Peptidomic approach identifies cruzioseptins, a new family of potent antimicrobial peptides in the splendid leaf frog, Cruziohyla calcarifer

Phyllomedusine frogs are an extraordinary source of biologically active peptides. At least 8 families of antimicrobial peptides have been reported in this frog clade, the dermaseptins being the most diverse. By a peptidomic approach, integrating molecular cloning, Edman degradation sequencing and tandem mass spectrometry, a new family of antimicrobial peptides has been identified in Cruziohyla calcarifer. These 15 novel antimicrobial peptides of 20–32 residues in length are named cruzioseptins. They are characterized by having a unique shared N-terminal sequence GFLD– and the sequence motifs –VALGAVSK– or –GKAAL(N/G/S) (V/A)V– in the middle of the peptide. Cruzioseptins have a broad spectrum of antimicrobial activity and low haemolytic effect. The most potent cruzioseptin was CZS-1 that had a MIC of 3.77 μM against the Gram positive bacterium, Staphylococcus aureus and the yeast Candida albicans. In contrast, CZS-1 was 3–fold less potent against the Gram negative bacterium, Escherichia coli (MIC 15.11 μM). CZS-1 reached 100% haemolysis at 120.87 μM. Skin secretions from unexplored species such as C. calcarifer continue to demonstrate the enormous molecular diversity hidden in the amphibian skin. Some of these novel peptides may provide lead structures for the development of a new class of antibiotics and antifungals of therapeutic use.

Providing a ‘whole-of-family’ approach to care: family-focused practices in mental health services

Introduction: Family members including children are all impacted by a family member’s mental illness. Although mental health services are increasingly encouraged to engage in family-focused practice, this is not a well-understood concept or practice in mental health care. Methods: An integrative review using systematic methods was conducted with international literature, with the aim of identifying concepts and practices of family-focused practice in child and youth and adult mental health services. Results: Findings from 40 peer-reviewed literature identified a range of understandings and applications of family-focused practice, including who comprises the ‘family’, whether the focus is family of origin or family of procreation or choice, and whether the context of practice is child and youth or adult. ‘Family’ as defined by its members forms the foundation for practice that aims to provide a whole-of-family approach to care. Six core practices comprise a family focus to care: assessment; psychoeducation; family care planning and goal-setting; liaison between families and services; instrumental, emotional and social support; and a coordinated system of care between families and services. Conclusion: By incorporating key principles and the core family-focused practices into their care delivery, clinicians can facilitate a whole-of-family approach to care and strengthen family members’ wellbeing and resilience, and their individual and collective health outcomes.

Collaborative Filtering with Data Classification : A Combined Approach to Hotel Recommendation Systems

Recommendation systems aim to help users make decisions more efficiently. The most widely used method in recommendation systems is collaborative filtering, of which, a critical step is to analyze a user's preferences and make recommendations of products or services based on similarity analysis with other users' ratings. However, collaborative filtering is less usable for recommendation facing the "cold start" problem, i.e. few comments being given to products or services. To tackle this problem, we propose an improved method that combines collaborative filtering and data classification. We use hotel recommendation data to test the proposed method. The accuracy of the recommendation is determined by the rankings. Evaluations regarding the accuracies of Top-3 and Top-10 recommendation lists using the 10-fold cross-validation method and ROC curves are conducted. The results show that the Top-3 hotel recommendation list proposed by the combined method has the superiority of the recommendation performance than the Top-10 list under the cold start condition in most of the times.

Random Access over Multi-Packet Reception Channels: A Mean-Field Approach

Thesis (Ph.D.)--University of Washington, 2016-06

Development of a transitioning approach to reduce surface water volumes in combined sewer systems

