Big-Data-Driven Materials Science and its FAIR Data Infrastructure

This chapter addresses the forth paradigm of materials research -- big-data driven materials science. Its concepts and state-of-the-art are described, and its challenges and chances are discussed. For furthering the field, Open Data and an all-embracing sharing, an efficient data infrastructure, and the rich ecosystem of computer codes used in the community are of critical importance. For shaping this forth paradigm and contributing to the development or discovery of improved and novel materials, data must be what is now called FAIR -- Findable, Accessible, Interoperable and Re-purposable/Re-usable. This sets the stage for advances of methods from artificial intelligence that operate on large data sets to find trends and patterns that cannot be obtained from individual calculations and not even directly from high-throughput studies. Recent progress is reviewed and demonstrated, and the chapter is concluded by a forward-looking perspective, addressing important not yet solved challenges.Comment: submitted to the Handbook of Materials Modeling (eds. S. Yip and W. Andreoni), Springer 2018/201

Circadian Rhythms in Visual Responsiveness in the Behaviorally Arrhythmic Drosophila Clock Mutant ClkJrk

An organism's biological day is characterized by a pattern of anticipatory physiological and behavioral changes that are governed by circadian clocks to align with the 24-h cycling environment. Here, we used flash electroretinograms (ERGs) and steady-state visually evoked potentials (SSVEPs) to examine how visual responsiveness in wild-type Drosophila melanogaster and the circadian clock mutant ClkJrk varies over circadian time. We show that the ERG parameters of wild-type flies vary over the circadian day, with a higher luminance response during the subjective night. The SSVEP response that assesses contrast sensitivity also showed a time-of-day dependence, including 2 prominent peaks within a 24-h period and a maximal response at the end of the subjective day, indicating a tradeoff between luminance and contrast sensitivity. Moreover, the behaviorally arrhythmic ClkJrk mutants maintained a circadian profile in both luminance and contrast sensitivity, but unlike the wild-types, which show bimodal profiles in their visual response, ClkJrk flies show a weakening of the bimodal character, with visual responsiveness tending to peak once a day. We conclude that the ClkJrk mutation mainly affects 1 of 2 functionally coupled oscillators and that the visual system is partially separated from the locomotor circadian circuits that drive bouts of morning and evening activity. As light exposure is a major mechanism for entrainment, our work suggests that a detailed temporal analysis of electrophysiological responses is warranted to better identify the time window at which circadian rhythms are most receptive to light-induced phase shifting

Anion gap, anion gap corrected for albumin, base deficit and unmeasured anions in critically ill patients: implications on the assessment of metabolic acidosis and the diagnosis of hyperlactatemia

Abstract Background Base deficit (BD), anion gap (AG), and albumin corrected anion gap (ACAG) are used by clinicians to assess the presence or absence of hyperlactatemia (HL). We set out to determine if these tools can diagnose the presence of HL using cotemporaneous samples. Methods We conducted a chart review of ICU patients who had cotemporaneous arterial blood gas, serum chemistry, serum albumin (Alb) and lactate(Lac) levels measured from the same sample. We assessed the capacity of AG, BD, and ACAG to diagnose HL and severe hyperlactatemia (SHL). HL was defined as Lac > 2.5 mmol/L. SHL was defined as a Lac of > 4.0 mmol/L. Results From 143 patients we identified 497 series of lab values that met our study criteria. Mean age was 62.2 ± 15.7 years. Mean Lac was 2.11 ± 2.6 mmol/L, mean AG was 9.0 ± 5.1, mean ACAG was 14.1 ± 3.8, mean BD was 1.50 ± 5.4. The area under the curve for the ROC for BD, AG, and ACAG to diagnose HL were 0.79, 0.70, and 0.72, respectively. Conclusion AG and BD failed to reliably detect the presence of clinically significant hyperlactatemia. Under idealized conditions, ACAG has the capacity to rule out the presence of hyperlactatemia. Lac levels should be obtained routinely in all patients admitted to the ICU in whom the possibility of shock/hypoperfusion is being considered. If an AG assessment is required in the ICU, it must be corrected for albumin for there to be sufficient diagnostic utility.</p

