119 research outputs found

    Predicting Grades

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    To increase efficacy in traditional classroom courses as well as in Massive Open Online Courses (MOOCs), automated systems supporting the instructor are needed. One important problem is to automatically detect students that are going to do poorly in a course early enough to be able to take remedial actions. Existing grade prediction systems focus on maximizing the accuracy of the prediction while overseeing the importance of issuing timely and personalized predictions. This paper proposes an algorithm that predicts the final grade of each student in a class. It issues a prediction for each student individually, when the expected accuracy of the prediction is sufficient. The algorithm learns online what is the optimal prediction and time to issue a prediction based on past history of students' performance in a course. We derive a confidence estimate for the prediction accuracy and demonstrate the performance of our algorithm on a dataset obtained based on the performance of approximately 700 UCLA undergraduate students who have taken an introductory digital signal processing over the past 7 years. We demonstrate that for 85% of the students we can predict with 76% accuracy whether they are going do well or poorly in the class after the 4th course week. Using data obtained from a pilot course, our methodology suggests that it is effective to perform early in-class assessments such as quizzes, which result in timely performance prediction for each student, thereby enabling timely interventions by the instructor (at the student or class level) when necessary.Comment: 15 pages, 15 figure

    Evaluating automated longitudinal tumor measurements for glioblastoma response assessment.

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    Automated tumor segmentation tools for glioblastoma show promising performance. To apply these tools for automated response assessment, longitudinal segmentation, and tumor measurement, consistency is critical. This study aimed to determine whether BraTumIA and HD-GLIO are suited for this task. We evaluated two segmentation tools with respect to automated response assessment on the single-center retrospective LUMIERE dataset with 80 patients and a total of 502 post-operative time points. Volumetry and automated bi-dimensional measurements were compared with expert measurements following the Response Assessment in Neuro-Oncology (RANO) guidelines. The longitudinal trend agreement between the expert and methods was evaluated, and the RANO progression thresholds were tested against the expert-derived time-to-progression (TTP). The TTP and overall survival (OS) correlation was used to check the progression thresholds. We evaluated the automated detection and influence of non-measurable lesions. The tumor volume trend agreement calculated between segmentation volumes and the expert bi-dimensional measurements was high (HD-GLIO: 81.1%, BraTumIA: 79.7%). BraTumIA achieved the closest match to the expert TTP using the recommended RANO progression threshold. HD-GLIO-derived tumor volumes reached the highest correlation between TTP and OS (0.55). Both tools failed at an accurate lesion count across time. Manual false-positive removal and restricting to a maximum number of measurable lesions had no beneficial effect. Expert supervision and manual corrections are still necessary when applying the tested automated segmentation tools for automated response assessment. The longitudinal consistency of current segmentation tools needs further improvement. Validation of volumetric and bi-dimensional progression thresholds with multi-center studies is required to move toward volumetry-based response assessment

    Extensive de novo solid-state NMR assignments of the 33kDa C-terminal domain of the Ure2 prion

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    We present the de novo resonance assignments for the crystalline 33kDa C-terminal domain of the Ure2 prion using an optimized set of five 3D solid-state NMR spectra. We obtained, using a single uniformly 13C, 15N labeled protein sample, sequential chemical-shift information for 74% of the N, Cα, Cβ triples, and for 80% of further side-chain resonances for these spin systems. We describe the procedures and protocols devised, and discuss possibilities and limitations of the assignment of this largest protein assigned today by solid-state NMR, and for which no solution-state NMR shifts were available. A comparison of the NMR chemical shifts with crystallographic data reveals that regions with high crystallographic B-factors are particularly difficult to assign. While the secondary structure elements derived from the chemical shift data correspond mainly to those present in the X-ray crystal structure, we detect an additional helical element and structural variability in the protein crystal, most probably originating from the different molecules in the asymmetric unit, with the observation of doubled resonances in several parts, including entire stretches, of the protein. Our results provide the point of departure towards an atomic-resolution structural analysis of the C-terminal Ure2p domain in the context of the full-length prion fibril

    Solid-state NMR sequential assignments of the amyloid core of Sup35pNM

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    Sup35pNM represents the N-terminal and middle (M) domains of the yeast Saccharomyces cerevisiae prion Sup35p. This fragment is commonly used for structural and functional studies of Sup35p. We here present a solid-state NMR study of fibrils formed by this fragment and show that sequential assignments can be obtained for the rigid and well-ordered parts of the protein using 3D spectroscopy. We describe in detail the sequential assignment of the 22 residues yielding strong, narrow signals with chemical shifts that correspond mostly to β-sheet secondary-structured amino acids that form the fibril core

