Elucidation of the gas-phase structure of a sugar-modified DNA analogue

Antisense oligonucleotides are medical agents for the treatment of genetic diseases that are designed to interact specifically with mRNA. This interaction either induces enzymatic degradation of the targeted RNA or modifies processing pathways, e.g. by inducing alternative splicing of the pre-mRNA. The latter mechanism applies to the treatment of Duchenne muscular dystrophy with a sugar-modified DNA analogue called tricyclo-DNA (tcDNA). In tcDNA the ribose sugar-moiety is extended to a three-membered ring system, which augments the binding affinity and the selectivity of the antisense oligonucleotide for its target. The advent of chemically modified nucleic acids for antisense therapy presents a challenge to diagnostic tools, which must be able to cope with a variety of structural analogues. Mass spectrometry meets this demand for non-enzyme based sequencing methods ideally, because the technique is largely unaffected by structural modifications of the analyte. Sequence coverage of a fully modified tcDNA 15mer can be obtained in a single tandem mass spectrometric experiment. Beyond sequencing experiments, tandem mass spectrometry was applied to elucidate the gas-phase structure and stability of tcDNA:DNA and tcDNA:RNA hybrid duplexes. Most remarkable is the formation of truncated duplexes upon collision-induced dissociation of these structures. Our data suggest that the cleavage site within the duplex is directed by the modified sugar-moiety. Moreover, the formation of truncated duplexes manifests the exceptional stability of the hybrid duplexes in the gas-phase. This stability arises from the modified sugar-moiety, which locks the tcDNA single strand into a conformation that is similar to RNA in A-form duplexes. The conformational particularity of tcDNA in the gas-phase was confirmed by ion mobility-mass spectrometry experiments on tcDNA, DNA, and RNA.

Gas-phase fragmentation and conformation of the sugar-modified antisense oligonucleotide tcDNA

Tricyclo-DNA (tcDNA) is a sugar- and backbone-modified analogue of DNA that is currently tested as antisense oligonucleotide for the treatment of Duchenne muscular dystrophy. The name tricyclo-DNA is derived from the modified sugar-moiety: the deoxyribose is extended to a three-membered ring system. This modification is designed to limit the flexibility of the structure, thus giving rise to entropically stabilized hybrid duplexes formed between tcDNA and complementary DNA or RNA oligonucleotides. While the structural modifications increase the biostability of the therapeutic agent, they also render the oligonucleotide inaccessible to enzyme-based sequencing methods. Tandem mass spectrometry constitutes an alternative sequencing technique for partially and fully modified oligonucleotides. For reliable sequencing, the fragmentation mechanism of the structure in question must be understood. Therefore, the presented work evaluates the effect of the modified sugar-moiety on the gas-phase dissociation of single stranded tcDNA. Moreover, our experiments reflect the exceptional gas-phase stability of hybrid duplexes that is most noticeable in the formation of truncated duplex ions upon collision-induced dissociation. The stability of the duplex arises from the modified sugar-moiety, as the rigid structure of the tcDNA single strand minimizes the change of the entropy for the annealing. Moreover, the tc-modification gives rise to extended conformations of the nucleic acids in the gas-phase, which was studied by ion mobility spectrometry-mass spectrometry.

Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06)

BACKGROUND Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer (mCRC) patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after completing first-line chemotherapy. PATIENTS AND METHODS In an open-label, phase III multicentre trial, patients with mCRC without disease progression after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned to continuing bevacizumab at a standard dose or no treatment. CT scans were done every 6 weeks until disease progression. The primary end point was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significance level of 10% and a statistical power of 85%. RESULTS The intention-to-treat population comprised 262 patients: median follow-up was 36.7 months. The median TTP was 4.1 [95% confidence interval (CI) 3.1-5.4] months for bevacizumab continuation versus 2.9 (95% CI 2.8-3.8) months for no continuation; HR 0.74 (95% CI 0.58-0.96). Non-inferiority could not be demonstrated. The median overall survival was 25.4 months for bevacizumab continuation versus 23.8 months (HR 0.83; 95% CI 0.63-1.1; P = 0.2) for no continuation. Severe adverse events were uncommon in the bevacizumab continuation arm. Costs for bevacizumab continuation were estimated to be ∼30,000 USD per patient. CONCLUSIONS Non-inferiority could not be demonstrated for treatment holidays versus continuing bevacizumab monotheray, after 4-6 months of standard first-line chemotherapy plus bevacizumab. Based on no impact on overall survival and increased treatment costs, bevacizumab as a single agent is of no meaningful therapeutic value. More efficient treatment approaches are needed to maintain control of stabilized disease following induction therapy. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, number NCT00544700.

