable: some kind of anti‐realism must be adopted. We go on to provide an argument against eliminativism about temporal thought. While it doesn't follow from this argument that fictionalism about temporal thought is true, we suggest that this nonetheless shows that fictionalism should be regarded as the preferred view.

Named after the principle of eternal life represented by Savitur (sun) invoked in the most important verses of the Rigveda (the Gayatri), Savitri represents the continuing cycle of life and hope. In the process of her journeys, she travels to the forests as well as the other world (the world of death in this case) successfully returning her husband to life. Festivities and vows celebrating and recollecting her life are common across India. This chapter examines Savitri’s journey in the Mahabharata and Sri Aurobindo’s Savitri.

Background: In recent years, some studies have shown that TIMELESS, as an oncogene, is involved in the malignant progression of cancers. However, its relationship with the prognosis of glioma patients is rarely reported. Our purpose is to explore the role of TIMELESS in glioma. Main body: Based on 1814 glioma samples from multiple databases such as TCGA, CGGA, GEO, we use a variety of bioinformatics methods to verify the mechanism of action of TIMELESS in glioma from mRNA to protein, from appearance to mechanism analysis, from clinical features to prognosis. Then, use the CMap tool to predict potential drugs that inhibit the expression of TIMELESS. First, we found TIMELESS is highly expressed in glioma from the mRNA level to the protein level. Second, TIMELESS is an independent risk factor for prognosis and has a suitable clinical diagnosis value in glioma. It was also positively correlated with WHO grade, age, histology, and negatively correlated with IDH1 mutation and 1p19q codeletion. Third, Base excision, cell cycle, and mismatch repair pathway were activated by TIMELESS in glioma. At last, we predict small molecules that potentially inhibit TIMELESS such as 8-azaguanine, gw8510, 6-thioguanosine, and ursodeoxycholic acid. Conclusion: This study is the first comprehensive analysis of TIMELESS, revealing the relationship between the novel oncogene and the clinical characteristics of patients with glioma, and the mechanism leading to poor prognosis. It also provides a potential biomarker for the diagnosis and treatment of glioma. Our research hopes to reveal the pathological progress of glioma at the genetic level.

This paper explores the lived experiences of women working in journalism in the UK. To do this, 20 interviews were conducted with women who worked in newspapers and magazines from the 1970s to the present day. The research was conceptualised using Bourdieu’s concept of habitus and works previously conducted in journalism studies on blokish culture in newsrooms. The purpose of the paper was to further explore blokish culture in newsrooms by looking into expectations of women and the work culture. Thematic analysis was used in analysing findings. The results show that not much has changed in newsroom culture and interviewees who worked in journalism across decades report the same issue with blokish culture and cultural masculinity in work expectations. Besides, results show that women face both direct and indirect sexism and deeply entrenched blokish culture that impedes opportunities for women. Results indicate that the situation in women’s magazines, as predominantly female-led environments, is more relaxed and women who work in magazines do not report blokish culture. Finally, abductive analysis of results showed a link between early socialisation and blokishness expressed in newsrooms among women who internalised masculine habitus.

This text offers a questioning on the ending of Lost from a temporal and aesthetic angle. As it has been the source of many strong controversies, the conclusion of Lost gives us an opportunity to wonder about the way we watch the show. Through our deformulation theory, we shall analyze how fiction unravels before us while accomplishing the impossible junction of two antinomic temporal lines. The show sets up a strong connection with the TV viewer as it elaborates a final double-speech whose second listener is the TV viewer. Through a subtle and coherent final cut, the authors of Lost connect our experiences, the temporal lines, and the characters in a same goal: producing an emotional catharsis, whose scope tends to indefinitely engrave the fiction in the collective memory. Lost reminds us that the value of the ending also consists in having shared some affect with someone else, since Lost is a fiction about Lost characters who, during the last moments of the fiction, find themselves. Ce texte propose de s’interroger sur la fin de Lost sous un angle temporel et esthétique. Source de nombreux débats intenses, la conclusion de Lost nous offre une occasion de nous interroger sur notre manière de regarder la série. En nous appuyant sur notre théorie de la déformulation, nous analyserons la manière dont la fiction se défait sous nos yeux tout en réalisant l’impossible jonction de deux lignes temporelles antinomiques. La série établit un lien fort avec le téléspectateur en élaborant un double discours final dont le second destinataire est le téléspectateur. Par un montage final subtil et cohérent, les auteurs de Lost lient nos expériences, les lignes temporelles, les personnages dans un même but, provoquer une catharsis émotionnelle, dont la portée, tend à inscrire la fiction dans la mémoire collective de manière indéfinie. Lost nous réapprend que la fin a de la valeur dans la mesure où nous avons partagé des affects avec autrui. Parce que Lost est une fiction sur des personnages perdus qui, dans les derniers instants de la fiction, se trouvent.

