Screening for AmpR-Specific Inhibitors to Combat P. aeruginosa Infections

Pseudomonas aeruginosa, a Gram-negative bacterium, an opportunistic pathogen that infects individuals suffering from reduced immunity or damaged tissue. The treatment of these infections has become a major problem due to its increasing antibiotic resistance. Many multi-drug resistant isolates of P. aeruginosa can thwart most antibiotic classes including ?- lactams, fluoroquinolones, and aminoglycosides. Its ability to combat ?-lactams is in part due to expression of AmpC, a major chromosomally encoded ?-lactamase. The expression of ampC is positively regulated by AmpR. Besides antibiotic resistance, AmpR is an important regulator of various factors that are required for establishing acute and chronic infections. Loss of ampR makes P. aeruginosa susceptible to ?-lactams and less virulent than the wild type. We hypothesize that AmpR is a potential therapeutic target. In the absence of new drugs in the pipeline, the aim of this study is to find an AmpR-specific inhibitor to assist and improve the use of currently available ?- lactam treatment. A small-molecule library from Torrey Pines Institute will be used in this study. Two reporter systems, lux and lacZ, fused to a PampC promotor will be used to assess AmpR activity. Positive hits will be those that inhibit 50% PampC activity in the presence of sub inhibitory concentration of imipenem, a ?- lactam. The top positive hits will be screened for their ability to cause human cell-cytotoxicity. The non-cytotoxic hits will be assessed for their ability to affect P. aeruginosa virulence and antibiotic resistance using various in vitro assays. Determination of potential AmpR inhibitors will prove to be useful in fighting off infections and may save countless patients suffering from these infections.

Os efeitos das queimadas na Amazônia em nível celular e molecular

The Amazon holds over half of the planet's remaining tropical forests and comprises the largest biodiversity in the world, accounting for approximately 60 % of the Brazilian territory. However, deforestation fires in the region causes serious problems to exposed human. The aim of this study was to evaluate the chemical compounds as well as the cellular and molecular effects after exposure to organic material extracted from particulate matter less than 10 µm (PM10) in the Amazon region. As for the chemical composition, n-alkanes analysis showed a prevalence of anthropogenic influence during the fires in the region. In addition, there was a predominance of monosaccharides from biomass burning markers. Also, the Polycyclic Aromatic Hydrocarbons (PAH) and their derivatives have also been identified in samples collected in the Amazon. By using the PAH concentrations was possible to calculate the BaP-equivalent and it was found that the dibenz(a) anthracene contributes with 83% to potential carcinogenic risk. As for the potential mutagenic risk, the benzo (a) pyrene is the HPA that has a major contribution in this analysis. It may be noted that the retene was the most abundant PAH. This compound was genotoxic and cause death by necrosis in the human lung cells. In biological tests, the data showed that organic PM10 is capable of causing genetic damage in both plant cells and in human lung cells. This damage cause an arrest in the G1 phase of the cell cycle exposed, increasing the expression of p53 and p21. Additionally, the PM10 caused cell death by apoptosis, increasing the foci of histone - H2AX. Given these results, it is important to emphasize the reduction and better control of biomass burning in the Amazon region thus improving the quality of health of the population being exposed. As clearly stated recently by the World Health Organization, the reduction of air pollution could save millions of lives annually.

Follow-up of the sponge and asteroid populations at the station Larsen A south (PS69/724-1 and PS77/253-1), Antarctic Peninsula, between 2007 and 2011

Over 30% of the Antarctic continental shelf is permanently covered by floating ice shelves, providing aphotic conditions for a depauperate fauna sustained by laterally advected food. In much of the remaining Antarctic shallows (<300 m depth), seasonal sea-ice melting allows a patchy primary production supporting rich megabenthic communities dominated by glass sponges (Porifera, Hexactinellida). The catastrophic collapse of ice shelves due to rapid regional warming along the Antarctic Peninsula in recent decades has exposed over 23,000 km**2 of seafloor to local primary production. The response of the benthos to this unprecedented flux of food is, however, still unknown. In 2007, 12 years after disintegration of the Larsen A ice shelf, a first biological survey interpreted the presence of hexactinellids as remnants of a former under-ice fauna with deep-sea characteristics. Four years later, we revisited the original transect, finding 2- and 3-fold increases in glass sponge biomass and abundance, respectively, after only two favorable growth periods. Our findings, along with other long-term studies, suggest that Antarctic hexactinellids, locked in arrested growth for decades, may undergo boom-and-bust cycles, allowing them to quickly colonize new habitats. The cues triggering growth and reproduction in Antarctic glass sponges remain enigmatic.