Detecting single-target changes in multiple object tracking: The case of peripheral vision

In the current study it is investigated whether peripheral vision can be used to monitor multi-ple moving objects and to detect single-target changes. For this purpose, in Experiment 1, a modified MOT setup with a large projection and a constant-position centroid phase had to be checked first. Classical findings regarding the use of a virtual centroid to track multiple ob-jects and the dependency of tracking accuracy on target speed could be successfully replicat-ed. Thereafter, the main experimental variations regarding the manipulation of to-be-detected target changes could be introduced in Experiment 2. In addition to a button press used for the detection task, gaze behavior was assessed using an integrated eye-tracking system. The anal-ysis of saccadic reaction times in relation to the motor response shows that peripheral vision is naturally used to detect motion and form changes in MOT because the saccade to the target occurred after target-change offset. Furthermore, for changes of comparable task difficulties, motion changes are detected better by peripheral vision than form changes. Findings indicate that capabilities of the visual system (e.g., visual acuity) affect change detection rates and that covert-attention processes may be affected by vision-related aspects like spatial uncertainty. Moreover, it is argued that a centroid-MOT strategy might reduce the amount of saccade-related costs and that eye-tracking seems to be generally valuable to test predictions derived from theories on MOT. Finally, implications for testing covert attention in applied settings are proposed.

Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial.

BACKGROUND Giant cell arteritis is an immune-mediated disease of medium and large-sized arteries that affects mostly people older than 50 years of age. Treatment with glucocorticoids is the gold-standard and prevents severe vascular complications but is associated with substantial morbidity and mortality. Tocilizumab, a humanised monoclonal antibody against the interleukin-6 receptor, has been associated with rapid induction and maintenance of remission in patients with giant cell arteritis. We therefore aimed to study the efficacy and safety of tocilizumab in the first randomised clinical trial in patients with newly diagnosed or recurrent giant cell arteritis. METHODS In this single centre, phase 2, randomised, double-blind, placebo-controlled trial, we recruited patients aged 50 years and older from University Hospital Bern, Switzerland, who met the 1990 American College of Rheumatology criteria for giant cell arteritis. Patients with new-onset or relapsing disease were randomly assigned (2:1) to receive either tocilizumab (8 mg/kg) or placebo intravenously. 13 infusions were given in 4 week intervals until week 52. Both groups received oral prednisolone, starting at 1 mg/kg per day and tapered down to 0 mg according to a standard reduction scheme defined in the study protocol. Allocation to treatment groups was done using a central computerised randomisation procedure with a permuted block design and a block size of three, and concealed using central randomisation generated by the clinical trials unit. Patients, investigators, and study personnel were masked to treatment assignment. The primary outcome was the proportion of patients who achieved complete remission of disease at a prednisolone dose of 0·1 mg/kg per day at week 12. All analyses were intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01450137. RESULTS Between March 3, 2012, and Sept 9, 2014, 20 patients were randomly assigned to receive tocilizumab and prednisolone, and ten patients to receive placebo and glucocorticoid; 16 (80%) and seven (70%) patients, respectively, had new-onset giant cell arteritis. 17 (85%) of 20 patients given tocilizumab and four (40%) of ten patients given placebo reached complete remission by week 12 (risk difference 45%, 95% CI 11-79; p=0·0301). Relapse-free survival was achieved in 17 (85%) patients in the tocilizumab group and two (20%) in the placebo group by week 52 (risk difference 65%, 95% CI 36-94; p=0·0010). The mean survival-time difference to stop glucocorticoids was 12 weeks in favour of tocilizumab (95% CI 7-17; p<0·0001), leading to a cumulative prednisolone dose of 43 mg/kg in the tocilizumab group versus 110 mg/kg in the placebo group (p=0·0005) after 52 weeks. Seven (35%) patients in the tocilizumab group and five (50%) in the placebo group had serious adverse events. INTERPRETATION Our findings show, for the first time in a trial setting, the efficacy of tocilizumab in the induction and maintenance of remission in patients with giant cell arteritis. FUNDING Roche and the University of Bern.

