Generation of human computational models with machine learning

Services in smart environments pursue to increase the quality of people?s lives. The most important issues when developing this kind of environments is testing and validating such services. These tasks usually imply high costs and annoying or unfeasible real-world testing. In such cases, artificial societies may be used to simulate the smart environment (i.e. physical environment, equipment and humans). With this aim, the CHROMUBE methodology guides test engineers when modeling human beings. Such models reproduce behaviors which are highly similar to the real ones. Originally, these models are based on automata whose transitions are governed by random variables. Automaton?s structure and the probability distribution functions of each random variable are determined by a manual test and error process. In this paper, it is presented an alternative extension of this methodology which avoids the said manual process. It is based on learning human behavior patterns automatically from sensor data by using machine learning techniques. The presented approach has been tested on a real scenario, where this extension has given highly accurate human behavior models,

BAC-VAC, a novel generation of (DNA) vaccines: A bacterial artificial chromosome (BAC) containing a replication-competent, packaging-defective virus genome induces protective immunity against herpes simplex virus 1

This study aimed to exploit bacterial artificial chromosomes (BAC) as large antigen-capacity DNA vaccines (BAC-VAC) against complex pathogens, such as herpes simplex virus 1 (HSV-1). The 152-kbp HSV-1 genome recently has been cloned as an F-plasmid-based BAC in Escherichia coli (fHSV), which can efficiently produce infectious virus progeny upon transfection into mammalian cells. A safe modification of fHSV, fHSVΔpac, does not give rise to progeny virus because the signals necessary to package DNA into virions have been excluded. However, in mammalian cells fHSVΔpac DNA can still replicate, express the HSV-1 genes, cause cytotoxic effects, and produce virus-like particles. Because these functions mimic the lytic cycle of the HSV-1 infection, fHSVΔpac was expected to stimulate the immune system as efficiently as a modified live virus vaccine. To test this hypothesis, mice were immunized with fHSVΔpac DNA applied intradermally by gold-particle bombardment, and the immune responses were compared with those induced by infection with disabled infectious single cycle HSV-1. Immunization with either fHSVΔpac or disabled infectious single cycle HSV-1 induced the priming of HSV-1-specific cytotoxic T cells and the production of virus-specific antibodies and conferred protection against intracerebral injection of wild-type HSV-1 at a dose of 200 LD50. Protection probably was cell-mediated, as transfer of serum from immunized mice did not protect naive animals. We conclude that BAC-VACs per se, or in combination with genetic elements that support replicative amplification of the DNA in the cell nucleus, represent a useful new generation of DNA-based vaccination strategies for many viral and nonviral antigens.

A method for the generation of conditional gene repair mutations in mice

Conditional gene repair mutations in the mouse can assist in cell lineage analyses and provide a valuable complement to conditional gene inactivation strategies. We present a method for the generation of conditional gene repair mutations that employs a loxP-flanked (floxed) selectable marker and transcriptional/translational stop cassette (neostop) located within the first intron of a target gene. In the absence of Cre recombinase, expression of the targeted allele is suppressed generating a null allele, while in the presence of Cre, excision of neostop restores expression to wild-type levels. To test this strategy, we have generated a conditional gene repair allele of the mouse Huntington’s disease gene homolog (Hdh). Insertion of neostop within the Hdh intron 1 generated a null allele and mice homozygous for this allele resembled nullizygous Hdh mutants and died after embryonic day 8.5. In the presence of a cre transgene expressed ubiquitously early in development, excision of neostop restored Hdh expression and rescued the early embryonic lethality. A simple modification of this strategy that permits the generation of conventional gene knockout, conditional gene knockout and conditional gene repair alleles using one targeting construct is discussed.