Mosquitoes exhibit activity rhythms, crucial for the transmission of pathogens, under the control of a circadian clock.Aedes aegyptiis one of the world’s leading vectors. For decades, several studies have linked the rise in ambient temperature with the increase in their activity. Here, we identify candidate genes whose expression is influenced by temperature cycles and may affectAedeslocomotor activity. We observed thattimelesscompletely lost its rhythmic expression in light/dark, with out-of-phase temperature cycles, and by RNAi mediated knockdown ofnocte, an important gene forDrosophilacircadian synchronization by temperature cycles. Thus,timelessandnocteare important genes for synchronization by temperature cycles inAedes aegypti. To reinforce our findings, we simulated in the laboratory the gradual temperature fluctuations that were as close as possible to daily temperature variations in Brazil. We observed that the activity and the expression of the molecular circadian clock ofAe. aegyptidiffers significantly from that of mosquitoes subjected to constant or rectangular abrupt changes in temperature. We suggest that for understanding the circadian behavior ofAedeswith possible implications for intervention strategies, the seminatural paradigm needs to replace the traditional laboratory study.

Chronotype is an important moderator of psychiatric illnesses, which seems to be controlled in some part by genetic factors. Clock genes are the most relevant genes for chronotype. In addition to the roles of individual genes, gene-gene interactions of clock genes substantially contribute to chronotype. We investigated genetic associations and gene-gene interactions of the clock genes BHLHB2, CLOCK, CSNK1E, NR1D1, PER1, PER2, PER3, and TIMELESS for chronotype in 1,293 healthy Korean individuals. Regression analysis was conducted to find associations between single nucleotide polymorphism (SNP) and chronotype. For gene-gene interaction analyses, the quantitative multifactor dimensionality reduction (QMDR) method, a nonparametric model-free method for quantitative phenotypes, were performed. No individual SNP or haplotype showed a significant association with chronotype by both regression analysis and single-locus model of QMDR. QMDR analysis identified NR1D1 rs2314339 and TIMELESS rs4630333 as the best SNP pairs among two-locus interaction models associated with chronotype (cross-validation consistency [CVC] = 8/10, p = 0.041). For the three-locus interaction model, the SNP combination of NR1D1 rs2314339, TIMELESS rs4630333, and PER3 rs228669 showed the best results (CVC = 4/10, p < 0.001). However, because the mean differences between genotype combinations were minor, the clinical roles of clock gene interactions are unlikely to be critical.

Many insects show daily and circadian changes in morphology and physiology in their compound eye. In this study, we investigated whether the compound eye had an intrinsic circadian rhythm in the cricket Gryllus bimaculatus. We found that clock genes period (per), timeless (tim), cryptochrome 2 (cry2), and cycle (cyc) were rhythmically expressed in the compound eye under 12-h light/12-h dark cycles (LD 12:12) and constant darkness (DD) at a constant temperature. After the optic nerves were severed (ONX), a weak but significant rhythmic expression persisted for per and tim under LD 12:12, while under DD, tim and cyc showed rhythmic expression. We also found that more than half of the ONX compound eyes exhibited weak but significant circadian electroretinographic rhythms. These results clearly demonstrate that the cricket compound eye possesses an intrinsic circadian oscillator which can drive the circadian light sensitivity rhythm in the eye, and that the circadian clock in the optic lobe exerts its influence on the oscillator in the eye.

2020 will go down in history as a tipping point when societies reassessed the fundamental objectives and principles that they had seen their communities develop. As a basis for investigating a broad sense of LifeStyle by Design, some 20 potentially rich narratives are used as the basis for these empirical analyses. They are our Virtual Living Lab at a time of unparalleled attitudinal and behavioural change and uncertainty. Social sharing is more authentic and trustworthy than traditional forms of mass communications. We explore our narratives in the UK and Japan and draw novel yet consistent, scalable implications for policy makers and public and private institutions alike. We track what people think is important to them and thus lay a foundation for engagement, in contrast to the traditional advertising communications approach of intrusion. Some of the new behaviours may become permanent, but there is a general need to streamline and simplify. People are against the complex, not because they want a simple life but because they want more time to enjoy enriched life experiences. At times of change, especially when uncertainty can bring negative outcomes, it is critical to be able to know what to say and how to say it so that leaders can establish trust and the right tone for the moment.