Bayesian adaptive designs for drug combinations in early phase clinical trials

Treating patients with combined agents is a growing trend in cancer clinical trials. Evaluating the synergism of multiple drugs is often the primary motivation for such drug-combination studies. Focusing on the drug combination study in the early phase clinical trials, our research is composed of three parts: (1) We conduct a comprehensive comparison of four dose-finding designs in the two-dimensional toxicity probability space and propose using the Bayesian model averaging method to overcome the arbitrariness of the model specification and enhance the robustness of the design; (2) Motivated by a recent drug-combination trial at MD Anderson Cancer Center with a continuous-dose standard of care agent and a discrete-dose investigational agent, we propose a two-stage Bayesian adaptive dose-finding design based on an extended continual reassessment method; (3) By combining phase I and phase II clinical trials, we propose an extension of a single agent dose-finding design. We model the time-to-event toxicity and efficacy to direct dose finding in two-dimensional drug-combination studies. We conduct extensive simulation studies to examine the operating characteristics of the aforementioned designs and demonstrate the designs' good performances in various practical scenarios.^

Bayesian Adaptive Designs for Early Phase Clinical Trials

My dissertation focuses mainly on Bayesian adaptive designs for phase I and phase II clinical trials. It includes three specific topics: (1) proposing a novel two-dimensional dose-finding algorithm for biological agents, (2) developing Bayesian adaptive screening designs to provide more efficient and ethical clinical trials, and (3) incorporating missing late-onset responses to make an early stopping decision. Treating patients with novel biological agents is becoming a leading trend in oncology. Unlike cytotoxic agents, for which toxicity and efficacy monotonically increase with dose, biological agents may exhibit non-monotonic patterns in their dose-response relationships. Using a trial with two biological agents as an example, we propose a phase I/II trial design to identify the biologically optimal dose combination (BODC), which is defined as the dose combination of the two agents with the highest efficacy and tolerable toxicity. A change-point model is used to reflect the fact that the dose-toxicity surface of the combinational agents may plateau at higher dose levels, and a flexible logistic model is proposed to accommodate the possible non-monotonic pattern for the dose-efficacy relationship. During the trial, we continuously update the posterior estimates of toxicity and efficacy and assign patients to the most appropriate dose combination. We propose a novel dose-finding algorithm to encourage sufficient exploration of untried dose combinations in the two-dimensional space. Extensive simulation studies show that the proposed design has desirable operating characteristics in identifying the BODC under various patterns of dose-toxicity and dose-efficacy relationships. Trials of combination therapies for the treatment of cancer are playing an increasingly important role in the battle against this disease. To more efficiently handle the large number of combination therapies that must be tested, we propose a novel Bayesian phase II adaptive screening design to simultaneously select among possible treatment combinations involving multiple agents. Our design is based on formulating the selection procedure as a Bayesian hypothesis testing problem in which the superiority of each treatment combination is equated to a single hypothesis. During the trial conduct, we use the current values of the posterior probabilities of all hypotheses to adaptively allocate patients to treatment combinations. Simulation studies show that the proposed design substantially outperforms the conventional multi-arm balanced factorial trial design. The proposed design yields a significantly higher probability for selecting the best treatment while at the same time allocating substantially more patients to efficacious treatments. The proposed design is most appropriate for the trials combining multiple agents and screening out the efficacious combination to be further investigated. The proposed Bayesian adaptive phase II screening design substantially outperformed the conventional complete factorial design. Our design allocates more patients to better treatments while at the same time providing higher power to identify the best treatment at the end of the trial. Phase II trial studies usually are single-arm trials which are conducted to test the efficacy of experimental agents and decide whether agents are promising to be sent to phase III trials. Interim monitoring is employed to stop the trial early for futility to avoid assigning unacceptable number of patients to inferior treatments. We propose a Bayesian single-arm phase II design with continuous monitoring for estimating the response rate of the experimental drug. To address the issue of late-onset responses, we use a piece-wise exponential model to estimate the hazard function of time to response data and handle the missing responses using the multiple imputation approach. We evaluate the operating characteristics of the proposed method through extensive simulation studies. We show that the proposed method reduces the total length of the trial duration and yields desirable operating characteristics for different physician-specified lower bounds of response rate with different true response rates.