Transcriptional and posttranslational plasticity and the generation of inflammatory pain

Inflammatory pain manifests as spontaneous pain and pain hypersensitivity. Spontaneous pain reflects direct activation of specific receptors on nociceptor terminals by inflammatory mediators. Pain hypersensitivity is the consequence of early posttranslational changes, both in the peripheral terminals of the nociceptor and in dorsal horn neurons, as well as later transcription-dependent changes in effector genes, again in primary sensory and dorsal horn neurons. This inflammatory neuroplasticity is the consequence of a combination of activity-dependent changes in the neurons and specific signal molecules initiating particular signal-transduction pathways. These pathways phosphorylate membrane proteins, changing their function, and activate transcription factors, altering gene expression. Two distinct aspects of sensory neuron function are changed as a result of these processes, basal sensitivity, or the capacity of peripheral stimuli to evoke pain, and stimulus-evoked hypersensitivity, the capacity of certain inputs to generate prolonged alterations in the sensitivity of the system. Posttranslational changes largely alter basal sensitivity. Transcriptional changes both potentiate the system and alter neuronal phenotype. Potentiation occurs as a result of the up-regulation in the dorsal root ganglion of centrally acting neuromodulators and simultaneously in the dorsal horn of their receptors. This means that the response to subsequent inputs is augmented, particularly those that induce stimulus-induced hypersensitivity. Alterations in phenotype includes the acquisition by A fibers of neurochemical features typical of C fibers, enabling these fibers to induce stimulus-evoked hypersensitivity, something only C fiber inputs normally can do. Elucidation of the molecular mechanisms responsible provides new opportunities for therapeutic approaches to managing inflammatory pain.

Toward a new generation of vaccines: The anti-cytokine therapeutic vaccines

Pathological conditions, such as cancers, viral infections, and autoimmune diseases, are associated with abnormal cytokine production, and the morbidity associated with many medical disorders is often directly a result of cytokine production. Because of the absence of negative feedback control occurring in some pathophysiologic situations, a given cytokine may flood and accumulate in the extracellular compartment of tissues or tumors thereby impairing the cytokine network homeostasis and contributing to local pathogenesis. To evaluate whether the rise of anti-cytokine Abs by vaccination is an effective way to treat these pathological conditions without being harmful to the organism, we have analyzed each step of the cytokine process (involving cytokine production, target response, and feedback regulation) and have considered them in the local context of effector–target cell microenvironment and in the overall context of the macroenvironment of the immune system of the organism. In pathologic tissues, Abs of high affinity, as raised by anti-cytokine vaccination, should neutralize the pool of cytokines ectopically accumulated in the extracellular compartment, thus counteracting their pathogenic effects. In contrast, the same Abs should not interfere with cytokine processes occurring in normal tissues, because under physiologic conditions cytokine production by effector cells (induced by activation but controlled by negative feedback regulation) does not accumulate in the extracellular compartment. These concepts are consistent with results showing that following animal and human anti-cytokine vaccination, induction of high-affinity Abs has proven to be safe and effective and encourages this approach as a pioneering avenue of therapy.

A genetically informed study of the processes underlying the association between parental marital instability and offspring adjustment

Parental divorce is associated with problematic offspring adjustment, but the relation may be due to shared genetic or environmental factors. One way to test for these confounds is to study offspring of twins discordant for divorce. The current analyses used this design to separate the mechanisms responsible for the association between parental divorce, experienced either before or after the age of 16, and offspring well-being. The results were consistent with a causal role of divorce in earlier initiation of sexual intercourse and emotional difficulties, in addition to a greater probability of educational problems, depressed mood, and suicidal ideation. In contrast, the increased risk for cohabitation and earlier initiation of drug use was explained by selection factors, including genetic confounds.

