Using Simian Virus 40 As A Model To Determine The Effects Of Replication And Transcription On Histone Methylation

ABSTRACT Simian Virus 40 (SV40) is a well-characterized virus whose small circular DNA genome is organized into chromatin and, as a consequence, undergoes many of the same biological processes observed in cellular chromatin. SV40 early transcription is repressed when the product of early transcription, T-antigen, binds to its cognate regulatory sequence, Site I, in the promoter of the SV40 minichromosome. We have subsequently shown that T-antigen binding to Site I results in the replication-dependent introduction of H3K9me1 into SV40 chromatin late in infection. Since H3K9me2 and H3K9me3 are also present late in infection, we determined whether their presence was also related to the status of ongoing transcription and replication. In order to determine the capacity of SV40 epigenetic regulation, we have analyzed SV40 chromatin from minichromosomes and virions for the presence of modified histones using various ChIP techniques and correlated these modifications with specific biological effects on the SV40 life cycle. Since repression is frequently epigenetically marked by the introduction of specific forms of methylated histone H3, we characterized the methylation of H3 tails during transcription and replication in wild-type SV40 minichromosomes and mutant minichromosomes which did not repress T-antigen expression. While repressed minichromosomes following replication were clearly marked with H3K9me1 and H3K4me1, minichromosomes repressed during early transcription were not similarly marked. Instead repression of early transcription was marked by a significant reduction in the level of H3K9me2. The replication dependent introduction of H3K9me1 and H3K4me1 into wild-type SV40 minichromosomes was also observed when replication was inhibited with aphidicolin. We observed that H3K9me2/me3 was specifically introduced when transcription was inhibited during active replication. The introduction of H3K9me2/me3 that occurred when transcription was inhibited was partially blocked when replication was also inhibited. The introduction of H3K9me2/me3 did not require the presence of H3K9me1 since similar results were obtained with the mutant cs1085 whose chromatin contains very little H3K9me1. Our results demonstrate that, like its cellular counterpart, SV40 chromatin is capable of passing biologically relevant transgenerational epigenetic information between infections. Our data suggest that methylation of H3K9 can occur either as a consequence of a specific repressive event such as T-antigen binding to Site I or as a result of a general repression of transcription in the presence of active replication. The results suggest that the nonproductive generation of transcription complexes as occurs following DRB treatment may be recognized by a \u27proof reading\u27 mechanism, which leads to the specific introduction of H3K9me2 and H3K9me3

Tissue- and Species-Specific Patterns of RNA metabolism in Post-Mortem Mammalian Retina and Retinal Pigment Epithelium.

Accurate analysis of gene expression in human tissues using RNA sequencing is dependent on the quality of source material. One major source of variation in mRNA quality is post-mortem time. While it is known that individual transcripts show differential post-mortem stability, few studies have directly and comprehensively analyzed mRNA stability following death, and in particular the extent to which tissue- and species-specific factors influence post-mortem mRNA stability are poorly understood. This knowledge is particularly important for ocular tissues studies, where tissues obtained post-mortem are frequently used for research or therapeutic applications. To directly investigate this question, we profiled mRNA levels in both neuroretina and retinal pigment epithelium (RPE) from mouse and baboon over a series of post-mortem intervals. We found substantial changes in gene expression as early as 15 minutes in the mouse and as early as three hours in the baboon eye tissues. Importantly, our findings demonstrate both tissue- and species- specific patterns of RNA metabolism, by identifying a set of genes that are either rapidly degraded or very stable in both species and/or tissues. Taken together, the data from this study lay the foundation for understanding RNA regulation post-mortem and provide novel insights into RNA metabolism in the tissues of the mammalian eye

An Annotated Bibliography of Selected Repertoire for Alto Saxophone and Piano for Developing College-Level Alto Saxophonists, with an Analysis of Yvon Bourrel's Sonate Pour Alto Saxophone Et Piano

