Performance of an Ocean Energy Conversion System with DFIG Sensorless Control

The 2009/28/EC Directive requires Member States of the European Union to adopt a National Action Plan for Renewable Energy. In this context, the Basque Energy Board, EVE, is committed to research activities such as the Mutriku Oscillating Water Column plant, OWC. This is an experimental facility whose concept consists of a turbine located in a pneumatic energy collection chamber and a doubly fed induction generator that converts energy extracted by the turbine into a form that can be returned to the network. The turbo-generator control requires a precise knowledge of system parameters and of the rotor angular velocity in particular. Thus, to remove the rotor speed sensor implies a simplification of the hardware that is always convenient in rough working conditions. In this particular case, a Luenberger based observer is considered and the effectiveness of the proposed control is shown by numerical simulations. Comparing these results with those obtained using a traditional speed sensor, it is shown that the proposed solution provides better performance since it increases power extraction in the sense that it allows a more reliable and robust performance of the plant, which is even more relevant in a hostile environment as the ocean.

Viability Conditions for a Compartmentalized Protometabolic System: A Semi-Empirical Approach

In this work we attempt to find out the extent to which realistic prebiotic compartments, such as fatty acid vesicles, would constrain the chemical network dynamics that could have sustained a minimal form of metabolism. We combine experimental and simulation results to establish the conditions under which a reaction network with a catalytically closed organization (more specifically, an (M, R)-system) would overcome the potential problem of self-suffocation that arises from the limited accessibility of nutrients to its internal reaction domain. The relationship between the permeability of the membrane, the lifetime of the key catalysts and their efficiency (reaction rate enhancement) turns out to be critical. In particular, we show how permeability values constrain the characteristic time scale of the bounded protometabolic processes. From this concrete and illustrative example we finally extend the discussion to a wider evolutionary context.

In Vitro and In Vivo Evaluation of a Folate-Targeted Copolymeric Submicrohydrogel Based on N-Isopropylacrylamide as 5-Fluorouracil Delivery System

Folate-targeted poly[(p-nitrophenyl acrylate)-co-(N-isopropylacrylamide)] nanohydrogel (F-SubMG) was loaded with 5-fluorouracil (5-FU) to obtain low (16.3 +/- 1.9 mu g 5-FU/mg F-SubMG) and high (46.8 +/- 3.8 mu g 5-FU/mg F-SubMG) load 5-FU-loaded F-SubMGs. The complete in vitro drug release took place in 8 h. The cytotoxicity of unloaded F-SubMGs in MCF7 and HeLa cells was low; although it increased for high F-SubMG concentration. The administration of 10 mu M 5-FU by 5-FU-loaded F-SubMGs was effective on both cellular types. Cell uptake of F-SubMGs took place in both cell types, but it was higher in HeLa cells because they are folate receptor positive. After subcutaneous administration (28 mg 5-FU/kg b.w.) in Wistar rats, F-SubMGs were detected at the site of injection under the skin. Histological studies indicated that the F-SubMGs were surrounded by connective tissue, without any signs of rejections, even 60 days after injection. Pharmacokinetic study showed an increase in MRT (mean residence time) of 5-FU when the drug was administered by drug-loaded F-SubMGs.

Risk management plan and pharmacovigilance system - biopharmaceuticals: biosimilars.

Editor literario del libro, Giancarlo Nota - All chapters are Open Access articles distributed under the Creative Commons Non Commercial-Share Alike-Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited.

High efficiency four-wave mixing induced by double-dark resonances in a five-level tripod system

A five-level tripod scheme is proposed for obtaining a high efficiency four-wave-mixing (FWM) process. The existence of double-dark resonances leads to a strong modification of the absorption and dispersion properties against a pump wave at two transparency windows. We show that both of them can be used to open the four-wave mixing channel and produce efficient mixing waves. In particular, higher FWM efficiency is always produced at the transparent window corresponding to the relatively weak-coupling field. By manipulating the intensity of the two coupling fields, the conversion efficiency of FWM can be controlled.

