Miracle-dz/UniFAR-FTUs huggingface dataset:
Mature iPSC-derived astrocytes of an ALS/FTD patient carrying the TDP43 A90V mutation display a mild reactive state and release polyP toxic to motoneurons

Astrocytes play a critical role in the maintenance of a healthy central nervous system and astrocyte dysfunction has been implicated in various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). There is compelling evidence that mouse and human ALS and ALS/FTD astrocytes can reduce the number of healthy wild-type motoneurons (MNs) in co-cultures or after treatment with astrocyte conditioned media (ACM), independently of their genotype. A growing number of studies have shown that soluble toxic factor(s) in the ACM cause non-cell autonomous MN death, including our recent identification of inorganic polyphosphate (polyP) that is excessively released from mouse primary astrocytes (SOD1, TARDBP, and C9ORF72) and human induced pluripotent stem cells (iPSC)-derived astrocytes (TARDBP) to kill MNs. However, others have reported that astrocytes carrying mutant TDP43 do not produce detectable MN toxicity. This controversy is likely to arise from the findings that human iPSC-derived astrocytes exhibit a rather immature and/or reactive phenotype in a number of studies. Here, we have succeeded in generating a highly homogenous population of functional quiescent mature astrocytes from control subject iPSCs. Using identical conditions, we also generated mature astrocytes from an ALS/FTD patient carrying the TDP43 A90V mutation. These mutant TDP43 patient-derived astrocytes exhibit key pathological hallmarks, including enhanced cytoplasmic TDP-43 and polyP levels. Additionally, mutant TDP43 astrocytes displayed a mild reactive signature and an aberrant function as they were unable to promote synaptogenesis of hippocampal neurons. The polyP-dependent neurotoxic nature of the TDP43 A90V mutation was further confirmed as neutralization of polyP in ACM derived from mutant TDP43 astrocytes prevented MN death. Our results establish that human astrocytes carrying the TDP43 A90V mutation exhibit a cell-autonomous pathological signature, hence providing an experimental model to decipher the molecular mechanisms underlying the generation of the neurotoxic phenotype.
Consolidation in spatially random unsaturated soils based on coupled flow‐deformation simulation

This paper integrates random field simulation of soil spatial variability with numerical modeling of coupled flow and deformation to investigate consolidation in spatially random unsaturated soil. The spatial variability of soil properties is simulated using the covariance matrix decomposition method. The random soil properties are imported into an interactive multiphysics software COMSOL to solve the governing partial differential equations. The effects of the spatial variability of Young's modulus and saturated permeability together with unsaturated hydraulic parameters on the dissipation of excess pore water pressure and settlement are investigated using an example of consolidation in a saturated‐unsaturated soil column because of loading. It is found that the surface settlement and the pore water pressure profile during the process of consolidation are significantly affected by the spatially varying Young's modulus. The mean value of the settlement of the spatially random soil is more than 100% greater than that of the deterministic case, and the surface settlement is subject to large uncertainty, which implies that consolidation settlement is difficult to predict accurately based on the conventional deterministic approach. The uncertainty of the settlement increases with the scale of fluctuation because of the averaging effect of spatial variability. The effects of spatial variability of saturated permeability ksat and air entry parameters are much less significant than that of elastic modulus. The spatial variability of air entry value parameters affects the uncertainties of settlement and excess pore pressure mostly in the unsaturated zone. Copyright © 2016 John Wiley & Sons, Ltd.
Bone fragility in sarcoidosis