In this study the author addresses the problem of finding quality repertoire for young college-level saxophonists. By examining graded repertoire lists from a variety of college and university saxophone instructors, the author has compiled a list of 180 works for alto saxophone and piano. Twenty-four well-known works of a difficulty-level appropriate for freshman and sophomore players are identified and annotated. Each annotation consists of bibliographical information, a biographical sketch of the composer, a difficulty rating of eight elements of performance, a discussion of performance considerations, and a bibliography of available recordings. The eight elements of performance included in the difficulty rating are: Meter, key signatures, tempo, note-values, rhythm, articulation, range, and dynamic levels. Each of these facets is graded using a six-point difficulty scale. One work from the select list, Yvon Bourrel's Sonate Pour Saxophone Alto et Piano, has been analyzed in greater detail with regard to thematic material and key areas to provide in-depth information that, hopefully, will help the student gain a deeper understanding of that work and as a result perform the piece with greater artistry

Pressen i Christiansand stiftamt 1768-1814: På leting etter en borgerlig offentlighetsform

This master's thesis aims to discover whether there existed expressions akin to a form of Habermas public sphere defined as a potential oppositional room against the authorities in the press of Christiansand stiftamt in the period 1768-1814. In the literature there exists a discrepancy between the amount of research about the other stiftsbyers press in the given period, and the press from Christiandsand stiftamt. This thesis thus aims to bring about something new from this local press and its placement within the history of the public sphere. Four different periodicals were pressed and published in the stiftamt, one weekly magazine, one journal, and two address-notifications papers. The first published periodical was the address-notification paper Kongelige Privelegerede Adresse-Contoirs Efterretninger udi Christiansand Stift (1768-1772). It had to be handwritten as there were no local printing press. This changed in 1779 with Andreas Swane’s arrival to the city. He established a printing press and published the weekly magazine Christiansandske Uge-Blade (1780-1788). While the other stiftsbyers address-notifications papers continued being published unabated, Kristiansand went without in a period of 18 years. In 1790 two bourgeois men came together to buy Swane’s printing press and gained the rights to publish a local address-notification paper, Kristiansands Adresse Kontorets Efterretninger. The paper is still alive today as an integrated part of the local paper Fædrelandsvennen. Early in the writing process it was discovered that the journal Bellona (1807-1809) not was worth further study in relation to the thesis’s topic. The terms of utterances varied greatly in the chosen period for the thesis. Denmark-Norway went from having material censored before publishing, to becoming first in the world to establish absolute freedom of the press. This affair lasted only for a short time, and in the years following 1799 the press was being heavily censored. The thesis methodological approach is thus constituted by exploring the terms of utterances in the given period for each of the periodicals, both in a normative sense, and by studying the literature, and then in comparing the contents of the periodicals with these. They thus gain the potential to serve as both affirmation and debilitation in relation to the above. Expressions akin to a type of the public sphere were found in the periodicals, both openly and hidden, also in periods of strict censorship. However, the king was never directly criticized despite the period for absolute freedom of the press and a later period of somewhat lax censorship. The thesis also concludes that the press in Christiansand stiftamt seemed to approach the different periods terms of utterances in an alike manner to the address-notification paper from Christiania, contrasting Bergens and Trondheims approach with the same. The thesis’s periodicals were also found to harbor a certain folksy element, though it remains unclear whether this was because of local culture, or the small number of possible subscribers and local commerce compared to the other stiftsbyer

A general deep reinforcement learning hyperheuristic framework for solving combinatorial optimization problems

Many problem-specific heuristic frameworks have been developed to solve combinatorial optimization problems, but these frameworks do not generalize well to other problem domains. Metaheuristic frameworks aim to be more generalizable compared to traditional heuristics, however their performances suffer from poor selection of low-level heuristics (operators) during the search process. An example of heuristic selection in a metaheuristic framework is the adaptive layer of the popular framework of Adaptive Large Neighborhood Search (ALNS). Here, we propose a selection hyperheuristic framework that uses Deep Reinforcement Learning (Deep RL) as an alternative to the adaptive layer of ALNS. Unlike the adaptive layer which only considers heuristics’ past performance for future selection, a Deep RL agent is able to take into account additional information from the search process, e.g., the difference in objective value between iterations, to make better decisions. This is due to the representation power of Deep Learning methods and the decision making capability of the Deep RL agent which can learn to adapt to different problems and instance characteristics. In this paper, by integrating the Deep RL agent into the ALNS framework, we introduce Deep Reinforcement Learning Hyperheuristic (DRLH), a general framework for solving a wide variety of combinatorial optimization problems and show that our framework is better at selecting low-level heuristics at each step of the search process compared to ALNS and a Uniform Random Selection (URS). Our experiments also show that while ALNS can not properly handle a large pool of heuristics, DRLH is not negatively affected by increasing the number of heuristics.publishedVersio