Predicting progression of mild cognitive impairment to dementia using neuropsychological data: a supervised learning approach using time windows

Background: Predicting progression from a stage of Mild Cognitive Impairment to dementia is a major pursuit in current research. It is broadly accepted that cognition declines with a continuum between MCI and dementia. As such, cohorts of MCI patients are usually heterogeneous, containing patients at different stages of the neurodegenerative process. This hampers the prognostic task. Nevertheless, when learning prognostic models, most studies use the entire cohort of MCI patients regardless of their disease stages. In this paper, we propose a Time Windows approach to predict conversion to dementia, learning with patients stratified using time windows, thus fine-tuning the prognosis regarding the time to conversion. Methods: In the proposed Time Windows approach, we grouped patients based on the clinical information of whether they converted (converter MCI) or remained MCI (stable MCI) within a specific time window. We tested time windows of 2, 3, 4 and 5 years. We developed a prognostic model for each time window using clinical and neuropsychological data and compared this approach with the commonly used in the literature, where all patients are used to learn the models, named as First Last approach. This enables to move from the traditional question "Will a MCI patient convert to dementia somewhere in the future" to the question "Will a MCI patient convert to dementia in a specific time window". Results: The proposed Time Windows approach outperformed the First Last approach. The results showed that we can predict conversion to dementia as early as 5 years before the event with an AUC of 0.88 in the cross-validation set and 0.76 in an independent validation set. Conclusions: Prognostic models using time windows have higher performance when predicting progression from MCI to dementia, when compared to the prognostic approach commonly used in the literature. Furthermore, the proposed Time Windows approach is more relevant from a clinical point of view, predicting conversion within a temporal interval rather than sometime in the future and allowing clinicians to timely adjust treatments and clinical appointments.FCT under the Neuroclinomics2 project [PTDC/EEI-SII/1937/2014, SFRH/BD/95846/2013]; INESC-ID plurianual [UID/CEC/50021/2013]; LASIGE Research Unit [UID/CEC/00408/2013

Enhanced multiclass SVM with thresholding fusion for speech-based emotion classification

As an essential approach to understanding human interactions, emotion classification is a vital component of behavioral studies as well as being important in the design of context-aware systems. Recent studies have shown that speech contains rich information about emotion, and numerous speech-based emotion classification methods have been proposed. However, the classification performance is still short of what is desired for the algorithms to be used in real systems. We present an emotion classification system using several one-against-all support vector machines with a thresholding fusion mechanism to combine the individual outputs, which provides the functionality to effectively increase the emotion classification accuracy at the expense of rejecting some samples as unclassified. Results show that the proposed system outperforms three state-of-the-art methods and that the thresholding fusion mechanism can effectively improve the emotion classification, which is important for applications that require very high accuracy but do not require that all samples be classified. We evaluate the system performance for several challenging scenarios including speaker-independent tests, tests on noisy speech signals, and tests using non-professional acted recordings, in order to demonstrate the performance of the system and the effectiveness of the thresholding fusion mechanism in real scenarios.Peer ReviewedPreprin

Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy

The mammalian target of rapamycin (mTOR) is an intracellular serine/threonine protein kinase positioned at a central point in a variety of cellular signaling cascades. The established involvement of mTOR activity in the cellular processes that contribute to the development and progression of cancer has identified mTOR as a major link in tumorigenesis. Consequently, inhibitors of mTOR, including temsirolimus, everolimus, and ridaforolimus (formerly deforolimus) have been developed and assessed for their safety and efficacy in patients with cancer. Temsirolimus is an intravenously administered agent approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for the treatment of advanced renal cell carcinoma (RCC). Everolimus is an oral agent that has recently obtained US FDA and EMEA approval for the treatment of advanced RCC after failure of treatment with sunitinib or sorafenib. Ridaforolimus is not yet approved for any indication. The use of mTOR inhibitors, either alone or in combination with other anticancer agents, has the potential to provide anticancer activity in numerous tumor types. Cancer types in which these agents are under evaluation include neuroendocrine tumors, breast cancer, leukemia, lymphoma, hepatocellular carcinoma, gastric cancer, pancreatic cancer, sarcoma, endometrial cancer, and non-small-cell lung cancer. The results of ongoing clinical trials with mTOR inhibitors, as single agents and in combination regimens, will better define their activity in cancer