Sea-floor videos and photographs (benthos) along 6 shelf profiles from the eastern Weddell Sea, Antarctica taken with remote operated vehicel CHEROKEE during Polarstern cruise ANT-XXI/2

The ROV operations had three objectives: (1) to check, whether the "Cherokee" system is suited for advanced benthological work in the high latitude Antarctic shelf areas; (2) to support the disturbance experiment, providing immediate visual Information; (3) to continue ecological work that started in 1989 at the hilltop situated at the northern margin of the Norsel Bank off the 4-Seasons Inlet (Weddell Sea). The "Cherokee" is was equipped with 3 video cameras, 2 of which support the operation. A high resolution Tritech Typhoon camera is used for scientific observations to be recorded. In addition, the ROV has a manipulator, a still camera, lights and strobe, compass, 2 lasers, a Posidonia transponder and an obstacle avoidance Sonar. The size of the vehicle is 160 X 90 X 90cm. In the present configuration without TMS (tether management system) the deployment has to start with paying out the full cable length, lay it in loops on deck and connect the glass fibres at the tether's spool winch. After a final technical check the vehicle is deployed into the water, actively driven perpendicular to the ship's axis and floatings are fixed to the tether. At a cable length of approx. 50 m, the tether is tightened to the depressor by several cable ties and both components are lowered towards the sea floor, the vehicle by the thruster's propulsion and the depressor by the ship's winch. At 5 m intervals the tether has to be tied to the single conductor cable. In good weather conditions the instruments supporting the navigation of the ROV, especially the Posidonia system, allow an operation mode to follow the ship's course if the ship's speed is slow. Together with the lasers which act as a scale in the images they also allow a reproducible scientific analysis since the transect can be plotted in a GIS system. Consequently, the area observed can be easily calculated. An operation as a predominantly drifting system, especially in areas with bottom near currents, is also possible, however, the connection of the tether at the rear of the vehicle is unsuitable for such conditions. The recovery of the system corresponds to that of the deployment. Most important is to reach the surface of the sea at a safe distance perpendicular to the ship's axis in order not to interfere with the ship's propellers. During this phase the Posidonia transponder system is of high relevance although it has to be switched off at a water depth of approx. 40 m. The minimum personal needed is 4 persons to handle the tether on deck, one person to operate the ship's winch, one pilot and one additional technician for the ROV's operation itself, one scientist, and one person on the ship's bridge in addition to one on deck for whale watching when the Posidonia system is in use. The time for the deployment of the ROV until it reaches the sea floor depends on the water depth and consequently on the length of the cable to be paid out beforehand and to be tightened to the single conductor cable. Deployment and recovery at intermediate water depths can last up to 2 hours each. A reasonable time for benthological observations close to the sea floor is 1 to 3 hours but can be extended if scientifically justified. Preliminary results: after a first test station, the ROV was deployed 3 times for observations related to the disturbance experiment. A first attempt to Cross the hilltop at the northern margin of the Norsel Bank close to the 4- Seasons Inlet was successful only for the first hundreds of metres transect length. The benthic community was dominated in biomass by the demosponge Cinachyra barbata. Due to the strong current of approx. 1 nm/h, the design of the system, and an expected more difficult current regime between grounded icebergs and the top of the hilltop the operation was stopped before the hilltop was reached. In a second attempt the hilltop was successfully crossed because the current and wind situation was much more suitable. In contrast to earlier expeditions with the "sprint" ROV it was the first time that both slopes, the smoother in the northeast and the steeper in the southwest were continuously observed during one cast. A coarse classification of the hilltop fauna shows patches dominated by single taxa: cnidarians, hydrozoans, holothurians, sea urchins and stalked sponges. Approximately 20 % of the north-eastern slope was devastated by grounding icebergs. Here the sediments consisted of large boulders, gravel or blocks of finer sediment looking like an irregularly ploughed field. On the Norsel Bank the Cinachyra concentrations were locally associated with high abundances of sea anemones. Total observation time amounted to 11.5 hours corresponding to almost 6-9 km transect length.

