Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk-sensitive control and dynamic games for partially observed discrete-time nonlinear systems

Solves a finite-horizon partially observed risk-sensitive stochastic optimal control problem for discrete-time nonlinear systems and obtains small noise and small risk limits. The small noise limit is interpreted as a deterministic partially observed dynamic game, and new insights into the optimal solution of such game problems are obtained. Both the risk-sensitive stochastic control problem and the deterministic dynamic game problem are solved using information states, dynamic programming, and associated separated policies. A certainty equivalence principle is also discussed. The authors' results have implications for the nonlinear robust stabilization problem. The small risk limit is a standard partially observed risk-neutral stochastic optimal control problem. >
Non-coding RNA and arrhythmias: expression, function, and molecular mechanism

Abstract Arrhythmias are a class of cardiac dysfunction characterized by heart rate disturbances and heart rhythm abnormalities, which are associated with substantial morbidity and mortality. Due to the limited understanding of pathological mechanism, current antiarrhythmic drugs and invasive therapies on arrhythmias lack sufficient efficacy and are always accompanied by potential adverse effects. Non-coding RNAs (including microRNAs, long non-coding RNAs, circular RNAs, and other small non-coding RNAs) have been demonstrated to be involved in the occurrence and development of various diseases including arrhythmias, which opens a new prospect for exploring the mechanism of arrhythmias and developing new therapeutic targets. Therefore, in this review, we aimed to provide an overview of the expression of ncRNAs in various arrhythmias, their roles in the arrhythmia’s development and pathophysiology, and the potential mechanism of ncRNAs in arrhythmias. As atrial fibrillation (AF) is the most common arrhythmia in clinical practice and current studies mainly focus on it, this review primarily discussed about AF. It was expected that this review may provide a basis for a better understanding of the mechanistic role of ncRNAs in arrhythmias and facilitate the development of mechanic-based therapeutic targets.
In silico screening of inhibitors against human dihydrofolate reductase to identify potential anticancer compounds

Abstract In all species, dihydrofolate reductase (DHFR) is an essential enzyme that regulates the cellular amount of tetrahydrofolate. Human DHFR (hDHFR) activity inhibition results in tetrahydrofolate depletion and cell death. This property has made hDHFR a therapeutic target for cancer. Methotrexate is a well-known hDHFR inhibitor, but its administration has shown some light to severe adverse effects. Therefore, we aimed to find new potential hDHFR inhibitors using structure-based virtual screening, ADMET prediction, molecular docking, and molecular dynamics simulations. Here, we used the PubChem database to find all compounds with at least 90% structural similarity to known natural DHFR inhibitors. To explore their interaction pattern and estimate their binding affinities, the screened compounds (2023) were subjected to structure-based molecular docking against hDHFR. The fifteen compounds that showed higher binding affinity to the hDHFR than the reference compound (methotrexate) displayed important molecular orientation and interactions with key residues in the enzyme’s active site. These compounds were subjected to Lipinski and ADMET prediction. PubChem CIDs: 46886812 and 638190 were identified as putative inhibitors. In addition, molecular dynamics simulations revealed that the binding of compounds (CIDs: 46886812 and 63819) stabilized the hDHFR structure and caused minor conformational changes. Our findings suggest that two compounds (CIDs: 46886812 and 63819) could be promising potential inhibitors of hDHFR in cancer therapy. Communicated by Ramaswamy H. Sarma
Perioperative FLOT plus ramucirumab for resectable esophagogastric adenocarcinoma: A randomized phase II/III trial of the German AIO and Italian GOIM