The circadian clock generates rhythms of approximately 24 h through periodic expression of the clock genes. In insects, the major clock genes period (per) and timeless (tim) are rhythmically expressed upon their transactivation by CLOCK/CYCLE, with peak levels in the early night. In Drosophila, clockwork orange (cwo) is known to inhibit the transcription of per and tim during the daytime to enhance the amplitude of the rhythm, but its function in other insects is largely unknown. In this study, we investigated the role of cwo in the clock mechanism of the cricket Gryllus bimaculatus. The results of quantitative RT-PCR showed that under a light/dark (LD) cycle, cwo is rhythmically expressed in the optic lobe (lamina-medulla complex) and peaks during the night. When cwo was knocked down via RNA interference (RNAi), some crickets lost their locomotor rhythm, while others maintained a rhythm but exhibited a longer free-running period under constant darkness (DD). In cwoRNAi crickets, all clock genes except for cryptochrome 2 (cry2) showed arrhythmic expression under DD; under LD, some of the clock genes showed higher mRNA levels, and tim showed rhythmic expression with a delayed phase. Based on these results, we propose that cwo plays an important role in the cricket circadian clock.

This study aims to examine factors that influence the timeless of financial report. The independent variable of this research are profitability, firmsize, and the public ownership, while the dependent variable is timeless. The population of this research are property and real estate companies which are listed in Indonesian Stock Exchange 2011-2014. The sample in this research is taken by using purposive sampling method with some carracteristics and consist of 30 companies. This research used secondary data from www.idx.co.id and the method of analysis used logistic regression analysis. The results show that the profitability is significantly influenced to the timeless of financial report, while both the firmsize and public ownership are not significantly influenced the timeless of financial report.

Protecting replication fork integrity during DNA replication is essential for maintaining genome stability. Here, we report that SDE2, a PCNA-associated protein, plays a key role in maintaining active replication and counteracting replication stress by regulating the replication fork protection complex (FPC). SDE2 directly interacts with the FPC component TIMELESS (TIM) and enhances its stability, thereby aiding TIM localization to replication forks and the coordination of replisome progression. Like TIM deficiency, knockdown of SDE2 leads to impaired fork progression and stalled fork recovery, along with a failure to activate CHK1 phosphorylation. Moreover, loss of SDE2 or TIM results in an excessive MRE11-dependent degradation of reversed forks. Together, our study uncovers an essential role for SDE2 in maintaining genomic integrity by stabilizing the FPC and describes a new role for TIM in protecting stalled replication forks. We propose that TIM-mediated fork protection may represent a way to cooperate with BRCA-dependent fork stabilization., The fork protection complex (FPC), including the proteins TIMELESS and TIPIN, stabilizes the replisome to ensure unperturbed fork progression during DNA replication. Here the authors reveal that that SDE2, a PCNA-associated protein, plays an important role in maintaining active replication and protecting stalled forks by regulating the replication fork protection complex (FPC).

How the replisome senses and deals with DNA secondary structures has been a mystery. A new study from the Sale and Pellegrini laboratories finds that the Timeless protein has a G-quadruplex binding domain that works together with the DDX11 helicase to facilitate replication of G4 DNA structures.

The aim of the research was to reveal the effectiveness of the use of the Robinson Strategy (SQ3R) in the development of reading absorption among middle-class second-grade students in the course of my timeless language course in Mecca. There are statistically significant differences at the level of significance (α≤0.05) between the average scoring of reading absorption skills (literal, inference, and monetary) in application (tribal-dimensional) in favor of the experimental group, and between the effect of the Robinson Strategy (SQ3R) in the development of reading absorption among middle-school students, the researcher recommended several recommendations, the most important of which is the use of the Robinson Strategy (SQ3R) in the teaching of Arabic language for the purposes of achieving effective learning.

