Cross-species and cross-platform gene expression studies with the Bioconductor-compliant R package 'annotationTools'.

Background: The variety of DNA microarray formats and datasets presently available offers an unprecedented opportunity to perform insightful comparisons of heterogeneous data. Cross-species studies, in particular, have the power of identifying conserved, functionally important molecular processes. Validation of discoveries can now often be performed in readily available public data which frequently requires cross-platform studies.Cross-platform and cross-species analyses require matching probes on different microarray formats. This can be achieved using the information in microarray annotations and additional molecular biology databases, such as orthology databases. Although annotations and other biological information are stored using modern database models ( e. g. relational), they are very often distributed and shared as tables in text files, i.e. flat file databases. This common flat database format thus provides a simple and robust solution to flexibly integrate various sources of information and a basis for the combined analysis of heterogeneous gene expression profiles.Results: We provide annotationTools, a Bioconductor-compliant R package to annotate microarray experiments and integrate heterogeneous gene expression profiles using annotation and other molecular biology information available as flat file databases. First, annotationTools contains a specialized set of functions for mining this widely used database format in a systematic manner. It thus offers a straightforward solution for annotating microarray experiments. Second, building on these basic functions and relying on the combination of information from several databases, it provides tools to easily perform cross-species analyses of gene expression data.Here, we present two example applications of annotationTools that are of direct relevance for the analysis of heterogeneous gene expression profiles, namely a cross-platform mapping of probes and a cross-species mapping of orthologous probes using different orthology databases. We also show how to perform an explorative comparison of disease-related transcriptional changes in human patients and in a genetic mouse model.Conclusion: The R package annotationTools provides a simple solution to handle microarray annotation and orthology tables, as well as other flat molecular biology databases. Thereby, it allows easy integration and analysis of heterogeneous microarray experiments across different technological platforms or species.

