Miracle-dz/UniFAR-FTUs huggingface dataset:
Type 2 diabetes gene TCF 7 L 2 polymorphism is not associated with fetal and postnatal growth in two birth cohort studies . TCF 7 L 2 and early growth

Dennis O Mook-Kanamori, MD 2, 3* d.mook@erasmusmc.nl Sandra WK de Kort, MD s.dekort@erasmusmc.nl Cornelia M van Duijn, PhD c.vanduijn@erasmusmc.nl Andre G Uitterlinden, PhD a.g. uitterlinden@erasmusmc.nl Albert Hofman, MD, PhD a.hofman@erasmusmc.nl Henriëtte A Moll, MD, PhD h.a. moll@erasmusmc.nl Eric AP Steegers, MD, PhD e.a. p.steegers@erasmusmc.nl Anita CS Hokken-Koelega, MD, PhD a.hokken@erasmusmc.nl Vincent WV Jaddoe, MD, PhD 2, 3 v.jaddoe@erasmusmc.nl
Planning robust temporal plans a comparison between CBTP and TGA approaches

Planning for real world applications, with explicit temporal representation and a robust execution is a very challenging problem. To tackle it, the planning community has proposed a number of original and successful approaches. However, there are other paradigms "outside" the Automated Planning field which may prove to be successful with respect to this objective. This paper presents a comparison of two "planning" approaches dealing with temporal and/or discrete uncertainties and with a strong emphasis on robust execution. The first approach is based on chronicles and constraint satisfaction techniques; it relies on a causal link partial order temporal planner, in our case IXTET. The second approach is based on timed game automata and reachability analysis, and uses the UPPAAL-TIGA system. The comparison is both qualitative (the kind of problems modeled and the properties of plans obtained) and quantitative (experimental results on a real example). To make this comparison possible, we propose a general scheme to translate a subset of IXTET planning problems into UPPAAL-TIGA game-reachability problems. A direct consequence of this automated process would be the possibility to apply validation and verification techniques available in the timed automata community.
A New Approach to Detection of Systematic Errors in Secondary Substation Monitoring Equipment Based on Short Term Load Forecasting

In recent years, Secondary Substations (SSs) are being provided with equipment that allows their full management. This is particularly useful not only for monitoring and planning purposes but also for detecting erroneous measurements, which could negatively affect the performance of the SS. On the other hand, load forecasting is extremely important since they help electricity companies to make crucial decisions regarding purchasing and generating electric power, load switching, and infrastructure development. In this regard, Short Term Load Forecasting (STLF) allows the electric power load to be predicted over an interval ranging from one hour to one week. However, important issues concerning error detection by employing STLF has not been specifically addressed until now. This paper proposes a novel STLF-based approach to the detection of gain and offset errors introduced by the measurement equipment. The implemented system has been tested against real power load data provided by electricity suppliers. Different gain and offset error levels are successfully detected.
High rates of hepatitis G virus infection in multitransfused patients with hemophilia.

The parallel measurement of serum antibodies to the hepatitis G virus (anti-HGV) and of viremia (HGV-RNA) should improve our understanding of HGV transmission by coagulation factor concentrates. The aim of this study was to assess the relationship between HGV, the type of concentrate infused, and liver disease in multitransfused hemophiliacs. To this end, anti-HGV and HGV-RNA were evaluated by an enzyme-linked immunosorbent assay and a nested-polymerase chain reaction assay in patients treated lifelong with nonvirus-inactivated plasma-derived concentrates (n = 128), virus-inactivated concentrates (n = 33), or recombinant factors (n = 7), and in 200 regular blood donors. The prevalence of serum HGV-RNA and anti-HGV was higher in the recipients of nonvirus-inactivated factors than in blood donors (HGV-RNA: 9% v 1.5%, P = .002; anti-HGV: 32% v 5%, P < .0001). In the recipients of virus-inactivated concentrates the prevalences of these markers were similar to those in blood donors (HGV-RNA: 3% v 1.5%; anti-HGV: 15% v 5%). The prevalence of either marker in the recipients of nonvirus-inactivated concentrates was higher than in the recipients of virus-inactivated factors (39% v 18%, P = .04). The former group had serum hepatitis C virus (HCV) RNA or anti-HCV more frequently than the latter group (HCV-RNA: 86% v 15%, P < .0001; anti-HCV: 96% v 18%, P < .0001). Serum alanine aminotransferase was persistently high in 83 (81%) patients with HCV-RNA alone, in 8 (89%) with HCV/HGV coinfection, and in none of the three patients with HGV-RNA only. Thus, HGV infection in hemophiliacs is more common than previous studies of HGV-RNA prevalence have suggested, but it resolved in most cases and caused chronic viremia only in a small number of patients, without biochemical evidence of persistent liver damage.
Project Halo: Towards a Digital Aristotle