Circadian rhythms, which are ubiquitous and adaptive, occur across all species, from microbes to humans, in which they organize and modify behavior and physiology. timeless (tim) is a canonical clock gene. The core composition of the Drosophila melanogaster endogenous circadian clock has been extensively investigated; however, in lepidopteran insects, including Bombyx mori, the mechanism is complicated and little is known regarding the participation of tim in the negative feedback loop responsible for behavioral activities. To arrive at a comprehensive understanding of the role of tim in the B. mori endogenous circadian clock, we exploited the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 gene editing system. We attempted to elucidate the functions of tim in the circadian clock of B. mori using Bmtim mutants. The knockouts affected two circadian behavioral activities: adult emergence and embryo hatching rhythms. Quantitative real-time polymerase chain reaction results confirmed that tim-knockouts induced relative reductions in the expression levels, and thereby the oscillation amplitudes, of Bmper and Bmclk messenger RNAs during both the photophase and scotophase. Additionally, the daily rhythmic expression of Bmdbt was upregulated in the photophase and downregulated in the scotophase in a tim-knockout. Our study reveals that tim is integral to the B. mori circadian clock and may be involved in regulating eclosion and hatching rhythms.

The concept of entanglement is at the heart of quantum physics. It plays a central role in all quantum phenomena involving composite systems. Interestingly, there is an intriguing idea that has attracted considerable attention recently, according to which quantum entanglement may also be essential for understanding the very emergence of time and dynamical evolution. Within this point of view, sometimes referred to as the timeless picture of quantum dynamics, the Universe is regarded as consisting of a clock and a system (or "rest of the Universe") that are jointly in a stationary quantum state, and time evolution arises as an emergent phenomenon rooted at the entanglement between the clock and the system. Here we provide a pedagogical and self-contained exposition, at the upper undergraduate level, of the role of entanglement in this timeless evolution approach to quantum mechanics. In particular, we give a detailed explanation of how the entanglement between the clock and the system is directly and quantitatively related to the average distinguishability between the states of the system at different times. Fil: Valdés-Hernández, A.. Universidad Nacional Autónoma de México; México Fil: Maglione, Cesar German. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina Fil: Majtey, Ana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina Fil: Plastino, Ángel Ricardo. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Bioinvestigaciones (Sede Junín); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

A new understanding of the hydrogenoid atoms, both in the non-relativistic domain and for the relativistic Dirac electron, as well as regarding the phenomenon of the Lamb shift, is provided in a model based on energy fluctuations of a timeless three-dimensional quantum vacuum corresponding to elementary processes of creation/annihilation of quanta.

Nucleic acids research / Special publication 48(12), 6996 - 7004 (2020). doi:10.1093/nar/gkaa456, The Tof1–Csm3 fork protection complex has a central role in the replisome—it promotes the progression of DNA replication forks and protects them when they stall, while also enabling cohesion establishment and checkpoint responses. Here, I present the crystal structure of the Tof1–Csm3 complex from Chaetomium thermophilum at 3.1 Å resolution. The structure reveals that both proteins together form an extended alpha helical repeat structure, which suggests a mechanical or scaffolding role for the complex. Expanding on this idea, I characterize a DNA interacting region and a cancer-associated Mrc1 binding site. This study provides the molecular basis for understanding the functions of the Tof1–Csm3 complex, its human orthologue the Timeless–Tipin complex and additionally the Drosophila circadian rhythm protein Timeless., Published by Information Retrieval Ltd.21517, London

We study a localization of gravity through the matching point between non-inertial frames and local inertial frames. This localization of gravity is done through defining relative gravitational red-shift. This lead to an emergence of a timeless state in a mathematically consistent way. In this timeless state of gravity, we find a geometric interpretation of the speed of light and mass. The experimental support of the timeless state is the quantum entanglement and internal symmetries that are independent of time. Therefore gravity would be responsible for measurements independent of time including quantum entanglement. Timeless state in that sense explain why do we have gravity/gauge correspondence. We conjecture that the universe emerged from a black hole with a global $SU(3)\times SU(2)\times U(1)$ symmetry on its event horizon that produces gauge fields Electromagnetism, weak and strong nuclear force through localization of this global symmetry. Through the localization in the gravity field, the timeless measurements such as spin will be correlated with the varying of timeless measurement which is relative gravitational red-shift. We present a gravitational or geometric interpretation of spin-0, spin-1, and spin-1/2 states. We present an interpretation of why do we measure matter rather than anti-matter. We found that the Higgs scalar field is represented by the gravitational red-shift at every point in the space around the black hole. We derive the numerical value of the cosmological constant that agrees with experimental observations.

The modern Celtic myth is a complex framework because of its variety of constituent elements. In essence, it consists of an empathetic celebration of otherness, based on a timeless narrativ...