Vibration as a method for muscular stimulation

Human reactions to vibration have been extensively investigated in the past. Vibration, as well as whole-body vibration (WBV), has been commonly considered as an occupational hazard for its detrimental effects on human condition and comfort. Although long term exposure to vibrations may produce undesirable side-effects, a great part of the literature is dedicated to the positive effects of WBV when used as method for muscular stimulation and as an exercise intervention. Whole body vibration training (WBVT) aims to mechanically activate muscles by eliciting neuromuscular activity (muscle reflexes) via the use of vibrations delivered to the whole body. The most mentioned mechanism to explain the neuromuscular outcomes of vibration is the elicited neuromuscular activation. Local tendon vibrations induce activity of the muscle spindle Ia fibers, mediated by monosynaptic and polysynaptic pathways: a reflex muscle contraction known as the Tonic Vibration Reflex (TVR) arises in response to such vibratory stimulus. In WBVT mechanical vibrations, in a range from 10 to 80 Hz and peak to peak displacements from 1 to 10 mm, are usually transmitted to the patient body by the use of oscillating platforms. Vibrations are then transferred from the platform to a specific muscle group through the subject body. To customize WBV treatments, surface electromyography (SEMG) signals are often used to reveal the best stimulation frequency for each subject. Use of SEMG concise parameters, such as root mean square values of the recordings, is also a common practice; frequently a preliminary session can take place in order to discover the more appropriate stimulation frequency. Soft tissues act as wobbling masses vibrating in a damped manner in response to mechanical excitation; Muscle Tuning hypothesis suggest that neuromuscular system works to damp the soft tissue oscillation that occurs in response to vibrations; muscles alters their activity to dampen the vibrations, preventing any resonance phenomenon. Muscle response to vibration is however a complex phenomenon as it depends on different parameters, like muscle-tension, muscle or segment-stiffness, amplitude and frequency of the mechanical vibration. Additionally, while in the TVR study the applied vibratory stimulus and the muscle conditions are completely characterised (a known vibration source is applied directly to a stretched/shortened muscle or tendon), in WBV study only the stimulus applied to a distal part of the body is known. Moreover, mechanical response changes in relation to the posture. The transmissibility of vibratory stimulus along the body segment strongly depends on the position held by the subject. The aim of this work was the investigation on the effects that the use of vibrations, in particular the effects of whole body vibrations, may have on muscular activity. A new approach to discover the more appropriate stimulus frequency, by the use of accelerometers, was also explored. Different subjects, not affected by any known neurological or musculoskeletal disorders, were voluntarily involved in the study and gave their informed, written consent to participate. The device used to deliver vibration to the subjects was a vibrating platform. Vibrations impressed by the platform were exclusively vertical; platform displacement was sinusoidal with an intensity (peak-to-peak displacement) set to 1.2 mm and with a frequency ranging from 10 to 80 Hz. All the subjects familiarized with the device and the proper positioning. Two different posture were explored in this study: position 1 - hack squat; position 2 - subject standing on toes with heels raised. SEMG signals from the Rectus Femoris (RF), Vastus Lateralis (VL) and Vastus medialis (VM) were recorded. SEMG signals were amplified using a multi-channel, isolated biomedical signal amplifier The gain was set to 1000 V/V and a band pass filter (-3dB frequency 10 - 500 Hz) was applied; no notch filters were used to suppress line interference. Tiny and lightweight (less than 10 g) three-axial MEMS accelerometers (Freescale semiconductors) were used to measure accelerations of onto patient’s skin, at EMG electrodes level. Accelerations signals provided information related to individuals’ RF, Biceps Femoris (BF) and Gastrocnemius Lateralis (GL) muscle belly oscillation; they were pre-processed in order to exclude influence of gravity. As demonstrated by our results, vibrations generate peculiar, not negligible motion artifact on skin electrodes. Artifact amplitude is generally unpredictable; it appeared in all the quadriceps muscles analysed, but in different amounts. Artifact harmonics extend throughout the EMG spectrum, making classic high-pass filters ineffective; however, their contribution was easy to filter out from the raw EMG signal with a series of sharp notch filters centred at the vibration frequency and its superior harmonics (1.5 Hz wide). However, use of these simple filters prevents the revelation of EMG power potential variation in the mentioned filtered bands. Moreover our experience suggests that the possibility of reducing motion artefact, by using particular electrodes and by accurately preparing the subject’s skin, is not easily viable; even though some small improvements were obtained, it was not possible to substantially decrease the artifact. Anyway, getting rid of those artifacts lead to some true EMG signal loss. Nevertheless, our preliminary results suggest that the use of notch filters at vibration frequency and its harmonics is suitable for motion artifacts filtering. In RF SEMG recordings during vibratory stimulation only a little EMG power increment should be contained in the mentioned filtered bands due to synchronous electromyographic activity of the muscle. Moreover, it is better to remove the artifact that, in our experience, was found to be more than 40% of the total signal power. In summary, many variables have to be taken into account: in addition to amplitude, frequency and duration of vibration treatment, other fundamental variables were found to be subject anatomy, individual physiological condition and subject’s positioning on the platform. Studies on WBV treatments that include surface EMG analysis to asses muscular activity during vibratory stimulation should take into account the presence of motion artifacts. Appropriate filtering of artifacts, to reveal the actual effect on muscle contraction elicited by vibration stimulus, is mandatory. However as a result of our preliminary study, a simple multi-band notch filtering may help to reduce randomness of the results. Muscle tuning hypothesis seemed to be confirmed. Our results suggested that the effects of WBV are linked to the actual muscle motion (displacement). The greater was the muscle belly displacement the higher was found the muscle activity. The maximum muscle activity has been found in correspondence with the local mechanical resonance, suggesting a more effective stimulation at the specific system resonance frequency. Holding the hypothesis that muscle activation is proportional to muscle displacement, treatment optimization could be obtained by simply monitoring local acceleration (resonance). However, our study revealed some short term effects of vibratory stimulus; prolonged studies should be assembled in order to consider the long term effectiveness of these results. Since local stimulus depends on the kinematic chain involved, WBV muscle stimulation has to take into account the transmissibility of the stimulus along the body segment in order to ensure that vibratory stimulation effectively reaches the target muscle. Combination of local resonance and muscle response should also be further investigated to prevent hazards to individuals undergoing WBV treatments.