Structural properties of InAlN single layers nearly latice-matched to GaN grown by plasma assisted molecular beal epitaxy

The high lattice mismatch between III-nitride binaries (InN, GaN and AlN) remains a key problem to grow high quality III-nitride heterostructures. Recent interest has been focused on the growth of high-quality InAlN layers, with approximately 18% of indium incorporation, in-plane lattice-matched (LM) to GaN. While a lot of work has been done by metal-organic vapour phase epitaxy (MOVPE) by Carlin and co-workers, its growth by molecular beam epitaxy (MBE) is still in infancy

Modulation instability-induced fading in phase-sensitive optical time-domain reflectometry

Phase-sensitive optical time-domain reflectometry (?OTDR) is a simple and effective tool allowing the distributed monitoring of vibrations along single-mode fibers. We show in this Letter that modulation instability (MI) can induce a position-dependent signal fading in long-range ?OTDR over conventional optical fibers. This fading leads to a complete masking of the interference signal recorded at certain positions and therefore to a sensitivity loss at these positions. We illustrate this effect both theoretically and experimentally. While this effect is detrimental in the context of distributed vibration analysis using ?OTDR, we also believe that the technique provides a clear and insightful way to evidence the Fermi?Pasta?Ulam recurrence associated with the MI process.

Single - and double energy swift and slow heavy ion irradiated optical waveguides in Er: Tungstene-Tellurite glass and BGO for telecom applications

The fabrication of broadband amplifiers in wavelength division multiplexing (WDM) around 1.55 m, as they exhibit large stimulated cross sections and broad emission bandwidth. Bi4Ge3O12 (eultine type BGO) - well known scintillator material, also a rare-earth host material, photorefractive waveguides produced in it only using light ions in the past. Recently: MeV N+ ions and swift O5+ and C5+ ions, too*. Bi12GeO20 (sillenite type BGO) - high photoconductivity and photorefractive sensitivity in the visible and NIR good candidate for real-time holography and optical phase conjugation, photorefractive waveguides produced in it only using light ions. No previous attempts of ion beam fabrication of waveguides in it.

Implementation of the Heated Pulsed Theory using actively heated fiber optics: measurements of soil volumetric water content and soil volumetric heat capacity