This paper presents a review on the fundamental performance limitations and design tradeoffs of feedback control systems, ranging from classical performance tradeoff issues to the more recent information-theoretic analysis, and from conventional feedback systems to networked control systems, with an attempt to document some of the key achievements in more than seventy years of intellectual inquiries into control performance limitation studies, as so embodied by the timeless contributions of Bode known as the Bode integral relations.

We investigate the matching point between non-inertial frames and local inertial frames. This localization of gravity lead to an emergence of a timeless state of the universe in a mathematically consistent way. We find a geometric interpretation of the speed of light and mass. I find also a relation between every mass measured and the black hole entropy which introduces an information-matter equation from gravity. The experimental evidence of the timeless state of the universe is the quantum entanglement. Since the spin measurement is the manifestation of quantum entanglement measurement. Therefore, the internal spin of quantum particles can be understood as a relative gravitational red-shift at two different points. Therefore the spin measurements introduce the quantum gravity measurements in local inertial frames. We found that uncertainty is reduced as the measurements happens closely to the gravitational source. Least computations of gravitational measurement is achieved when the relative gravitational red-shift is equal to the difference in gravitational red-shift.

I localize gravity to match its measurements with the local inertial frame of special relativity. I find a geometric interpretation of the speed of light and mass. I find also a relation between every mass measured and the black hole entropy which introduces information-matter equation from gravity. Through localization of gravity, a timeless state of the universe emerges and the uncertainty principle does not hold since the velocity concept is replaced by distance in this timeless state. This would resolve the problem of time because timeless state of the universe emerges naturally and mathematically consistent. This would suggest that gravity form the hidden one variable of quantum mechanics which would complete the relation between quantum mechanics and gravity. The experimental evidence of timeless state of the universe is the quantum entanglement. Since the spin measurement is the manifestation of quantum entanglement. Therefore, the spin of quantum particle can be originated from geometrical or gravitational red-shift. We introduce also a principle of least computation which is achieved when the ratio equal to the difference in the process of local gravitational measurements.

Daily temporal organisation of behavioural and physiological functions offers a fitness advantage for most animals. Optimized temporal niches are determined by an interplay between external environmental rhythms and internal circadian clocks. While daily light:dark cycles serve as a robust time cue (Zeitgeber) to synchronise circadian clocks, it is not clear how animals experiencing only weak environmental cues deal with this problem. Like humans, flies of the genus Drosophila originate in sub-Saharan Africa and spread North in Europe up to the polar circle where they experience extremely long days in the summer or even constant light (LL). LL is known to disrupt clock function, due to constant activation of the deep brain photoreceptor CRYPTOCHROME (CRY), which induces constant degradation of the clock protein TIMELESS (TIM). Temperature cycles are able to overcome these arrhythmia inducing effects of LL, reinstating clock protein oscillations and rhythmic behaviour. We show here that for this to occur a recently evolved natural allele (ls-tim) of the timeless gene is required, whereby the presence of this allele within the central clock neurons is sufficient. The ls-tim allele encodes a longer, less-light sensitive form of TIM (L-TIM) in addition to the shorter (S-TIM) form, the only form encoded by the ancient s-tim allele. Only after blocking light-input by removing functional CRY, s-tim flies are able to synchronise molecular and behavioural rhythms to temperature cycles in LL. Additional removal of light input from the visual system results in a phase advance of molecular and behavioural rhythms, showing that the visual system contributes to temperature synchronization in LL. We show that ls-tim, but not s-tim flies can synchronise their behavioural activity to semi-natural LL and temperature cycle conditions reflecting long Northern Europe summer days, the season when Drosophila populations massively expand. Our observations suggest that this functional gain associated with ls-tim is driving the Northern spread of this allele by directional selection.

SummaryThe daily changes of light and dark exemplify a prominent cue for the synchronization of internal circadian clocks to external time. The match between external and internal time is crucial for the fitness of organisms and desynchronization has been linked to numerous physical and mental health problems in humans. Organisms therefore developed complex and not fully understood mechanisms to synchronize their circadian clock to light. In mammals and in Drosophila both the visual system and dedicated non-image forming photoreceptors contribute to light resetting of the circadian clock. In the fruit fly, light-dependent degradation of the clock protein TIMELESS (TIM) by the blue light photoreceptor Cryptochrome is considered the main mechanism for clock synchronization, although the visual system also contributes. In order to understand the nature of the visual system contribution, we generated a genetic variant exhibiting extremely slow phototransduction kinetics, yet normal sensitivity. We show that in this variant the visual system is able to contribute its full share to circadian clock entrainment, both with regard to behavioral and molecular synchronization to light:dark cycles. This function depends on an alternative Phospholipase C-ß enzyme, encoded by PLC21C, presumably playing a dedicated role in clock resetting by light. We show that this pathway requires the ubiquitin ligase CULLIN-3, presumably mediating CRY-independent degradation of TIM during light:dark cycles. Our results suggest that visual system contribution to circadian clock entrainment operates on a drastically slower time scale compared with fast, visual and image forming phototransduction. Our findings are therefore consistent with the general idea that the visual system samples light over prolonged periods of time (hours) in order to reliably synchronize their internal clocks with the external time.