Feasibility platform for stroke studies: an online tool to improve eligibility criteria for clinical trials

BACKGROUND AND PURPOSE Eligibility criteria are a key factor for the feasibility and validity of clinical trials. We aimed to develop an online tool to assess the potential effect of inclusion and exclusion criteria on the proportion of patients eligible for an acute stroke trial. METHODS We identified relevant inclusion and exclusion criteria of acute stroke trials. Based on these criteria and using a cohort of 1537 consecutive patients with acute ischemic stroke from 3 stroke centers, we developed a web portal feasibility platform for stroke studies (FePASS) to estimate proportions of eligible patients for acute stroke trials. We applied the FePASS resource to calculate the proportion of patients eligible for 4 recent stroke studies. RESULTS Sixty-one eligibility criteria were derived from 30 trials on acute ischemic stroke. FePASS, publicly available at http://fepass.uni-muenster.de, displays the proportion of patients in percent to assess the effect of varying values of relevant eligibility criteria, for example, age, symptom onset time, National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale, on this proportion. The proportion of eligible patients for 4 recent stroke studies ranged from 2.1% to 11.3%. Slight variations of the inclusion criteria could substantially increase the proportion of eligible patients. CONCLUSIONS FePASS is an open access online resource to assess the effect of inclusion and exclusion criteria on the proportion of eligible patients for a stroke trial. FePASS can help to design stroke studies, optimize eligibility criteria, and to estimate the potential recruitment rate.

A Platform to Emulate Ambient Assisted Living Environments

According to the opinion of clinicians, emerging medical conditions can be timely detected by observing changes in the activities of daily living and/or in the physiological signals of a person. To accomplish such purpose, it is necessary to properly monitor both the person’s physiological signals as well as the home environment with sensing technology. Wireless sensor networks (WSNs) are a promising technology for this support. After receiving the data from the sensor nodes, a computer processes the data and extracts information to detect any abnormality. The computer runs algorithms that should have been previously developed and tested in real homes or in living-labs. However, these installations (and volunteers) may not be easily available. In order to get around that difficulty, this paper suggests the making of a physical model to emulate basic actions of a user at home, thus giving autonomy to researchers wanting to test the performance of their algorithms. This paper also studies some data communication issues in mobile WSNs namely how the orientation of the sensor nodes in the body affects the received signal strength, as well as retransmission aspects of a TDMA-based MAC protocol in the data recovery process.

A Service Integration Platform for Collaborative Networks

Integrated manufacturing constitutes a complex system made of heterogeneous information and control subsystems. Those subsystems are not designed to the cooperation. Typically each subsystem automates specific processes, and establishes closed application domains, therefore it is very difficult to integrate it with other subsystems in order to respond to the needed process dynamics. Furthermore, to cope with ever growing marketcompetition and demands, it is necessary for manufacturing/enterprise systems to increase their responsiveness based on up-to-date knowledge and in-time data gathered from the diverse information and control systems. These have created new challenges for manufacturing sector, and even bigger challenges for collaborative manufacturing. The growing complexity of the information and communication technologies when coping with innovative business services based on collaborative contributions from multiple stakeholders, requires novel and multidisciplinary approaches. Service orientation is a strategic approach to deal with such complexity, and various stakeholders' information systems. Services or more precisely the autonomous computational agents implementing the services, provide an architectural pattern able to cope with the needs of integrated and distributed collaborative solutions. This paper proposes a service-oriented framework, aiming to support a virtual organizations breeding environment that is the basis for establishing short or long term goal-oriented virtual organizations. The notion of integrated business services, where customers receive some value developed through the contribution from a network of companies is a key element.