Generation of triangular pulses in normally dispersive fibre

In this scheme, nonlinearity and dispersion in the NDF lead to various reshaping processes of an initial, conventional pulse according to the chirping value and power level at the input of the fibre. In particular, we have observed that triangular-shaped pulses can be generated for sufficiently high energies and a positive initial chirp parameter. In our experiments, 2.8 ps-FWHM, transform-limited pulses generated from a mode-locked fibre laser source at a repetition rate of 1.25 GHz were pre-chirped by propagating the pulses through different lengths of standard mono-mode fibre. The chirped pulses were then amplified to different power levels before being launched into a 2.3 km section of True Wave fibre (TWF). The corresponding numerically calculated pulse temporal intensity profile and numerical and experimental second-harmonic generation frequency-resolved optical gating (SHG FROG) spectrograms were also derived. In conclusion, we have presented numerical modelling results which show the system design parameters required for the generation of triangular-shaped pulses in a nonlinear NDF, and experimentally demonstrated triangular pulse shaping in conventional NDF.

Generation of Testing Source Code for Object-Oriented Programs

Красимир Манев, Антон Желязков, Станимир Бойчев - В статията е представена имплементацията на последната фаза на автоматичен генератор на тестови данни за структурно тестване на софтуер, написан на обектно-ориентиран език за програмиране – генерирането на изходен код на тестващия модул. Някои детайли от имплементацията на останалите фази, които са важни за имплементацията на последната фаза, са представени първо. След това е описан и алгоритъмът за генериране на кода на тестващия модул.

Temporal and spatio-temporal regimes of generation of Raman fibre lasers

Temporal dynamics of Raman fibre lasers tend to have very complex nature, owing to great cavity lengths and high nonlinearity, being stochastic on short time scales and quasi-continuous on longer time scales. Generally fibre laser intensity dynamics is represented by one-dimensional time-series, which in case of quasi-continuous wave generation in Raman fibre lasers gives little insight into the processes underlying the operation of a laser. New methods of analysis and data representation could help to uncover the underlying physical processes, understand the dynamics or improve the performance of the system. Using intrinsic periodicity of laser radiation, one dimensional intensity time series of a Raman fibre laser was analysed over fast and slow variation time. This allowed to experimentally observe various spatio-temporal regimes of generation, such as laminar, turbulent, partial mode-lock, as well as transitions between them and identify the mechanisms responsible for the transitions. Great cavity length and high nonlinearity also make it difficult to achieve stable high repetition rate mode-locking in Raman fibre lasers. Using Faraday parametric instability in extremely simple linear cavity experimental configuration, a very high order harmonic mode-locking was achieved in ò.ò kmlong Raman fibre laser. The maximum achieved pulse repetition rate was 12 GHz, with 7.3 ps long Gaussian shaped pulses. There is a new type of random lasers – random distributed feedback Raman fibre laser, which temporal properties cannot be controlled by conventionalmode-locking or Q-switch techniques and mechanisms. By adjusting the pump configuration, a very stable pulsed operation of random distributed feedback Raman fibre laser was achieved. Pulse duration varied in the range from 50 to 200 μs depending on the pump power and the cavity length. Pulse repetition rate scaling on the parameters of the system was experimentally identified.

An integrated multi-agent framework for optimizing time, cost and environmental impact of construction processes

Environmentally conscious construction has received a significant amount of research attention during the last decades. Even though construction literature is rich in studies that emphasize the importance of environmental impact during the construction phase, most of the previous studies failed to combine environmental analysis with other project performance criteria in construction. This is mainly because most of the studies have overlooked the multi-objective nature of construction projects. In order to achieve environmentally conscious construction, multi-objectives and their relationships need to be successfully analyzed in the complex construction environment. The complex construction system is composed of changing project conditions that have an impact on the relationship between time, cost and environmental impact (TCEI) of construction operations. Yet, this impact is still unknown by construction professionals. Studying this impact is vital to fulfill multiple project objectives and achieve environmentally conscious construction. This research proposes an analytical framework to analyze the impact of changing project conditions on the relationship of TCEI. This study includes green house gas (GHG) emissions as an environmental impact category. The methodology utilizes multi-agent systems, multi-objective optimization, analytical network process, and system dynamics tools to study the relationships of TCEI and support decision-making under the influence of project conditions. Life cycle assessment (LCA) is applied to the evaluation of environmental impact in terms of GHG. The mixed method approach allowed for the collection and analysis of qualitative and quantitative data. Structured interviews of professionals in the highway construction field were conducted to gain their perspectives in decision-making under the influence of certain project conditions, while the quantitative data were collected from the Florida Department of Transportation (FDOT) for highway resurfacing projects. The data collected were used to test the framework. The framework yielded statistically significant results in simulating project conditions and optimizing TCEI. The results showed that the change in project conditions had a significant impact on the TCEI optimal solutions. The correlation between TCEI suggested that they affected each other positively, but in different strengths. The findings of the study will assist contractors to visualize the impact of their decision on the relationship of TCEI.

