670 research outputs found

    Recommendation of an integrated index for the quality of educational services using multivariate statistics

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    In this work, the analysis of the surveys was carried out through a factorial analysis, which facilitates the evaluation of the validity of the selected construct for the case under study, as well as evaluating the quality of the service for each factor, with a view to determining the level of quality of the educational service, for which it integrates elements of descriptive and multivariate statistics with the management of the quality of the educational service. They are used as fundamental statistical techniques, descriptive analysis, factor analysis and analysis of variance. As a final result, it was concluded that the students of five UNITEC careers evaluated the educational service they receive as very satisfactory (4 points), highlighting the tangible elements as the most weighted factor. A significant aspect is that there are no significant differences in the perceptions of students from different careers and different sections

    Building block libraries and structural considerations in the self-assembly of polyoxometalate and polyoxothiometalate systems

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    Inorganic metal-oxide clusters form a class of compounds that are unique in their topological and electronic versatility and are becoming increasingly more important in a variety of applications. Namely, Polyoxometalates (POMs) have shown an unmatched range of physical properties and the ability to form structures that can bridge several length scales. The formation of these molecular clusters is often ambiguous and is governed by self-assembly processes that limit our ability to rationally design such molecules. However, recent years have shown that by considering new building block principles the design and discovery of novel complex clusters is aiding our understanding of this process. Now with current progress in thiometalate chemistry, specifically polyoxothiometalates (POTM), the field of inorganic molecular clusters has further diversified allowing for the targeted development of molecules with specific functionality. This chapter discusses the main differences between POM and POTM systems and how this affects synthetic methodologies and reactivities. We will illustrate how careful structural considerations can lead to the generation of novel building blocks and further deepen our understanding of complex systems

    Phenotypic drug screen uncovers the metabolic GCH1/BH4 pathway as key regulator of EGFR/KRAS-mediated neuropathic pain and lung cancer

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    Increased tetrahydrobiopterin (BH4) generated in injured sensory neurons contributes to increased pain sensitivity and its persistence. GTP cyclohydrolase 1 (GCH1) is the rate-limiting enzyme in the de novo BH4 synthetic pathway, and human single-nucleotide polymorphism studies, together with mouse genetic modeling, have demonstrated that decreased GCH1 leads to both reduced BH4 and pain. However, little is known about the regulation of Gch1 expression upon nerve injury and whether this could be modulated as an analgesic therapeutic intervention. We performed a phenotypic screen using about 1000 bioactive compounds, many of which are target-annotated FDA-approved drugs, for their effect on regulating Gch1 expression in rodent injured dorsal root ganglion neurons. From this approach, we uncovered relevant pathways that regulate Gch1 expression in sensory neurons. We report that EGFR/KRAS signaling triggers increased Gch1 expression and contributes to neuropathic pain; conversely, inhibiting EGFR suppressed GCH1 and BH4 and exerted analgesic effects, suggesting a molecular link between EGFR/KRAS and pain perception. We also show that GCH1/BH4 acts downstream of KRAS to drive lung cancer, identifying a potentially druggable pathway. Our screen shows that pharmacologic modulation of GCH1 expression and BH4 could be used to develop pharmacological treatments to alleviate pain and identified a critical role for EGFR-regulated GCH1/BH4 expression in neuropathic pain and cancer in rodents

    Inter-hemispheric EEG coherence analysis in Parkinson's disease : Assessing brain activity during emotion processing

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    Parkinson’s disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3–AF4, F7–F8, F3–F4, FC5–FC6, T7–T8, P7–P8, and O1–O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities

    Development and validation of a physical activity monitor for use on a wheelchair

