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Yes / Background and Objective: Though devices for hair growth based on low levels of light have shown encouraging results, further improvements of their efficacy is impeded by a lack of knowledge on the exact molecular targets that mediate physiological response in skin and hair follicle. The aim of this study was to investigate the expression of selected light-sensitive receptors in the human hair follicle and to study the impact of UV-free blue light on hair growth ex vivo. Material and Methods: The expression of Opsin receptors in human skin and hair follicles has been characterised using RT-qPCR and immunofluorescence approaches. The functional significance of Opsin 3 was assessed by silencing its expression in the hair follicle cells followed by a transcriptomic profiling. Proprietary LED-based devices emitting two discrete visible wavelengths were used to access the effects of selected optical parameters on hair growth ex vivo and outer root sheath cells in vitro. Results: The expression of OPN2 (Rhodopsin) and OPN3 (Panopsin, Encephalopsin) was detected in the distinct compartments of skin and anagen hair follicle. Treatment with 3.2 J/cm2 of blue light with 453 nm central wavelength significantly prolonged anagen phase in hair follicles ex vivo that was correlated with sustained proliferation in the light-treated samples. In contrast, hair follicle treatment with 3.2 J/cm2 of 689 nm light (red light) did not significantly affect hair growth ex vivo. Silencing of OPN3 in the hair follicle outer root sheath cells resulted in the altered expression of genes involved in the control of proliferation and apoptosis, and abrogated stimulatory effects of blue light (3.2 J/cm2; 453 nm) on proliferation in the outer root sheath cells. Conclusions: We provide the first evidence that 1) OPN2 and OPN3 are expressed in human hair follicle, and 2) 453 nm blue light at low radiant exposure exerts a positive effect on hair growth ex vivo, potentially via interaction with OPN3. / This study was supported by the European Marie-Curie Actions Programme, Grant agreement no.: 607886

Eines der größten Probleme bei der kontrollierten Kernfusion ist die immense thermische Belastung der mit dem Plasma in Berührung kommenden Materialien. Um den Energiefluß aus dem Plasma auf eine möglichst große Fläche zu verteilen, werden die betroffenen Komponenten in der Regel so angebracht, da"s das magnetische Feld annähernd parallel zur Oberfläche verläuft. Im Rahmen dieser Arbeit wurden ein spezieller drehbarer Meßkopf zur winkelabhängigen Messung des Strom- und Energieflusses entwickelt und ausführliche experimentelle Untersuchungen zur Winkelabhängigkeit der Teilchen- und Energieflüsse auf eine Fläche durchgeführt. Zum Verständnis der zu Grunde liegenden Mechanismen wird basierend auf den Gyrationsbahnen der Teilchen ein analytisches Modell entwickelt und dessen qualitative Übereinstimmung mit den experimentellen Befunden festgestellt. Die Durchführung der Experimente erfolgte am Plasmagenerator PSI-2, einem linearen Divertor-Simulator mit einem moderaten magnetischen Feld. Der Aufbau des Meßkopfes als ebene Sonde in einer isolierten Fläche enspricht dabei in etwa der einer sogenannten ,,flush-mounted probe''''. Die äußeren Maße der Sonde sind dabei vergleichbar mit dem Ionengyroradius ri}. Während die Elektronen bei den Experimenten stark magnetisiert sind, variieren die Bedingungen für die Ionen zwischen unmagnetisiert und magnetisiert je nach Ionenmasse und Magnetfeldstärke. Bei den Experimenten wurden verschiedene Größen der Plasmarandschicht als Funktionen des Winkels zwischen der Oberflächennormale der Sonde und dem Vektor des magnetischen Feldes bestimmt. / In fusion experiments, the energy flux to the target plates is an important issue. In order to spread the heat load, surfaces are usually designed to intersect magnetic field lines at very shallow angles. In the course of this work, a sensitive probe allowing simultaneous measurements of energy flux and current density as functions of a bias voltage was developed. Extensive experimental data on the particle and energy flux densities as functions of the angle between a surface and the confining magnetic field are provided. An analytical model is developed in order to reveal the physics involved; it is in good qualitative agreement with the experimental results. The experiments were conducted at the PSI-2 facility, a linear divertor simulator with moderate magnetic field strength. The probe was rotated in a spatially homogeneous plasma. The active area, a tungsten covered Peltier module, was immersed in a ceramic surface, closely resembling the geometry of a flush mounted probe. Its dimensions were comparable to the ion gyro radius ri. While the electrons were strongly magnetized, the ion conditions varied between unmagnetized and magnetized depending on the ion species. Sheath parameters were determined as functions of the angle alpha between the probe surface normal and the magnetic field.

