Ionenkanäle leiten Ionenströme über neuronale Membranen, wodurch Aktionspotentiale erzeugt und weitergeleitet werden. Sie spielen eine zentrale Rolle bei der Regulierung der Erregbarkeit und des Aktivierungsverhaltens von Neuronen. KCNQs sind eine wichtige Familie von spannungsgesteuerten Kaliumkanälen; ihre Dysfunktion kann zu verschiedenen neurologischen Krankheiten führen, einschließlich Erkrankung an Epilepsie und Taubheit. Es wurde gezeigt, dass KCNQ2 und KCNQ3 den M-Strom verantwortlich sind. Letzterer ist für die Regulierung des repetitiven Feuerns von Pyramidenzellen entscheidend. Im Gegensatz zu KCNQ2, ist die funktionelle Bedeutung von KCNQ3 noch nicht aufgeklärt. In dieser Arbeit zeigen wir mittels extrazellulärer Elektrophysiologie in vivo, dass bei konstitutiven Kcnq3 Knockoutmäusen die hippokampalen Pyramidenzellen vermehrt burstartig feuern. Außerdem weisen diese Tiere eine verminderte Spike-Frequenz-Anpassung auf und die Wahrscheinlichkeit des Burst-Feuerns während zwei verschiedener Oszillationen – Theta gegen Nicht-Theta – kann nicht mehr unterscheiden werden. Des Weiteren zeigen Kcnq3-Knockout- Pyramidenzellen während der Theta-Oszillation weder eine dominante Phasenpräferenz, noch eine Koordination ihrer Burst-Feuerung. Die Thetawellen Phasenpräzision tritt weiterhin bei dem vorübergehend verstärkten Feuern auf. Das räumliche selektive Feuern von mutmaßlichen Ortszellen blieb auch bei den Knockout-Mäusen erhalten, aber es ist hauptsächlich vom Burst- Feuern abhängig. Diese Studie zeigt, dass der KCNQ3-Ionenkanal eine wichtige Rolle bei der Regulierung der neuronalen Erregbarkeit und der Informationsverarbeitung spielt, und gibt damit Einblicke in die Bedeutsamkeit der KCNQ3-Ionenkanäle bezüglich der neurologischen Störungen. / Ion channels conduct ion flows across neuronal membrane whereby action potential is generated and propagated. They play a central role in regulating the excitability and firing behavior of a neuron. Among them, the KCNQs present a prominent family of voltage-gated potassium channels. Dysfunction of KCNQ2–5 channels can lead to varied neurological diseases including early onset epilepsy and deafness. In cortex and hippocampus, KCNQ2 and KCNQ3 have been demonstrated to underlie the non-inactivating M-current critical for controlling the repetitive firing of pyramidal cells. However, the functional significance of KCNQ3, unlike that of KCNQ2, remains elusive. Here, by applying in vivo extracellular electrophysiology in Kcnq3 constitutive knockout mice and the wild-type littermates, we find that hippocampal pyramidal cells lacking KCNQ3 exhibit increased burst firing. Moreover, the spike frequency adaptation of their bursts is diminished, and the burst propensity during two different field oscillations – theta versus non-theta – becomes indistinguishable. During theta oscillations, Kcnq3 knockout pyramidal cells no longer display unimodal phase preference and do not coordinate their burst firing. But phase advancement along successive theta cycles continues to occur at times of transiently intensified firing. The selective firing of place cells is largely preserved in the knockout while mainly relying on bursts. These results suggest that KCNQ3 channels indeed play a significant and specific role in regulating the neurons’ excitability and information processing, thus providing crucial mechanistic insights into the relevance of the KCNQ3 channels in neurological disorders.