Summary The daily changes of light and dark exemplify a prominent cue for the synchronization of circadian clocks with the environment. The match between external and internal time is crucial for the fitness of organisms, and desynchronization has been linked to numerous physical and mental health problems. Organisms therefore developed complex and not fully understood mechanisms to synchronize their circadian clock to light. In mammals and in Drosophila, both the visual system and non-image-forming photoreceptors contribute to circadian clock resetting. In Drosophila, light-dependent degradation of the clock protein TIMELESS by the blue light photoreceptor Cryptochrome is considered the main mechanism for clock synchronization, although the visual system also contributes. To better understand the visual system contribution, we generated a genetic variant exhibiting extremely slow phototransduction kinetics, yet normal sensitivity. In this variant, the visual system is able to contribute its full share to circadian clock entrainment, both with regard to behavioral and molecular light synchronization. This function depends on an alternative phospholipase C-β enzyme, encoded by PLC21C, presumably playing a dedicated role in clock resetting. We show that this pathway requires the ubiquitin ligase CULLIN-3, possibly mediating CRY-independent degradation of TIMELESS during light:dark cycles. Our results suggest that the PLC21C-mediated contribution to circadian clock entrainment operates on a drastically slower timescale compared with fast, norpA-dependent visual phototransduction. Our findings are therefore consistent with the general idea that the visual system samples light over prolonged periods of time (h) in order to reliably synchronize their internal clocks with the external time.

We have used the Cambridge Protein Trap resource (CPTI) to screen for flies whose locomotor rhythms are rhythmic in constant light (LL) as a means of identifying circadian photoreception genes. From the screen of ∼150 CPTI lines, we obtained seven hits, two of which targeted the glutamate pathway, Got1 (Glutamate oxaloacetate transaminase 1) and Gs2 (Glutamine synthetase 2). We focused on these by employing available mutants and observed that variants of these genes also showed high levels of LL rhythmicity compared with controls. It was also clear that the genetic background was important with a strong interaction observed with the common and naturally occurring timeless (tim) polymorphisms, ls-tim and s-tim. The less circadian photosensitive ls-tim allele generated high levels of LL rhythmicity in combination with Got1 or Gs2, even though ls-tim and s-tim alleles do not, by themselves, generate the LL phenotype. The use of dsRNAi for both genes as well as for Gad (Glutamic acid decarboxylase) and the metabotropic glutamate receptor DmGluRA driven by clock gene promoters also revealed high levels of LL rhythmicity compared to controls. It is clear that the glutamate pathway is heavily implicated in circadian photoreception. TIM levels in Got1 and Gs2 mutants cycled and were more abundant than in controls under LL. Got1 but not Gs2 mutants showed diminished phase shifts to 10 min light pulses. Neurogenetic dissection of the LL rhythmic phenotype using the gal4/gal80 UAS bipartite system suggested that the more dorsal CRY-negative clock neurons, DNs and LNds were responsible for the LL phenotype. Immunocytochemistry using the CPTI YFP tagged insertions for the two genes revealed that the DN1s but not the DN2 and DN3s expressed Got1 and Gs2, but expression was also observed in the lateral neurons, the LNds and s-LNvs. Expression of both genes was also found in neuroglia. However, downregulation of glial Gs2 and Got1 using repo-gal4 did not generate high levels of LL rhythmicity, so it is unlikely that this phenotype is mediated by glial expression. Our results suggest a model whereby the DN1s and possibly CRY-negative LNds use glutamate signaling to supress the pacemaker s-LNvs in LL.

