Reconfigurable optically-controlled waveguide for terahertz applications

The development of tunable waveguide components for systems that require multifunctionality, at terahertz frequencies is investigated using the photoconductivity e ect. Specifically, by the photo-generation of free charged carriers highly conducting plasma regions are created and by changing the light pattern in real time, various tunable components can be implemented. The aim of this thesis is to present a novel reconfigurable optically-controlled terahertz waveguide switch as an illustrative example of this approach, addressing the challenges and limitations involved in simulation, implementation and measurement of such devices and is organised in the following chapters. Chapter 1 gives the background theory of the fundamental principles of optoelectronic devices and presents a literature survey of existing optically-controlled structures across a wide frequency spectrum. Chapter 2 presents a comparative study of four commercial software packages with the aim to show that it is not always straightforward to select the most appropriate boundary conditions and define a material's parameter within a software when terahertz structures are modelled. A study of various modelling approaches using commercially-available software packages has been undertaken; a number of approaches have been identified and the most appropriate solutions are indicated. Chapter 3 presents a microwave plasma switch as a proof-of-concept scaled demonstrator. In this preliminary experiment a metal pipe rectangular waveguide (similar to WR-650 standard) has been implemented, which can be reconfigured as an ON-OFF switch using a plasma column formed by commercially available discharge tubes. This provides a good starting point for more sophisticated devices as presented in the following chapters. In Chapter 4 a novel optically-controlled waveguide plasma switch for terahertz applications is presented. The switch is excited by a continuous wave (CW) laser source and the photoconductivity profile, due to the laser illumination, is described in detail. The performance of the switch is studied by means of full-wave numerical simulations and various parametric studies are undertaken to provide physical insight in the device performance. The thermal characteristics of the device are also investigated. Chapter 5 gives in detail the processing steps for the microfabrication of various prototypes with the assembly of the prototypes being also discussed. The waveguide experimental setup is described in detail and the measurement results obtained are presented. In particular, emphasis has been given on the alignment of the devices with the Vector Network Analyser waveguide heads. Finally, Chapter 6 gives a summary of the work presented in this thesis and potentially new research directions are indicated as future work.Open Acces

Demystifying Material Parameters for Terahertz Electromagnetic Simulation

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Impact of a single nucleotide polymorphism on the 3D protein structure and ubiquitination activity of E3 ubiquitin ligase arkadia

Single nucleotide polymorphisms (SNPs) are genetic variations which can play a vital role in the study of human health. SNP studies are often used to identify point mutations that are associated with diseases. Arkadia (RNF111) is an E3 ubiquitin ligase that enhances transforming growth factor-beta (TGF-β) signaling by targeting negative regulators for degradation. Dysregulation of the TGF-β pathway is implicated in cancer because it exhibits tumor suppressive activity in normal cells while in tumor cells it promotes invasiveness and metastasis. Τhe SNP CGT > TGT generated an amino-acid (aa) substitution of Arginine 957 to Cysteine on the enzymatic RING domain of Arkadia. This was more prevalent in a tumor than in a normal tissue sample of a patient with colorectal cancer. This prompted us to investigate the effect of this mutation in the structure and activity of Arkadia RING. We used nuclear magnetic resonance (NMR) to analyze at an atomic-level the structural and dynamic properties of the R957C Arkadia RING domain, while ubiquitination and luciferase assays provided information about its enzymatic functionality. Our study showed that the R957C mutation changed the electrostatic properties of the RING domain however, without significant effects on the structure of its core region. However, the functional studies revealed that the R957C Arkadia exhibits significantly increased enzymatic activity supporting literature data that Arkadia within tumor cells promotes aggressive and metastatic behavior

Transthyretin regulates thyroid hormone levels in the choroid plexus, but not in the brain parenchyma: study in a transthyretin-null mouse model

6 pages, 3 figures, 2 tables.-- Presented in part in abstract form at the 26th Annual Meeting of the European Thyroid Association, Milan, Italy, August 28 to September 1, 1999.-- This is part of the Ph.D. thesis of J.A.P., University of Porto, Porto, Portugal.Transthyretin (TTR) is the major T4-binding protein in rodents. Using a TTR-null mouse model we asked the following questions. 1) Do other T4 binding moieties replace TTR in the cerebrospinal fluid (CSF)? 2) Are the low whole brain total T4 levels found in this mouse model associated with hypothyroidism, e.g. increased 5'-deiodinase type 2 (D2) activity and RC3-neurogranin messenger RNA levels? 3) Which brain regions account for the decreased total whole brain T4 levels? 4) Are there changes in T3 levels in the brain? Our results show the following. 1) No other T4-binding protein replaces TTR in the CSF of the TTR-null mice. 2) D2 activity is normal in the cortex, cerebellum, and hippocampus, and total brain RC3-neurogranin messenger RNA levels are not altered. 3) T4 levels measured in the cortex, cerebellum, and hippocampus are normal. However T4 and T3 levels in the choroid plexus are only 14% and 48% of the normal values, respectively. 4) T3 levels are normal in the brain parenchyma. The data presented here suggest that TTR influences thyroid hormone levels in the choroid plexus, but not in the brain. Interference with the blood-choroid-plexus-CSF-TTR-mediated route of T4 entry into the brain caused by the absence of TTR does not produce measurable features of hypothyroidism. It thus appears that TTR is not required for T4 entry or for maintenance of the euthyroid state in the mouse brain.This work was supported by Grants PRAXIS (Portugal) SAU/2/96 and BIA/459/94.Peer reviewe