In response to DNA damage during S phase, cells slow DNA replication. This slowing is orchestrated by the intra-S checkpoint and involves inhibition of origin firing and reduction of replication fork speed. Slowing of replication allows for tolerance of DNA damage and suppresses genomic instability. Although the mechanisms of origin inhibition by the intra-S checkpoint are understood, major questions remain about how the checkpoint regulates replication forks: Does the checkpoint regulate the rate of fork progression? Does the checkpoint affect all forks, or only those encountering damage? Does the checkpoint facilitate the replication of polymerase-blocking lesions? To address these questions, we have analyzed the checkpoint in the fission yeast Schizosaccharomyces pombe using a single-molecule DNA combing assay, which allows us to unambiguously separate the contribution of origin and fork regulation towards replication slowing, and allows us to investigate the behavior of individual forks. Moreover, we have interrogated the role of forks interacting with individual sites of damage by using three damaging agents—MMS, 4NQO and bleomycin—that cause similar levels of replication slowing with very different frequency of DNA lesions. We find that the checkpoint slows replication by inhibiting origin firing, but not by decreasing fork rates. However, the checkpoint appears to facilitate replication of damaged templates, allowing forks to more quickly pass lesions. Finally, using a novel analytic approach, we rigorously identify fork stalling events in our combing data and show that they play a previously unappreciated role in shaping replication kinetics in response to DNA damage.

Skytte med eldhandvapen skapar buller, utsläpp av farliga ämnen och risk för att avlossade projektiler missar sina mål och istället hamnar utanför skjutbanan. Att förlägga skjutbanor inomhus löser vissa av dessa problem. Samtidigt kan risken för att utsättas för farliga ämnen öka för dem som brukar skjutbanan. En nyckelfaktor för att omhänderta dessa farliga ämnen och därmed skapa en god arbetsmiljö på inomhusskjutbanan är att ventilationen fungerar på rätt sätt. Syftet med detta arbete är främst att utvärdera hur ventilationen på inomhusskjutbanor bör utformas för att ventilera bort de hälsofarliga ämnen som uppstår. Arbetet har särskilt fokuserat på blyföroreningar men resultatet är generaliserbart även för många andra föroreningar som är aktuella. Arbetet är en del av Fortifikationsverkets pågående projekt om framtidens inomhusskjutbanor. Gränssättande för ventilationen är att arbetsmiljön på en inomhusskjutbana måste uppfylla relevanta arbetsmiljökrav. Utöver frågan om ventilation belyses även andra aspekter som är av vikt för att säkra en god arbetsmiljö. Arbetet har baserats på en forskningsöversikt där material från 1975 och fram till idag har studerats. Sökningarna har skett både strukturerat och riktat. Den strukturerade sökningen har skett i Web of Science och Scopus. Arbetet har identifierat de normer som används internationellt och som också har legat till grund för många av de skjutbanor som uppförts i Sverige. Vidare har arbetet identifierat den ursprungliga rapport som merparten av den tillgängliga litteraturen baserats på. I denna ursprungliga rapport har vi även identifierat viktiga frågetecken angående vilka grundförutsättningar som denna rapport baserats på. Resultatet av forskningsöversikten är att skjutbanor bör projekteras med laminärt flöde (“kolvströmning”) från skyttarna och mot kulfånget. Ventilationen bör projekteras med ett flöde på mellan 0,25 och 0,4 m/s. Ett bra verktyg under projekteringen är CFD-simuleringar. Med dessa kan olika tekniska lösningar utvärderas och för befintliga skjutbanor kan även orsak till eventuella problem undersökas. CFD-simuleringsresultaten bör i görligaste mån verifieras mot uppmätta värden. Vidare är både städning och personlig hygien viktiga faktorer för att arbetsmiljön på en inomhusskjutbana skall vara god. Ytskikt som är lätta att städa skall väljas och förutsättningar för att hantera både tvätt av arbetskläder och personlig hygien skall finnas. Dessa resultat knyts ihop under diskussionskapitlet där två grundläggande scenarier formuleras, ett för en nybyggnation och ett för en ombyggnad av en befintlig inomhusskjutbana. / The use of firearms creates noise pollution, release of toxic elements and a risk that the projectiles miss the targets and end up outside of the firing range. One of the solutions to these issues is to erect walls and a roof around the range, and thus create an indoor firing range. This might however increase the range users’ exposure to toxic elements related to the discharge of firearms. To mitigate this the indoor firing range needs a properly designed and well-functioning ventilation system. The purpose of this study is to evaluate how ventilation systems for indoor firing ranges should be designed in order to remove the toxic elements released when shooting. The study is primarily focused on lead pollution, but the results can also be generalised for a multitude of other relevant pollutants. The study is part of the Swedish