The overarching goal of this research is to establish a successful forum for a transition from the existing paradigm of managing wastewater infrastructure to a more sustainable paradigm that achieves a more efficient utilisation of wastewater assets. A transitioning approach to support a more efficient utilisation of surface water and wastewater assets and infrastructure is proposed and developed. The determined transitioning approach possesses key stages namely developing the arena, developing the agenda, case study, and monitoring. The case study stage investigates a drainage utility identifying their improvement drivers, the removal of surface water through detailed drainage modelling and the financial examination of the costs incurred under the various scenarios conducted. Understanding the implications of removing/attenuating surface water from the network is improved through obtaining data by detailed drainage modelling. Infoworks software is used to investigate and assess the current and future operational scenarios of a wastewater system operating over one calendar year. Modelling scenarios were conducted removing surface water from selected areas focusing on the volumes requiring pumping and durations of pumping station(s) operation prior to treatment during storm conditions. The financial implication of removing surface water in combined sewer systems is examined in three main components. Firstly the costs of electricity incurred at the single sewage pumping station (SPS) investigated during the various scenarios modelled require to be addressed. Secondly the costs to retrofit sustainable urban drainage system (SUDS) solutions needs to be identified. Thirdly the implications of removing surface water for the drainage utility at the national level and the potential saving for householder’s committing to a surface water disconnection rebate scheme. When addressed at the macro level i.e., with over 2,100 pumping stations, some operating in sequence and contained within one drainage utility annually treating 315,360 megalitres the significance of the same multiple quantifiable and intangible benefits becomes amplified. The research aims, objectives and findings are presented to the identified and convened stakeholders. The transitioning approach developed encourages positive discourse between stakeholders. The level of success of the transitioning approach determined is then tested using a quantitative methodology through the completion of questionnaires. From the questionnaires completed the respondents unanimously agreed that surface water flows should be removed as well as reduced from the combined sewer system. The respondents agreed that the removal of surface water from a typical combined sewer system is justified by applying a transitioning approach focusing on the energy consumption required to pump increased volumes during storm events. This response is significant based upon the economic evidence and is contrary to the respondents previous position that finance was their most influencing factor. When provided with other potentially available benefits the respondents were even more supportive of the justification to remove surface water from the combined sewer system. The combined findings of the work presented in this thesis provide further justification that the transitioning approach applied to the removal of surface water from a typical combined sewer system, as determined in this research has been successful.

Energy systems analysis of transboundary river basins in a nexus approach: the Sava river basin study case

Resource management policies are frequently designed and planned to target specific needs of particular sectors, without taking into account the interests of other sectors who share the same resources. In a climate of resource depletion, population growth, increase in energy demand and climate change awareness, it is of great importance to promote the assessment of intersectoral linkages and, by doing so, understand their effects and implications. This need is further augmented when common use of resources might not be solely relevant at national level, but also when the distribution of resources ranges over different nations. This dissertation focuses on the study of the energy systems of five south eastern European countries, which share the Sava River Basin, using a water-food(agriculture)-energy nexus approach. In the case of the electricity generation sector, the use of water is essential for the integrity of the energy systems, as the electricity production in the riparian countries relies on two major technologies dependent on water resources: hydro and thermal power plants. For example, in 2012, an average of 37% of the electricity production in the SRB countries was generated by hydropower and 61% in thermal power plants. Focusing on the SRB, in terms of existing installed capacities, the basin accommodates close to a tenth of all hydropower capacity while providing water for cooling to 42% of the net capacity of thermal power currently in operation in the basin. This energy-oriented nexus study explores the dependency on the basin’s water resources of the energy systems in the region for the period between 2015 and 2030. To do so, a multi-country electricity model was developed to provide a quantification ground to the analysis, using the open-source software modelling tool OSeMOSYS. Three main areas are subject to analysis: first, the impact of energy efficiency and renewable energy strategies in the electricity generation mix; secondly, the potential impacts of climate change under a moderate climate change projection scenario; and finally, deriving from the latter point, the cumulative impact of an increase in water demand in the agriculture sector, for irrigation. Additionally, electricity trade dynamics are compared across the different scenarios under scrutiny, as an effort to investigate the implications of the aforementioned factors in the electricity markets in the region.

Improving the use of G-CSF during chemotherapy using physiological mathematical modelling : a quantitative systems pharmacology approach