Introdução: Os processos degenerativos vêm sendo considerados determinantes da progressão do déficit neurológico na esclerose múltipla (EM) e são associados sobretudo à perda neuronal e axonal. A patologia na substância branca (SB) manifesta-se pela quebra de membranas e perda da complexidade microestrutural dos tratos cerebrais, o que pode ser estudado indiretamente pelas alterações nos índices de fração de anisotropia (FA) e difusividade média (DM), obtidos por meio das análises das imagens por tensores de difusão (diffusion tensor imaging - DTI). Essa técnica oferece outros dois índices mais específicos, a difusividade axial () e difusividade radial (), que são associados aos processos de perda axonal e desmielinização, respectivamente. A perda neuronal na substância cinzenta (SC) pode ser avaliada pelo grau de atrofia do córtex cerebral. Este estudo tem como objetivos mensurar os índices de DTI na maior comissura cerebral, o corpo caloso (CC), e o grau e distribuição da atrofia cortical em indivíduos com EM remitente-recorrente (EMRR) e baixos escores de incapacidade funcional, correlacionando essas alterações com o volume de lesões macroscópicas e os principais parâmetros clínicos. Método: 31 indivíduos (22 mulheres, idade média 30,5 anos ± 8,7) com EMRR e um grupo controle (GC) composto por 34 indivíduos saudáveis (27 mulheres, idade média 32,3 anos ± 7,8) realizaram exames de crânio em aparelho de ressonância magnética de 3 Tesla (3T), sendo adquiridas imagens de DTI com 32 direções de gradiente, obtendo-se os índices de FA, DM, e de cinco segmentos na secção sagital do corpo caloso (CC). Através da segmentação de imagens volumétricas ponderadas em T1 foram obtidas as espessuras corticais regionais nos grupos. Esses resultados foram correlacionados com os volumes lesionais de imagens ponderadas em T1 e T2/FLAIR e os escores da escala expandida do estado de incapacidade (Expanded Disability Status Scale - EDSS), considerando-se significativos resultados com p< 0,05. Resultados: Os índices de FA, DM e do CC estavam difusamente alterados no grupo EMRR e a , alterada significativamente no esplênio, tronco médio anterior e tronco médio posterior do CC. Observou-se atrofia cortical significativa no terço anterior dos lobos temporais, bilateralmente, e nas regiões parietal inferior, insular e fronto-orbitária direitas, com uma tendência à atrofia no giro frontal superior esquerdo. As FA, DM e correlacionaram-se com os volumes lesionais T1 e, mais significativamente, com os volumes lesionais T2/FLAIR, porém não houve correlação entre os volumes lesionais e a . A espessura cortical no grupo EMRR apresentou correlações com ambos os volumes lesionais, mais significativamente com as lesões em T1. O escore médio da EDSS era 1,1 ± 0,9 (variando de 0-3), apresentando correlações com a DM e a no esplênio, tronco médio anterior e posterior do CC, com uma correlação com a no tronco médio posterior. O EDSS correlacionou-se com a espessura cortical na topografia do giro frontal superior esquerdo. Discussão e conclusão: Houve alteração difusa nos índices de FA, DM e nos segmentos do CC, com acometimento mais localizado, predominantemente médio posterior, da , o que pode sugerir desmielinização difusa do CC, porém axonopatia ou degeneração mais acentuada em algumas regiões da SB. A atrofia cortical também apresentou uma distribuição regional característica, afetando sobretudo as regiões temporais, bilateralmente, parietal inferior, insular e fronto-orbitária direitas. As correlações encontradas entre os índices de DTI e a espessura cortical e os volumes lesionais demonstraram que, ao menos em parte, as degenerações das SB e SC podem ser relacionadas à degeneração Walleriana, secundária ao acúmulo de placas lesionais. As correlações entre a DM, de alguns segmentos do CC e a espessura cortical do giro frontal superior com os escores da EDSS favoreceram à hipótese de que a degeneração tecidual na EM foi um fator preponderante na progressão do déficit neurológico na EMRR / Introduction: The degenerative processes are gaining attention as predictors of the neurological deficit in multiple sclerosis (MS), being reflected by the degree of axon loss and central nervous system atrophy. The white matter pathology (WM) is characterized by cellular membranes disruption and loss of the microstructural complexity, which can be accessed by the diffusion tensor imaging (DTI) indices of fractional anisotropy (FA) and mean diffusivity (MD). This imaging technique also offers two more specific indices: the axial diffusivity () and radial