Purpose: Few studies have suggested that sarcoidosis may be associated with low bone mineral density (BMD) and fragility fractures. However, studies on bone mineral loss or fractures in sarcoidosis are conflicting. This study aimed to evaluate: 1) the history of fragility fractures in patients with sarcoidosis; 2) the correlation of bone fragility with severity of sarcoidosis disease. Methods: We selected 252 sarcoidosis patients (54.7 ± 12.1 years) and age- and sex-matched healthy controls. We evaluated BMD at the lumbar spine (BMD-LS), femoral neck, and total hip (BMD-TH), and also the occurrence of any fracture. Forced expiratory volume in one second, forced vital capacity, and diffusion capacity for carbon monoxide (DLCO) were also assessed. Results: BMD T-scores were lower in sarcoidosis patients than in healthy controls, but the difference was statistically significant only for BMD-LS (p < 0.01) and BMD-TH (p < 0.05). Moreover, BMD-LS and BMD-TH values were significantly associated with DLCO (%) (p < 0.05). The prevalence of fragility fracture was higher in patients with sarcoidosis than in controls (30.6% vs. 12.3%). The sarcoidosis patients with a higher number of vertebral fractures (>3) also showed reduced values on pulmonary function test parameters, particularly DLCO (%). Conclusions: This study shows that fragility fractures are significantly more frequent in patients with sarcoidosis than in control subjects. Furthermore, a greater number of vertebral fractures was linked to worse pulmonary function tests.
High-Resolution Historical Climate Simulations over Alaska

AbstractWeather and climate variability strongly influence the people, infrastructure, and economy of Alaska. However, the sparse observational network in Alaska limits our understanding of meteorological variability, particularly of precipitation processes that influence the hydrologic cycle. Here, a new 14-yr (September 2002–August 2016) dataset for Alaska with 4-km grid spacing is described and evaluated. The dataset, generated with the Weather Research and Forecasting (WRF) Model, is useful for gaining insight into meteorological and hydrologic processes, and provides a baseline against which to measure future environmental change. The WRF fields are evaluated at annual, seasonal, and daily time scales against observation-based gridded and station records of 2-m air temperature, precipitation, and snowfall. Pattern correlations between annual mean WRF and observation-based gridded fields are r = 0.89 for 2-m temperature, r = 0.75 for precipitation, r = 0.82 for snow-day fraction, r = 0.55 for first sn.
Pre‐Actuation and Optimal State Transition Based Precise Tracking for Maximum Phase System

Precise trajectory tracking for the maximum phase system can be achieved by the stable inversion method. However, its side effect is requiring the sufficient extended zero trajectory. To overcome this drawback, firstly, this paper introduces the concept of stable initial state which is of vital importance to achieve precise output tracking. And then several methods have been presented to obtain the stable initial state. Both the standard method and the pre‐actuation method can be seen as the simplified stable inversion method under certain conditions, but the two methods only perform approximate output tracking. To achieve precise trajectory tracking, the optimal state transition method and the combination method consisting of the pre‐actuation and the optimal state transition are introduced. Finally, the optimal combination method is proposed to obtain the best overall tracking effect. In brief, different methods are fit for different situation but the optimal combination method is the finest method in practical situation. The effectiveness of the proposed methods are verified through numerical simulations for the maximum phase system.
Biomarker-Based Assessment Model for Detecting Sepsis: A Retrospective Cohort Study

The concept of the quick sequential organ failure assessment (qSOFA) simplifies sepsis detection, and the next SOFA should be analyzed subsequently to diagnose sepsis. However, it does not include the concept of suspected infection. Thus, we simply developed a biomarker-based assessment model for detecting sepsis (BADS). We retrospectively reviewed the electronic health records of patients admitted to the intensive care unit (ICU) of a 2000-bed university tertiary referral hospital in South Korea. A total of 989 patients were enrolled, with 77.4% (n = 765) of them having sepsis. The patients were divided into a ratio of 8:2 and assigned to a training and a validation set. We used logistic regression analysis and the Hosmer–Lemeshow test to derive the BADS and assess the model. BADS was developed by analyzing the variables and then assigning weights to the selected variables: mean arterial pressure, shock index, lactate, and procalcitonin. The area under the curve was 0.754, 0.615, 0.763, and 0.668 for BADS, qSOFA, SOFA, and acute physiology and chronic health evaluation (APACHE) II, respectively, showing that BADS is not inferior in sepsis prediction compared with SOFA. BADS could be a simple scoring method to detect sepsis in critically ill patients quickly at the bedside.
A hybrid ontology‐based semantic and machine learning model for the prediction of spring breakup