Structuring and moodleing a course: case studies at the polytechnic of Porto - School of engineering

This work presents a comparative study covering four different courses lectured at the Polytechnic of Porto - School of Engineering, in respect to the usage of a particular Learning Management System, i.e. Moodle, and its impact on students' results. Even though positive correlation factors exist, e.g. between the number of Moodle accesses versus the final exam grade obtained by each student, the explanation behind it may not be straightforward. Mapping this particular factor to course numbers reveals that the quality of the resources might be preponderant and not only their quantity. This paper also addresses teachers who used this platform as a complement to their courses (b-learning) and identifies some particular issues they should be aware in order to potentiate students' engagement and learning.

Engaging students by moodleing a course? Case studies at the Polytechnic of Porto–School of Engineering

This work presents a comparative study covering four different courses lectured at the Polytechnic of Porto - School of Engineering, regarding the usage of a particular Learning Management System, i.e. Moodle, and its impact on students' results. This study addresses teachers who used this platform as a complement to their courses (b-learning) and identifies some particular issues in order to potentiate students' engagement and learning. Even though positive correlation factors exist, e.g. between the number of Moodle accesses versus the final exam grade obtained by each student, the explanation behind it may not be straightforward. Mapping this particular factor to course numbers reveals that the quality of the resources might be preponderant and not only their quantity. These results point to the fact that some dynamic resources might enlarge students' engagement.

Standard commercial education robotic platform: intermediate solution to teaching robotics

Teaching robotics to students at the beginning of their studies has become a huge challenge. Simulation environments can be an effective solution to that challenge where students can interact with simulated robots and have the first contact with robotic constraints. From our previous experience with simulation environments it was possible to observe that students with lower background knowledge in robotics where able to deal with a limited number of constraints, implement a simulated robotic platform and study several sensors. The question is: after this first phase what should be the best approach? Should the student start developing their own hardware? Hardware development is a very important part of an engineer's education but it can also be a difficult phase that could lead to discouragement and loss of motivation in some students. Considering the previous constraints and first year engineering students’ high abandonment rate it is important to develop teaching strategies to deal with this problem in a feasible way. The solution that we propose is the integration of a low-cost standard robotic platform WowWee Rovio as an intermediate solution between the simulation phase and the stage where the students can develop their own robots. This approach will allow the students to keep working in robotic areas such as: cooperative behaviour, perception, navigation and data fusion. The propose approach proved to be a motivation step not only for the students but also for the teachers. Students and teachers were able to reach an agreement between the level of demand imposed by the teachers and satisfaction/motivation of the students.

Post-MAPS: An interactive acquisition platform for gastroenterology

Post-MAPS is a web platform that collects gastroenterological exam data from several european hospital centers, to be used in future clinical studies and was developed in partnership with experts from the gastroenterological area and information technology (IT) technicians. However, although functional, this platform has some issues that are crucial for its functioning, and can render user interaction unpleasant and exhaustive. Accordingly, we proposed the development of a new web platform, in which we aimed for an improvement in terms of usability, data uni cation and interoperability. Therefore, it was necessary to identify and study different ways of acquiring clinical data and review some of the existing clinical databases in order to understand how they work and what type of data they store, as well as their impact and contribution to clinical knowledge. Closely linked to the data model is the ability to share data with other systems, so, we also studied the concept of interoperability and analyzed some of the most widely used international standards, such as DICOM, HL7 and openEHR. As one of the primary objectives of this project was to achieve a better level of usability, practices related to Human Computer-Interaction, such as requirement analysis, creation of conceptual models, prototyping, and evaluation were also studied. Before we began the development, we conducted an analysis of the previous platform, from a functional point of view, which allowed us to gather not only a list of architectural and interface issues, but also a list of improvement opportunities. It was also performed a small preliminary study in order to evaluate the platform's usability, where we were able to realize that perceived usability is different between users, and that, in some aspects, varies according to their location, age and years of experience. Based on the information gathered during the platform's analysis and in the conclusions of the preliminary study, a new platform was developed, prepared for all potential users, from the inexperienced to the most comfortable with technology. It presents major improvements in terms of usability, also providing several new features that simplify the users' work, improving their interaction with the system, making their experience more enjoyable.