Physical oceanography, sea-bed photographs and videos of benthos from the Weddell Sea taken with remote operated vehicle CHEROKEE during POLARSTERN cruise ANT-XXIII/8

The marine ecosystem on the eastern shelf of the Antarctic Peninsula was surveyed 5 and 12 years after the climate-induced collapse of the Larsen A and B ice shelves. An impoverished benthic fauna was discovered, that included deep-sea species presumed to be remnants from ice-covered conditions. The current structure of various ecosystem components appears to result from extremely different response rates to the change from an oligotrophic sub-ice-shelf ecosystem to a productive shelf ecosystem. Meiobenthic communities remained impoverished only inside the embayments. On local scales, macro- and mega-epibenthic diversity was generally low, with pioneer species and typical Antarctic megabenthic shelf species interspersed. Antarctic Minke whales and seals utilised the Larsen A/B area to feed on presumably newly established krill and pelagic fish biomass. Ecosystem impacts also extended well beyond the zone of ice-shelf collapse, with areas of high benthic disturbance resulting from scour by icebergs discharged from the Larsen embayments.

Sea-floor images from ROV transects during POLARSTERN cruise ANT-XVII/3 (EASIZ III) to the Weddell Sea, Antarctica

Transects of a Remotely Operated Vehicle (ROV) providing sea-bed videos and photographs were carried out during POLARSTERN expedition ANT-XVII/3 focussing on the ecology of benthic assemblages on the Antarctic shelf in the South-Eastern Weddell Sea. The ROV-system sprint 103 was equiped with two video- and one still camera, lights, flash-lights, compass, and parallel lasers providing a scale in the images, a tether-management system (TMS), a winch, and the board units. All cameras used the same main lense and could be tilted. Videos were recorded in Betacam-format and (film-)slides were made by decision of the scientific pilot. The latter were mainly made under the aspect to improve the identification of organisms depicted in the videos because the still photographs have a much higher optical resolution than the videos. In the photographs species larger than 3 mm, in the videos larger than 1 cm are recognisable and countable. Under optimum conditions the transects were strait; the speed and direction of the ROV were determined by the drift of the ship in the coastal current, since both, the ship and the ROV were used as a drifting system; the option to operate the vehicle actively was only used to avoide obstacles and to reach at best a distance of only approximately 30 cm to the sea-floor. As a consequence the width of the photographs in the foreground is approximately 50 cm. Deviations from this strategy resulted mainly from difficult ice- and weather conditions but also from high current velocity and local up-welling close to the sea-bed. The sea-bed images provide insights into the general composition of key species, higher systematic groups and ecological guilds. Within interdisciplinary approaches distributions of assemblages can be attributed to environmental conditions such as bathymetry, sediment characteristics, water masses and current regimes. The images also contain valuable information on how benthic species are associated to each other. Along the transects, small- to intermediate-scaled disturbances, e.g. by grounding icebergs were analysed and further impact to the entire benthic system by local succession of recolonisation was studied. This information can be used for models predicting the impact of climate change to benthic life in the Southern Ocean. All these approaches contribute to a better understanding of the fiunctioning of the benthic system and related components of the entire Antarctic marine ecosystem. Despite their scientific value the imaging methods meet concerns about the protection of sensitive Antarctic benthic systems since they are non-invasive and they also provide valuable material for education and outreach purposes.

Common Bound: The Small Groups of Methodism

The system of small groups John Wesley established to promote a proper life of discipleship in early Methodist converts was, in many respects, the strength of the Methodist movement. Those who responded to Wesley’s initial invitation to “flee the wrath to come” were organized into large gatherings called “societies,” which were then subdivided into smaller bands, class meetings, select societies, and penitent bands. The smaller groups gave Wesley the opportunity, through a system of appointed leaders, to keep track of the spiritual progress of every member in his movement, which grew to tens of thousands by the time of his death in 1791. As Methodism shifted from renewal movement to institutional church in the nineteenth century, however, growth slowed, and participation in such groups declined rapidly. By the early twentieth century, classes and bands were virtually extinct in every sector of Methodism save the African-American tradition. In recent years, scholars in various sectors of the Wesleyan tradition, particularly David Lowes Watson and Kevin Watson, have called for a recovery of these small groups for purposes of renewal in the church. There is no consensus, however, concerning what exactly contributed to the vitality of these groups during Wesley’s ministry.