Fortifications Agency (Fortifikationsverket) project regarding the design of future indoor firing ranges. The design parameters for ventilation systems at indoor firing ranges are regulated by the occupational safety and health regulations. In the final part of the study the authors also address other important aspects to create a safe working environment at indoor firing ranges. This study is conducted as a research review where literature from 1975 up until today has been studied. Search terms based on permutations of “shooting”, “firing”, “range”, “ventilation” and “firearm” have been used in the Web of Science and Scopus databases. The resulting list, after being culled for duplicates and “false positives”, contained approximately 70 articles. Reviewing these articles let us identify the design parameters used both internationally and nationally in Sweden. We also identified the original report that most of the internationally available literature is based upon. In this Bachelor of Science thesis, we also raise some questions related to the original report and the prerequisites it was based upon. The result of the research survey is that the ventilation for indoor firing ranges should be designed for laminar flow (piston flow) in the direction from the shooters towards the bullet trap. The air flow should be between 0,25 and 0,4 m/s (50 to 75 feet per minute). A good tool when designing the range ventilation is CFD simulations. CFD simulations allow for early phase evaluation of different design solutions. Similar simulations can also be used when problem solving problems on already existing ranges, if any. Furthermore, both cleaning and personal hygiene are crucial components to achieve a safe working environment at indoor firing ranges. To facilitate cleaning the range should have surface materials that are non-porous and easy to clean. Washing facilities for work clothes and personal hygiene should be present. These results are addressed as part of the discussion chapter in the Bachelor of Science thesis where two basic scenarios are formulated, one for building a new indoor firing range, and one for redesigning an existing indoor firing range.

Short-term synaptic plasticity (STP) is a phenomenon that has been closely associated with how neurons communicate with each other. I study communication between neurons tied to synapses endowed with short-term plasticity (dynamic synapses). This is achieved by using mathematical models of neural phenomena that align with those found in real neurons. In addition to dynamic synapses, a model of static synapses is created, on which control experiments are performed. The response of postsynaptic neurons, to spiking-sequences from presynaptic neurons, is examined in order to infer how information is transmitted across cells. During these computational experiments, it was found that the range of firing rates to which postsynaptic neurons responded, depends heavily on certain parameters of STP-processes. These parameters are the time constants for short-term synaptic depression and facilitation: the two time-dependent processes that define STP. Some results confirm those of the existing literature, while this work places an added emphasis on the sensitivity of the propagation of rate codes to the aforementioned parameters of synapses. This is relevant because it has been found that real synapses display a wide range of time constants in the nervous system. Hence, understanding how this variation carries a significant impact on rate-coding schemes is vital when engaging in further studies of neural rate codes. / Synaptisk plasticitet på kort sikt (STP) är ett fenomen som har blivit nära förknippat med hur nervceller kommunicerar med varandra. Jag studerar kommunikation mellan nervceller som är kopplade till synapser som är försedda med kortsiktig synaptisk plasticitet (dynamiska synapser). Detta har åstadkommits genom matematisk modellering av fenomen i nervsystemet som är konsekventa med de som är funna i verkliga nervceller. Utöver dynamiska synapser, så skapas även en modell av statiska synapser på vilka kontrollexperiment utövas. Gensvaret av postsynaptiska nervceller, på sekvenser av nervimpulser från presynaptiska nervceller, kartläggs för att studera hur information transmitteras mellan celler. I dessa beräkningsmässiga experiment så var det funnet att spannet av frekvenser för vilka postsynaptiska nervceller visade gensvar, var kraftigt beroende på specifika parametrar för STP-processer. Dessa parametrar är tidskonstanterna för synaptisk depression på kort sikt samt synaptisk facilitering på kort sikt: de två tidsberoende processerna som definierar STP. Vissa resultat bekräftade de som återfinns i den befintliga literaturen, samtidigt som detta arbete placerar adderad tyngd på känsligheten som frekvensmässiga koder uppvisar för ovannämnda synaptiska parametrar. Detta är relevant eftersom det är känt att verkliga synapser uppvisar ett brett spann av tidskonstanter i nervsystemet. Följdaktigen är det centralt att förstå hur denna variation innehar signifikant påverkan på frekvenskoder vid fortsatta studier inom frekvensmässiga neurala koder.

