Functional data analytic approach of modeling ECG T-wave shape to measure cardiovascular behavior

The T-wave of an electrocardiogram (ECG) represents the ventricular repolarization that is critical in restoration of the heart muscle to a pre-contractile state prior to the next beat. Alterations in the T-wave reflect various cardiac conditions; and links between abnormal (prolonged) ventricular repolarization and malignant arrhythmias have been documented. Cardiac safety testing prior to approval of any new drug currently relies on two points of the ECG waveform: onset of the Q-wave and termination of the T-wave; and only a few beats are measured. Using functional data analysis, a statistical approach extracts a common shape for each subject (reference curve) from a sequence of beats, and then models the deviation of each curve in the sequence from that reference curve as a four-dimensional vector. The representation can be used to distinguish differences between beats or to model shape changes in a subject's T-wave over time. This model provides physically interpretable parameters characterizing T-wave shape, and is robust to the determination of the endpoint of the T-wave. Thus, this dimension reduction methodology offers the strong potential for definition of more robust and more informative biomarkers of cardiac abnormalities than the QT (or QT corrected) interval in current use.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS273 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Causal Mediation Analysis with a Three-Dimensional Image Mediator

Causal mediation analysis is increasingly abundant in biology, psychology, and epidemiology studies, etc. In particular, with the advent of the big data era, the issue of high-dimensional mediators is becoming more prevalent. In neuroscience, with the widespread application of magnetic resonance technology in the field of brain imaging, studies on image being a mediator emerged. In this study, a novel causal mediation analysis method with a three-dimensional image mediator is proposed. We define the average casual effects under the potential outcome framework, explore several sufficient conditions for the valid identification, and develop techniques for estimation and inference. To verify the effectiveness of the proposed method, a series of simulations under various scenarios is performed. Finally, the proposed method is applied to a study on the causal effect of mother$^{\prime}$s delivery mode on child$^{\prime}$s IQ development. It is found that the white matter in certain regions of the frontal-temporal areas has mediating effects.Comment: 35 pages, 9 figure

A Downward-looking Three-dimensional Imaging Method for Airborne FMCW SAR Based on Array Antennas

AbstractWith regard to problems in conventional synthetic aperture radar (SAR), such as imaging distortion, beam limitation and failure in acquiring three-dimensional (3-D) information, a downward-looking 3-D imaging method based on frequency modulated continuous wave (FMCW) and digital beamforming (DBF) technology for airborne SAR is presented in this study. Downward-looking 3-D SAR signal model is established first, followed by introduction of virtual antenna optimization factor and discussion of equivalent-phase-center compensation. Then, compensation method is provided according to reside video phase (RVP) and slope term for FMCW SAR. As multiple receiving antennas are applied to downward-looking 3-D imaging SAR, range cell migration correction (RCMC) turns to be more complex, and corrective measures are proposed. In addition, DBF technology is applied in realizing cross-track resolution. Finally, to validate the proposed method, magnitude of slice, peak sidelobe ratio (PSLR), integrated sidelobe ratio (ISLR) and two-dimensional (2-D) contour plot of impulse response function (IRF) of point target in three dimensions are demonstrated. Satisfactory performances are shown by simulation results

Genus Two Quasi-Siegel Modular Forms and Gromov-Witten Theory of Toric Calabi-Yau Threefolds

We first develop theories of differential rings of quasi-Siegel modular and quasi-Siegel Jacobi forms for genus two. Then we apply them to the Eynard-Orantin topological recursion of certain local Calabi-Yau threefolds equipped with branes, whose mirror curves are genus two hyperelliptic curves. By the proof of the Remodeling Conjecture, we prove that the corresponding open- and closed- Gromov-Witten potentials are essentially quasi-Siegel Jacobi and quasi-Siegel modular forms for genus two, respectively

Mapping the scientific research on integrated care: a bibliometric and social network analysis

BackgroundIntegrated care (IC) is the cornerstone of the sustainable development of the medical and health system. A thorough examination of the existing scientific literature on IC is essential for assessing the present state of knowledge on this subject. This review seeks to offer an overview of evidence-based knowledge, pinpoint existing knowledge gaps related to IC, and identify areas requiring further research.MethodsData were retrieved from the Web of Science Core Collection, from 2010 to 2020. Bibliometrics and social network analysis were used to explore and map the knowledge structure, research hotspots, development status, academic groups and future development trends of IC.ResultsA total of 7,501 articles were obtained. The number of publications on IC was rising in general. Healthcare science services were the most common topics. The United States contributed the highest number of articles. The level of collaboration between countries and between authors was found to be relatively low. The keywords were stratified into four clusters: IC, depression, integrative medicine, and primary health care. In recent years, complementary medicine has become a hotspot and will continue to be a focus.ConclusionThe study provides a comprehensive analysis of global research hotspots and trends in IC, and highlights the characteristics, challenges, and potential solutions of IC. To address resource fragmentation, collaboration difficulties, insufficient financial incentives, and poor information sharing, international collaboration needs to be strengthened to promote value co-creation and model innovation in IC. The contribution of this study lies in enhancing people’s understanding of the current state of IC research, guiding scholars to discover new research perspectives, and providing valuable references for researchers and policymakers in designing and implementing effective IC strategies

