The pedunculopontine tegmental (PPT) nucleus is a brainstem structure thought to be important in the regulation of sleep/wake states. The PPT is comprised of three distinct types of neurons (cholinergic, GABAergic, and glutamatergic), and each may serve different functions. It remains unknown how PPT neurons affect specific sleep/wake states and which of their axonal projections mediate their effect. Therefore, we used optogenetics to selectively activate glutamatergic PPT (PPTglut) neurons at both the cell soma and axon terminals in a temporally and spatially precise manner. The purpose of these experiments was to determine the role of PPTglut neurons during wake, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, and to identify the key projections through which PPTglut neurons produce their effects. Using transgenic mice, we transfected PPTglut neurons with an adeno-associated viral vector to induce expression of a light-dependent ion channel, channelrhodopsin-2 (ChR2). While recording electroencephalography (EEG), electromyography (EMG), and video feed, we photostimulated the transfected PPTglut neurons and measured the effects on sleep/wake states of the mice. Stimulation of the PPTglut soma during NREM sleep produced a frequency-dependent wake response. With increasing frequency of stimulation, we observed an increase in the speed of the wake response, as well as the amplitude and duration of the wake response. Stimulating the PPTglut soma increased time spent in wake, decreased NREM sleep, and slightly decreased REM sleep. We also noticed that mice did not exhibit spontaneous body movements during stimulation of the PPTglut soma. Stimulating individual PPTglut axon terminal fields partially recapitulated the phenotype observed with stimulation of the cell soma. Photostimulation of axon terminals in the basal forebrain, lateral hypothalamus, and thalamus elicited a fast wake response, stimulation of both the basal forebrain and lateral hypothalamus terminal fields produced a strong wake response, but long-lasting wakefulness was observed only with high-frequency stimulation of axon terminals in the lateral hypothalamus. In summary, photostimulation of PPTglut neurons promotes wake, and slightly decreases REM sleep. Our experiments strongly support the role of PPTglut neurons in promoting wakefulness from NREM sleep, and this wake response is carried out through several axonal projections which, in sum, recapitulate the wake phenotype observed with stimulation of the cell soma in the PPT itself. Further exploration of the axonal projections of PPTglut neurons is warranted to elucidate the neuronal targets through which this response is carried out. / 2019-07-03T00:00:00Z

Diploma thesis is focused on creation of educational materials supporting the education of biochemistry, specifically amino acids and proteins, at secondary level. At first the analysis of Czech chemistry textbooks concerning the two topics - amino acids and proteins was performed. The major problems found were related to the insufficient graphical representation of biomolecules, unsatisfactory motivational components and insufficient integration of the topic with biology or everyday life experience. The supporting educational materials, presented in this work, supplement the widely used chemistry textbooks. The materials includes a graphic oriented presentation, interactive animations demonstrating the process of denaturation and precipitating of proteins at macroscopic and molecular level, poster presenting the structural formulas of standard amino acids, 3D models of selected proteins, additional texts supporting the current topics concerning amino acids and proteins and the laboratory protocols for students. The presented support materials were evaluated at the secondary school conditions. They were tested in one class and the improvement of student's understanding of the topic was compared to the second class employing only the classical educational methods. The comparison of the results of...

"One of the general processes of interest in Pulsed Plasma Thrusters is the ablation of the solid fuel. In general, ablation occurs when a short pulse of applied energy removes a portion of the fuel surface. Although this ablation process is relatively straight-forward in simple materials that sublimate, ablation in Pulsed Plasma Thrusters is significantly more complicated. This is caused by the transient conditions and the complex behavior of Teflon that does not sublimate but rather undergoes both physical and chemical changes prior to leaving the surface. These two effects combine to make Teflon ablation a highly nonlinear function of heat flux, material property variations, changing molecular weight, and phase transformation behavior. To gain greater insight into the ablation process, a one-dimensional ablation model is developed that addresses the more detailed thermal and thermodynamic behavior of Teflon during simulated operation of a Pulsed Plasma Thruster. The mathematical model is based on the work of Clark (1971), which focused on two-phase, one-dimensional Teflon ablation in the context of thermal protection systems. The model is modified for use in simulated PPT operations and implemented numerically using an adaptive non-uniform grid, explicit finite-difference techniques, and a volume fraction method to capture the interface between the crystalline and amorphous Teflon phases. The ablation model is validated against analytical heat transfer and ablation solutions and compared with previous experimental results. The Teflon ablation model is used to analyze several general ablation scenarios in addition to specific PPT conditions to gain greater insight into long-duration thruster firing, post-pulse material ablation, variable heat flux effects, variable material property effects, and the impact of surface re-crystallization on particulate emission. These simulations are considered in the context of prior experimental investigations of Pulsed Plasma Thrusters. The results of these simulations demonstrate the success of the numerical ablation model in predicting experimental trend and suggest potential paths of moderately improving thruster efficiency and operational repeatability in the future. "