La diminution des doses administrées ou même la cessation complète d'un traitement chimiothérapeutique est souvent la conséquence de la réduction du nombre de neutrophiles, qui sont les globules blancs les plus fréquents dans le sang. Cette réduction dans le nombre absolu des neutrophiles, aussi connue sous le nom de myélosuppression, est précipitée par les effets létaux non spécifiques des médicaments anti-cancéreux, qui, parallèlement à leur effet thérapeutique, produisent aussi des effets toxiques sur les cellules saines. Dans le but d'atténuer cet impact myélosuppresseur, on administre aux patients un facteur de stimulation des colonies de granulocytes recombinant humain (rhG-CSF), une forme exogène du G-CSF, l'hormone responsable de la stimulation de la production des neutrophiles et de leurs libération dans la circulation sanguine. Bien que les bienfaits d'un traitement prophylactique avec le G-CSF pendant la chimiothérapie soient bien établis, les protocoles d'administration demeurent mal définis et sont fréquemment déterminés ad libitum par les cliniciens. Avec l'optique d'améliorer le dosage thérapeutique et rationaliser l'utilisation du rhG-CSF pendant le traitement chimiothérapeutique, nous avons développé un modèle physiologique du processus de granulopoïèse, qui incorpore les connaissances actuelles de pointe relatives à la production des neutrophiles des cellules souches hématopoïétiques dans la moelle osseuse. À ce modèle physiologique, nous avons intégré des modèles pharmacocinétiques/pharmacodynamiques (PK/PD) de deux médicaments: le PM00104 (Zalypsis®), un médicament anti-cancéreux, et le rhG-CSF (filgrastim). En se servant des principes fondamentaux sous-jacents à la physiologie, nous avons estimé les paramètres de manière exhaustive sans devoir recourir à l'ajustement des données, ce qui nous a permis de prédire des données cliniques provenant de 172 patients soumis au protocol CHOP14 (6 cycles de chimiothérapie avec une période de 14 jours où l'administration du rhG-CSF se fait du jour 4 au jour 13 post-chimiothérapie). En utilisant ce modèle physio-PK/PD, nous avons démontré que le nombre d'administrations du rhG-CSF pourrait être réduit de dix (pratique actuelle) à quatre ou même trois administrations, à condition de retarder le début du traitement prophylactique par le rhG-CSF. Dans un souci d'applicabilité clinique de notre approche de modélisation, nous avons investigué l'impact de la variabilité PK présente dans une population de patients, sur les prédictions du modèle, en intégrant des modèles PK de population (Pop-PK) des deux médicaments. En considérant des cohortes de 500 patients in silico pour chacun des cinq scénarios de variabilité plausibles et en utilisant trois marqueurs cliniques, soient le temps au nadir des neutrophiles, la valeur du nadir, ainsi que l'aire sous la courbe concentration-effet, nous avons établi qu'il n'y avait aucune différence significative dans les prédictions du modèle entre le patient-type et la population. Ceci démontre la robustesse de l'approche que nous avons développée et qui s'apparente à une approche de pharmacologie quantitative des systèmes (QSP). Motivés par l'utilisation du rhG-CSF dans le traitement d'autres maladies, comme des pathologies périodiques telles que la neutropénie cyclique, nous avons ensuite soumis l'étude du modèle au contexte des maladies dynamiques. En mettant en évidence la non validité du paradigme de la rétroaction des cytokines pour l'administration exogène des mimétiques du G-CSF, nous avons développé un modèle physiologique PK/PD novateur comprenant les concentrations libres et liées du G-CSF. Ce nouveau modèle PK a aussi nécessité des changements dans le modèle PD puisqu’il nous a permis de retracer les concentrations du G-CSF lié aux neutrophiles. Nous avons démontré que l'hypothèse sous-jacente de l'équilibre entre la concentration libre et liée, selon la loi d'action de masse, n'est plus valide pour le G-CSF aux concentrations endogènes et mènerait en fait à la surestimation de la clairance rénale du médicament. En procédant ainsi, nous avons réussi à reproduire des données cliniques obtenues dans diverses conditions (l'administration exogène du G-CSF, l'administration du PM00104, CHOP14). Nous avons aussi fourni une explication logique des mécanismes responsables de la réponse physiologique aux deux médicaments. Finalement, afin de mettre en exergue l’approche intégrative en pharmacologie adoptée dans cette thèse, nous avons démontré sa valeur inestimable pour la mise en lumière et la reconstruction des systèmes vivants complexes, en faisant le parallèle avec d’autres disciplines scientifiques telles que la paléontologie et la forensique, où une approche semblable a largement fait ses preuves. Nous avons aussi discuté du potentiel de la pharmacologie quantitative des systèmes appliquées au développement du médicament et à la médecine translationnelle, en se servant du modèle physio-PK/PD que nous avons mis au point.

Development of a new analytical approach based on cellulose membrane and chelator for differentiation of labile and inert metal species in aquatic systems