Project Halo is a multistaged effort, sponsored by Vulcan Inc, aimed at creating Digital Aristotle, an application that will encompass much of the world's scientific knowledge and be capable of applying sophisticated problem solving to answer novel questions. Vulcan envisions two primary roles for Digital Aristotle: as a tutor to instruct students in the sciences and as an interdisciplinary research assistant to help scientists in their work. As a first step towards this goal, we have just completed a six-month pilot phase designed to assess the state of the art in applied knowledge representation and reasoning (KR&/R). Vulcan selected three teams, each of which was to formally represent 70 pages from the advanced placement (AP) chemistry syllabus and deliver knowledge-based systems capable of answering questions on that syllabus. The evaluation quantified each system's coverage of the syllabus in terms of its ability to answer novel, previously unseen questions and to provide human- readable answer justifications. These justifications will play a critical role in building user trust in the question-answering capabilities of Digital Aristotle. Prior to the final evaluation, a "failure taxonomy' was collaboratively developed in an attempt to standardize failure analysis and to facilitate cross-platform comparisons. Despite differences in approach, all three systems did very well on the challenge, achieving performance comparable to the human median. The analysis also provided key insights into how the approaches might be scaled, while at the same time suggesting how the cost of producing such systems might be reduced. This outcome leaves us highly optimistic that the technical challenges facing this effort in the years to come can be identified and overcome. This article presents the motivation and longterm goals of Project Halo, describes in detail the six-month first phase of the project -- the Halo Pilot -- its KR&R challenge, empirical evaluation, results, and failure analysis. The pilot's outcome is used to define challenges for the next phase of the project and beyond.
Microstructural Characterization of Normal and Malignant Human Prostate Tissue With Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumours Magnetic Resonance Imaging

ObjectiveThe aim of this study was to demonstrate the feasibility of the recently introduced Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumours (VERDICT) framework for imaging prostate cancer with diffusion-weighted magnetic resonance imaging (DW-MRI) within a clinical setting. Materials and MethodsThe VERDICT framework is a noninvasive microstructure imaging technique that combines an in-depth diffusion MRI acquisition with a mathematical model to estimate and map microstructural tissue parameters such as cell size and density and vascular perfusion. In total, 8 patients underwent 3-T MRI using 9 different b values (100–3000 s/mm2). All patients were imaged before undergoing biopsy. Experiments with VERDICT analyzed DW-MRI data from patients with histologically confirmed prostate cancer in areas of cancerous and benign peripheral zone tissue. For comparison, we also fitted commonly used diffusion models such as the apparent diffusion coefficient (ADC), the intravoxel incoherent motion (IVIM), and the kurtosis model. We also investigated correlations of ADC and kurtosis with VERDICT parameters to gain some biophysical insight into the various parameter values. ResultsEight patients had prostate cancer in the peripheral zone, with Gleason score 3 + 3 (n = 1), 3 + 4 (n = 6), and 4 + 3 (n = 1). The VERDICT model identified a significant increase in the intracellular and vascular volume fraction estimates in cancerous compared with benign peripheral zone, as well as a significant decrease in the volume of the extracellular-extravascular space (EES) (P = 0.05). This is in agreement with manual segmentation of the biopsies for prostate tissue component analysis, which found proliferation of epithelium, loss of surrounding stroma, and an increase in vasculature. The standard ADC and kurtosis parameters were also significantly different (P = 0.05) between tissue types. There was no significant difference in any of the IVIM parameters (P = 0.11 to 0.29). The VERDICT parametric maps from voxel-by-voxel fitting clearly differentiated cancer from benign regions. Kurtosis and ADC parameters correlated most strongly with VERDICT’s intracellular volume fraction but also moderately with the EES and vascular fractions. ConclusionsThe VERDICT model distinguished tumor from benign areas, while revealing differences in microstructure descriptors such as cellular, vascular, and EES fractions. The parameters of ADC and kurtosis models also discriminated between cancer and benign regions. However, VERDICT provides more specific information that disentangles the various microstructural features underlying the changes in ADC and kurtosis. These results highlight the clinical potential of the VERDICT framework and motivate the construction of a shorter, clinically viable imaging protocol to enable larger trials leading to widespread translation of the method.
Strain-rate effects in quartz sand