<p>Denne studien har fokus på PP-rådgiverens perspektiv på arbeid med problematferd i skolen. Jeg valgte å vinkle min prosjektbeskrivelse og det videre arbeidet mot en studie av Pedagogisk - Psykologisk tjeneste (heretter PP-tjenesten). Nærmere bestemt rettes blikket mot PP-rådgiverens erfaringer med og perspektiv på arbeid med hjelpetrengende elever i skolen, deres foresatte og lærere. Å undersøke slike perspektiv kan ha interesse fordi PP-tjenesten har et særlig godt kjennskap til skolen og det som skjer der gjennom sin rolle som skolens hjelpetjeneste. Analysen bygger på intervju av 12 Pedagogisk-psykologiske rådgivere på 4 PP-kontor i Nord-Norge 1999 -2000 og på direkte observasjon i 30 møter av ulike typer som ble gjennomført på disse kontorene. ”Grounded Theory” er brukt som metodologi og metode. Jeg utviklet 5 substantive koder: 1) ”faglig usikkerhet”, 2) ”skjønn og fagkunnskap”, 3) ”å arbeide eklektisk” 4) ”respons på antatte forventninger” og 5) ”diagnosekommunikasjon”. På basis av de substantive kodene utviklet jeg følgende substantive kode: ”å jobbe eklektisk på basis av skjønn og fagkunnskap gir ulik grad av faglig usikkerhet”. I tillegg har jeg utviklet ulike ”typer” PP-rådgivere, ”eksperten”, ”brannslukkeren” og ”analytikeren”. De teoretiske hypotesene som ble utviklet i dette arbeidet har blitt relatert og drøftet i forhold til annen relevant forskning som for eksempel Bernsteins begrep ”den pedagogiske anordning”, der diskurser og makt er sentralt.</p>

Denne studien har fokus på PP-rådgiverens perspektiv på arbeid med problematferd i skolen. Jeg valgte å vinkle min prosjektbeskrivelse og det videre arbeidet mot en studie av Pedagogisk - Psykologisk tjeneste (heretter PP-tjenesten). Nærmere bestemt rettes blikket mot PP-rådgiverens erfaringer med og perspektiv på arbeid med hjelpetrengende elever i skolen, deres foresatte og lærere. Å undersøke slike perspektiv kan ha interesse fordi PP-tjenesten har et særlig godt kjennskap til skolen og det som skjer der gjennom sin rolle som skolens hjelpetjeneste. Analysen bygger på intervju av 12 Pedagogisk-psykologiske rådgivere på 4 PP-kontor i Nord-Norge 1999 -2000 og på direkte observasjon i 30 møter av ulike typer som ble gjennomført på disse kontorene. ”Grounded Theory” er brukt som metodologi og metode. Jeg utviklet 5 substantive koder: 1) ”faglig usikkerhet”, 2) ”skjønn og fagkunnskap”, 3) ”å arbeide eklektisk” 4) ”respons på antatte forventninger” og 5) ”diagnosekommunikasjon”. På basis av de substantive kodene utviklet jeg følgende substantive kode: ”å jobbe eklektisk på basis av skjønn og fagkunnskap gir ulik grad av faglig usikkerhet”. I tillegg har jeg utviklet ulike ”typer” PP-rådgivere, ”eksperten”, ”brannslukkeren” og ”analytikeren”. De teoretiske hypotesene som ble utviklet i dette arbeidet har blitt relatert og drøftet i forhold til annen relevant forskning som for eksempel Bernsteins begrep ”den pedagogiske anordning”, der diskurser og makt er sentralt.