River ice breakups carry the potential for high flows and flooding and are of great interest to accurately predict. A challenge in forecasting these events is the management of the massive amounts of data associated with an ice season. This study couples ontological and machine learning models in a new hybrid modeling framework to predict spring breakup on a national scale. The Ice Season Ontology sorts the data and allows for a user‐friendly means of analyzing any ice season, providing insight on which variables are most and least central. With this, a refined variable selection is able to be made for machine learning models. The most successful developed model, a random forest, produced highly accurate forecasts when applied to a national scale case study, with a mean absolute error of 10.85 days and an R2 of . 884. This new modeling framework provides a means for decision‐making support for river bound communities and a new methodology for modeling applications in other fields.
Final Technical Report on BSS Models and Methods for Non-Independent BSS

This report summarizes the research conducted on non-independent blind source separation within the BLISS project and presents an overview of related methods proposed in the literature. The methods are diversified, but they can in general be divided into two major groups. The first group consists of methods which aim at measuring and visualizing the dependences remaining after application of standard independent component analysis algorithms. The methods in the second major group incorporate models of the dependences into the separation algorithms themselves. Both types of techniques have been investigated within the BLISS project.
Comparative Genetic Characterization of CTX-M-Producing Escherichia coli Isolated from Humans and Pigs with Diarrhea in Korea Using Next-Generation Sequencing

Pathogenic E. coli causes intra- and extraintestinal diseases in humans and pigs and third-generation cephalosporins are the primary option for the treatment of these diseases. The objective of this study was to investigate the characteristics and correlation between CTX-M-producing E. coli from humans and pigs regarding CTX-M-producing E. coli using next-generation sequencing and bioinformatic tools. Among the 24 CTX-M–producing E. coli, three types of CTX-M genes (CTX-M-12, CTX-M-14, and CTX-M-15) were detected in humans and four types of CTX-M genes (CTX-M-14, CTX-M-15, CTX-M-55, and CTX-M-101) were detected in pigs. A total of 24 CTX-M–producing E. coli isolates also showed the following antimicrobial resistance genes: other B-Lactam resistance gene (75.0%); aminoglycoside resistance genes (75.0%); phenicol resistance genes (70.8%); tetracycline resistance genes (70.8%); sulfonamide resistance genes (66.7%); quinolone resistance genes (62.5%); trimethoprim resistance genes (54.2%); and fosfomycin resistance genes (8.3%). FII (92.3%) and FIB (90.9%) were the most common plasmid replicon in humans and pigs, respectively. A total of thirty-eight different genes associated with virulence 24 CTX-M–producing E. coli and all isolates contained at least more than one virulence gene. A total of 24 CTX-M–producing E. coli isolates showed 15 diverse sequence types (STs): thirteen isolates from human belonged to 6 different STs, and 11 isolates from pig belonged to 9 different STs. The presence of virulence genes in E. coli together with antimicrobial resistance genes (including CTX-M genes) emphasizes the necessity of comprehensive surveillance and persistent monitoring of the food chain to avoid all types of bacterial contamination, regardless of human or pig origin.
Mapping of the Cladosporium fulvum resistance gene Cf-16, a major gene involved in leaf mold disease in tomato

Tomato (Solanum lycopersicum) is widely cultivated and consumed worldwide. Tomato leaf mold, caused by Cladosporium fulvum, is one of the most devastating diseases in tomato production. At present, some tomato leaf mold resistance (Cf series) genes used in production gradually lose resistance due to the continuous and rapid differentiation of C. fulvum physiological races. The Cf-16 gene derived from the “Ontario7816” tomato cultivar has shown effective resistance in field trials for many years, but few studies have reported on the mapping of the Cf-16 gene, which has not been cloned, limiting its utilization in tomato breeding. Here, we mapped Cf-16 using a novel comprehensive strategy including bulk segregation analysis (BSA), genome resequencing and SSR molecular markers. A genetic analysis revealed that Cf-16 resistance in “Ontario7816” is controlled by one major dominant locus. The Cf-16 gene was mapped in a region of 2.6 cM at chromosome 6 between two markers, namely, TGS447 and TES312, by using an F2 population from a cross between the resistant cultivar “Ontario7816” and susceptible line “Moneymaker. ” Two nucleotide-binding-site-leucine-rich repeat (NBS-LRR) resistance genes, namely, XM_004240667. 3 and XM_010323727. 1, were identified in this interval. They are strong candidates for the Cf-16 gene. The mapping of Cf-16 may speed up its utilization for breeding resistant tomato varieties and represents an important step forward in our understanding of the mechanism underlying resistance to tomato leaf mold.
Precision Medicine: Disease Subtyping and Tailored Treatment