diffusivity (), which are useful to differentiate between axon loss and demyelination, respectively. The gray matter (GM) neuronal loss can be accessed by the degree of cortical atrophy. The aim of this study is to measure the DTI indices in the greatest WM commisure, the corpus callosum (CC), and the degree and distribution of cortical atrophy in patients with relapsing remitting MS (RRMS) and low disability scores, correlating them to the macroscopic lesion load and the main clinical scores. Method: 31 RRMS patients (22 women, mean age 30.5 years ± 8.7) and 34 healthy control (HC) subjects (27 women, mean age 32.3 years ± 7.8) were submitted to brain examinations in a 3T magnetic resonance image scanner. From DTI with 32 gradient encoding directions were extracted the indices of FA, MD, and , which were measured in 5 segments of the mid-sagital section of the corpus callosum (CC). The cortical thickness was obtained from the segmentation of volumetric T1 images. These results were correlated with the macroscopic lesion loads in the T1 and T2/FLAIR images and the scores in the Expanded Disability Status Scale EDSS, considering significant the results with p< 0.05. Results: The FA, MD and were diffusively abnormal in all 5 segments of the CC in the RRMS group and the was abnormal only in the splenium, anterior midbody and posterior mid-body. The anterior area of the both temporal lobes and right inferior parietal, some orbital-frontal and insular regions showed significant atrophy, with a tendency of atrophy in the superior frontal gyrus. The FA, MD and correlated with the T1 lesion load and, more significantly, with the T2/FLAIR lesion load. The cortical thickness correlated with T1 and T2/FLAIR lesion loads, more significantly with the T1 lesion load. The mean EDSS in the RRMS group was 1.1 ± 0.9 (range 0-3), correlating with the MD and of the splenium, anterior and posterior mid-body of the CC. The EDSS correlated to cortical thickness in the topography of the superior frontal gyrus. Discussion and conclusion: The FA, MD and are diffusively abnormal in the CC, with abnormalities in the , restricted to the medial and posterior segments. These results can be interpreted as signs of diffuse demyelination in the CC and a predominance of axonopathy or more advanced degeneration in some segments. The cortical atrophy also followed a characteristic regional distribution, affecting predominantly the bilateral temporal lobes, and inferior parietal, orbital-frontal and insular regions, in the right hemisphere. The correlations found between the DTI indices and the cortical thickness and the macroscopic lesion loads show that, at least partially, the WM and GM degeneration can be related to Wallerian degeneration secondary to macroscopic lesion accumulation. The correlations between the DM, , in some of the CC segments, and cortical thickness, in the superior frontal gyrus, and the EDSS scores reinforces the hypothesis that the degenerative processes in MS can play a role in the disability status of the patients

A glicoproteína oligodendrocítica da mielina (MOG) e proteína básica da mielina (MBP) têm sido implicadas como os antígenos-alvo mais importantes nos processos desmielinizantes do sistema nervoso central (SNC), e mais importantes autoantígenos que surgiram dos estudos com o modelo animal para a esclerose múltipla (EM), a encefalomielite autoimune experimental (EAE). Os primeiros autoanticorpos detectados no soro e liquido cefalorraquidiano (LCR) de pacientes com EM foram anticorpos contra antígenos da mielina. O diagnóstico diferencial da EM inclui a presença de bandas oligoclonais (BOCs) no LCR e ausência no soro, demonstrando dessa forma síntese intratecal de imunoclobulinas G (IgG). As técnicas de detecção de anticorpos mais utilizadas atualmente são ELISA, ensaio baseado em células e western blot (WB). Neste contexto, o estudo da anti-MOG e anti-MBP e seu papel na EM podem ser estudados através da técnica de espectroscopia de força atômica (AFS). Esta é uma técnica altamente sensível que permite a detecção molecular, com a interação de uma ponta funcionalizada de microscópio de força atômica (AFM) com uma amostra, a qual fornece desta forma a força de adesão (Fad) específica para o sistema. Nesta pesquisa, foi inserido na ponta de AFM funcionalizada os peptídeos encefalitogênicos MOG92-106 e MBP85-99, para detectar e estudar os anticorpos específicos IgG anti- MOG92-106 e MBP85-99, no soro e LCR de pacientes na amostra, utilizando a técnica AFS. Sendo assim, este estudo foi realizado de forma inédita