The scale of the energy business today and a favorable and promising economic environment for the production of natural gas, requires study of the thermophysical behavior of fluids: sophisticated experimentation yielding accurate, new volumetric data, and development and improvement of thermodynamic models. This work contains theoretical and experimental contributions in the form of 1) the revision and update of a field model to calculate compressibility factors starting from the gross heating value and the mole fractions of diluents in natural gas mixtures; 2) new reference quality volumetric data, gathered with state of the art techniques such as magnetic suspension densimetry and isochoric phase boundary determinations; 3) a rigorous first-principles uncertainty assessment for density measurements; and 4) a departure technique for the extension of these experimental data for calculating energy functions. These steps provide a complete experimental thermodynamic characterization of fluid samples. A modification of the SGERG model, a standard virial-type model for prediction of compressibility factors of natural gas mixtures, matches predictions from the master GERG-2008 equation of state, using least squares routines coded at NIST. The modification contains new values for parametric constants, such as molecular weights and the universal gas constant, as well as a new set of coefficients. A state-of-the-art high-pressure, single-sinker magnetic suspension densimeter is used to perform density measurements over a wide range of temperatures and pressures. This work contains data on nitrogen, carbon dioxide, and a typical residual gas mixture (95% methane, 4% ethane, and 1% propane). Experimental uncertainty results from a rigorous, first-principles estimation including composition uncertainty effects. Both low- and high-pressure isochoric apparatus are used to perform phase boundary measurements. Isochoric P-T data can determine the phase boundaries. Combined with density measurements, isochoric data provides isochoric densities. Further mathematical treatment, including noxious volume and thermal expansion corrections, and isothermal integration, leads to energy functions and thus to a full thermodynamic characterization.

ABSTRACT Evidence from knockout studies in male mice and from experiments in male rats,in which expression of the estrogen receptor alpha (ERα) gene was inhibited in the medial preoptic area (MPO), suggests that ERα is important in the control of male rat mating behavior. Therefore, in this experiment, we tested the hypothesis that activation of ERα in the MPO is sufficient to maintain mating behavior in castrated male rats receiving subcutaneously (s.c.) dihydrotestosterone (DHT), a non-aromatizable androgen. Accordingly, castrated rats treated with DHT s.c. received MPO implants of either: (i) propyl-pyrazole-triol (PPT) (Stauffer, et al 2000; Katzenellenbogen, et al 2000), a selective ERα agonist, (ii) E2 (positive controls) or (iii) cholesterol (negative controls)and sexual behavior was monitored. PPT was as effective as E2 at maintaining mating behavior suggesting that, in the MPO, ERα is sufficient to mediate responses to E2 that underlie male rat mating behavior.

No description available.

