Cockayne syndrome (CS) is a rare, segmental premature aging disorder in which the majority of cases are caused by mutations in the Cockayne syndrome group B protein (CSB). CSB is a multifunctional protein implicated in DNA repair, transcription and chromatin remodeling. The results presented here demonstrate that CSB plays an important role in telomere maintenance and DSB repair. We find that CS cells accumulate telomere doublets, have increased telomere-bound TRF1, decreased TERRA levels and a defect in telomerase-dependent telomere lengthening. These results imply that CS patients may be defective in telomere maintenance. We also uncover a novel and important role of CSB in DNA DSB repair. We show that CSB facilitates HR and supresses NHEJ during S and G2 phase. We find that CSB interacts with RIF1 and is recruited by RIF1 to DSBs in S phase. At DSBs, CSB remodels the chromatin extensively, which in turn limits RIF1 recruitment and promotes BRCA1 accumulation. The chromatin remodeling activity of CSB requires not only damage-induced phosphorylation on S10 by ATM but also cell cycle-dependent phosphorylation of S158 by cyclin A-CDK2. Both modifications are needed for the intramolecular interaction of CSB N-terminal domain with its ATPase domain. This intramolecular interaction has previously been reported to regulate the ATPase activity of CSB. Taken together, these results suggest that ATM and CDK2 control of CSB to promote chromatin remodeling, which in turn inhibits RIF1 in DNA DSB repair pathway choice. / Thesis / Doctor of Philosophy (PhD)

This study researches the possibility of creating immersion through the use of breaks in fiction that includes the player inside of the game world through the use of their real name, age gender and more. The qualitative method is used in the form of semi-structured interviews with two groups of respondents (one consisting of experienced players and one with inexperienced) who were made to play an artefact, in the form of a visual novel like experience set in a chat room. The reason for having two groups was to find out if their experiences would differ or not.The results of the study show that the majority of the respondents were able to immerse themselves in the artefact and that the fiction breaks and the use of the player’s real life information played a role in achieving this. However a minority of the respondents did not agree with this and stated that they found the fiction breaks distracting and that the use of them broke their immersion. This, along with the fact that the artefact mostly focused on the narrative rather than gameplay, makes it hard for the study to draw any definitive conclusions for video games at large. It does however show that it is possible for fiction breaks to immerse the player.

When soluble boron is used to control reactivity, there are two particular events which can challenge long-term core cooling (LTCC) during the small break loss-of-coolant accident (SBLOCA): boron precipitation and boron dilution. The initial consequences of the SBLOCA are mitigated by the emergency safety systems, but the core continues to boil. As boron is less volatile than steam, the steam is virtually boron free. All the boron remains in the core, the boron concentration in the core rises. If the solubility limit is reached, precipitation could occur. The boron precipitation event was historically considered to be bounded by the large break accident. However, there are characteristics of the SBLOCA which cannot be neglected and an SBLOCA specific methodology is required. On the opposite end of the boron concentration spectrum is the SBLOCA boron dilution event. The steam generators remove heat from the primary and condense the steam. The condensation of the boron-free steam can result in the accumulation of a deborated slug of water. If natural circulation restarts, the slug can be transported toward the core and potentially reduce the core boron concentration enough to induce a recriticality. This thesis describes two analytical methodologies for these SBLOCA LTCC events. The two methodologies have a similar approach. Both use transient system analyses for inputs to and justification of the follow-on boron concentration calculations. For boron precipitation, a maximized concentration is calculated with the Small Break Boron Precipitation model. For boron dilution, a minimized core inlet concentration is calculated using computational fluid dynamics. / Master of Science

Yes / The existing analytical solutions of dam-break flow do not consider simultaneously the effects of wet downstream bottom and bed slope on the dam-break wave propagation. In this study, a new analytical solution for the shallow-water equations (SWE) is developed to remove this limitation to simulate the wave caused by an instantaneous dam-break. The approach adopts the method of characteristics and has been applied to simulate the dam-break flows with different downstream water depths and slopes. The analytical solutions have been compared with predictions by the lattice Boltzmann method and the agreement is good. Although the proposed analytical solution treats an idealized case, it is nonetheless suitable for assessing the robustness and accuracy of numerical models based on the SWE without the frictional slope. / The National Key Research and Development Program of China (Grant No: 2018YFC1505000), National Natural Science Foundation of China (Grant Nos: 51879179; 51579166) and Sichuan Science and Technology Program (No. 2019JDTD0007); Open Fund from the State Key Laboratory of Hydraulics and Mountain River Engineering, Sichuan University (SKHL1809). .