High-Dose siRNAs Upregulate Mouse Eri-1 at both Transcription and Posttranscription Levels

The eri-1 gene encodes a 3′ exonuclease that can negatively regulate RNA interference via siRNase activity. High-dose siRNAs (hd-siRNAs) can enhance Eri-1 expression, which in return degrade siRNAs and greatly reduces RNAi efficiency. Here we report that hd-siRNAs induce mouse Eri-1 (meri-1) expression through the recruitment of Sp1, Ets-1, and STAT3 to the meri-1 promoter and the formation of an Sp1-Ets-1-STAT3 complex. In addition, hd-siRNAs also abolish the 3′ untranslated region (UTR) mediated posttranscriptional repression of meri-1. Our findings demonstrate the molecular mechanism underlying the upregulation of meri-1 by hd-siRNA

Flames: Benchmarking Value Alignment of Chinese Large Language Models

The widespread adoption of large language models (LLMs) across various regions underscores the urgent need to evaluate their alignment with human values. Current benchmarks, however, fall short of effectively uncovering safety vulnerabilities in LLMs. Despite numerous models achieving high scores and 'topping the chart' in these evaluations, there is still a significant gap in LLMs' deeper alignment with human values and achieving genuine harmlessness. To this end, this paper proposes the first highly adversarial benchmark named Flames, consisting of 2,251 manually crafted prompts, ~18.7K model responses with fine-grained annotations, and a specified scorer. Our framework encompasses both common harmlessness principles, such as fairness, safety, legality, and data protection, and a unique morality dimension that integrates specific Chinese values such as harmony. Based on the framework, we carefully design adversarial prompts that incorporate complex scenarios and jailbreaking methods, mostly with implicit malice. By prompting mainstream LLMs with such adversarially constructed prompts, we obtain model responses, which are then rigorously annotated for evaluation. Our findings indicate that all the evaluated LLMs demonstrate relatively poor performance on Flames, particularly in the safety and fairness dimensions. Claude emerges as the best-performing model overall, but with its harmless rate being only 63.08% while GPT-4 only scores 39.04%. The complexity of Flames has far exceeded existing benchmarks, setting a new challenge for contemporary LLMs and highlighting the need for further alignment of LLMs. To efficiently evaluate new models on the benchmark, we develop a specified scorer capable of scoring LLMs across multiple dimensions, achieving an accuracy of 77.4%. The Flames Benchmark is publicly available on https://github.com/AIFlames/Flames

Optimization of phenoxazinone synthase production by response surface methodology and its application in Congo red decolourization

Background: Enzymatic decolourization has been recently proposed as a promising and eco-friendly method for treatment of synthetic dye-contaminated wastewaters. However, the processes require large quantities of enzymes, attracting significant attention in developing efficient methods for mass production of multifunctional enzymes. Several methods such as response surface methodology (RSM) and orthogonal experiment have been applied to optimize the parameters in bioprocesses for enzyme production. Results: In the present study, a laccase-like enzyme, phenoxazinone synthase (PHS) originated from Streptomyces antibioticus was recombinantly expressed in Escherichia coli BL21 (DE3). The production of PHS in E. coli BL21 was optimized by response surface methodology based on Box-Behnken design. A full third-order polynomial model was generated by data analysis with Statistica 8.0 in which the optimal conditions for PHS production were calculated to be 1.525 mM CuSO4 and 16.096 hrs induction at temperature of 29.88oC. The highest PHS production under optimal conditions was calculated to be 4098.51 U/l using the established model. Average PHS production obtained from actual production processes carried out under the calculated optimal conditions was 4052.00 U/l, very close to the value predicted by the model. Crude PHS was subsequently tested in Congo red decolourization which exhibited a low decolourization rate of 27% without mediator. Several mediators were found to improve PHS-catalyzed Congo red decolourization, with the highest rate of 73.89% obtained with 2,2\u81f-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) as mediator under optimized conditions of 4000 U/l PHS activity, 10 \u3bcM ABTS, 100 \u3bcM Congo red, and 8 hrs reaction time. Conclusion: Our results indicated that PHS recombinantly produced in E. coli BL21 was a prospective enzyme for decolorizing reactive dye Congo red