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    Study design: Keeping physically active is important for people who mobilize using a wheelchair. However, current tools to measure physical activity in the wheelchair are either not validated or limited in their application. The purpose of this study was to develop and validate a monitoring system to measure wheelchair movement.<p></p> Methods: The system developed consisted of a tri-axial accelerometer placed on the wheel of a wheelchair and an analysis algorithm to interpret the acceleration signals. The two accelerometer outputs in the plane of the wheel were used to calculate the angle of the wheel. From this, outcome measures of wheel revolutions, absolute angle and duration of movement were derived and the direction of movement (forwards or backwards) could be distinguished. Concurrent validity was assessed in comparison with video analysis in 14 people with spinal cord injury using their wheelchair on an indoor track and outdoor wheelchair skills course. Validity was assessed using intraclass correlation coefficients (ICC(2,1)) and Bland–Altman plots.<p></p> Results: The monitoring system demonstrated excellent validity for wheel revolutions, absolute angle and duration of movement (ICC(2,1)>0.999, 0.999, 0.981, respectively) in both manual and powered wheelchairs, when the wheelchair was propelled forwards and backwards, and for movements of various durations.<p></p> Conclusion: This study has found this monitoring system to be an accurate and objective tool for measuring detailed information on wheelchair movement and manoeuvring regardless of the propulsion technique, direction and speed

    Update of the Cancer Potency Database (CPDB) to enable derivations of Thresholds Of Toxicological Concern (TTC) for cancer potency

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    The purpose of this study was to update the existing Cancer Potency Database (CPDB) in order to support the development of a dataset of compounds, with associated points of departure (PoDs), to enable a review and update of currently applied values for the Threshold of Toxicological Concern (TTC) for cancer endpoints. This update of the current CPDB, last reviewed in 2012, includes the addition of new data (44 compounds and 158 studies leading to additional 359 dose-response curves). Strict inclusion criteria were established and applied to select compounds and studies with relevant cancer potency data. PoDs were calculated from dose-response modeling, including the benchmark dose (BMD) and the lower 90% confidence limits (BMDL) at a specified benchmark response (BMR) of 10%. The updated full CPDB database resulted in a total of 421 chemicals which had dose-response data that could be used to calculate PoDs. This candidate dataset for cancer TTC is provided in a transparent and adaptable format for further analysis of TTC to derive cancer potency thresholds

    High Resolution In Vivo Bioluminescent Imaging for the Study of Bacterial Tumour Targeting

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    The ability to track microbes in real time in vivo is of enormous value for preclinical investigations in infectious disease or gene therapy research. Bacteria present an attractive class of vector for cancer therapy, possessing a natural ability to grow preferentially within tumours following systemic administration. Bioluminescent Imaging (BLI) represents a powerful tool for use with bacteria engineered to express reporter genes such as lux. BLI is traditionally used as a 2D modality resulting in images that are limited in their ability to anatomically locate cell populations. Use of 3D diffuse optical tomography can localize the signals but still need to be combined with an anatomical imaging modality like micro-Computed Tomography (μCT) for interpretation

    Ultraviolet radiation shapes seaweed communities

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    Mechanisms Underlying Stage-1 TRPL Channel Translocation in Drosophila Photoreceptors

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    Background: TRP channels function as key mediators of sensory transduction and other cellular signaling pathways. In Drosophila, TRP and TRPL are the light-activated channels in photoreceptors. While TRP is statically localized in the signaling compartment of the cell (the rhabdomere), TRPL localization is regulated by light. TRPL channels translocate out of the rhabdomere in two distinct stages, returning to the rhabdomere with dark-incubation. Translocation of TRPL channels regulates their availability, and thereby the gain of the signal. Little, however, is known about the mechanisms underlying this trafficking of TRPL channels. Methodology/Principal Findings: We first examine the involvement of de novo protein synthesis in TRPL translocation. We feed flies cycloheximide, verify inhibition of protein synthesis, and test for TRPL translocation in photoreceptors. We find that protein synthesis is not involved in either stage of TRPL translocation out of the rhabdomere, but that re-localization to the rhabdomere from stage-1, but not stage-2, depends on protein synthesis. We also characterize an ex vivo eye preparation that is amenable to biochemical and genetic manipulation. We use this preparation to examine mechanisms of stage-1 TRPL translocation. We find that stage-1 translocation is: induced with ATP depletion, unaltered with perturbation of the actin cytoskeleton or inhibition of endocytosis, and slowed with increased membrane sterol content. Conclusions/Significance: Our results indicate that translocation of TRPL out of the rhabdomere is likely due to protei
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