Item and task difficulty in a B2 reading examination: perceptions of test-takers and CEFR alignment experts compared with psychometric measurements

The article presents a study of a CEFR B2-level reading subtest that is part of the Slovenian national secondary school leaving examination in English as a foreign language, and compares the test-taker actual performance (objective difficulty) with the test-taker and expert perceptions of item difficulty (subjective difficulty). The study also analyses the test-takers’ comments on item difficulty obtained from a while-reading questionnaire. The results are discussed in the framework of the existing research in the fields of (the assessment of) reading comprehension, and are addressed with regard to their implications for item-writing, FL teaching and curriculum development.

MEG-measured visually induced gamma-band oscillations in chronic schizophrenia: Evidence for impaired generation of rhythmic activity in ventral stream regions

Background: Gamma-band oscillations are prominently impaired in schizophrenia, but the nature of the deficit and relationship to perceptual processes is unclear. Methods: 16 patients with chronic schizophrenia (ScZ) and 16 age-matched healthy controls completed a visual paradigm while magnetoencephalographic (MEG) data was recorded. Participants had to detect randomly occurring stimulus acceleration while viewing a concentric moving grating. MEG data were analyzed for spectral power (1-100 Hz) at sensorand source-level to examine the brain regions involved in aberrant rhythmic activity, and for contribution of differences in baseline activity towards the generation of low- and highfrequency power. Results: Our data show reduced gamma-band power at sensor level in schizophrenia patients during stimulus processing while alpha-band and baseline spectrum were intact. Differences in oscillatory activity correlated with reduced behavioral detection rates in the schizophrenia group and higher scores on the “Cognitive Factor” of the Positive and Negative Syndrome Scale. Source reconstruction revealed that extra-striate (fusiform/lingual gyrus), but not striate (cuneus), visual cortices contributed towards the reduced activity observed at sensorlevel in ScZ patients. Importantly, differences in stimulus-related activity were not due to differences in baseline activity. Conclusions: Our findings highlight that MEG-measured high-frequency oscillations during visual processing can be robustly identified in ScZ. Our data further suggest impairments that involve dysfunctions in ventral stream processing and a failure to increase gamma-band activity in a task-context. Implications of these findings are discussed in the context of current theories of cortical-subcortical circuit dysfunctions and perceptual processing in ScZ.

The role of biological processes in affecting the dynamics and fate of microplastics in coastal marine systems