    Solid-state NMR sequential assignments of the amyloid core of full-length Sup35p

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    Sup35p is a yeast prion and is responsible for the [PSI +] trait in Saccharomyces cerevisiae. With 685 amino acids, full-length soluble and fibrillar Sup35p are challenging targets for structural biology as they cannot be investigated by X-ray crystallography or NMR in solution. We present solid-state NMR studies of fibrils formed by the full-length Sup35 protein. We detect an ordered and rigid core of the protein that gives rise to narrow and strong peaks, while large parts of the protein show either static disorder or dynamics on time scales which interfere with dipolar polarization transfer or shorten the coherence lifetime. Thus, only a small subset of resonances is observed in 3D spectra. Here we describe in detail the sequential assignments of the 22 residues for which resonances are observed in 3D spectra: their chemical shifts mostly corresponding to β-sheet secondary structure. We suspect that these residues form the amyloid core of the fibril

    Atopy as an independent predictor for long-term patient and graft survival after kidney transplantation

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    BackgroundAtopy is a genetic condition predisposing individuals to develop immunoglobulin E (IgE) against common allergens through T-helper 2 (Th2) polarization mechanisms. The impact of atopy on graft survival in solid organ transplantation is unknown.MethodologyWe analyzed 268 renal allograft recipients from the Swiss Transplant Cohort Study, a prospective multicenter cohort studying patients after solid organ transplantation, with a 9-year median follow-up (IQR 3.0). We used the Phadiatop assay to measure IgE antibodies against a mixture of common inhaled allergens (grass, tree, herbs, spores, animals, and mites) to identify pre-transplantation atopic patients (>0.35 KU/L).ResultsOf 268 kidney transplant recipients, 66 individuals were atopic (24.6%). Atopic patients were significantly younger than non-atopic patients (49.6 vs 58.0 years old, P = 0.002). No significant difference was found for gender, cold/warm ischemia time, preformed donor-specific antibodies (DSA), HLA mismatches, induction and maintenance immunosuppressive therapy, CMV serostatus, or cause of kidney failure. Patient and graft survival at ten years of follow-up were significantly better in the atopic group, 95.2% versus 69.2% patient survival (P < 0.001), and 87.9% versus 60.8% graft survival (P < 0.001), respectively. A multivariate Cox analysis revealed that atopy predicted recipient and graft survival independently of age and living donor donation. Finally, we found similar rates of biopsy-proven acute cellular and antibody-mediated rejections between atopic and non-atopic recipients.ConclusionAtopy was associated with better long-term patient and graft survival, independently of age and living donor donation after kidney transplantation. Yet, atopy should not be used as a predictor for acute rejection

    The NORMAN Suspect List Exchange (NORMAN-SLE): facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry

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    Background: The NORMAN Association (https://www.norman-.network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-.network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for "suspect screening" lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https:// zenodo.org/communities/norman-.sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA's CompTox Chemicals Dashboard (https://comptox. epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the "one substance, one assessment" approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-.network.com/nds/SLE/)

    4D-Var inversion of European NH3 emissions Using CrIS NH3 measurements and GEOS-Chem adjoint with bi-directional and uni-directional flux schemes

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    We conduct the first 4D-Var inversion of NH3 accounting for NH3 bi-directional flux, using CrIS satellite NH3 observations over Europe in 2016. We find posterior NH3 emissions peak more in springtime than prior emissions at continental to national scales, and annually they are generally smaller than the prior emissions over central Europe, but larger over most of the rest of Europe. Annual posterior anthropogenic NH3 emissions for 25 European Union members (EU25) are 25% higher than the prior emissions and very close (<2% difference) to other inventories. Our posterior annual anthropogenic emissions for EU25, the UK, the Netherlands, and Switzerland are generally 10%–20% smaller than when treating NH3 fluxes as uni-directional emissions, while the monthly regional difference can be up to 34% (Switzerland in July). Compared to monthly mean in-situ observations, our posterior NH3 emissions from both schemes generally improve the magnitude and seasonality of simulated surface NH3 and bulk NHx wet deposition throughout most of Europe, whereas evaluation against hourly measurements at a background site shows the bi-directional scheme better captures observed diurnal variability of surface NH3. This contrast highlights the need for accurately simulating diurnal variability of NH3 in assimilation of sun-synchronous observations and also the potential value of future geostationary satellite observations. Overall, our top-down ammonia emissions can help to examine the effectiveness of air pollution control policies to facilitate future air pollution management, as well as helping us understand the uncertainty in top-down NH3 emissions estimates associated with treatment of NH3 surface exchange

    Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016

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    Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders. Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach. Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable). Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies. Funding: Bill & Melinda Gates Foundation
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