Yes / A sudden dam failure is usually simulated by the rapid removal of a gate in laboratory tests and numerical simulations. The gate-opening time is often determined according to the Lauber and Hager instantaneous collapse criterion (referred to as Lauber-Hager criterion) established for a rectangular open channel with a dry bed. However, this criterion is not suitable for non-rectangular channels or initial wet-bed conditions. In this study, the effect of the gate-opening time on the wave evolution is investigated by using the large eddy simulation (LES) model. The instantaneous dam break, namely the dam break without a gate, is simulated for comparison. A gate-opening criterion for generating dam-break flow in non-rectangular wet bed channel is proposed in this study, which can be used as an extension of the Lauber-Hager criterion and provides a more comprehensive and reasonable estimate of the gate opening time. / National Natural Science Foundation of China (Grant No: 51879179), the Open Fund from the State Key Laboratory of Hydraulics and Mountain River Engineering, Sichuan University (SKHL1809) and Sichuan Science and Technology Program (No. 2019JDTD0007).

Yes / The bed slope and the tailwater depth are two important ones among the factors that affect the propagation of the dam-break flood and Favre waves. Most previous studies have only focused on the macroscopic characteristics of the dam-break flows or Favre waves under the condition of horizontal bed, rather than the internal movement characteristics in sloped channel. The present study applies two numerical models, namely, large eddy simulation (LES) and shallow water equations (SWEs) models embedded in the CFD software package FLOW-3D to analyze the internal movement characteristics of the dam-break flows and Favre waves, such as water level, the velocity distribution, the fluid particles acceleration and the bed shear stress, under the different bed slopes and water depth ratios. The results under the conditions considered in this study show that there is a flow state transition in the flow evolution for the steep bed slope even in water depth ratio α = 0.1 (α is the ratio of the tailwater depth to the reservoir water depth). The flow state transition shows that the wavefront changes from a breaking state to undular. Such flow transition is not observed for the horizontal slope and mild bed slope. The existence of the Favre waves leads to a significant increase of the vertical velocity and the vertical acceleration. In this situation, the SWEs model has poor prediction. Analysis reveals that the variation of the maximum bed shear stress is affected by both the bed slope and tailwater depth. Under the same bed slope (e.g., S0 = 0.02), the maximum bed shear stress position develops downstream of the dam when α = 0.1, while it develops towards the end of the reservoir when α = 0.7. For the same water depth ratio (e.g., α = 0.7), the maximum bed shear stress position always locates within the reservoir at S0 = 0.02, while it appears in the downstream of the dam for S0 = 0 and 0.003 after the flow evolves for a while. The comparison between the numerical simulation and experimental measurements shows that the LES model can predict the internal movement characteristics with satisfactory accuracy. This study improves the understanding of the effect of both the bed slope and the tailwater depth on the internal movement characteristics of the dam-break flows and Favre waves, which also provides a valuable reference for determining the flood embankment height and designing the channel bed anti-scouring facility. / National Natural Science Foundation of China (Grant No: 51879179, 52079081), the Open Fund from the State Key Laboratory of Hydraulics and Mountain River Engineering, Sichuan University (SKHL1809) and the Sichuan Science and Technology Program (No. 2019JDTD0007)

Former studies show that the break-up from prostitution can be seen as a process with several stages which the person has to go through and that there are several factors which can affect the break-up. The aim of this study is to create an understanding for and illustrate how a break-up from prostitution can look like. We have interviewed three ex-prostitutes about their own break-up and three social workers who work with helping individuals to exit prostitution. We have analyzed the material through the theory of exit process by Helen Fuch Ebaugh (1988) and through former studies. All the ex-prostitutes and the social workers in our study described the break-up from prostitution as a process. All our respondents agreed on that there are several different factors affecting a break-up from prostitution, whereof close relationships and the own motivation to make a change are the most significant ones. Formal support from professionals is also considered having an impact on the exit process as well as during the period after the break-up. In summary, the break-up process from prostitution is very complex, can be emotionally exhausting and may vary to a great extent between individuals.