Theology, News and Notes - Vol. 55, No. 03

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1163/thumbnail.jp

Et dult i riktig retning: Hvilken effekt har normativ sosial dulting på kjøp av handlenett, og hvilken kundegruppe påvirkes i størst grad? VÅR 2018

Det rettes stadig mer fokus på miljøutfordringer, deriblant problematikken rundt forbruk av plast i dagens samfunn. Denne bacheloroppgaven tar utgangspunkt i atferdsøkonomiens antakelser om at mennesker ikke er rasjonelle, som er et motstykke til den tradisjonelle økonomiske oppfatningen om at mennesket handler rasjonelt, sett i lys av et økonomisk perspektiv. Atferdsøkonomien belyser fenomenet dulting, som er en retning innenfor faget som tar stilling til menneskelige svakheter gjennom å kombinere økonomiske intensiver - belønning i form av økonomisk gevinst - med psykologiske innsikter. Dette danner utgangspunktet for oppgaven, som undersøker hvorvidt dulting som spiller på sosial påvirkning kan være en mulig måte å redusere kjøp av plastbæreposer, gjennom økt kjøp av handlenett. Problemstillingen lyder dermed som følger; Hvilken effekt har normativ sosial dulting på kjøp av handlenett og plastbæreposer hos Rema 1000 Eidsvåg, og hvilken kundegruppe påvirkes i størst grad? Problemstillingen besvares gjennom fire hypoteser som baserer seg på antakelser om effekten av dultet, og hvilken kundegruppe som i størst grad lar seg påvirke av dette. Metoden som anvendes for å besvare problemstillingen er et eksperimentelt opplegg, der det har blitt gjennomført et felteksperiment med én kontrollgruppe og én eksperimentgruppe. Der eksperimentgruppen ble utsatt for dultet, mens kontrollgruppen ikke ble det. Resultatene fra undersøkelsen støtter hypotese én som er påstanden om at normativ sosial dulting vil ha en effekt i form av økt kjøp av handlenett i tidsrammen eksperimentet finner sted. Hypotese to, tre og fire forkastes og støttes ikke av undersøkelsen. Det skjer dermed ikke en reduksjon i salg av plastbæreposer som en følge av dultet. Samtidig ble hypotesene som stilte spørsmål om hvilke kundegrupper (H3, H4) som i størst grad lar seg påvirke av dultet konkludert som lite pålitelige, da undersøkelsens omfang ikke egnet seg til å støtte disse hypotesene. Studien oppsummeres med at H1, som forøvrig var hovedformålet med undersøkelsen, støttes, og avsluttes gjennom å belyse utgangspunkt for videre forskning

The role of insomnia in the treatment of chronic fatigue

AbstractBackgroundThe definition of Chronic Fatigue Syndrome (CFS) overlaps with definitions of insomnia, but there is limited knowledge about the role of insomnia in the treatment of chronic fatigue.AimsTo test if improvement of insomnia during treatment of chronic fatigue was associated with improved outcomes on 1) fatigue and 2) cortisol recovery span during a standardized stress exposure.MethodsPatients (n=122) with chronic fatigue received a 3.5-week inpatient return-to-work rehabilitation program based on Acceptance and Commitment Therapy, and had been on paid sick leave>8weeks due their condition. A physician and a psychologist examined the patients, assessed medication use, and SCID-I diagnoses. Patients completed self-report questionnaires measuring fatigue, pain, depression, anxiety, and insomnia before and after treatment. A subgroup (n=25) also completed the Trier Social Stress Test for Groups (TSST-G) before and after treatment. Seven cortisol samples were collected during each test and cortisol spans for the TSST-G were calculated.ResultsA hierarchical regression analysis in nine steps showed that insomnia improvement predicted improvement in fatigue, independently of age, gender, improvement in pain intensity, depression and anxiety. A second hierarchical regression analysis showed that improvement in insomnia significantly predicted the cortisol recovery span after the TSST-G independently of improvement in fatigue.ConclusionImprovement in insomnia severity had a significant impact on both improvement in fatigue and the ability to recover from a stressful situation. Insomnia severity may be a maintaining factor in chronic fatigue and specifically targeting this in treatment could increase treatment response