In 1941 Ernestine Hill published My Love Must Wait, a biographical novel based on the life of navigator Matthew Flinders. In the same year, Eleanor Dark published The Timeless Land, imagining the arrival of European settlers in the Sydney region from the perspectives of multiple historical figures. In this article we examine how each author represents the important figure of Bennelong, a man of the Wangal people who was kidnapped by Governor Phillip and who later travelled to England with him. While both works can be criticized as essentialist, paternalist or racist, there are significant differences in the ways each author portrays him. We argue that Dark’s decision to narrate some of her novel from the point of view of Bennelong and other Indigenous people enabled different understandings of Australian history for both historians and fiction writers. Dark’s “imaginative leap”, as critic Tom Griffiths has termed it, catalysed a new way of thinking about the 1788 invasion and early decades of the colonization of Australia. The unfinished cultural work undertaken by these novels continues today, as demonstrated by subsequent Australian novels which revisit encounters between Indigenous inhabitants and European colonists, including Thomas Keneally’s The Chant of Jimmie Blacksmith (1972), Richard Flanagan’s Wanting (2008), and Rohan Wilson’s The Roving Party (2011). Like Dark, these authors situate parts of their novels within the consciousness of Indigenous figures from the historical record. We analyse the diverse challenges and possibilities presented by these literary heirs of Eleanor Dark.

This article provides a historical perspective to understand better whether hospitality persists as a measure of society across contexts. Focusing on Homer and later Tragedians, it charts ancient literature’s deep interest in the tensions of balancing obligations to provide hospitality and asylum, and the responsibilities of well-being owed to host-citizens by their leaders. Such discourse appears central at key transformative moments, such as the Greek polis democracy of the fifth century BCE, hospitality becoming the marker between civic society and the international community, confronting the space between civil and human rights. At its center was the question of: Who is the host? The article goes on to question whether the seventeenth-century advent of the nation state was such a moment, and whether in the twenty-first century we observe a shift towards states’ treatment of their own subjects as primary in measuring society, with hospitality becoming the exception to be explained.

The article reproduces a slightly edited author’s ‘personal manifesto’ presented as a paper at a Workshop on the ‘Future of World Order’ in Tripoli, Libya in May 2003. The present version contains some further thoughts topical in the present time. As originally presented the paper sought to address four major issues: US domination in the newly mono-polar world; the pathologies of international power relations in a world characterised by huge disparities in access to multiple technologies; differing, hierarchically-structured patterns of organising and containing inter- and intra-national conflicts; and the need for moral, political and intellectual leadership in the then Brave New World of US hegemony.

The animal circadian timing system interprets environmental time cues and internal metabolic status to orchestrate circadian rhythms of physiology, allowing animals to perform necessary tasks in a time-of-day-dependent manner. Normal progression of circadian rhythms is dependent on the daily cycling of core transcriptional factors that make up cell-autonomous molecular oscillators. InDrosophila, PERIOD (PER), TIMELESS (TIM), CLOCK (CLK), and CYCLE (CYC) are core clock proteins that function in a transcriptional–translational feedback mechanism to regulate the circadian transcriptome. Posttranslational modifications of core clock proteins provide precise temporal control over when they are active as regulators of clock-controlled genes. In particular, phosphorylation is a key regulatory mechanism that dictates the subcellular localization, stability, and transcriptional activity of clock proteins. Previously, casein kinase 1α (CK1α) has been identified as a kinase that phosphorylates mammalian PER1 and modulates its stability, but the mechanisms by which it modulates PER protein stability is still unclear. UsingDrosophilaas a model, we show that CK1α has an overall function of speeding up PER metabolism and is required to maintain the 24 h period of circadian rhythms. Our results indicate that CK1α collaborates with the key clock kinase DOUBLETIME (DBT) in both the cytoplasm and the nucleus to regulate the timing of PER-dependent repression of the circadian transcriptome. Specifically, we observe that CK1α promotes PER nuclear localization by antagonizing the activity of DBT to inhibit PER nuclear translocation. Furthermore, CK1α enhances DBT-dependent PER phosphorylation and degradation once PER moves into the nucleus.SIGNIFICANCE STATEMENTCircadian clocks are endogenous timers that integrate environmental signals to impose temporal control over organismal physiology over the 24 h day/night cycle. To maintain the 24 h period length of circadian clocks and to ensure that circadian rhythms are in synchrony with the external environment, key proteins that make up the molecular oscillator are extensively regulated by phosphorylation to ensure that they perform proper time-of-day-specific functions. Casein kinase 1α (CK1α) has previously been identified as a kinase that phosphorylates mammalian PERIOD (PER) proteins to promote their degradation, but the mechanism by which it modulates PER stability is unclear. In this study, we characterize the mechanisms by which CK1α interacts with DOUBLETIME (DBT) to achieve the overall function of speeding up PER metabolism and to ensure proper time-keeping.