Essential fatty acids for premenstrual syndrome and their effect on prolactin and total cholesterol levels: a randomized, double blind, placebo-controlled study

<p>Abstract</p> <p>Objective</p> <p>To evaluate the effectiveness and safety of polyunsaturated fatty acids for the treatment of the premenstrual syndrome (PMS) using a graded symptom scale and to assess the effect of this treatment on basal plasma levels of prolactin and total cholesterol.</p> <p>Methods</p> <p>A randomized, double-blind, placebo-controlled study was conducted with 120 women with PMS divided into three groups and treated with 1 or 2 grams of the medication or placebo. Symptoms were recorded over a 6-month period using the Prospective Record of the Impact and Severity of Menstruation (PRISM) calendar. Total cholesterol and prolactin levels were measured. Analysis of variance (ANOVA), Pearson's chi-square test, Wilcoxon's nonparametric signed-rank test for paired samples and the Mann-Whitney nonparametric test for independent samples were used in the statistical analysis.</p> <p>Results</p> <p>There were no differences in age, marital status, schooling or ethnicity between the groups. In the group treated with 1 gram of the medication, a significant reduction was found when the median PRISM score recorded in the luteal phase at baseline (99) was compared with the median score recorded in the 3^rdmonth (58) and in the 6^thmonth of evaluation (35). In the 2-gram group, these differences were even more significant (baseline score: 98; 3^rdmonth: 48; 6^thmonth: 28). In the placebo group, there was a significant reduction at the 3^rdbut not at the 6^thmonth (baseline: 96.5; 3^rdmonth: 63.5; 6^thmonth: 62). The difference between the phases of the menstrual cycle was greater in the 2-gram group compared to the group treated with 1 gram of the medication. There were no statistically significant differences in prolactin or total cholesterol levels between baseline values and those recorded after six months of treatment.</p> <p>Conclusion</p> <p>The difference between the groups using the medication and the placebo group with respect to the improvement in symptomatology appears to indicate the effectiveness of the drug. Improvement in symptoms was higher when the 2-gram dose was used. This medication was not associated with any changes in prolactin or total cholesterol levels in these women.</p

Tropheryma whipplei, the Whipple's disease bacillus, induces macrophage apoptosis through the extrinsic pathway

Tropheryma whipplei, the etiological agent of Whipple's disease, is an intracellular bacterium that infects macrophages. We previously showed that infection of macrophages results in M2 polarization associated with induction of apoptosis and interleukin (IL)-16 secretion. In patients with Whipple's disease, circulating levels of apoptotic markers and IL-16 are increased and correlate with the activity of the disease. To gain insight into the understanding of the pathophysiology of this rare disease, we examined the molecular pathways involved in T. whipplei-induced apoptosis of human macrophages. Our data showed that apoptosis induction depended on bacterial viability and inhibition of bacterial protein synthesis reduced the apoptotic program elicited by T. whipplei. Induction of apoptosis was also associated with a massive degradation of both pro- and anti-apoptotic mediators. Caspase-specific inhibition experiments revealed that initiator caspases 8 and 10 were required for apoptosis, in contrast to caspases 2 and 9, in spite of cytochrome-c release from mitochondria. Finally, the effector caspases 3 and 6 were mandatory for apoptosis induction. Collectively, these data suggest that T. whipplei induces apoptosis through the extrinsic pathway and that, beside M2 polarization of macrophages, apoptosis induction contributes to bacterial replication and represents a virulence trait of this intracellular pathogen