Medicago truncatula as a platform for Molecular Farming: a study of the subcellular localization of a human recombinant protein!

Dissertation presented at Faculdade de Ciências e Tecnologia of Universidade Nova de Lisboa to obtain the Degree of Master in Biotecnology

Understanding the microbial ecology and ecophysiology of enhanced biological phosphorus removal processes through metabolic modelling and experimental studies

Dissertation to obtain the degree of Master in Chemical and Biochemical Engineering

EORTC Radiation Oncology Group quality assurance platform: establishment of a digital central review facility.

OBJECTIVE: Quality assurance (QA) in clinical trials is essential to ensure treatment is safely and effectively delivered. As QA requirements have increased in complexity in parallel with evolution of radiation therapy (RT) delivery, a need to facilitate digital data exchange emerged. Our objective is to present the platform developed for the integration and standardization of QART activities across all EORTC trials involving RT. METHODS: The following essential requirements were identified: secure and easy access without on-site software installation; integration within the existing EORTC clinical remote data capture system; and the ability to both customize the platform to specific studies and adapt to future needs. After retrospective testing within several clinical trials, the platform was introduced in phases to participating sites and QART study reviewers. RESULTS: The resulting QA platform, integrating RT analysis software installed at EORTC Headquarters, permits timely, secure, and fully digital central DICOM-RT based data review. Participating sites submit data through a standard secure upload webpage. Supplemental information is submitted in parallel through web-based forms. An internal quality check by the QART office verifies data consistency, formatting, and anonymization. QART reviewers have remote access through a terminal server. Reviewers evaluate submissions for protocol compliance through an online evaluation matrix. Comments are collected by the coordinating centre and institutions are informed of the results. CONCLUSIONS: This web-based central review platform facilitates rapid, extensive, and prospective QART review. This reduces the risk that trial outcomes are compromised through inadequate radiotherapy and facilitates correlation of results with clinical outcomes.

Experimental Modeling and Control Strategies on an Open Mobile Robot Platform PRIM

This research work deals with the problem of modeling and design of low level speed controller for the mobile robot PRIM. The main objective is to develop an effective educational tool. On one hand, the interests in using the open mobile platform PRIM consist in integrating several highly related subjects to the automatic control theory in an educational context, by embracing the subjects of communications, signal processing, sensor fusion and hardware design, amongst others. On the other hand, the idea is to implement useful navigation strategies such that the robot can be served as a mobile multimedia information point. It is in this context, when navigation strategies are oriented to goal achievement, that a local model predictive control is attained. Hence, such studies are presented as a very interesting control strategy in order to develop the future capabilities of the system

Malaria diagnosis from pooled blood samples: comparative analysis of real-time PCR, nested PCR and immunoassay as a platform for the molecular and serological diagnosis of malaria on a large-scale

Malaria diagnoses has traditionally been made using thick blood smears, but more sensitive and faster techniques are required to process large numbers of samples in clinical and epidemiological studies and in blood donor screening. Here, we evaluated molecular and serological tools to build a screening platform for pooled samples aimed at reducing both the time and the cost of these diagnoses. Positive and negative samples were analysed in individual and pooled experiments using real-time polymerase chain reaction (PCR), nested PCR and an immunochromatographic test. For the individual tests, 46/49 samples were positive by real-time PCR, 46/49 were positive by nested PCR and 32/46 were positive by immunochromatographic test. For the assays performed using pooled samples, 13/15 samples were positive by real-time PCR and nested PCR and 11/15 were positive by immunochromatographic test. These molecular methods demonstrated sensitivity and specificity for both the individual and pooled samples. Due to the advantages of the real-time PCR, such as the fast processing and the closed system, this method should be indicated as the first choice for use in large-scale diagnosis and the nested PCR should be used for species differentiation. However, additional field isolates should be tested to confirm the results achieved using cultured parasites and the serological test should only be adopted as a complementary method for malaria diagnosis.