The technology of production of ceramic roof tiles on the basis of low-melting red-burning clay, namely on the basis of clay from the Sadovoye deposit of the Sverdlovsk region, is proposed. Samples of ceramic roof tiles, molded by plastic and semi-dry way, were obtained with properties that meet the requirements of Russian standards and correspond to the quality of Röben ceramic roof tiles. The production technology involves the use of high-speed burning way in the temperature range of 1150–1200 °С. / Предложена технология производства керамической черепицы на основе легкоплавких красножгущихся глин, а именно на основе глины Садового месторождения Свердловской области. Получены образцы керамической черепицы со свойствами удовлетворяющими требования российских стандартов и соответствующих по качеству керамической черепице производства Roben. Водопоглощение таких изделий составляет 6,2–6,9 %, кажущаяся плотность – 2,19–2,31 г/см3, изделия водонепроницаемы более 4 ч и выдерживают морозостойкость более 150 циклов.

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[pt] Esta tese é composta de três capítulos que analisam aspectos do mercado de trabalho. O primeiro capítulo estima o efeito da mudança na Lei do Aviso Prévio em 2011 no Brasil. A nova lei tornou as demissões sem justa causa mais caras para as firmas, e o aumento do custo se deu de maneira crescente no tempo de serviço do empregado. O aviso prévio é parte do arcabouço da legislação de proteção ao emprego, e tem intenção preservar vínculos que, embora não desejados no curto prazo, seriam viáveis no longo prazo. No entanto, os resultados apontam para o aumento das demissões nas firmas mais afetadas e um ambiente de maior rotatividade. Tais resultados são especialmente desfavoráveis considerando o ambiente já de elevada rotatividade no Brasil. Argumentamos com um modelo teórico que o desenho da nova lei é consistente com os resultados, na medida em que se elevou não apenas o custo de demissão, mas também o custo esperado da continuidade do vínculo empregatício. O segundo capítulo avalia os efeitos da expansão das usinas de etanol no Mato Grosso do Sul (MS), pela perspectiva de realocação do trabalho. Seguindo os trabalhadores ao longo dos períodos, encontramos mecanismos que permitiram o ajuste da mão de obra às novas demandas por trabalho geradas por este grande investimento. Exploramos as realocações entre setores, ocupações e regiões. O terceiro capítulo estima impactos da modernização da agricultura (a partir de inovações da década de 1970) no Brasil Central, considerando os efeitos na força de trabalho e nas decisões de investimento em educação. Mostramos que este evento afetou a demanda por trabalho na região, gerando ganhos para a população adulta como um todo. Dessa forma, os incentivos para os mais jovens nas escolhas entre trabalhar (com ganhos imediatos do emprego) e investir em capital humano (e esperar ganhos potencialmente mais altos no futuro) também mudaram. / [en] This thesis consists of three essays on labor markets. The first chapter estimates the effect of the change in the Advance Notice Law in 2011 in Brazil. The new law made unjustified (without cause) dismissals more expensive for firms, and the cost gradually increased with tenure. Advance notice is part of the framework of employment protection legislation and is intended to preserve job contracts that, although undesirable in the short term, would be viable in the long term. However, results point to an increase in layoffs in the most affected firms and a higher turnover environment. These results are especially unfavorable considering the already high turnover rate in Brazil. I argue with a theoretical model that the design of the new law is consistent with the results because it increased not only the cost of dismissal but also the expected cost of continuity of employment. The second chapter evaluates the effects of the expansion of the ethanol mills in Mato Grosso do Sul (MS), from labor reallocation perspective. Tracking workers over the years, the analysis indicated mechanisms that enabled labor adjustment to the new labor demands generated by this large investment. I explore the reallocation across sectors, occupations, and regions. The third chapter estimates the impact of the modernization of agriculture (from the innovations of the 1970s) in Central Brazil, considering the effects on the labor force and investment decisions in education. The analysis shows that this event affected labor demand in the region, generating gains for the adult population. In this way, incentives have also changed for young people to make choices between working, with immediate job gains, and investing in human capital, and thus expect potentially higher gains in the future.