Syfte: Syftet med studien var att utvärdera NIBUT (Non-Invasive Break-Up Time) och TBUT (Tear Break-Up Time) hos heltidsstuderande vid Linnéuniversitetet samt bidra till en ökad förståelse av ögonhälsan hos denna grupp. Metod: Tårfilmens stabilitet kontrollerades med NIBUT och TBUT, tiden mättes direkt efter en blinkning till första uppsprickningen av tårfilmens yta eller ny blinkning. NIBUT utfördes icke invasivt i Sirius och TBUT mättes i biomikroskop med fluorescein. Deltagarna fick inledningsvis svara på en enkät som gjorde det möjligt att analysera insamlad data utifrån ålder, kön, termin, skärmtid och poäng på DEQ-5 (5-Item Dry Eye Questionnaire). Svaren från DEQ-5 möjliggjorde att resultaten från NIBUT och TBUT mätningarna kunde jämföras mot upplevda symtom på torra ögon. Resultat: Studien inkluderade 36 studenter i åldersspannet 18–39 år (medianålder 23 år, IQR 5,25 år). NIBUT och TBUT visade en positiv signifikant korrelation (p <0,001). En kortare TBUT korrelerade negativt med en högre totalpoäng på DEQ-5 (p = 0,004) samt antalet terminer som studerats (p = 0,025). NIBUT visade inte några liknande samband. Referensvärdet för torra ögon diagnostisering med hjälp av NIBUT och TBUT är en tid <10 sekunder. Över hälften av deltagarna i studien, NIBUT 58% och TBUT 53%, hade en nedsatt break-up time <10 sekunder. Vilket kan vara en indikation för torra ögon problematik. Slutsats: Denna studie visar att det finns ett signifikant samband mellan NIBUT och TBUT mätningarna. Kortare TBUT har visat en signifikant korrelation med högre totalpoäng på DEQ-5, likaså har signifikanta samband mellan TBUT och fler lästa terminer konstaterats. Trots korrelationen mellan NIBUT och TBUT påverkades resultaten av skillnader mellan de två mätmetoderna. / Purpose: The purpose of the studies was to evaluate NIBUT (Non-Invasive Break-Up Time) and TBUT (Tear Break-Up Time) in full-time students at Linnaeus University and to contribute to an increased understanding of the eye health of this group. Method: The stability of the tear film was checked with NIBUT and TBUT, the time was measured directly after a blink to the first break-up of the tear film surface or a new blink. NIBUT was performed non-invasively in Sirius and TBUT was measured in a biomicroscope with fluorescein. The participants initially had to answer a questionnaire that made it possible to analyze collected data based on age, sex, number of semesters studied, screen time and score on the DEQ-5 (5-Item Dry Eye Questionnaire). The responses from the DEQ-5 allowed the results from the NIBUT and TBUT measurements to be compared against perceived symptoms of dry eye. Results: The study included 36 students in the age range 18–39 years (median age 23 years, IQR 5.25 years). NIBUT and TBUT showed a positive significant correlation (p <0.001). A shorter TBUT correlated negatively with a higher DEQ-5 total score (p = 0.004) as well as the number of semesters studied (p = 0.025). NIBUT did not show any similar correlations. The reference value for dry eye diagnosis using NIBUT and TBUT is a time <10 seconds. Over half of the participants in the study, NIBUT 58% and TBUT 53%, had a reduced break-up time <10 seconds. Which can be an indication of dry eye problems. Conclusion: This study shows that there is a significant connection between the NIBUT and TBUT measurements. Shorter TBUT has shown a significant correlation with higher total scores on the DEQ-5, likewise significant connections between TBUT and more semesters read have been established. Despite the correlation between NIBUT and TBUT, the results were influenced by differences between the two measurement methods.