Soil-filled wire and geotextile gabions are commonly used to construct defensive infrastructure in military bases, where the attenuating properties of soil are used to protect personnel and key assets from the effects of blast and fragmentation. The behaviour of soils in these extreme loading regimes is not well understood, and so designers require data at these high pressures and strain rates in order to develop robust soil constitutive models and adapt to new threats. The one-dimensional compression of three sandy soils was compared under quasi-static loading to axial stresses of 800 MPa. Trends in behaviour were identified with respect to the particle size distributions of the soils, and were found to correspond to the relationships observed at lower stresses. Split Hopkinson pressure bar (SHPB) experiments were used to investigate the strain rate dependence of this behaviour. Measurements of radial stress indicated that an increase in the axial stiffness of the soils between strain rates of 10^-3 s^-1 and 10^3 s^-1 was likely due to radial inertial effects. Potential sources of error were identified in the SHPB experiments, leading to the implementation of a dispersion-correction algorithm, which improved the measurement of axial stresses. Analysis of the electromagnetic activity around the specimen isolated the cause of erroneous radial stress measurements. Quasi-static experiments were used to investigate the effect of moisture content on soil stiffness at high pressures, and SHPB experiments at the same moisture contents were used to consider the effect of strain rate on the quasi-static behaviour. Recovery SHPB experiments were designed to enable reliable post-test particle size analyses to be performed, and the range of moisture contents was expanded to investigate the change in soil behaviour on reaching full saturation. Reduced triaxial compression experiments were used to define the yield surface of a sand to a mean stress of 400 MPa. The high-pressure compression and yield strength data was used to calibrate LS-DYNA soil models, and the performance of the models was assessed through modelling of the SHPB experiments.
The functional anatomy of attention: a DCM study

Recent formulations of attention—in terms of predictive coding—associate attentional gain with the expected precision of sensory information. Formal models of the Posner paradigm suggest that validity effects can be explained in a principled (Bayes optimal) fashion in terms of a cue-dependent setting of precision or gain on the sensory channels reporting anticipated target locations, which is updated selectively by invalid targets. This normative model is equipped with a biologically plausible process theory in the form of predictive coding, where precision is encoded by the gain of superficial pyramidal cells reporting prediction error. We used dynamic causal modeling to assess the evidence in magnetoencephalographic responses for cue-dependent and top-down updating of superficial pyramidal cell gain. Bayesian model comparison suggested that it is almost certain that differences in superficial pyramidal cells gain—and its top-down modulation—contribute to observed responses; and we could be more than 80% certain that anticipatory effects on post-synaptic gain are limited to visual (extrastriate) sources. These empirical results speak to the role of attention in optimizing perceptual inference and its formulation in terms of predictive coding.
A Bayesian Approach for Blind Separation of Sparse Sources

We present a Bayesian approach for blind separation of linear instantaneous mixtures of sources having a sparse representation in a given basis. The distributions of the coefficients of the sources in the basis are modeled by a Student t distribution, which can be expressed as a scale mixture of Gaussians, and a Gibbs sampler is derived to estimate the sources, the mixing matrix, the input noise variance and also the hyperparameters of the Student t distributions. The method allows for separation of underdetermined (more sources than sensors) noisy mixtures. Results are presented with audio signals using a modified discrete cosine transform basis and compared with a finite mixture of Gaussians prior approach. These results show the improved sound quality obtained with the Student t prior and the better robustness to mixing matrices close to singularity of the Markov chain Monte Carlo approach
Diffusion tensor imaging reveals adolescent binge ethanol‐induced brain structural integrity alterations in adult rats that correlate with behavioral dysfunction