Immune and inflammatory responses in TNF alpha-deficient mice: A critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response

To investigate the role of TNF alpha in the development of in vivo immune response we have generated TNF alpha-deficient mice by gene targeting. Homozygous mutant mice are viable and fertile, develop lymph nodes and Peyer's patches and show no apparent phenotypic abnormalities, indicating that TNF alpha is not required for normal mouse development. In the absence of TNF alpha mice readily succumb to L. monocytogenes infections and show reduced contact hypersensitivity responses. Furthermore, TNF alpha knockout mice are resistant to the systemic toxicity of LPS upon D-galactosamine sensitization, yet they remain sensitive to high doses of LPS alone. Most interestingly, TNF alpha knockout mice completely lack splenic primary B cell follicles and cannot form organized follicular dendritic cell (FDC) networks and germinal centers. However, despite the absence of B cell follicles, Ig class-switching can still occur, yet deregulated humoral immune responses against either thymus-dependent (TD) or thymus-independent (TI) antigens are observed. Complementation of TNF alpha functioning by the expression of either human or murine TNF alpha transgenes is sufficient to reconstitute these defects, establishing a physiological role for TNF alpha in regulating the development and organization of splenic follicular architecture and in the maturation of the humoral immune response

Neuronal migration and ventral subtype identity in the telencephalon depend on SOX1

Little is known about the molecular mechanisms and intrinsic factors that are responsible for the emergence of neuronal subtype identity. Several transcription factors that are expressed mainly in precursors of the ventral telencephalon have been shown to control neuronal specification, but it has been unclear whether subtype identity is also specified in these precursors, or if this happens in postmitotic neurons, and whether it involves the same or different factors. SOX1, an HMG box transcription factor, is expressed widely in neural precursors along with the two other SOXB1 subfamily members, SOX2 and SOX3, and all three have been implicated in neurogenesis. SOX1 is also uniquely expressed at a high level in the majority of telencephalic neurons that constitute the ventral striatum (VS). These neurons are missing in Sox1-null mutant mice. In the present study, we have addressed the requirement for SOX1 at a cellular level, revealing both the nature and timing of the defect. By generating a novel Sox1-null allele expressing β-galactosidase, we found that the VS precursors and their early neuronal differentiation are unaffected in the absence of SOX1, but the prospective neurons fail to migrate to their appropriate position. Furthermore, the migration of non-Sox1-expressing VS neurons (such as those expressing Pax6) was also affected in the absence of SOX1, suggesting that Sox1-expressing neurons play a role in structuring the area of the VS. To test whether SOX1 is required in postmitotic cells for the emergence of VS neuronal identity, we generated mice in which Sox1 expression was directed to all ventral telencephalic precursors, but to only a very few VS neurons. These mice again lacked most of the VS, indicating that SOX1 expression in precursors is not sufficient for VS development. Conversely, the few neurons in which Sox1 expression was maintained were able to migrate to the VS. In conclusion, Sox1 expression in precursors is not sufficient for VS neuronal identity and migration, but this is accomplished in postmitotic cells, which require the continued presence of SOX1. Our data also suggest that other SOXB1 members showing expression in specific neuronal populations are likely to play continuous roles from the establishment of precursors to their final differentiation

Looking for stability: Experiences of rehabilitation for Congolese survivors of torture in Athens and the role of the Congolese community in their support

Introduction: On-going conflict and political instability in the Democratic Republic of Congo (DRC) has led to increasing numbers of people fleeing their country for Europe. Many need rehabilitation services upon arrival in Greece after experiencing torture in DRC.  The scarcity of state resources and the limited capacity of non-governmental organisations to assist survivors of torture means many needs remain unmet. This study explored the experiences of rehabilitation for male Congolese survivors of torture living in Athens, as well as the potential role of the wider Congolese community in Athens in supporting rehabilitation.  Methods: This qualitative study included in-depth interviews with survivors of torture attending a rehabilitation clinic and key informant interviews with representatives of the wider Congolese community in Athens. Data was thematically analysed to construct and develop codes and themes. Results: 19 survivors and 10 key informants were interviewed. For many survivors, rehabilitation was an unclear concept. Despite the appreciation for services received at the clinic and the amelioration of physical and psychological symptoms, survivors felt rehabilitation was incomplete as it did not meet their accommodation needs nor provide stability through granting refugee status. Survivors were wary of trusting other Congolese people after experiencing torture and did not always associate themselves with the local Congolese community. The role of local Congolese leaders and organisations was not seen as replacing the clinical element of rehabilitation but aiding in practical issues such as information sharing and integration, especially in partnership with other organisations. Discussion: Systemic shortcomings in Greece, including poor access to accommodation and insecure asylum status, impeded processes of rehabilitation. Many participants found themselves navigating an unstable and unpredictable landscape in their journey towards “feeling whole again.” The role of the wider Congolese community in Athens in supporting rehabilitation remains complex and a lack of trust threatens social cohesion. Nonetheless, the willingness of the community to be more proactive should not be ignored by organisations and policy-makers. &nbsp

Sexual violence against migrants and asylum seekers. The experience of the MSF clinic on Lesvos Island, Greece.