utilizando a AFS, auxiliando diretamente na investigação da EM e doenças desmielinizantes relacionadas. / Myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP) have been implied as the most important target antigens in demyelinating processes of central nervous system (CNS) and the most important antigens candidates whom arised from the animal model for multiple sclerosis (MS), the experimental autoimmune encephalomyelitis (EAE). The first autoantibodies detected in serum and cerebrospinal fluid (CSF) of MS patients were antibodies against myelin antigens. Differential diagnostic to MS includes the presence of oligoclonal bands (OCBs) in CSF and absence in serum, which demonstrate intrathecal IgG synthesis. Most applied techniques to detection of antibodies nowadays are ELISA, cell-based assay and western blot (WB). In this context, the study of anti-MOG role in e disease may be supported through its detection by atomic force spectroscopy (AFS) technique. AFS is a highly sensitive technique that allows molecular detection as a functionalized atomic force microscope (AFM) tip interacts with the sample, providing the system specific adhesion force (Fad). In this research, it was attached in the functionalized AFM tip the notable encephalitogenic peptides MOG92-106 and MBP85-99 to detect and study the specific antibodies anti-MOG92-106 and anti-MBP85-99 on the sample with AFS technique. Thus, this study was applied for the first time in research with AFS, assisting directly to MS and other demyelinating diseases investigation.

Putting on or taking off clothes helps the body to stay within the comfortable temperature range (toavoid shivering or sweating) at different activity levels and ambient conditions. Clothes with built-inthermo-regulating properties would mean maintained comfort without putting on or taking off clothesthat frequently. Integration of phase change materials (PCMs) in clothes is one way of achievingthermo-regulating properties. When the body temperature goes up, the PCM melts and absorbs theheat from the body in the form of latent heat (cooling effect). When the temperature drops, the PCMcrystallizes and the stored heat is released again (warming effect).Research on thermo regulating fibres of the bi-component type containing PCM in the core has beenconducted at Swerea IVF in Mölndal, Sweden, for some time. It has been found that high molecularweight HDPE is a suitable viscosity modifier for hydrocarbon waxes used as PCM. The preparation ofcore materials has so far been done in a batch wise fashion in the way that molten wax has beensoaked into pelletized HDPE at around 180°C during prolonged times followed by melt compoundingin a Brabender batch kneader (0.3 kg per batch). Besides being very impractical for larger productionvolumes the method involves long residence times at high temperatures which may induce thermaldegradation reactions. The objective of the present diploma (master’s thesis) work was to develop acontinuous mixing method to produce PCM/HDPE blends and to test the resulting material in bicomponentfibers with a Nylon (PA6) sheath and to characterize the resulting fiber properties in termsof strength and latent heat.It was proven possible to compound HDPE with large amounts (70%) of octadecane (PCM) on aBrabender twin screw extruder. HDPE was metered to the extruder hoper by means of a screw feederand wax was continuously fed to the hoper in the liquid state by means of a heated membrane pump.To facilitate mixing HDPE in form of powder instead of pellets was used. The extruded threads weresolidified in a water bath followed by granulation. Bi-component fibers were successfully producedfrom such materials. Fibers containing 15 to 42% Octadecane were produced showing heat of fusionsin the range 26 to 86 J/g and tenacities in the range 33 to 16 cN/tex. The heat of fusion of the fiberscompares favorable with existing commercial products showing values in the range 5-15 J/g (acrylicand cellulosic fibres containing microencapsulated hydrocarbon waxes). The peak melting point ofoctadecane measured by DSC was found to be depressed some 4-5°C in the fibers compared to pureoctadecane (28°C). Such a melting point depression is important to consider when choosing type ofhydrocarbon wax. / Program: Magisterutbildning i textilteknologi