This multicenter, randomized phase II/III study evaluated the addition of the vascular endothelial growth factor receptor‐2 inhibitor ramucirumab to FLOT as perioperative treatment for resectable esophagogastric adenocarcinoma. Patients received either FLOT alone (Arm A) or combined with ramucirumab followed by ramucirumab monotherapy (Arm B). The primary endpoint for the phase II portion was the pathological complete or subtotal response (pCR/pSR) rate. Baseline characteristics were comparable between both arms with a high rate of tumors signet‐ring cell component (A:47% B:43%). No between‐arm difference in pCR/pSR rate was seen (A:29% B:26%), therefore the transition to phase III was not pursued. Nevertheless, the combination was associated with a significantly increased R0‐resection rate compared with FLOT alone (A:82% B:96%; P = .009). In addition, the median disease‐free survival was numerically improved in Arm B (A:21 months B:32 months, HR 0.75, P = 0.218), while the median overall survival was similar in both treatment arms (A:45 months B:46 months, HR 0.94, P = 0.803). Patients with Siewert type I tumors receiving transthoracic esophagectomy with intrathoracic anastomosis showed an increased risk of serious postoperative complications after ramucirumab treatment, therefore recruitment of those patients was stopped after the first‐third of the study. Overall, surgical morbidity and mortality was comparable, whereas more non‐surgical grade ≥ 3 adverse events were observed with the combination, especially anorexia (A:1% B:11%), hypertension (A:4% B:13%) and infections (A:19% B:33%). The combination of ramucirumab and FLOT as perioperative treatment shows efficacy signals, particularly in terms of R0 resection rates, for a study population with a high proportion of prognostically poor histological subtypes, and further evaluation in this subgroup seems warranted.
Observation of Anomalous Transport of Strongly Multiple Scattered Light in Thin Disordered Slabs

We present results of experiments on the transport of light through thin random media. Total transmission and time-resolved propagation measurements were performed using strongly scattering samples of varying thickness L. For Ly, , 8, where , is the transport mean free path, the observed decay times from the long-time exponential behavior exhibit strong deviations from diffusion theory and radiative transport theory, whereas the total transmission measurements do not. For the thinnest sample sLy, . 2d a reduction of the diffusion coefficient with a factor of 2 was observed. [S0031-9007(97)04617-6]
Integrated Proteomics Unveils Nuclear PDE3A2 as a Regulator of Cardiac Myocyte Hypertrophy

Background: Signaling by cAMP is organized in multiple distinct subcellular nanodomains regulated by cAMP-hydrolyzing PDEs (phosphodiesterases). Cardiac β-adrenergic signaling has served as the prototypical system to elucidate cAMP compartmentalization. Although studies in cardiac myocytes have provided an understanding of the location and properties of a handful of cAMP subcellular compartments, an overall view of the cellular landscape of cAMP nanodomains is missing. Methods: Here, we combined an integrated phosphoproteomics approach that takes advantage of the unique role that individual PDEs play in the control of local cAMP, with network analysis to identify previously unrecognized cAMP nanodomains associated with β-adrenergic stimulation. We then validated the composition and function of one of these nanodomains using biochemical, pharmacological, and genetic approaches and cardiac myocytes from both rodents and humans. Results: We demonstrate the validity of the integrated phosphoproteomic strategy to pinpoint the location and provide critical cues to determine the function of previously unknown cAMP nanodomains. We characterize in detail one such compartment and demonstrate that the PDE3A2 isoform operates in a nuclear nanodomain that involves SMAD4 (SMAD family member 4) and HDAC-1 (histone deacetylase 1). Inhibition of PDE3 results in increased HDAC-1 phosphorylation, leading to inhibition of its deacetylase activity, derepression of gene transcription, and cardiac myocyte hypertrophic growth. Conclusions: We developed a strategy for detailed mapping of subcellular PDE-specific cAMP nanodomains. Our findings reveal a mechanism that explains the negative long-term clinical outcome observed in patients with heart failure treated with PDE3 inhibitors.
A Prospective, Multicenter Study of Developmental Dysplasia of the Hip: What Can Patients Expect After Open Reduction?