Eternity could be considered as both timeless “now” as well as the totalityof infinite time. In Western thought those two notions (or two meanings) coexist fora long time, however their senses, origins and context of functioning are different. Distinctionbetween those two meanings leads us to better comprehension of the very co cept of the eternity, and also provides us an useful tools to solve some classical philosophicalproblems connected with this concept, for example: problems of the eternity of the mathematics truths, eternity of the God or of the world.

Whether cardiac output in decapod crustaceans is under circadian control has long been debated, with mixed evidence for and against the hypothesis. Moreover, the locus of the clock system controlling cardiac activity, if it is under circadian control, is unknown. However, a report that the crayfish heart in organ culture maintains a circadian oscillation in heartbeat frequency suggests the presence of a peripheral pacemaker within the cardiac neuromuscular system itself. Because the decapod heart is neurogenic, with contractions controlled by the five motor and four premotor neurons that make up the cardiac ganglion (CG), a likely locus for a circadian clock is the CG itself. Here, a CG-specific transcriptome was generated for the lobster, Homarus americanus, and was used to assess the presence/absence of transcripts encoding putative clock-related proteins in the ganglion. Using known Homarus brain/eyestalk ganglia clock-related proteins as queries, BLAST searches of the CG transcriptome were conducted for the five proteins that form the core clock, i.e., clock, cryptochrome 2, cycle, period and timeless, as well as for a variety of clock-associated, clock input pathway and clock output pathway proteins. With the exception of pigment dispersing hormone receptor [PDHR], a putative clock output pathway protein, one or more transcripts encoding each of the proteins searched for were identified from the CG assembly; no PDHR-encoding transcripts were found. RT-PCR confirmed the expression of all core clock transcripts in multiple independent CG cDNAs; RNA-Seq data suggest that both the motor and premotor neurons could contribute to the cellular locus of a pacemaker. These data provide support for the possible existence of an intrinsic circadian clock in the H. americanus CG, and form a foundation for guiding future anatomical, molecular and physiological investigations of circadian signaling in the lobster cardiac neuromuscular system.

Most living organisms developed the innate clock system to anticipate daily environmental changes and to enhance their chances of survival. timeless (tim) is a canonical clock gene. It has been extensively studied in Drosophila melanogaster (Diptera: Drosophilidae) as a key component of the endogenous circadian clock, but its role is largely unknown in some agriculture pests. Laodelphax striatellus (Fallén) (Hemiptera: Delphacidae), an important rice pest, exhibits a robust locomotor rhythm. In the present study, we cloned tim gene (ls-tim) from L. striatellus and investigated its function in the regulation of behavioral rhythms. Quantitative real-time polymerase chain reaction revealed a circadian expression pattern of ls-tim under different light conditions with a trough in the photophase and a peak in the late scotophase. After the knockdown of ls-tim via RNA interference (RNAi), the adults showed an earlier onset of locomotor activity under light/dark cycles and became arrhythmic in constant darkness. ls-tim RNAi also abolished the timing of adult emergence that normally occurs in the early photophase. These results suggest that ls-tim is essential for the light-entrained circadian rhythms in L. striatellus and provide more insights into the endogenous clock network underlying the behavioral and physiological rhythms of this insect.

The question of voice is a central and timeless political issue. Who gets to speak? Who is silenced? Who is listening? One of the main arenas for voice in modern, advanced democracies is the media. Media infrastructures, technologies, institutions and organizations are a precondition for political voice in large-scale societies, but are also an important factor in distributing the possibilities for voice among different groups and sectors of the population. In this article, we take on the question of voice in relation to social class and aim to analyse how the medium of television gives voice to people from different social classes. This study operationalizes the theoretical notion of voice by asking the following questions: who has the opportunity to appear and speak on television, to whom do they speak and under what circumstances does this communication occur? Based on a content analysis of television in Sweden, the results from this study show that voice is distributed in a highly unequal manner. It also shows that the relations enacted by television appearances conform to the social hierarchy. Whereas people from the ruling class frequently speak to people from the working and middle classes, they are rarely spoken to by members of a class that is positioned below their own. Television thus constructs a social hierarchy of voice and authority that reproduces and legitimizes already existing social hierarchies.