Existe una creciente necesidad de hacer el mejor uso del agua para regadío. Una alternativa eficiente consiste en la monitorización del contenido volumétrico de agua (θ), utilizando sensores de humedad. A pesar de existir una gran diversidad de sensores y tecnologías disponibles, actualmente ninguna de ellas permite obtener medidas distribuidas en perfiles verticales de un metro y en escalas laterales de 0.1-1,000 m. En este sentido, es necesario buscar tecnologías alternativas que sirvan de puente entre las medidas puntuales y las escalas intermedias. Esta tesis doctoral se basa en el uso de Fibra Óptica (FO) con sistema de medida de temperatura distribuida (DTS), una tecnología alternativa de reciente creación que ha levantado gran expectación en las últimas dos décadas. Específicamente utilizamos el método de fibra calentada, en inglés Actively Heated Fiber Optic (AHFO), en la cual los cables de Fibra Óptica se utilizan como sondas de calor mediante la aplicación de corriente eléctrica a través de la camisa de acero inoxidable, o de un conductor eléctrico simétricamente posicionado, envuelto, alrededor del haz de fibra óptica. El uso de fibra calentada se basa en la utilización de la teoría de los pulsos de calor, en inglés Heated Pulsed Theory (HPP), por la cual el conductor se aproxima a una fuente de calor lineal e infinitesimal que introduce calor en el suelo. Mediante el análisis del tiempo de ocurrencia y magnitud de la respuesta térmica ante un pulso de calor, es posible estimar algunas propiedades específicas del suelo, tales como el contenido de humedad, calor específico (C) y conductividad térmica. Estos parámetros pueden ser estimados utilizando un sensor de temperatura adyacente a la sonda de calor [método simple, en inglés single heated pulsed probes (SHPP)], ó a una distancia radial r [método doble, en inglés dual heated pulsed probes (DHPP)]. Esta tesis doctoral pretende probar la idoneidad de los sistemas de fibra óptica calentada para la aplicación de la teoría clásica de sondas calentadas. Para ello, se desarrollarán dos sistemas FO-DTS. El primero se sitúa en un campo agrícola de La Nava de Arévalo (Ávila, España), en el cual se aplica la teoría SHPP para estimar θ. El segundo sistema se desarrolla en laboratorio y emplea la teoría DHPP para medir tanto θ como C. La teoría SHPP puede ser implementada con fibra óptica calentada para obtener medidas distribuidas de θ, mediante la utilización de sistemas FO-DTS y el uso de curvas de calibración específicas para cada suelo. Sin embargo, la mayoría de aplicaciones AHFO se han desarrollado exclusivamente en laboratorio utilizando medios porosos homogéneos. En esta tesis se utiliza el programa Hydrus 2D/3D para definir tales curvas de calibración. El modelo propuesto es validado en un segmento de cable enterrado en una instalación de fibra óptica y es capaz de predecir la respuesta térmica del suelo en puntos concretos de la instalación una vez que las propiedades físicas y térmicas de éste son definidas. La exactitud de la metodología para predecir θ frente a medidas puntuales tomadas con sensores de humedad comerciales fue de 0.001 a 0.022 m3 m-3 La implementación de la teoría DHPP con AHFO para medir C y θ suponen una oportunidad sin precedentes para aplicaciones medioambientales. En esta tesis se emplean diferentes combinaciones de cables y fuentes emisoras de calor, que se colocan en paralelo y utilizan un rango variado de espaciamientos, todo ello en el laboratorio. La amplitud de la señal y el tiempo de llegada se han observado como funciones del calor específico del suelo. Medidas de C, utilizando esta metodología y ante un rango variado de contenidos de humedad, sugirieron la idoneidad del método, aunque también se observaron importantes errores en contenidos bajos de humedad de hasta un 22%. La mejora del método requerirá otros modelos más precisos que tengan en cuenta el diámetro del cable, así como la posible influencia térmica del mismo. ABSTRACT There is an increasing need to make the most efficient use of water for irrigation. A good approach to make irrigation as efficient as possible is to monitor soil water content (θ) using soil moisture sensors. Although, there is a broad range of different sensors and technologies, currently, none of them can practically and accurately provide vertical and lateral moisture profiles spanning 0-1 m depth and 0.1-1,000 m lateral scales. In this regard, further research to fulfill the intermediate scale and to bridge single-point measurement with the broaden scales is still needed. This dissertation is based on the use of Fiber Optics with Distributed Temperature Sensing (FO-DTS), a novel approach which has been receiving growing interest in the last two decades. Specifically, we employ the so called Actively Heated Fiber Optic (AHFO) method, in which FO cables are employed as heat probe conductors by applying electricity to the stainless steel armoring jacket or an added conductor symmetrically positioned (wrapped) about the FO cable. AHFO is based on the classic Heated Pulsed Theory (HPP) which usually employs a heat probe conductor that approximates to an infinite line heat source which injects heat into the soil. Observation of the timing and magnitude of the thermal response to the energy input provide enough information to derive certain specific soil thermal characteristics such as the soil heat capacity, soil thermal conductivity or soil water content. These parameters can be estimated by capturing the soil thermal response (using a thermal sensor) adjacent to the heat source (the heating and the thermal sources are mounted together in the so called single heated pulsed probe (SHPP)), or separated at a certain distance, r (dual heated pulsed method (DHPP) This dissertation aims to test the feasibility of heated fiber optics to implement the HPP theory. Specifically, we focus on measuring soil water content (θ) and soil heat capacity (C) by employing two types of FO-DTS systems. The first one is located in an agricultural field in La Nava de Arévalo (Ávila, Spain) and employ the SHPP theory to estimate θ. The second one is developed in the laboratory using the procedures described in the DHPP theory, and focuses on estimating both C and θ. The SHPP theory can be implemented with actively heated fiber optics (AHFO) to obtain distributed measurements of soil water content (θ) by using reported soil thermal responses in Distributed Temperature Sensing (DTS) and with a soil-specific calibration relationship. However, most reported AHFO applications have been calibrated under laboratory homogeneous soil conditions, while inexpensive efficient calibration procedures useful in heterogeneous soils are lacking. In this PhD thesis, we employ the Hydrus 2D/3D code to define these soil-specific calibration curves. The model is then validated at a selected FO transect of the DTS installation. The model was able to predict the soil thermal response at specific locations of the fiber optic cable once the surrounding soil hydraulic and thermal properties were known. Results using electromagnetic moisture sensors at the same specific locations demonstrate the feasibility of the model to detect θ within an accuracy of 0.001 to 0.022 m3 m-3. Implementation of the Dual Heated Pulsed Probe (DPHP) theory for measurement of volumetric heat capacity (C) and water content (θ) with Distributed Temperature Sensing (DTS) heated fiber optic (FO) systems presents an unprecedented opportunity for environmental monitoring. We test the method using different combinations of FO cables and heat sources at a range of spacings in a laboratory setting. The amplitude and phase-shift in the heat signal with distance was found to be a function of the soil volumetric heat capacity (referred, here, to as Cs). Estimations of Cs at a range of θ suggest feasibility via responsiveness to the changes in θ (we observed a linear relationship in all FO combinations), though observed bias with decreasing soil water contents (up to 22%) was also reported. Optimization will require further models to account for the finite radius and thermal influence of the FO cables, employed here as “needle probes”. Also, consideration of the range of soil conditions and cable spacing and jacket configurations, suggested here to be valuable subjects of further study and development.