Adolescence is characterized by considerable brain maturation that coincides with the development of adult behavior. Binge drinking is common during adolescence and can have deleterious effects on brain maturation because of the heightened neuroplasticity of the adolescent brain. Using an animal model of adolescent intermittent ethanol [AIE; 5.0 g/kg, intragastric, 20 percent EtOH w/v; 2 days on/2 days off from postnatal day (P)25 to P55], we assessed the adult brain structural volumes and integrity on P80 and P220 using diffusion tensor imaging (DTI). While we did not observe a long‐term effect of AIE on structural volumes, AIE did reduce axial diffusivity (AD) in the cerebellum, hippocampus and neocortex. Radial diffusivity (RD) was reduced in the hippocampus and neocortex of AIE‐treated animals. Prior AIE treatment did not affect fractional anisotropy (FA), but did lead to long‐term reductions of mean diffusivity (MD) in both the cerebellum and corpus callosum. AIE resulted in increased anxiety‐like behavior and diminished object recognition memory, the latter of which was positively correlated with DTI measures. Across aging, whole brain volumes increased, as did volumes of the corpus callosum and neocortex. This was accompanied by age‐associated AD reductions in the cerebellum and neocortex as well as RD and MD reductions in the cerebellum. Further, we found that FA increased in both the cerebellum and corpus callosum as rats aged from P80 to P220. Thus, both age and AIE treatment caused long‐term changes to brain structural integrity that could contribute to cognitive dysfunction.
The Multiple Phases of Interstellar and Halo Gas in a Possible Group of Galaxies at z ∼ 1

We used HIRES/Keck profiles (R ∼ 6 km s-1) of Mg II and Fe II in combination with Hubble Space Telescope (HST) Faint Object Spectrograph (FOS) spectra (R ∼ 230 km s-1) to place constraints on the physical conditions (metallicities, ionization conditions, and multiphase distribution) of absorbing gas in three galaxies at z = 0.9254, 0.9276, and 0.9343 along the line of sight to PG 1206+459. The chemical and ionization species covered in the FOS/HST spectra are H I, Si II, C II, N II, Fe III, Si III, Si IV, N III, C III, C IV, S VI, N V, and O VI, with ionization potentials ranging from 13.6 to 138 eV. The multiple Mg II clouds exhibit complex kinematics and the C IV, N V, and O VI are exceptionally strong in absorption. We assumed that the Mg II clouds are photoionized by the extragalactic background and determined the allowed ranges of their physical properties as constrained by the absorption strengths in the FOS spectra. A main result of this paper is that the low-resolution spectra can provide meaningful constraints on the physical conditions of the Mg II clouds, including allowed ranges of cloud-to-cloud variations within a system. We find that the Mg II clouds, which have a typical size of approximately 100 pc, give rise to the Si IV, the majority of which arises in a single, very large (∼5 kpc), higher ionization cloud. However, the Mg II clouds cannot account for the strong C IV, N V, and O VI absorption. We conclude that the Mg II clouds are embedded in extended (10–20 kpc), highly ionized gas that gives rise to C IV, N V, and O VI; these are multiphase absorption systems. The high-ionization phases have near-solar metallicity and are consistent with Galactic-like coronae surrounding the individual galaxies, as opposed to a very extended common "halo" encompassing all three galaxies.
PLACID

Deep Convolutional Neural Networks (DCNNs) exhibit remarkable performance in a number of pattern recognition and classification tasks. Modern DCNNs involve many millions of parameters and billions of operations. Inference using such DCNNs, if implemented as software running on an embedded processor, results in considerable execution time and energy consumption, which is prohibitive in many mobile applications. Field-programmable gate array (FPGA)-based acceleration of DCNN inference is a promising approach to improve both energy consumption and classification throughput. However, the engineering effort required for development and verification of an optimized FPGA-based architecture is significant. In this article, we present PLACID, an automated PLatform for Accelerator CreatIon for DCNNs. PLACID uses an analytical approach to characterization and exploration of the implementation space. PLACID enables generation of an accelerator with the highest throughput for a given DCNN on a specific target FPGA platform. Subsequently, it generates an RTL level architecture in Verilog, which can be passed onto commercial tools for FPGA implementation. PLACID is fully automated, and reduces the accelerator design time from a few months down to a few hours. Experimental results show that architectures synthesized by PLACID yield 2× higher throughput density than the best competing approach.
A Simulation Study of the Combined Thermoelectric Extracellular Stimulation of the Sciatic Nerve of the Xenopus Laevis: The Localized Transient Heat Block