Microplastics (MP) are omnipresent contaminants in the marine environment. Ingestion of MP has been reported for a wide range of marine biota, but to what extent the uptake by organisms affects the dynamics and fate of MP in the marine system has received little attention. My thesis explored this topic by integrating laboratory tests and experiments, field quantitative surveys of MP distribution and dynamics, and the use of specialised analytical techniques such as Attenuated-Total-Reflectance- (ATR) and imaging- Fourier Transformed Infrared Spectroscopy (FTIR). I compared different methodologies to extract MP from wild invertebrate specimens, and selected the use of potassium hydroxide (KOH) as the most cost-effective approach. I used this approach to analyse the MP contamination in various invertebrate species with different ecological traits from European salt marshes. I found that 96% of the analysed specimens (330) did not contain any MP. As preliminary environmental analyses showed high levels of environmental MP contamination, I hypothesised that most MP do not accumulate into organisms but are rather fast egested. I subsequently used laboratory multi-trophic experiments and a long-term field experiment using the filter-feeding mussel Mytilus galloprovincialis and the detritus feeding polychaete Hediste diversicolor to test the aforementioned hypothesis. Overall, results showed that MP are ingested but rapidly egested by marine invertebrates, which may limit MP transfer via predator-prey interactions but at the same time enhance their transfer via detrital pathways in the sediments. These processes seem to be extremely variable over time, with potential unexplored environmental consequences. This rapid dynamics also limits the conclusions that can be derived from static observations of MP contents in marine organisms, not fully capturing the real levels of potential contaminations by marine species. This emphasises the need to consider such dynamics in future work to measure the uptake rates by organisms in natural systems.

An Efficient Protocol For The Generation Of Monocyte Derived Dendritic Cells Using Serum-free Media For Clinical Applications In Post Remission Aml Patients.

Protocols for the generation of dendritic cells (DCs) using serum as a supplementation of culture media leads to reactions due to animal proteins and disease transmissions. Several types of serum-free media (SFM), based on good manufacture practices (GMP), have recently been used and seem to be a viable option. The aim of this study was to evaluate the results of the differentiation, maturation, and function of DCs from Acute Myeloid Leukemia patients (AML), generated in SFM and medium supplemented with autologous serum (AS). DCs were analyzed by phenotype characteristics, viability, and functionality. The results showed the possibility of generating viable DCs in all the conditions tested. In patients, the X-VIVO 15 medium was more efficient than the other media tested in the generation of DCs producing IL-12p70 (p=0.05). Moreover, the presence of AS led to a significant increase of IL-10 by DCs as compared with CellGro (p=0.05) and X-Vivo15 (p=0.05) media, both in patients and donors. We concluded that SFM was efficient in the production of DCs for immunotherapy in AML patients. However, the use of AS appears to interfere with the functional capacity of the generated DCs.

Construction Of A Manual Of Work Processes And Techniques From Centro De Dispensação De Medicamentos De Alto Custo (cedmac), Hospital De Clínicas, Unicamp.

The Centers for High Cost Medication (Centros de Medicação de Alto Custo, CEDMAC), Health Department, São Paulo were instituted by project in partnership with the Clinical Hospital of the Faculty of Medicine, USP, sponsored by the Foundation for Research Support of the State of São Paulo (Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP) aimed at the formation of a statewide network for comprehensive care of patients referred for use of immunobiological agents in rheumatological diseases. The CEDMAC of Hospital de Clínicas, Universidade Estadual de Campinas (HC-Unicamp), implemented by the Division of Rheumatology, Faculty of Medical Sciences, identified the need for standardization of the multidisciplinary team conducts, in face of the specificity of care conducts, verifying the importance of describing, in manual format, their operational and technical processes. The aim of this study is to present the methodology applied to the elaboration of the CEDMAC/HC-Unicamp Manual as an institutional tool, with the aim of offering the best assistance and administrative quality. In the methodology for preparing the manuals at HC-Unicamp since 2008, the premise was to obtain a document that is participatory, multidisciplinary, focused on work processes integrated with institutional rules, with objective and didactic descriptions, in a standardized format and with electronic dissemination. The CEDMAC/HC-Unicamp Manual was elaborated in 10 months, with involvement of the entire multidisciplinary team, with 19 chapters on work processes and techniques, in addition to those concerning the organizational structure and its annexes. Published in the electronic portal of HC Manuals in July 2012 as an e-Book (ISBN 978-85-63274-17-5), the manual has been a valuable instrument in guiding professionals in healthcare, teaching and research activities.