This body of work details the exploitation of an incredibly powerful neural culture system, which enables the in vitrostudy of events involved in peripheral nervous system (PNS) development. Using a myelinating dorsal root ganglion (DRG) explant culture system, node of Ranvier formation and maintenance and the associated generation and maturation of myelin segments was examined. In addition, Schwann cell (SC) development, dynamics, and migration were extensively studied. First, in characterizing these cultures, the discrete axonal localization of specific ankyrin isoforms was revealed. Ankyrins are peripheral membrane proteins that immobilize classes of integral membrane proteins to the spectrin based-membrane skeleton. Ankyrins interact with proteins such as the voltage-dependent/gated sodium channel (vgsc) and members of the L1 family of cell adhesion molecules. These interactions are physiologically relevant to the formation of membrane specializations involved in axon guidance and the initiation and propagation of action potentials. We examined ankyrinB and ankyrinG expression in cultured DRG explants, which allowed visualization of individual axons. AnkyrinB and ankyrinG exhibited differential localizations to specific axonal populations. This was evident as early as one day in vitro and persisted over time. In mature pre-myelinated cultures, axons having an apparent diameter of less than 1 µm predominantly expressed ankyrinB, whereas axons having a diameter greater than or equal to 1 µm predominantly expressed ankyrinG (based on immunocytochemical reactivity). When myelination was induced, ankyrinGwas appropriately localized to sites of nodal development flanked by myelinating glial processes in the large caliber axons. These observations suggest that axons destined for myelination may express a distinct complement of peripheral, and perhaps integral, membrane proteins as compared to those observed in non-myelinated axons. These distinguishing features may play a role in the selection of axons for myelination. This work was followed with defining the role axo-glial interactions play in organizing domains along the axon being myelinated. Nodes of Ranvier are specialized, highly polarized axonal domains crucial to the propagation of saltatory action potentials. In the PNS, axon-glial cell contacts have been implicated in SC differentiation and the formation of nodes of Ranvier. SC microvilli establish axonal contact at mature nodes, and their components have been observed to localize early to sites of developing nodes. However, a role for these contacts in node formation remains controversial. Using the myelinating explant culture system, we observed that SCs reorganize and polarize microvillar components, such as the ezrin-binding phosphoprotein 50kDa (EBP50)/regulatory co-factor of the sodium-hydrogen exchanger isoform 3 (NHERF-1), actin, and the activated ezrin, radixin, and moesin (ERM) family of proteins, concomitant with myelination in response to inductive signals. These components were targeted to the SC distal tips where live cell imaging revealed novel, dynamic growth cone-like behavior. Further, localized activation of the Rho signaling pathway at SC tips gave rise to these microvillar component-enriched “caps” and influenced the efficiency of node formation. Extending these findings, a more profound examination of SC dynamics was undertaken. This was a particularly important experimental transition, as SC motility is crucial in the development and regeneration of the PNS. The seemingly equivalent bipolarity of mature SCs represents a conundrum in terms of directed motility. Fluorescence time-lapse microscopy of transfected SCs within the myelinating DRG explants revealed a novel cycling of these cells between static, bipolar and motile, unipolar morphologies via asymmetric process retraction and extension. Concentrations of PIP2 (phosphatidylinositol (4,5)-bisphosphate), activated ERMs, and EBP50 delineated the transitory asymmetry associated with the generation and neuron-like migration of the unipolar cell. EBP50 over-expression enhanced unipolar SC migration, suggesting a new role for this adaptor protein in cell motility. Further, the ERMs themselves were found to be essential to both motility and process dynamics with ERM disruption yielding a dysfunctional, multipolar SC phenotype. We propose this novel form of motility may be associated with the correct alignment and spacing of SCs along axons prior to elaboration of the myelin sheath. These compiled studies present significant advances in understanding and examining axo-glial interactions in the PNS. This work establishes the foundation for further, novel exploration of normal PNS development and the regeneration and repair mechanisms involved in PNS injury and disease states.