Over the last century, sociological studies of group dynamics have revealed three common traits that are crucial to highly functioning groups: interdependence created by the existence of a common goal, interaction among group members that is “promotive” or cooperative in nature, and high levels of feedback associated with personal responsibility and individual accountability. All three of these were prevalent in the early Methodist groups. Interdependence existed around a shared goal, which for Wesley and the Methodists was holiness. That interdependence was cooperative in nature; individuals experienced the empowering grace of God as they each pursued the goal in the company of fellow pilgrims. Finally, the groups existed for purposes of feedback and accountability as individuals took responsibility both for themselves and others as they progressed together toward the goal of holy living. Wesley seemed to instinctively understand the essential nature of each of these characteristics in maintaining the vitality of the movement when he spoke of the importance of preserving the “doctrine, spirit and discipline” of early Methodism. Analysis of some of the present-day attempts to restore Wesley’s groups reveals frequent neglect to one or more of these three components. Perhaps most critical to recovering the vitality of the early Methodist groups will be reclaiming the goal of sanctification and coming to a consensus on what its pursuit means in the present day.

Age, body mass, mass change and dispersal distance of suckling and weaned grey seal (Halichoerus grypus) pups

Grey seal, Halichoerus grypus, pups in the breeding colony at Froan, Norway, have a bimodal pattern of early aquatic behaviour. About 40% of the pups spend their time ashore to save energy, which can be allocated to growth or deposition of energy-rich adipose tissue. The other 60% of the pups enter the sea during suckling and the early postweaning period, and disperse to other locations within the breeding colony. Pups may swim distances up to 12 km. Neonatal aquatic dispersal behaviour may lead to increased energy expenditure for thermoregulation and swimming, and thus lead to a low rate of body mass gain during suckling and a high rate of body mass loss after weaning. Thus, we examined relationships between natal aquatic dispersal behaviour and change in body mass (DeltaBM) in suckling and weaned pups. Suckling pups that had dispersed >2000 m had a significantly lower DBM than suckling pups that dispersed <2000 m or that did not disperse. In weaned pups, there were no effects of aquatic dispersal behaviour on DBM. We suggest that the bimodal natal aquatic dispersal behaviour in grey seals at the study site reflects two different strategies for postweaning survival: to stay ashore and get fat, or to take a swim and acquire diving and feeding skills.

Assisting End-users in Filling Out Web Services

With the quick advance of web service technologies, end-users can conduct various on-line tasks, such as shopping on-line. Usually, end-users compose a set of services to accomplish a task, and need to enter values to services to invoke the composite services. Quite often, users re-visit websites and use services to perform re-occurring tasks. The users are required to enter the same information into various web services to accomplish such re-occurring tasks. However, repetitively typing the same information into services is a tedious job for end-users. It can negatively impact user experience when an end-user needs to type the re-occurring information repetitively into web services. Recent studies have proposed several approaches to help users fill in values to services automatically. However, prior studies mainly suffer the following drawbacks: (1) limited support of collecting and analyzing user inputs; (2) poor accuracy of filling values to services; (3) not designed for service composition. To overcome the aforementioned drawbacks, we need maximize the reuse of previous user inputs across services and end-users. In this thesis, we introduce our approaches that prevent end-users from entering the same information into repetitive on-line tasks. More specifically, we improve the process of filling out services in the following 4 aspects: First, we investigate the characteristics of input parameters. We propose an ontology-based approach to automatically categorize parameters and fill values to the categorized input parameters. Second, we propose a comprehensive framework that leverages user contexts and usage patterns into the process of filling values to services. Third, we propose an approach for maximizing the value propagation among services and end-users by linking a set of semantically related parameters together and similar end-users. Last, we propose a ranking-based framework that ranks a list of previous user inputs for an input parameter to save a user from unnecessary data entries. Our framework learns and analyzes interactions of user inputs and input parameters to rank user inputs for input parameters under different contexts.