Ett offentligt uppköpserbjudande innebär att ett aktiebolag, budgivaren, lämnar ett erbjudande ställt på generella villkor till aktieägarna i ett annat aktiebolag, målbolaget, i syfte att förvärva aktierna i det sistnämnda bolaget. Offentliga uppköpserbjudanden är vanligt förekommande på den svenska värdepappersmarknaden och eftersom transaktioner av detta slag är väldigt komplexa är det av stor vikt att förtroendet för marknaden upprätthålls under sådana förfaranden.  En viktig faktor för att upprätthålla förtroendet för aktiemarknaden på ett effektivt sätt är att självreglering föreligger. För Sveriges del utgörs självregleringen av-seende offentliga uppköpserbjudaden av de s.k. Takeover-reglerna (TO-reglerna). Den senaste revideringen av TO-reglerna skedde den 1 februari år 2015 och med-förde ett förbud mot s.k. budrelaterade arrangemang, även kallat break-up fees. Break-up fees är ett avtal som ingås mellan budgivare och målbolag i syfte att målbolaget ska vara skyldigt att utge en ersättning till budgivaren ifall förvärvet inte fullföljs. Break-up fees skapades under 1980-talet i USA och används flitigt än i dag på den amerikanska aktiemarknaden i syfte att främst åstadkomma en ”försäkringsfunktion” för budgivaren vid takeovers. För budgivaren är offentliga uppköpserbjudanden nämligen ofta förenade med stora kostnader till följd av omfattande förberedelser. Genom denna ”försäkring” uppnås en kostnadstäckningsfunktion och minskar således den ekonomiska risken som är förenad med takeovers. Den senaste revideringen har sin grund i de ändringar som tidigare hade skett i den brittiska motsvarigheten till TO-reglerna. I Storbritannien ansågs det vara nödvändigt att införa ett förbud mot break-up fees eftersom denna typ av avtal ansågs begränsa målbolaget vid takeover-förfaranden. Break-up fees ansågs således resultera i en otillbörlig fördel för budgivaren. Liknande resonemang anfördes under arbetet med de svenska reglerna vilket resulterade i ett svenskt förbud mot break-up fees. Förbudet är emellertid inte absolut utan Aktiemarknadsnämnden (AMN) har möjlighet att lämna dispens från förbudet.  Även om break-up fees är vanligt förekommande i USA har avtal av detta slag endast förekommit i mycket ringa omfattning i Sverige. Till följd av detta väcker förbudet mot break-up fees en stor osäkerhet beträffande de konsekvenser som förbudet kommer resultera i och huruvida förbudet borde ha införts i svensk rätt. Den amerikanska forskningen visar att break-up fees resulterar bl.a. i att målbolag försätts i en god förhandlingsposition, uppnår riskminimering till följd av ovannämnda kostnadstäckning, skapar förtroende för aktiemarknaden i allmänhet och transaktionen i synnerhet. Forskningen visar även att fler takeovers fullföljs ifall en break-up fee har ingåtts mellan parterna.  I detta arbete förs resonemang beträffande anledningen till att de svenska TO-reglerna har följt utvecklingen av de motsvarande brittiska reglerna och således införandet av förbud mot break-up fees. Det diskuteras även huruvida målbolagsstyrelsen är förhindrad att p.g.a. det aktuella förbudet fullgöra sina skyldigheter enligt gällande rätt. Vidare diskuteras hur aktieägarskyddet vid offentliga uppköpserbjudanden är uppbyggt i svensk rätt mot bakgrund av brittisk och amerikansk rätt samt huruvida förbudet mot break-up fees kan anses resultera i att målbolagsstyrelsens roll försvagas och aktieägarskyddet försvagas. Därtill kommer att en de lege ferenda-diskussion förs vari fenomenet break-up fees jämförs med gällande rätt rörande försvarsåtgärder. I syfte att belysa de konsekvenser som förbudet kan medföra problematiseras även förbudet mot break-up fees mot bakgrund av bestämmelsen avseende insiderbrott och break-up fees praktiska funktioner i olika rättssystem. Undertecknad kommer i detta arbete fram till att förbudet mot break-up fees torde bl.a. resultera i att budgivare och målbolag kommer hädanefter att söka sig till att uppnå andra deal protection-avtal. Vidare torde förbudet varken resultera i att målbolagets roll stärks eller i ett ökat skydd för målbolagets aktieägare. Därtill anses förbudet resultera i en maktobalans mellan AMN och målbolagsstyrelsen, vilket är negativ ur ett företagsekonomiskt perspektiv. Mot bakgrund av detta och ett antal andra skäl kommer undertecknad fram till slutsatsen att ett förbud mot break-up fees borde ej ha införts i svensk rätt.

The biology of seed dormancy and germination of 46 species representing 11 of the 12 tribes in Convolvulaceae were compared in laboratory (mostly), field and greenhouse experiments. Seeds were tested for kind of dormancy and storage behavior; artificial or simulated natural treatments were applied to break physical dormancy (PY); the initial route of water entry (“water gap”) into seeds was identified; the morphoanatomy of the water gap was compared in seeds of 17 species; ontogenetical differences between water gap and seed coat away from the hilum were described in Ipomoea lacunosa seeds; cycling of sensitivity to dormancy break was elucidated in seeds of I. lacunosa, I. hederacea, Cuscuta australis and Jaquemontia ovalifolia; and mechanism of opening of the water gap was determined for seeds of I. lacunosa and of I hederacea. Seeds of only three of the 46 species were nondormant. Two of these were recalcitrant (Maripa panamensis and Erycibe henryi), and the other one was orthodox (Bonamia menziesii). Seeds of the other 43 species were orthodox and had PY except those of Cuscuta europea, which also had physiological dormancy (PD) i.e. combinational dormancy (PY + PD). Two bulges adjacent to the micropyle were identified as the water gap in all seeds with PY except those of Cuscuta, in which the hilar fissure is the water gap. Anatomy of the bulges (water gap) adjacent to the micropyle differs from that of seed coat away from the bulges. A different sequence and phase of anticlinal and periclinal cell divisions during development created weak transitional zones between bulge - hilum and bulge - seed coat away from hilum. Water vapor pressure changes below the bulges caused formation of the opening(s) in water gap. Seeds of I. lacunosa I. hederacea, C. australis and J. ovalifolia cycle between sensitive and insensitive states to dormancy break, but not between PY and nondormancy. Seed dormancy and storage characteristics and anatomy and morphology of dormancy of seeds of Convolvulaceae closely follow the molecular phylogeny of the family. I suggest that PY in seeds of subfamily Convolvuloideae evolved from nondormant recalcitrant seeds of an ancestor closely related to Erycibeae.