The electrical behavior of the Xenopus laevis nerve fibers was studied when combined electrical (cuff electrodes) and optical (infrared laser, low power sub-5 mW) stimulations are applied. Assuming that the main effect of the laser irradiation on the nerve tissue is the localized temperature increase, this paper analyzes and gives new insights into the function of the combined thermoelectric stimulation on both excitation and blocking of the nerve action potentials (AP). The calculations involve a finite-element model (COMSOL) to represent the electrical properties of the nerve and cuff. Electric-field distribution along the nerve was computed for the given stimulation current profile and imported into a NEURON model, which was built to simulate the electrical behavior of myelinated nerve fiber under extracellular stimulation. The main result of this study of combined thermoelectric stimulation showed that local temperature increase, for the given electric field, can create a transient block of both the generation and propagation of the APs. Some preliminary experimental data in support of this conclusion are also shown.
Recurrent BRAF Gene Fusions in a Subset of Pediatric Spindle Cell Sarcomas: Expanding the Genetic Spectrum of Tumors With Overlapping Features With Infantile Fibrosarcoma

Infantile fibrosarcomas (IFS) represent a distinct group of soft tissue tumors occurring in patients under 2 years of age and most commonly involving the extremities. Most IFS show recurrent ETV6-NTRK3 gene fusions, sensitivity to chemotherapy, and an overall favorable clinical outcome. However, outside these well-defined pathologic features, no studies have investigated IFS lacking ETV6-NTRK3 fusions, or tumors with the morphology resembling IFS in older children. This study was triggered by the identification of a novel SEPT7-BRAF fusion in an unclassified retroperitoneal spindle cell sarcoma in a 16-year-old female by targeted RNA sequencing. Fluorescence in situ hybridization screening of 9 additional tumors with similar phenotype and lacking ETV6-NTRK3 identified 4 additional cases with BRAF gene rearrangements in the pelvic cavity (n=2), paraspinal region (n=1), and thigh (n=1) of young children (0 to 3 y old). Histologically, 4 cases including the index case shared a fascicular growth of packed monomorphic spindle cells, with uniform nuclei and fine chromatin, and a dilated branching vasculature; while the remaining case was composed of compact cellular sheets of short spindle to ovoid cells. In addition, a minor small blue round cell component was present in 1 case. Mitotic activity ranged from 1 to 9/10 high power fields. Immunohistochemical stains were nonspecific, with only focal smooth muscle actin staining demonstrated in 3 cases tested. Of the remaining 5 BRAF negative cases, further RNA sequencing identified 1 case with EML4-NTRK3 in an 1-year-old boy with a foot IFS, and a second case with TPM3-NTRK1 fusion in a 7-week-old infant with a retroperitoneal lesion. Our findings of recurrent BRAF gene rearrangements in tumors showing morphologic overlap with IFS expand the genetic spectrum of fusion-positive spindle cell sarcomas, to include unusual presentations, such as older children and adolescents and predilection for axial location, thereby opening new opportunities for kinase-targeted therapeutic intervention.
Hypothalamus–pituitary–adrenal axis evaluation in patients with hypothalamo–pituitary disorders: comparison of different provocative tests

Background The insulin tolerance test (ITT) is the gold standard test to evaluate hypothalamic–pituitary–adrenal (HPA) axis in suspected ACTH insufficiency. When contraindicated, alternative tests have been proposed such as metyrapone and ACTH stimulation test. 250 µg ACTH is a supramaximal dose and unreliable in this setting. The diagnostic reliability of 1·0 µg ACTH test is controversial and very low doses have been proposed.