Development of a Cationic Mucic Acid Polymer-Based Nanoparticle siRNA Delivery System

Cancer chemotherapy has advanced from highly toxic drugs to more targeted treatments in the last 70 years. Chapter 1 opens with an introduction to targeted therapy for cancer. The benefits of using a nanoparticle to deliver therapeutics are discussed. We move on to siRNA in particular, and why it would be advantageous as a therapy. Specific to siRNA delivery are some challenges, such as nuclease degradation, quick clearance from circulation, needing to enter cells, and getting to the cytosol. We propose the development of a nanoparticle delivery system to tackle these challenges so that siRNA can be effective.

Chapter 2 of this thesis discusses the synthesis and analysis of a cationic mucic acid polymer (cMAP) which condenses siRNA to form a nanoparticle. Various methods to add polyethylene glycol (PEG) for stabilizing the nanoparticle in physiologic solutions, including using a boronic acid binding to diols on mucic acid, forming a copolymer of cMAP with PEG, and creating a triblock with mPEG on both ends of cMAP. The goal of these various pegylation strategies was to increase the circulation time of the siRNA nanoparticle in the bloodstream to allow more of the nanoparticle to reach tumor tissue by the enhanced permeation and retention effect. We found that the triblock mPEG-cMAP-PEGm polymer condensed siRNA to form very stable 30-40 nm particles that circulated for the longest time – almost 10% of the formulation remained in the bloodstream of mice 1 h after intravenous injection.

Chapter 3 explores the use of an antibody as a targeting agent for nanoparticles. Some antibodies of the IgG1 subtype are able to recruit natural killer cells that effect antibody dependent cellular cytotoxicity (ADCC) to kill the targeted cell to which the antibody is bound. There is evidence that the ADCC effect remains in antibody-drug conjugates, so we wanted to know whether the ADCC effect is preserved when the antibody is bound to a nanoparticle, which is a much larger and complex entity. We utilized antibodies against epidermal growth factor receptor with similar binding and pharmacokinetics, cetuximab and panitumumab, which differ in that cetuximab is an IgG1 and panitumumab is an IgG2 (which does not cause ADCC). Although a natural killer cell culture model showed that gold nanoparticles with a full antibody targeting agent can elicit target cell lysis, we found that this effect was not preserved in vivo. Whether this is due to the antibody not being accessible to immune cells or whether the natural killer cells are inactivated in a tumor xenograft remains unknown. It is possible that using a full antibody still has value if there are immune functions which are altered in a complex in vivo environment that are intact in an in vitro system, so the value of using a full antibody as a targeting agent versus using an antibody fragment or a protein such as transferrin is still open to further exploration.

In chapter 4, nanoparticle targeting and endosomal escape are further discussed with respect to the cMAP nanoparticle system. A diboronic acid entity, which gives an order of magnitude greater binding (than boronic acid) to cMAP due to the vicinal diols in mucic acid, was synthesized, attached to 5kD or 10kD PEG, and conjugated to either transferrin or cetuximab. A histidine was incorporated into the triblock polymer between cMAP and the PEG blocks to allow for siRNA endosomal escape. Nanoparticle size remained 30-40 nm with a slightly negative ca. -3 mV zeta potential with the triblock polymer containing histidine and when targeting agents were added. Greater mRNA knockdown was seen with the endosomal escape mechanism than without. The nanoparticle formulations were able to knock down the targeted mRNA in vitro. Mixed effects suggesting function were seen in vivo.

Chapter 5 summarizes the project and provides an outlook on siRNA delivery as well as targeted combination therapies for the future of personalized medicine in cancer treatment.