A new procedure was developed in this study, based on a system equipped with a cellulose membrane and a tetraethylenepentamine hexaacetate chelator (MD-TEPHA) for in situ characterization of the lability of metal species in aquatic systems. To this end, the DM-TEPHA system was prepared by adding TEPHA chelator to cellulose bags pre-purified with 1.0 mol L-1 of HCl and NaOH solutions. After the MD-TEPHA system was sealed, it was examined in the laboratory to evaluate the influence of complexation time (0-24 h), pH (3.0, 4.0, 5.0, 6.0 and 7.0), metal ions (Cu, Cd, Fe, Mn and Ni) and concentration of organic matter (15, 30 and 60 mg L-1) on the relative lability of metal species by TEPHA chelator. The results showed that Fe and Cu metals were complexed more slowly by TEPHA chelator in the MD-TEPHA system than were Cd, Ni and Mn in all pH used. It was also found that the pH strongly influences the process of metal complexation by the MD-TEPHA system. At all the pH levels, Cd, Mn and Ni showed greater complexation with TEPHA chelator (recovery of about 95-75%) than did Cu and Fe metals. Time also affects the lability of metal species complexed by aquatic humic substances (AHS); while Cd, Ni and Mn showed a faster kinetics, reaching equilibrium after about 100 min, and Cu and Fe approached equilibrium after 400 min. Increasing the AHS concentration decreases the lability of metal species by shifting the equilibrium to AHS-metal complexes. Our results indicate that the system under study offers an interesting alternative that can be applied to in situ experiments for differentiation of labile and inert metal species in aquatic systems. (c) 2006 Elsevier B.V. All rights reserved.

Transcription of alternative oxidase (AOX) and plastid terminal oxidase (PTOX) during stress-regulated root tissue growth in Daucus carota L. - An approach to identify functional marker candidates for breeding on carrot yield stability

A presente tese explora a hipótese de utilização dos genes da oxidase alternativa (AOX) e da oxidase terminal da plastoquinona (PTOX) como genes-alvo para o desenvolvimento de marcadores funcionais (MF) para avaliar a performance do crescimento em cenoura, fator determinante da produtividade. Para avaliar se os referidos genes estão associados com o crescimento da cenoura procedeu—se ao seu isolamento e posterior análise dos seus perfis de transcrição em diversos sistemas biológicos. O sistema in vitro selecionado, denominado sistema de culturas primárias, permitiu avaliar alterações na quantidade de transcritos desses genes durante os processos de reprogramação celular e crescimento. Ao nível da planta foi também estudado o efeito do frio na expressão precoce dos genes AOX. Ambos os genes DcAOX1 e DcAOX2a revelaram uma resposta rápida e um padrão semelhante apos stresse (inoculação in vitro e resposta ao frio). Foi igualmente verificado um incremento na expressão do gene DcPTOX durante a fase inicial do processo de reprogramação celular. Estudos de expressão dos genes AOX durante o desenvolvimento da raiz da cenoura revelaram que o gene DcAOX2a será potencialmente o gene mais envolvido neste processo. De modo a avaliar a hipótese de envolvimento do gene DcPTOX no crescimento da raíz procederam—se a estudos de expressão ao nível do tecido meristemático. Todavia, para um mais completo entendimento da ligação entre DcPTOX e o crescimento secundário e/ou acumulação de carotenos, a expressão do gene DcPTOX foi também avaliada em raízes de cenoura durante o desenvolvimento, utilizando cultivares caracterizadas por distintos conteúdos de carotenos. Os resultados obtidos demonstraram a associação do gene DcPTOX a ambos os processos. O envolvimento da PTOX no crescimento adaptativo da raiz foi analisado com um ensaio que permitiu identificar, no tecido meristemático, uma resposta precoce do gene DcPTOX face a uma diminuição da temperatura. Adicionalmente, foi efetuada a seleção de genes de referência para uma analise precisa da expressão génica por RT-qPCR em diversos sistemas biológicos de cenoura, e a importância do seu estudo ao nível do sistema biológico foi realçada. Os resultados desta tese são encorajadores para prosseguir os estudos de utilização dos genes AOX e PTOX como MF no melhoramento da performance do crescimento adaptativo em cenoura, fator determinante para a produtividade; ABSTRACT: This thesis explores the hypothesis of using the alternative oxidase (AOX) and theplastid terminal oxidase (PTOX) as target genes for functional marker (FM) development for yield-determining growth performance in carrot. To understand if these genes are associated to growth, different AOX gene family members and the single PTOX gene were isolated, and their expression patterns evaluated in diverse carrot plant systems. An in-vitro primary culture system was selected to study AOX and PTOX transcript changes during cell reprogramming and growth performance. At plant level, a putative early response of AOX to chilling was also evaluated. In fact, both DcAOXl and DcAOXZa were early responsive and showed similar patterns under stress conditions (in vitro inoculation and chilling). A role for DcPTOX during earliest events of cell reprogramming was also suggested. Next, the expression profiles of AOX gene family members during carrot tap root development were investigated. DcAOXZa was identified as the most responsive gene to root development. In order to evaluate if DcPTOX is associated with carrot tap root growth performance, DcPTOX transcript levels were measured in the central root meristem. To further understand whether DcPTOX is associated with secondary growth and/or carotenoids accumulation, DcPTOX expression was also studied in deveIOping carrot tap roots in cultivars with different carotenoids contents. The results indicated that DcPTOX associates to both carotenoid biosynthesis and secondary growth during storage root development. To obtain further insights into the involvement of PTOX on adaptive growth, the early effects of temperature decrease were explored in the root meristem, where a short—term early response in DcPTOX was found, probably associated with adaptive growth. Furthermore, a selection of the most suitable reference genes for accurate RT—qPCR analysis in several carrot experimental systems was performed and discussed. The present research provides the necessary toolbox for continuing studies in carrot AOX and PTOX genes as promising resources for FM candidates in order to assist breeding on yield—determining adaptive growth performance.