Group‑delivered cognitive behavioural therapy versus waiting list in the treatment of insomnia in primary care: study protocol for a pragmatic, multicentre randomized controlled trial

Background Insomnia is common in the general population and is a risk factor for ill-health, which highlights the importance of treating insomnia effectively and cost-efficiently. Cognitive-behavioural therapy for insomnia (CBT-I) is recommended as first-line treatment due to its long-term effectiveness and few side-effects, but its availability is limited. The aim of this pragmatic, multicentre randomized controlled trial is to investigate the effectiveness of group-delivered CBT-I in primary care compared to a waiting-list control group. Methods A pragmatic multicentre randomized controlled trial will be conducted with about 300 participants recruited across 26 Healthy Life Centres in Norway. Participants will complete online screening and provide consent before enrolment. Those who meet the eligibility criteria will be randomized to a group-delivered CBT-I or to a waiting list according to a 2:1 ratio. The intervention consists of four two-hour sessions. Assessments will be performed at baseline, 4 weeks, 3- and 6 months post-intervention, respectively. The primary outcome is self-reported insomnia severity at 3 months post-intervention. Secondary outcomes include health-related quality of life, fatigue, mental distress, dysfunctional beliefs and attitudes about sleep, sleep reactivity, 7-day sleep diaries, and data obtained from national health registries (sick leave, use of relevant prescribed medications, healthcare utilization). Exploratory analyses will identify factors influencing treatment effectiveness, and we will conduct a mixed-method process evaluation to identify facilitators and barriers of participants’ treatment adherence. The study protocol was approved by the Regional Committee for Medical and Health Research ethics in Mid-Norway (ID 465241). Discussion This large-scale pragmatic trial will investigate the effectiveness of group-delivered cognitive behavioural therapy versus waiting list in the treatment of insomnia, generating findings that are generalizable to day-to-day treatment of insomnia in interdisciplinary primary care services. The trial will identify those who would benefit from the group-delivered therapy, and will investigate the rates of sick leave, medication use, and healthcare utilization among adults who undergo the group-delivered therapy.publishedVersio

Smidig i historiske fotspor : Et komparativt studie av to etablerte virksomheter som utforsker samspillet mellom strategi, struktur og smidig som respons på et næringsliv som endres gjennom digital utvikling

Our research study has investigated how two established companies respond to digital and market challenges by exploring the interplay between strategy, structure, and agility as illuminated by leaders' perceptions. The research question we have examined is: How do leaders in established businesses navigate the interplay between strategy, structure, and agility in response to continuously changing environments? The study employed an exploratory, comparative case analysis method. We have investigated two established businesses, both of which have experience with digital development and have demonstrated organizational adaptability by implementing large-scale agile methodology through multi-team systems. Previous research has only to a limited extent addressed the interaction between strategy, structure, and agility during organizational transformation processes in established Norwegian businesses. Our research has culminated in a triadic model for increased competitive advantage in a digital world, highlighting how the interplay between strategy, structure, and agility has impacted organizational transformation. We have identified several components critical for making this interplay work: 1) Drivers for change, 2) Strategic competence development, 3) Balanced autonomy, 4) Evolution of leadership roles, and 5) Common language and values. Through our analysis, we have also revealed that leaders in these companies have incorporated a range of operational implementation mechanisms to effectively advance organizational transformation processes. These are competence exchange, prioritization tools, product strategy, glossary, interaction model, culture document, new roles, and new learning arenas. This emphasizes both a strategic and tactical need to view the interplay between strategy, structure, and agility in response to continuously changing environments. Further research should build on our model to explore the variation in how different organizations manage this transformation, which will enrich the academic perspective.nhhma