BEPS-projektet startades år 2012 för att förhindra att skattesubjekt använder kryphål i skatteavtalen och staternas nationella lagstiftningar för att erhålla skatteförmåner. År 2013 utgav OECD en handlingsplan som identifierar 15 åtgärder som ämnas vidtas. Åtgärdspunkt 6 reglerar problematiken kring hur skatteavtal missbrukas genom att skattesubjekt ”shoppar” efter jurisdiktionen med det skatteavtal som leder till den förmånligaste beskattningen. Åtgärdspunkt 6 föreslår att en specifik LOB-regel eller en generalklausul, PPT-regeln, införs i OECDs modellavtal för att motverka det aktuella förfarandet. LOB-regeln reglerar i vilka specifika situationer en skatteförmån är tillämplig och kan beviljas medan PPT-regeln är av allmän karaktär och innehåller allmänt hållna formuleringar för att täcka in förhållanden som är svåra att förutse på förhand. Uppsatsens syfte är att utreda huruvida de föreslagna reglerna kan uppfylla ändamålet med åtgärdspunkten, att motverka missbruk av skatteavtal. Om detta inte är möjligt undersöks om Sverige kan motverka sådana förfaranden genom att tillämpa generalklausulen mot skatteflykt som återfinns i skatteflyktslagen. Författarna bedömmer att LOB-regeln är allt för komplex i sin nuvarande lydelse vilket försvårar en tillämpning av regeln. Eftersom PPT-regeln är vag ger den utrymme för godtyckliga bedömningar, vilket inte ger ett förutsebart utfall när det inte finns klar vägledning. Författarna är med hänsyn till detta av uppfattningen att reglerna i dess nuvarande lydelse och form inte kan leva upp till syftet med åtgärdspunkt 6.  Enligt Peru-målet är skatteflyktslagen rent principiellt tillämplig på förfaranden som omfattas av skatteavtal. Generalklausulen ska då prövas mot förfarandet. Det fjärde rekvisitet, i strid med lagstiftnings syfte, är dock svårtillämpat och domstolens bedömningar varierar. Författarnas anser dock att genom att införa i skatteavtalen att dess syfte inte är att tillåta missbruk av avtalet kan generalklauslen motverka det aktuella förfarandet och skydda mot erodering av den svenska skattebasen vad gäller missbruk av skatteavtal. / In 2012 the BEPS project started with the purpose of preventing tax subjects from using loopholes in the tax treaties and national tax laws in order to receive tax benefits. In 2013, the OECD published an action plan that identifies 15 actions that is meant to be taken regarding this issue. Action 6 regulates treaty abuse through treaty shopping, which means that a tax subject is searching for the tax jurisdiction with the tax treaty that leads to the most beneficial taxation. To prevent this, Action 6 suggests that a specific LOB-rule and a general anti-avoidance rule, PPT-rule, should be included in the OECD model convention. The LOB-rule regulates in which specific situations a treaty benefit can be granted. The PPT-rule is more general and contains general wordings to cover situations that is difficult to foresee. The purpose of this thesis is to examine whether the proposed rules can fulfill the purpose of Action 6, to prevent treaty abuse. If not possible, it will be determined if Sweden can prevent treaty abuse by applying the general anti-avoidance rule against tax evasion stated in the Swedish skatteflyktslagen. The authors of the thesis are of the opinion that the LOB-rule is too complex in its current wording which makes it difficult to apply. Since the PPT-rule is vague, there is a wide scope for arbitrary assessments leads to an unpredictable outcome when the guidance is unclear. Therefore, the authors find that the rules in its current wordings cannot satisfy the purpose of Action 6.  According to the Peru-judgement the skatteflyktslagen can be applicable to situations that are covered by a tax treaty. The transaction should be tested against the general antiavoidance. The fourth prerequisite, in contravention of the purpose of the legislation, is difficult of apply and the judgements of the court varies. The authors believe that if the treaty preamble includes a statement which clarifies that the intention of the treaty is not to allow treaty abuse, the Swedish general anti-avoidance rule can prevent treaty abuse and thereby protect the Swedish tax base against BEPS regarding treaty abuse.

<p>Cancer immunotherapy aims at reversing the immunosuppressive tumor environment and enhancing anti-tumor immunity. This thesis comprises studies on murine models for prostate (TRAMP-C2) and bladder (MB49) cancer with the aim to explore if the introduction of an adenoviral vector expressing CD40 ligand (AdCD40L) can induce anti-tumor immune responses.</p><p>We show in subcutaneous mouse models that AdCD40L treatment suppresses tumor growth. Bladder cancer is known to secrete immunosuppressive IL-10 which may inhibit T cell function. We show that introducing AdCD40L into mouse bladder tumors inhibits IL-10 production and reverses immunosuppression. AdCD40L-transduced mouse prostate cancer cells showed caspase activation and reduced cell viability. Vaccination with CD40L-modified prostate cancer cells induces anti-tumor responses and protects mice against rechallenge with native TRAMP-C2 cells. In order to enhance AdCD40L therapy, we explored the possibility of combining it with the histone deacetylase inhibitor FK228, also known as depsipeptide. We show that FK228 upregulates coxsackie and adenovirus receptor expression and thereby enhances adenoviral-mediated CD40L expression in both murine and human prostate cancer cells. Increasing amounts of FK228 or AdCD40L reduces prostate cancer cell viability, while the combined treatment gives at least an additive therapeutic effect. Moreover, we show that AdCD40L transduction of prostate cancer cells induces endogenous CD40 expression and sensitize them for CD40L-mediated therapy.</p><p>In order to conduct prostate-specific gene therapy, prostate-specific promoters can be used to drive transgene expression. However, there are no reports on prostate-specific promoters that are transcriptionally active in mouse cells. Here we show that by using the two-step transcription activation system (TSTA), we can enhance the activity of a recombinant human promoter sequence and obtain activity in mouse prostate cancer cells as well. This finding paves the way for future studies of prostate-specific gene therapy in immunocompetent mouse models.</p>