H-infinity control design for time-delay linear systems: a rational transfer function based approach

The aim of this paper is to present new results on H-infinity control synthesis for time-delay linear systems. We extend the use of a finite order LTI system, called comparison system to H-infinity analysis and design. Differently from what can be viewed as a common feature of other control design methods available in the literature to date, the one presented here treats time-delay systems control design with classical numeric routines based on Riccati equations arisen from H-infinity theory. The proposed algorithm is simple, efficient and easy to implement. Some examples illustrating state and output feedback design are solved and discussed in order to put in evidence the most relevant characteristic of the theoretical results. Moreover, a practical application involving a 3-DOF networked control system is presented.

An Approach to Manage Reconfigurations and Reduce Area Cost in Hard Real-Time Reconfigurable Systems

This article presents a methodology to build real-time reconfigurable systems that ensure that all the temporal constraints of a set of applications are met, while optimizing the utilization of the available reconfigurable resources. Starting from a static platform that meets all the real-time deadlines, our approach takes advantage of run-time reconfiguration in order to reduce the area needed while guaranteeing that all the deadlines are still met. This goal is achieved by identifying which tasks must be always ready for execution in order to meet the deadlines, and by means of a methodology that also allows reducing the area requirements.

Collaborative Networked Organizations as System of Systems: A Model-Based Engineering Approach

Part 6: Engineering and Implementation of Collaborative Networks

DIFFUSE-INTERFACE FIELD APPROACH TO MODELING SELF-ASSEMBLY OF HETEROGENEOUS COLLOIDAL SYSTEMS AND RELATED DIPOLE-DIPOLE INTERACTION PHENOMENA

Colloid self-assembly under external control is a new route to fabrication of advanced materials with novel microstructures and appealing functionalities. The kinetic processes of colloidal self-assembly have attracted great interests also because they are similar to many atomic level kinetic processes of materials. In the past decades, rapid technological progresses have been achieved on producing shape-anisotropic, patchy, core-shell structured particles and particles with electric/magnetic charges/dipoles, which greatly enriched the self-assembled structures. Multi-phase carrier liquids offer new route to controlling colloidal self-assembly. Therefore, heterogeneity is the essential characteristics of colloid system, while so far there still lacks a model that is able to efficiently incorporate these possible heterogeneities. This thesis is mainly devoted to development of a model and computational study on the complex colloid system through a diffuse-interface field approach (DIFA), recently developed by Wang et al. This meso-scale model is able to describe arbitrary particle shape and arbitrary charge/dipole distribution on the surface or body of particles. Within the framework of DIFA, a Gibbs-Duhem-type formula is introduced to treat Laplace pressure in multi-liquid-phase colloidal system and it obeys Young-Laplace equation. The model is thus capable to quantitatively study important capillarity related phenomena. Extensive computer simulations are performed to study the fundamental behavior of heterogeneous colloidal system. The role of Laplace pressure is revealed in determining the mechanical equilibrium of shape-anisotropic particles at fluid interfaces. In particular, it is found that the Laplace pressure plays a critical role in maintaining the stability of capillary bridges between close particles, which sheds light on a novel route to in situ firming compact but fragile colloidal microstructures via capillary bridges. Simulation results also show that competition between like-charge repulsion, dipole-dipole interaction and Brownian motion dictates the degree of aggregation of heterogeneously charged particles. Assembly and alignment of particles with magnetic dipoles under external field is studied. Finally, extended studies on the role of dipole-dipole interaction are performed for ferromagnetic and ferroelectric domain phenomena. The results reveal that the internal field generated by dipoles competes with external field to determine the dipole-domain evolution in ferroic materials.