On the layout of a least weight single span structure with uniform load. Some comments and improvements

Beghini et al (Struct Multidisc Optim doi:10.1007/s00158-013-1030-6, 2013) have published a very interesting paper arriving to practically the same nearly optimal solutions for the so named “bridge prob- lem” that the Writers published a year before, but using an alternative and remarkable approach to the problem. In spite of this general agreement, the Writers think that some details of the paper can be improved and there are results that can be given a clear and mean- ingful interpretation thanks to an old and practically unknown theorem on optimal slenderness.

Novel dual-band single circular polarization antenna feeding network for satellite communications

In this paper a novel dual-band single circular polarization antenna feeding network for satellite communications is presented. The novel antenna feed chain1 is composed of two elements or subsystems, namely a diplexer and a bi-phase polarizer. In comparison with the classic topology based on an orthomode transducer and a dual-band polarizer, the proposed feed chain presents several advantages, such as compactness, modular design of the different components, broadband operation and versatility in the subsystems interconnection. The design procedure of this new antenna feed configuration is explained. Different examples of antenna feeding networks at 20/30 GHz are presented. It is pointed out the excellent results obtained in terms of isolation and axial ratio.

Power Converter Topologies for a High Performance Transformer Rectifier Unit in Aircraft Applications

This paper presents some power converter architectures and circuit topologies, which can be used to achieve the requirements of the high performance transformer rectifier unit in aircraft applications, mainly as: high power factor with low THD, high efficiency and high power density. The voltage and the power levels demanded for this application are: three-phase line-to-neutral input voltage of 115 or 230V AC rms (360 – 800Hz), output voltage of 28V DC or 270V DC(new grid value) and the output power up to tens of kilowatts.