Background: Although there are several predominantly single-center case series in the literature, relatively little prospectively collected data exist regarding the outcomes of open hip reduction (OR) for infantile developmental dysplasia of the hip (DDH). The purpose of this prospective, multi-center study was to determine the outcomes after OR in a diverse patient population. Methods: The prospectively collected database of an international multicenter study group was queried for all patients treated with OR for DDH. Minimum follow-up was 1 year. Proximal femoral growth disturbance (PFGD) was defined by consensus review using Salter’s criteria. Persistent acetabular dysplasia was defined as an acetabular index >90th percentile for age. Statistical analyses were performed to compare preoperative and operative characteristics that predicted re-dislocation, PFGD, and residual acetabular dysplasia. Results: A cohort of 232 hips (195 patients) was identified; median age at OR was 19 months (interquartile range 13 to 28) and median follow-up length was 21 months (interquartile range 16 to 32). Re-dislocation occurred in 7% of hips (n=16/228). The majority (81%; n=13/16) occurred in the first year after initial OR. Excluding patients with repeat dislocation, 94.5% of hips were IHDI 1 at most recent follow-up. On the basis of strict radiographic review, some degree of PFGD was present in 44% of hips (n=101/230) at most recent follow-up. Seventy-eight hips (55%) demonstrated residual dysplasia compared with established normative data. Hips that had a pelvic osteotomy at index surgery had about half the rate of residual dysplasia (39%; n=32/82) versus those without a pelvic osteotomy with at least 2 years follow-up (78%; n=46/59). Conclusions: In the largest prospective, multicenter study to date, OR for infantile DDH was associated with a 7% risk of re-dislocation, 44% risk of PFGD, and 55% risk of residual acetabular dysplasia at short term follow-up. The incidence of these adverse outcomes is higher than previous reports. Patients treated with concomitant pelvic osteotomy had lower rates of residual dysplasia. These prospectively collected, multicenter data provide better generalizable information to improve family education and appropriately set expectations. Level of Evidence: Level II, prospective comparative study.
A virtuous cycle between invertebrate and robotics research: perspective on a decade of Living Machines research

Many invertebrates are ideal model systems on which to base robot design principles due to their success in solving seemingly complex tasks across domains while possessing smaller nervous systems than vertebrates. Three areas are particularly relevant for robot designers: Research on flying and crawling invertebrates has inspired new materials and geometries from which robot bodies (their morphologies) can be constructed, enabling a new generation of softer, smaller, and lighter robots. Research on walking insects has informed the design of new systems for controlling robot bodies (their motion control) and adapting their motion to their environment without costly computational methods. And research combining wet and computational neuroscience with robotic validation methods has revealed the structure and function of core circuits in the insect brain responsible for the navigation and swarming capabilities (their mental faculties) displayed by foraging insects. The last decade has seen significant progress in the application of principles extracted from invertebrates, as well as the application of biomimetic robots to model and better understand how animals function. This Perspectives paper on the past 10 years of the Living Machines conference outlines some of the most exciting recent advances in each of these fields before outlining lessons gleaned and the outlook for the next decade of invertebrate robotic research.
Enhanced insulin‐regulated phagocytic activities support extreme health span and longevity in multiple populations

The immune system plays a central role in many processes of age‐related disorders and it remains unclear if the innate immune system may play roles in shaping extreme longevity. By an integrated analysis with multiple bulk and single cell transcriptomic, so as DNA methylomic datasets of white blood cells, a previously unappreciated yet commonly activated status of the innate monocyte phagocytic activities is identified. Detailed analyses revealed that the life cycle of these monocytes is enhanced and primed to a M2‐like macrophage phenotype. Functional characterization unexpectedly revealed an insulin‐driven immunometabolic network which supports multiple aspects of phagocytosis. Such reprogramming is associated to a skewed trend of DNA demethylation at the promoter regions of multiple phagocytic genes, so as a direct transcriptional effect induced by nuclear‐localized insulin receptor. Together, these highlighted that preservation of insulin sensitivity is a key to healthy lifespan and extended longevity, via boosting the function of innate immune system in advanced ages.
An integrated complete-genome sequencing and systems biology approach to predict antimicrobial resistance genes in the virulent bacterial strains of Moraxella catarrhalis