On the Dynamics of the Adenylate Energy System: Homeorhesis vs Homeostasis

Biochemical energy is the fundamental element that maintains both the adequate turnover of the biomolecular structures and the functional metabolic viability of unicellular organisms. The levels of ATP, ADP and AMP reflect roughly the energetic status of the cell, and a precise ratio relating them was proposed by Atkinson as the adenylate energy charge (AEC). Under growth-phase conditions, cells maintain the AEC within narrow physiological values, despite extremely large fluctuations in the adenine nucleotides concentration. Intensive experimental studies have shown that these AEC values are preserved in a wide variety of organisms, both eukaryotes and prokaryotes. Here, to understand some of the functional elements involved in the cellular energy status, we present a computational model conformed by some key essential parts of the adenylate energy system. Specifically, we have considered (I) the main synthesis process of ATP from ADP, (II) the main catalyzed phosphotransfer reaction for interconversion of ATP, ADP and AMP, (III) the enzymatic hydrolysis of ATP yielding ADP, and (IV) the enzymatic hydrolysis of ATP providing AMP. This leads to a dynamic metabolic model (with the form of a delayed differential system) in which the enzymatic rate equations and all the physiological kinetic parameters have been explicitly considered and experimentally tested in vitro. Our central hypothesis is that cells are characterized by changing energy dynamics (homeorhesis). The results show that the AEC presents stable transitions between steady states and periodic oscillations and, in agreement with experimental data these oscillations range within the narrow AEC window. Furthermore, the model shows sustained oscillations in the Gibbs free energy and in the total nucleotide pool. The present study provides a step forward towards the understanding of the fundamental principles and quantitative laws governing the adenylate energy system, which is a fundamental element for unveiling the dynamics of cellular life.

Interaction between the 5-HT system and the basal ganglia: functional implication and therapeutic perspective in Parkinson's disease

The neurotransmitter serotonin (5-HT) has a multifaceted function in the modulation of information processing through the activation of multiple receptor families, including G-protein-coupled receptor subtypes (5-HT1, 5-HT2, 5-HT4-7) and ligand-gated ion channels (5-HT3). The largest population of serotonergic neurons is located in the midbrain, specifically in the raphe nuclei. Although the medial and dorsal raphe nucleus (DRN) share common projecting areas, in the basal ganglia (BG) nuclei serotonergic innervations come mainly from the DRN. The BG are a highly organized network of subcortical nuclei composed of the striatum (caudate and putamen), subthalamic nucleus (STN), internal and external globus pallidus (or entopeduncular nucleus in rodents, GPi/EP and GPe) and substantia nigra (pars compacta, SNc, and pars reticulata, SNr). The BG are part of the cortico-BG-thalamic circuits, which play a role in many functions like motor control, emotion, and cognition and are critically involved in diseases such as Parkinson's disease (PD). This review provides an overview of serotonergic modulation of the BG at the functional level and a discussion of how this interaction may be relevant to treating PD and the motor complications induced by chronic treatment with L-DOPA.

Proteomic Analysis of the Ubiquitin Landscape in the Drosophila Embryonic Nervous System and the Adult Photoreceptor Cells

Background Ubiquitination is known to regulate physiological neuronal functions as well as to be involved in a number of neuronal diseases. Several ubiquitin proteomic approaches have been developed during the last decade but, as they have been mostly applied to non-neuronal cell culture, very little is yet known about neuronal ubiquitination pathways in vivo. Methodology/Principal Findings Using an in vivo biotinylation strategy we have isolated and identified the ubiquitinated proteome in neurons both for the developing embryonic brain and for the adult eye of Drosophila melanogaster. Bioinformatic comparison of both datasets indicates a significant difference on the ubiquitin substrates, which logically correlates with the processes that are most active at each of the developmental stages. Detection within the isolated material of two ubiquitin E3 ligases, Parkin and Ube3a, indicates their ubiquitinating activity on the studied tissues. Further identification of the proteins that do accumulate upon interference with the proteasomal degradative pathway provides an indication of the proteins that are targeted for clearance in neurons. Last, we report the proof-of-principle validation of two lysine residues required for nSyb ubiquitination. Conclusions/Significance These data cast light on the differential and common ubiquitination pathways between the embryonic and adult neurons, and hence will contribute to the understanding of the mechanisms by which neuronal function is regulated. The in vivo biotinylation methodology described here complements other approaches for ubiquitome study and offers unique advantages, and is poised to provide further insight into disease mechanisms related to the ubiquitin proteasome system.