Simple Summary The genomics-based concept of precision medicine began to emerge following the completion of the Human Genome Project. In contrast to evidence-based medicine, precision medicine will allow doctors and scientists to tailor the treatment of different subpopulations of patients who differ in their susceptibility to specific diseases or responsiveness to specific therapies. In this review, we examine the history, development, and future perspective of precision medicine. We also discuss the concepts, principles, tools, and applications of precision medicine and related fields. Abstract The genomics-based concept of precision medicine began to emerge following the completion of the Human Genome Project. In contrast to evidence-based medicine, precision medicine will allow doctors and scientists to tailor the treatment of different subpopulations of patients who differ in their susceptibility to specific diseases or responsiveness to specific therapies. The current precision medicine model was proposed to precisely classify patients into subgroups sharing a common biological basis of diseases for more effective tailored treatment to achieve improved outcomes. Precision medicine has become a term that symbolizes the new age of medicine. In this review, we examine the history, development, and future perspective of precision medicine. We also discuss the concepts, principles, tools, and applications of precision medicine and related fields. In our view, for precision medicine to work, two essential objectives need to be achieved. First, diseases need to be classified into various subtypes. Second, targeted therapies must be available for each specific disease subtype. Therefore, we focused this review on the progress in meeting these two objectives.
Layout Dependence Stress Investigation in through Glass via Interposer Architecture Using a Submodeling Simulation Technique and a Factorial Design Approach

The multi-chiplet technique is expected to be a promising solution to achieve high-density system integration with low power consumption and high usage ratio. This technique can be integrated with a glass interposer to accomplish a competitive low fabrication cost compared with the silicon-based interposer architecture. In this study, process-oriented stress simulation is performed by the element activation and deactivation technique in finite element analysis architecture. The submodeling technique is also utilized to mostly conquer the scale mismatch and difficulty in mesh gridding design. It is also used to analyze the thermomechanical responses of glass interposers with chiplet arrangements and capped epoxy molding compounds (EMC) during curing. A three-factor, three-level full factorial design is applied using the analysis of variance method to explore the significance of various structural design parameters for stress generation. Analytic results reveal that the maximum first principal stresses of 130.75 and 17.18 MPa are introduced on the sidewall of Cu-filled via and the bottom of the glass interposer, respectively. Moreover, the EMC thickness and through glass via pitch are the dominant factors in the adopted vehicle. They significantly influence the stress magnitude during heating and cooling.
Dual-band multiple-input multiple-output antenna based on half split cylindrical dielectric resonator

Abstract In this article, a dual-band half split cylindrical dielectric resonator antenna is proposed for multiple-input multiple-output (MIMO) applications. The dual-band operation is achieved by simultaneously exciting and modes in an aperture coupled fed half split cylindrical dielectric resonator. The topology of four element MIMO antenna is such that it provides both spatial and polarization diversities. Over both the operating bands, the measured port-to-port isolation is better than 20 dB. The proposed antenna exhibits broadside radiation with cross polarization level below dB in both xz- and yz-plane. The peak gain of antenna is 4.88 and 5.32 dBi at lower and upper operating frequency, respectively. The MIMO performance of the proposed antenna is found to be good with ECC0.06. Moreover, the channel capacity of the proposed MIMO is near to uncorrelated case for uniform propagation scenario. The proposed antenna could be suitable for LTE 22/LTE 42 and WLAN applications.
Factors Affecting Human Papillomavirus Vaccine Trends in the United States of America