Abstract Moraxella catarrhalis is a symbiotic as well as mucosal infection-causing bacterium unique to humans. Currently, it is considered as one of the leading factors of acute middle ear infection in children. As M. catarrhalis is resistant to multiple drugs, the treatment is unsuccessful; therefore, innovative and forward-thinking approaches are required to combat the problem of antimicrobial resistance (AMR). To better comprehend the numerous processes that lead to antibiotic resistance in M. catarrhalis, we have adopted a computational method in this study. From the NCBI-Genome database, we investigated 12 strains of M. catarrhalis. We explored the interaction network comprising 74 antimicrobial-resistant genes found by analyzing M. catarrhalis bacterial strains. Moreover, to elucidate the molecular mechanism of the AMR system, clustering and the functional enrichment analysis were assessed employing AMR gene interactions networks. According to the findings of our assessment, the majority of the genes in the network were involved in antibiotic inactivation; antibiotic target replacement, alteration and antibiotic efflux pump processes. They exhibit resistance to several antibiotics, such as isoniazid, ethionamide, cycloserine, fosfomycin, triclosan, etc. Additionally, rpoB, atpA, fusA, groEL and rpoL have the highest frequency of relevant interactors in the interaction network and are therefore regarded as the hub nodes. These genes can be exploited to create novel medications by serving as possible therapeutic targets. Finally, we believe that our findings could be useful to advance knowledge of the AMR system present in M. catarrhalis.
Time-varying modeling and intelligent compensation control of singletendon-sheath structure of surgical robot

Graphical abstract The inaccurate force and position control of tendon sheath system (TSS) due to nonlinear friction during surgery seriously hinders its development in the field of precision surgical robots. To this end, this paper proposes a time-varying bending angle estimation method under the state of sensorless offline identification combined with robot kinematics by analyzing the friction of the TSS and the deformation of the robot during the movement, and establishes a force and position transfer model with time-varying path trajectory (SJM model). The model uses B-spline curve to fit tendon-sheath trajectory. In order to further improve the control accuracy of force and position, a new intelligent feedforward control strategy that integrates the SJM model and a neural network algorithm is proposed. In order to gain an in-depth understanding of the transmission process of force and position and to demonstrate the validity of the SJM model, an experimental platform for the TSS was built. A feedforward control system under the MATLAB environment was built with the aim of verifying the accuracy of the intelligent feedforward control strategy. The system innovatively combines the SJM model with BP and RBF neural networks, respectively. The experimental results showed that the correlation coefficients (R2) of force and position transfer are above 99.10% and 99.48%, respectively. Ultimately, we compared the intelligent feedforward and intelligent control strategy under a single neural network, and observed that the intelligent feedforward control strategy has a better effect.
Region-based image denoising through wavelet and fast discrete curvelet transform

Image denoising always is one of important research topics in the image processing field. In this paper, fast discrete curvelet transform (FDCT) and undecimated wavelet transform (UDWT) are proposed for image denoising. A noisy image is first denoised by FDCT and UDWT separately. The whole image space is then divided into edge region and non-edge regions. After that, wavelet transform is performed on the images denoised by FDCT and UDWT respectively. Finally, the resultant image is fused through using both of edge region wavelet cofficients of the image denoised by FDCT and non-edge region wavelet cofficients of the image denoised by UDWT. The proposed method is validated through numerical experiments conducted on standard test images. The experimental results show that the proposed algorithm outperforms wavelet-based and curvelet-based image denoising methods and preserve linear features well.
Molecular frame photoemission in dissociative ionization of H2 and D2 induced by high harmonic generation femtosecond XUV pulses