Computational Methods for Identifying Hypertrophic Cardiomyopathy using 12-lead ECG

Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease where the heart muscle is partially thickened and blood flow is - potentially fatally - obstructed. It is one of the leading causes of sudden cardiac death in young people. Electrocardiography (ECG) and Echocardiography (Echo) are the standard tests for identifying HCM and other cardiac abnormalities. The American Heart Association has recommended using a pre-participation questionnaire for young athletes instead of ECG or Echo tests due to considerations of cost and time involved in interpreting the results of these tests by an expert cardiologist. Initially we set out to develop a classifier for automated prediction of young athletes’ heart conditions based on the answers to the questionnaire. Classification results and further in-depth analysis using computational and statistical methods indicated significant shortcomings of the questionnaire in predicting cardiac abnormalities. Automated methods for analyzing ECG signals can help reduce cost and save time in the pre-participation screening process by detecting HCM and other cardiac abnormalities. Therefore, the main goal of this dissertation work is to identify HCM through computational analysis of 12-lead ECG. ECG signals recorded on one or two leads have been analyzed in the past for classifying individual heartbeats into different types of arrhythmia as annotated primarily in the MIT-BIH database. In contrast, we classify complete sequences of 12-lead ECGs to assign patients into two groups: HCM vs. non-HCM. The challenges and issues we address include missing ECG waves in one or more leads and the dimensionality of a large feature-set. We address these by proposing imputation and feature-selection methods. We develop heartbeat-classifiers by employing Random Forests and Support Vector Machines, and propose a method to classify full 12-lead ECGs based on the proportion of heartbeats classified as HCM. The results from our experiments show that the classifiers developed using our methods perform well in identifying HCM. Thus the two contributions of this thesis are the utilization of computational and statistical methods for discovering shortcomings in a current screening procedure and the development of methods to identify HCM through computational analysis of 12-lead ECG signals.

DESIGN OF A MINIATURIZED SOP INTEGRATED GNSS RF FRONT-END MODULE

Navigation devices used to be bulky and expensive and were not widely commercialized for personal use. Nowadays, all useful electronic devices are turning into being handheld so that they can be conveniently used anytime and anywhere. One can claim that almost any mobile phone, used today, has quite strong navigational capabilities that can efficiently work anywhere in the globe. No matter where you are, you can easily know your exact location and make your way smoothly to wherever you would like to go. This couldn’t have been made possible without the existence of efficient and small microwave circuits responsible for the transmission and reception of high quality navigation signals. This thesis is mainly concerned with the design of novel highly miniaturized and efficient filtering components working in the Global Navigational Satellite Systems (GNSS) frequency band to be integrated within an efficient Radio Frequency (RF) front-end module (FEM). A System-on-Package (SoP) integration technique is adopted for the design of all the components in this thesis. Two novel miniaturized filters are designed, where one of them is a wideband filter targeting the complete GNSS band with a fractional bandwidth of almost 50% at a center frequency of 1.385 GHz. This filter utilizes a direct inductive coupling topology to achieve the required wide band performance. It also has very good out-of-band rejection and low IL. Whereas the other dual band filter will only cover the lower and upper GNSS bands with a rejection notch in between the two bands. It has very good inter band rejection. The well-known “divide and conquer” design methodology was applied for the design of this filter to help save valuable design and optimization time. Moreover, the performance of two commercially available ultra-Low Noise Amplifiers (LNAs) is studied. The complete RF FEM showed promising preliminary performance in terms of noise figure, gain and bandwidth, where it out performed other commercial front-ends in these three aspects. All the designed circuits are fabricated and tested. The measured results are found to be in good agreements with the simulations.

Supporting Run-time Monitoring of UML-RT through Customizable Monitoring Configurations in PapyrusRT

Model Driven Engineering uses the principle that code can automatically be generated from software models which would potentially save time and cost of development. By this methodology, a systems structure and behaviour can be expressed in more abstract, high level terms without some of the accidental complexity that the use of a general purpose language can bring. Models are the actual implementation of the system unlike in traditional software development where models are often used for documentation purposes only. However once the code is generated from the model, testing and debugging activities tend to happen on the code level and the model is not updated. We believe that monitoring on the model level could potentially facilitate quality assurance activities as the errors are detected in the early phase of development. In this thesis, we create a Monitoring Configuration for an open source model driven engineering tool called PapyrusRT in Eclipse. We support the run-time monitoring of UML-RT elements with a tracing tool called LTTng. We annotate the model with monitoring information to be used by the code generator for adding tracepoint statements for the corresponding elements. We provide the option of a timing specification to discover latency errors on the model. We validate the results by creating and tracing real time models in PapyrusRT.