A two-year experimental campaign is described during which diamond-like carbon and plastic targets with thicknesses from 20 nanometers to 15 micrometers were irradiated by the Texas Petawatt Laser. Target composition and thickness were varied to modify the specifics of the laser-matter interaction. Plasma mirrors were selectively implemented to affect the contrast of the laser system and provide additional control of the physical processes under investigation. A number of particle diagnostics were implemented to measure the distribution of laser accelerated ions and electrons. In addition, optical diagnostics were fielded to measure the intensity profile of the laser and measure the density of the target pre-plasma. The results of these experiments suggest that the Texas Petawatt laser pulse has pre-pulse and pedestal features with intensities at least 10⁻⁸ of the main pulse. Micronscale targets were able to survive these features and maintain a relatively sharp density gradient until the arrival of the main laser pulse, allowing for ion acceleration. Electron spectra measured in this configuration show an average temperature of 10 MeV, with no v angular dependence out to at least 60 degrees. By contrast, interferometric plasma density measurements and a lack of any observable ion acceleration suggest that nanoscale targets were destroyed well before the main pulse. In this case, the peak of the laser pulse interacted with a cloud of plasma between 10⁻³ and 10⁻² of critical density. The contrast improvement offered by the implementation of plasma mirrors was seen to increase the maximum energy of laser accelerated protons from targets thicker than 1 micrometer. In addition, the plasma mirrors allowed nanoscale targets to survive pre-pulse and pedestal features and support the production of ion beams. Proton spectra show that ions were accelerated to greater maximum energies from nanoscale targets than from more traditional micron-scale targets. This effect can be attributed to a reduction in the target pre-plasma scale length upon the introduction of plasma mirrors. These results indicate that the manipulation of target properties and laser contrast can significantly affect the interaction between an ultrahigh intensity laser and a target. / text

To initiate algal virus research in the Bay of Quinte, three stations were sampled biweekly throughout 2011. By targeting algal virus DNA polymerase, major capsid protein genes (MCP), and a Microcystis aeruginosa cyanophage (Ma-LMM01) tail sheath protein gene, PCR amplification revealed diverse and unique Phycodnaviruses (viruses of eukaryotic algae) and cyanophage. When analysed statistically, patterns of virus abundance suggested that the seasonality of any one virus cannot be generalised to predict that of other viruses, even among closely related viruses. This study also demonstrated a strong relationship between algal virus abundance and host biomass. It was found that despite the apparent heterogeneity of virus abundance across the Bay, virus abundance patterns clustered by sampling date and geographic location. By providing evidence for diverse algal viruses with complex seasonality, this work highlights significant gaps in the current understanding of Bay of Quinte phytoplankton ecology.

To initiate algal virus research in the Bay of Quinte, three stations were sampled biweekly throughout 2011. By targeting algal virus DNA polymerase, major capsid protein genes (MCP), and a Microcystis aeruginosa cyanophage (Ma-LMM01) tail sheath protein gene, PCR amplification revealed diverse and unique Phycodnaviruses (viruses of eukaryotic algae) and cyanophage. When analysed statistically, patterns of virus abundance suggested that the seasonality of any one virus cannot be generalised to predict that of other viruses, even among closely related viruses. This study also demonstrated a strong relationship between algal virus abundance and host biomass. It was found that despite the apparent heterogeneity of virus abundance across the Bay, virus abundance patterns clustered by sampling date and geographic location. By providing evidence for diverse algal viruses with complex seasonality, this work highlights significant gaps in the current understanding of Bay of Quinte phytoplankton ecology.