We report the first results of molecular frame photoelectron emission for dissociative photoionization (DPI) of H2 and D2 molecules induced by a spectrally filtered single high harmonic of a few femtosecond duration, using coincident electron–ion velocity vector correlation techniques. For the studied photon energies around 32 eV, where the resonant excitation of the Q1 and Q2 doubly excited states occurs, autoionization and nuclear dynamics are coupled on a few femtosecond timescale, giving rise to quantum interferences. Molecular frame photoelectron angular distributions (MFPADs), traced as a function of the kinetic energy release of the atomic fragments, provide the most sensitive observables for such complex dynamics. These results compare well with recent spectrally resolved experiments using synchrotron radiation which are also reported. As a novel XUV light source running at multi-kHz repetition rate and synchronized with laser pulses, high-order harmonic generation (HHG) opens new possibilities for extending these investigations to time-resolved studies at the femtosecond scale.
Application of a local linear autoregressive model to BOD time series

In this paper, we analyze the biochemical oxygen demand data collected over two years from McDowell Creek, Charlotte, North Carolina, U.S.A. , by fitting an autoregressive model with time-dependent coefficients. The local linear smoothing technique is developed and implemented to estimate the coefficient functions of the autoregressive model. A nonparametric version of the Akaike information criterion is developed to determine the order of the model and to select the optimal bandwidth. We also propose a hypothesis testing technique, based on the residual sum of squares and F-test, to detect whether certain coefficients in the model are really varying or whether any variables are significant. The approximate null distributions of the test are provided. The proposed model has some advantages, such as it is determined completely by data, it is easily implemented and it provides a better prediction. Copyright © 2000 John Wiley & Sons, Ltd.
Temperature dysregulation during therapeutic hypothermia predicts long-term outcome in neonates with HIE

Few reliable or easily obtainable biomarkers to predict long-term outcome in infants with hypoxic-ischemic encephalopathy (HIE) have been identified. We previously showed that mattress temperature (MT), as proxy for disturbed temperature regulation during therapeutic hypothermia (TH), predicts injury on early MRI and holds promise as physiologic biomarker. To determine whether MT in neonates treated with TH for moderate-severe HIE is associated with long-term outcome at 18–22 months, we performed a secondary analysis of the Optimizing Cooling trial using MT data from 167 infants treated at a core temperature of 33.5°C. Median MTs from four time-epochs (0–6 h, 6–24 h, 24–48 h, and 48–72 h of TH) were used to predict death or moderate-severe neurodevelopmental impairment (NDI), using epoch-specific derived and validated MT cutoffs. Median MT of infants who died or survived with NDI was consistently 1.5–3.0°C higher throughout TH. Infants requiring a median MT above the derived cut-offs had a significantly increased odds of death or NDI, most notably at 0–6 h (aOR 17.0, 95%CI 4.3–67.4). By contrast, infants who remained below cut-offs across all epochs had 100% NDI-free survival. MTs in neonates with moderate-severe HIE during TH are highly predictive of long-term outcome and can be used as physiologic biomarker.
The performance of hybrid adaptive beamforming algorithm for jammers suppression

Adaptive array processing is of growing importance in the fields of communications, radar, and sonar, where the designer almost invariably faces the problem of interference suppression. In general, under some situations, the conventional Frost's (1972) beamforming algorithm may have some problems associated with performance degradation in multiple jammers environment. It causes the convergence time to be essentially dependent on the jammer powers ratio. A new hybrid adaptive beamforming algorithm is derived in the transformed domain for multiple jammers suppression. Here, three popular orthonormal transformations-i.e., discrete Hartley, discrete cosine, and discrete Fourier transforms-are considered. Overall performance improvement, in terms of convergence rate and the computational requirement, is investigated. From the simulation results, we observed that the new presented beamforming algorithm is more robust than the conventional Frost's beamforming algorithm in terms of jammers suppression and the convergence rate. >