Serological and Genetic Evidence for Altered Complement System Functionality in Systemic Lupus Erythematosus: Findings of the GAPAID Consortium

Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption we examined ex vivo immune complex formation on autoantigen arrays. We recruited patients with SLE (n = 211), with other systemic autoimmune diseases (n = 65) and non-autoimmune control subjects (n = 149). Standard clinical and laboratory data were collected and serum complement levels were determined. The genotype of SNP rs1143679 in the ITGAM gene was also determined. Ex vivo formation of immune complexes, with respect to IgM, IgG, complement C4 and C3 binding, was examined using a functional immunoassay on autoantigen microarray comprising nucleic acids, proteins and lipids. Complement consumption of nucleic acids increased upon binding of IgM and IgG even when serum complement levels were decreased due to consumption in SLE patients. A negative correlation between serum complement levels and ex vivo complement deposition on nucleic acid autoantigens is demonstrated. On the contrary, complement deposition on tested protein and lipid autoantigens showed positive correlation with C4 levels. Genetic analysis revealed that the non-synonymous variant rs1143679 in complement receptor type 3 is associated with an increased production of anti-dsDNA IgG antibodies. Notwithstanding, homozygous carriers of the previously reported susceptible allele (AA) had lower levels of dsDNA specific IgM among SLE patients. Both the non-synonymous variant rs1143679 and the high ratio of nucleic acid specific IgG/IgM were associated with multiple organ involvement. In summary, secondary complement deficiency in SLE does not impair opsonization of nucleic-acid-containing autoantigens but does affect other antigens and potentially other complement dependent processes. Dysfunction of the receptor recognizing complement opsonized immune complexes promotes the development of class-switched autoantibodies targeting nucleic acids.

HACCP based management system for improving quality of freshwater giant prawn, Macrobrachium rosenbergii

The study was conducted on the present status of HACCP based quality management system of golda, Macrobrachium rosenbergii farms in Fulpur region of Mymensingh. Information was collected on general condition of farms, culture systems and post-harvest quality management. In almost all farms, there is no or inadequate infrastructure facilities such as, road access, electric supply, telecommunications, ice, feed storage facility, vehicle for golda transportation, washing and toilet facilities. The problems associated with sanitation and hygiene was: widespread use of cow dung, poultry manure and construction of open toilet within the vicinity of prawn culture pond. Different grades of commercially available and locally prepared feeds were used for golda culture in the pond. Golda post-larvae (PL) of 40-50 days old were stocked with carp species. The price of golda PL ranged from Tk. 1.00 to Tk. 1.25/piece. The pond size varied from 50 decimal (0.2 ha) to 2.5 acre (1.0 ha) with an average depth of 2-2.5 m. The culture period of golda varied from April-May to November-December and survival rate ranged between 75 and 80%. Production of golda varied from 250-500 kg/acre (625-1,250 kg/ha). Harvested golda were transported to city market within 4 h. Two size grading were generally followed during pricing, e.g. Tk. 500 to 550/kg for >100 g size and Tk. 300/kg for <100 g size. The cost-benefit ratio was found to remain around 1:1.25 depending on availability of PL. Water quality parameters such as, water temperature, pH, dissolved oxygen, total alkalinity and chlorophyll a in five golda farms in Fulpur region were monitored. Water temperature ranged from 29°C to 33°C, dissolved oxygen from 2.28 to 4.13 mg/l, pH between 6.65 and 7.94, alkalinity from 44 to 70 mg/l and chlorophyll a concentration from 61.88 to 102.34 µg/l in the five investigated ponds. The Aerobic Plate Count (APC) of the water sample was within the range of 2.0x10^6 - 2.96x10^7 CFU/ml and of soil samples within the range of 6.9x10^6 - 7.73x10^6 CFU/g. Streptococcus sp., Bacillus sp., Escherichia coli, Staphylococcus sp., Pseudomonas sp. and Salmonella sp. were isolated from pond water and sediment. Different feed samples used for golda was analyzed for proximate composition. Moisture content ranged around 14.14-21.22%, crude protein 20.55-44.1%, lipid 4.67-12.54% and ash 9.7-27.69%. The TVB-N values and peroxide values of feeds used as starter, grower and fish meal were found within the acceptable ranges and samples were free from pathogenic organisms. A training was organized for the golda farmers on HACCP, water quality and post-harvest quality management of prawn.