Ecophysiology of Adonis distorta, a high-mountain species endemic of the Central Apennines

Morphological, anatomical and physiological plant and leaf traits of A. distorta, an endemic species of the Central Apennines on the Majella Massif, growing at 2,675 m a.s.l, were analyzed. The length of the phenological cycle starts immediately after the snowmelt at the end of May, lasting 128 ± 10 days. The low A. distorta height  (Hmax= 64 ± 4 mm) and total leaf area (TLA= 38 ± 9 cm2) associated to a high leaf mass area (LMA =11.8±0.6 mg cm−2) and a relatively high leaf tissue density (LTD = 124.6±14.3 mg cm−3) seem to be adaptive traits to the stress factors of the environment where it grows. From a physiological point of view, the high A. distorta photosynthetic rates (PN =19.6 ± 2.3 µmol m−2 s−1) and total chlorophyll content (Chla+b = 0.88 ± 0.13 mg g−1) in July are justified by the favorable temperature. PN decreases by 87% in September at the beginning of plant senescence. Photosynthesis and leaf respiration (RD) variations allow A. distorta to maintain a positive carbon balance during the growing season becoming indicative of the efficiency of plant carbon use. The results could be an important tool for conservation programmes of the A. distorta wild populations.

Market reforms and privatisation in the English National Health Service

The article examines developments in the marketisation and privatisation of the English National Health Service, primarily since 1997. It explores the use of competition and contracting out in ancillary services and the levering into public services of private finance for capital developments through the Private Finance Initiative. A substantial part of the article examines the repeated restructuring of the health service as a market in clinical services, initially as an internal market but subsequently as a market increasing opened up to private sector involvement. Some of the implications of market processes for NHS staff and for increased privatisation are discussed. The article examines one episode of popular resistance to these developments, namely the movement of opposition to the 2011 health and social care legislative proposals. The article concludes with a discussion of the implications of these system reforms for the founding principles of the NHS and the sustainability of the service.

Community social innovation: a view of experiences of housing occupation from the Social Work perspective

This work aims to reflect on the concept of social innovation, questioning its explanatory capacity for the discipline of social work. For this purpose, certain on-going debates with regard to this concept are examined and certain minimum dimensions are offered to enable an analysis of the social innovation strategies that certain affected groups implement to meet social needs. The approach is to construct «glasses» that permit an analytical engagement with new realities and with the strategies used by certain social groups to resolve situations of severe vulnerability. Finally, a case study is presented: a strategic group known as the Corrala Utopía that seeks to respond to severe housing problems and is developing in the city of Seville. The article highlights the elements of community social innovation emerging from the experience studied.

Los más pequeños toman la palabra: La Escuela Infantil que a ellos les gustaría

El derecho a ser escuchado y participar en aquellos asuntos que afectan a los niños es un derecho fundamental de la infancia escasamente respetado por el adulto, quien tiende a silenciar su voz, infravalorando su visión y posible aportación. Ante esta realidad, la Escuela Infantil se erige como un marco privilegiado para la escucha y la participación de la infancia en aquellos temas que les afectan, contribuyendo a la formación de ciudadanos democráticos. A partir de un marco de escucha donde se concibe al pequeño como un sujeto activo, competente y experto en su propia vida, se ha llevado a cabo una investigación que ha adoptado el formato de estudio de caso, en la que se ha recogido a través de las técnicas del dibujo y de las conversaciones con niños, la visión que poseen los más pequeños sobre la Escuela Infantil, analizando el bienestar del niño en el contexto escolar, el sentido y finalidad que los niños otorgan a la escuela; el grado de satisfacción con la misma; sus gustos y preferencias en el contexto escolar; la autonomía y libertad que dicen poseer en la escuela; su visión sobre los aspectos organizativos que rigen el funcionamiento del centro y su perspectiva sobre cómo es y cómo les gustaría que fuera la participación de las familias en la escuela. Finalmente, se recogen sus propuestas de mejora para hacer de la Escuela Infantil a la que asisten su escuela ideal. Los resultados del estudio ponen de manifiesto la demanda de los niños de una Escuela Infantil diferente a la que conocen y la existencia de un pensamiento divergente del pensamiento adulto que es necesario escuchar y tener en consideración, siendo sus aportaciones de gran valía para poder iniciar procesos de innovación y mejora educativa.