Sexual violence can have destructive impact on the lives of people. It is more common in unstable conditions such as during displacement. On the Greek island of Lesvos, Médecins Sans Frontières provided medical care to survivors of sexual violence among the population of asylum seekers arriving there. This study aimed to describe the patterns of sexual violence reported by migrants and asylum seekers and the clinical care provided to them. Methods This is s a descriptive study using routine program data. The study population consisted of migrants and asylum seekers treated for conditions related to sexual violence at the Médecins Sans Frontières clinic on Lesvos Island (September 2017-January 2018). Results We enrolled 215 survivors of sexual violence who reported and were treated, of whom 60 (28%) were male. The majority of incidents reported (90%) were cases of rape; 174 (81%) of survivors were from Africa and 185 (86%) occurred over a month before presentation. Half the incidents (118) occurred in transit, mainly in Turkey, and 76 (35%) in the country of origin; 10 cases (5%) on Lesvos were also observed. The perpetrator was known in 23% of the cases. Only XXX received mental health care, and the need exceeded the capacity of available mental care services. Conclusion Even though the majority of cases delayed seeking medical care after the incident, it is crucial that access to mental health services is guaranteed for those in need. Such access and protection measures for people in transit need to be put in place along migration routes, including in countries nominally considered safe, and secure routes need to be developed

Rnf165/Ark2C enhances BMP-smad signaling to mediate motor axon extension

Little is known about extrinsic signals required for the advancement of motor neuron (MN) axons, which extend over long distances in the periphery to form precise connections with target muscles. Here we present that Rnf165 (Arkadia-like; Arkadia2; Ark2C) is expressed specifically in the nervous system and that its loss in mice causes motor innervation defects that originate during development and lead to wasting and death before weaning. The defects range from severe reduction of motor axon extension as observed in the dorsal forelimb to shortening of presynaptic branches of the phrenic nerve, as observed in the diaphragm. Molecular functional analysis showed that in the context of the spinal cord Ark2C enhances transcriptional responses of the Smad1/5/8 effectors, which are activated (phosphorylated) downstream of Bone Morphogenetic Protein (BMP) signals. Consistent with Ark2C-modulated BMP signaling influencing motor axons, motor pools in the spinal cord were found to harbor phosphorylated Smad1/5/8 (pSmad) and treatment of primary MN with BMP inhibitor diminished axon length. In addition, genetic reduction of BMP-Smad signaling in Ark2C+/− mice caused the emergence of Ark2C−/−-like dorsal forelimb innervation deficits confirming that enhancement of BMP-Smad responses by Ark2C mediates efficient innervation. Together the above data reveal an involvement of BMP-Smad signaling in motor axon advancement

Graded Smad2/3 activation is converted directly into levels of target gene expression in embryonic stem cells

The Transforming Growth Factor (TGF) β signalling family includes morphogens, such as Nodal and Activin, with important functions in vertebrate development. The concentration of the morphogen is critical for fate decisions in the responding cells. Smad2 and Smad3 are effectors of the Nodal/Activin branch of TGFβ signalling: they are activated by receptors, enter the nucleus and directly transcribe target genes. However, there have been no studies correlating levels of Smad2/3 activation with expression patterns of endogenous target genes in a developmental context over time. We used mouse Embryonic Stem (ES) cells to create a system whereby levels of activated Smad2/3 can be manipulated by an inducible constitutively active receptor (Alk4*) and an inhibitor (SB-431542) that blocks specifically Smad2/3 activation. The transcriptional responses were analysed by microarrays at different time points during activation and repression. We identified several genes that follow faithfully and reproducibly the Smad2/3 activation profile. Twenty-seven of these were novel and expressed in the early embryo downstream of Smad2/3 signalling. As they responded to Smad2/3 activation in the absence of protein synthesis, they were considered direct. These immediate responsive genes included negative intracellular feedback factors, like SnoN and I-Smad7, which inhibit the transcriptional activity of Smad2/3. However, their activation did not lead to subsequent repression of target genes over time, suggesting that this type of feedback is inefficient in ES cells or it is counteracted by mechanisms such as ubiquitin-mediated degradation by Arkadia. Here we present an ES cell system along with a database containing the expression profile of thousands of genes downstream of Smad2/3 activation patterns, in the presence or absence of protein synthesis. Furthermore, we identify primary target genes that follow proportionately and with high sensitivity changes in Smad2/3 levels over 15–30 hours. The above system and resource provide tools to study morphogen function in development