Background Routine immunization of both girls and boys starting from nine years of age with the human papillomavirus (HPV) vaccine is the current recommendation. The objective of this retrospective study using National Health and Nutrition Examination Survey data was to evaluate the influence of sociodemographic factors on the series initiation and completion of the HPV vaccine from 2011 to 2020. Methodology The chi-square test was used to examine the statistical significance of the association between categorical variables and receipt of the HPV vaccine. The Cochran-Armitage test for trend was employed to assess the statistical significance of temporal trends in risk factors associated with rates of HPV vaccination. These trends were further quantified by a significant rate ratio by comparing them against the most recent survey years. Results HPV vaccine uptake was higher in the 9-14-year age group across survey years and had increased for both males and females over that time. The first dose of the HPV vaccine was most likely to be received by the 11-18-year age group. In the most recent survey of 2017-2020, the highest number of vaccination series completion was achieved for Gardasil®. Conclusions Improved physician efforts and strategies to vaccinate males, low socioeconomic strata patients, and ethnic minorities in more numbers are needed.
The Nonlinear ME Effect of FeNiMoSiB/PZT-5A Composite Under Step Magnetic Field Excitation for Magnetic Field Sensing

Under a high-amplitude ac excitation field, the magnetostrictive/piezoelectric composite exhibits the nonlinear magnetoelectric (ME) effect. A weak dc/ac magnetic field can be measured by demodulating the odd harmonics generated by the composite structure due to the nonlinear ME effect. The ac excitation magnetic field created by an external signal source will introduce crosstalk noise. Here, a novel method for measuring the weak magnetic field via FeNiMoSiB/PZT-5A/FeNiMoSiB composite excited by step magnetic field is presented. The ME composite excited by the step magnetic field will vibrate at its natural frequency to significantly enhance the ME effect. In addition, the resonance frequency of the ME composite is not affected by the excitation signal, which reduces the noise introduced by the external excitation source. Due to the nonlinear ME effect, the induced ME voltage is modulated by a weak dc/ac magnetic field to be measured. The weak magnetic field signal can be recovered from the ME voltage by the lock-in demodulation method. The ME unit for sensing the magnetic field is designed based on the longitudinal free vibration model excited by a step magnetic field. In the experiment, the step magnetic fields generated by a 2-kHz bipolar square-wave signal are used to excite the ME composite. The sensitivity of 29.77 mV/Oe and linearity error of 0.22% are achieved in the dc magnetic field of −3 to 3 Oe. The sensitivity to 1–50-kHz ac magnetic field to be measured in the flat area is about 37.5 mV/Oe.
Does flexibility promote the implementation of civil war cease-fire agreements?

Abstract Transition from war to peace often leads to new challenges. Conflict scholars suggest that these challenges lead groups to be unable to commit credibly and suggest mechanisms for decreasing the fear of being the victim, and increasing the costs, of reneging. However, international law and international political economy scholars debate the utility of making agreements flexible. This paper argues that provisions intended to increase the flexibility of agreements are detrimental to implementation because they operate under the assumption that groups are in a repeated game, and because they can lead to an even more severe commitment problem. Using a newly collected dataset on civil war cease-fire agreements, duration analyses suggest agreements with more flexibility-enhancing provisions exhibit a higher likelihood of violations. Although provisions calling for third-party enforcement – a mechanism for reducing fear and increasing costs – seem to decrease the likelihood of violations, this effect disappears when flexibility-enhancing provisions are considered.
Transient wave imaging of anomalies: a numerical study

Asymptotic formulas, time reversal, kirchhoff imaging, back-propagation imaging, MUSIC imaging. In this paper, we first numerically test the validity of the asymptotic formulas for computing the scattered acoustic pressure by a small three-dimensional anomaly in the near and far fields. We then propose three methods for detecting the anomaly from far-field measurements. We implement time reversal, back-propagation, Kirchhoff and MUSIC imaging techniques.