Telemetric recordings of single neuron activity and visual scenes in monkeys walking in an open field

This paper describes a portable recording system and methods for obtaining chronic recordings of single units and tracking rhesus monkey behavior in an open field. The integrated system consists of four major components: (1) microelectrode assembly; (2) h

Murine MyaK, a member of a family of yeast YAK1-related genes, is highly expressed in hormonally modulated epithelia in the reproductive system and in the embryonic central nervous system

We have cloned a mouse homologue (designated Myak) of the yeast protein kinase YAK1. The 1210 aa open reading frame contains a putative protein kinase domain, nuclear localization sequences and PEST sequences. Myak appears to be a member of a growing family of YAK1-related genes that include Drosophila and human Minibrain as well as a recently identified rat gene ANPK that encode a steroid hormone receptor interacting protein. RNA blot analysis revealed that Myak is expressed at low levels ubiquitously but at high levels in reproductive tissues, including testis, epididymis, ovary, uterus, and mammary gland, as well as in brain and kidney. In situ hybridization analysis on selected tissues revealed that Myak is particularly abundant in the hormonally modulated epithelia of the epididymis, mammary gland, and uterus, in round spermatids in the testis, and in the corpora lutea in the ovary, Myak is also highly expressed in the aqueduct of the adult brain and in the brain and spinal cord of day 12.5 embryos, Mol. Reprod. Dev. 55:372-378, 2000. (C) 2000 Wiley-Liss, Inc.

An error free passive UHF RFID system using a new form of wireless signal distribution

A wide area and error free ultra high frequency (UHF) radio frequency identification (RFID) interrogation system based on the use of multiple antennas used in cooperation to provide high quality ubiquitous coverage, is presented. The system uses an intelligent distributed antenna system (DAS) whereby two or more spatially separated transmit and receive antenna pairs are used to allow greatly improved multiple tag identification performance over wide areas. The system is shown to increase the read accuracy of 115 passive UHF RFID tags to 100% from <60% over a 10m × 8m open plan office area. The returned signal strength of the tag backscatter signals is also increased by an average of 10dB and 17dB over an area of 10m 8m and 10m × 4m respectively. Furthermore, it is shown that the DAS RFID system has improved immunity to tag orientation. Finally, the new system is also shown to increase the tag read speed/rate of a population of tags compared with a conventional RFID system. © 2012 IEEE.

Auto-calibration of a camera system using Image Alignment

Calibration of a camera system is a necessary step in any stereo metric process. It correlates all cameras to a common coordinate system by measuring the intrinsic and extrinsic parameters of each camera. Currently, manual calibration of a camera system is the only way to achieve calibration in civil engineering operations that require stereo metric processes (photogrammetry, videogrammetry, vision based asset tracking, etc). This type of calibration however is time-consuming and labor-intensive. Furthermore, in civil engineering operations, camera systems are exposed to open, busy sites. In these conditions, the position of presumably stationary cameras can easily be changed due to external factors such as wind, vibrations or due to an unintentional push/touch from personnel on site. In such cases manual calibration must be repeated. In order to address this issue, several self-calibration algorithms have been proposed. These algorithms use Projective Geometry, Absolute Conic and Kruppa Equations and variations of these to produce processes that achieve calibration. However, most of these methods do not consider all constraints of a camera system such as camera intrinsic constraints, scene constraints, camera motion or varying camera intrinsic properties. This paper presents a novel method that takes all constraints into consideration to auto-calibrate cameras using an image alignment algorithm originally meant for vision based tracking. In this method, image frames are taken from cameras. These frames are used to calculate the fundamental matrix that gives epipolar constraints. Intrinsic and extrinsic properties of cameras are acquired from this calculation. Test results are presented in this paper with recommendations for further improvement.