Functional extreme learning machine

IntroductionExtreme learning machine (ELM) is a training algorithm for single hidden layer feedforward neural network (SLFN), which converges much faster than traditional methods and yields promising performance. However, the ELM also has some shortcomings, such as structure selection, overfitting and low generalization performance.MethodsThis article a new functional neuron (FN) model is proposed, we takes functional neurons as the basic unit, and uses functional equation solving theory to guide the modeling process of FELM, a new functional extreme learning machine (FELM) model theory is proposed.ResultsThe FELM implements learning by adjusting the coefficients of the basis function in neurons. At the same time, a simple, iterative-free and high-precision fast parameter learning algorithm is proposed.DiscussionThe standard data sets UCI and StatLib are selected for regression problems, and compared with the ELM, support vector machine (SVM) and other algorithms, the experimental results show that the FELM achieves better performance

Leptomeningeal enhancement of myelin oligodendrocyte glycoprotein antibody-associated encephalitis: uncovering novel markers on contrast-enhanced fluid-attenuated inversion recovery images

BackgroundMyelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a newly defined autoimmune inflammatory demyelinating central nervous system (CNS) disease characterized by antibodies against MOG. Leptomeningeal enhancement (LME) on contrast-enhanced fluid-attenuated inversion recovery (CE-FLAIR) images has been reported in patients with other diseases and interpreted as a biomarker of inflammation. This study retrospectively analyzed the prevalence and distribution of LME on CE-FLAIR images in children with MOG antibody-associated encephalitis (MOG-E). The corresponding magnetic resonance imaging (MRI) features and clinical manifestations are also presented.MethodsThe brain MRI images (native and CE-FLAIR) and clinical manifestations of 78 children with MOG-E between January 2018 and December 2021 were analyzed. Secondary analyses evaluated the relationship between LME, clinical manifestations, and other MRI measures.ResultsForty-four children were included, and the median age at the first onset was 70.5 months. The prodromal symptoms were fever, headache, emesis, and blurred vision, which could be progressively accompanied by convulsions, decreased level of consciousness, and dyskinesia. MOG-E showed multiple and asymmetric lesions in the brain by MRI, with varying sizes and blurred edges. These lesions were hyperintense on the T2-weighted and FLAIR images and slightly hypointense or hypointense on the T1-weighted images. The most common sites involved were juxtacortical white matter (81.8%) and cortical gray matter (59.1%). Periventricular/juxtaventricular white matter lesions (18.2%) were relatively rare. On CE-FLAIR images, 24 (54.5%) children showed LME located on the cerebral surface. LME was an early feature of MOG-E (P = 0.002), and cases without LME were more likely to involve the brainstem (P = 0.041).ConclusionLME on CE-FLAIR images may be a novel early marker among patients with MOG-E. The inclusion of CE-FLAIR images in MRI protocols for children with suspected MOG-E at an early stage may be useful for the diagnosis of this disease

Programmable Base Editing of the Sheep Genome Revealed No Genome-Wide Off-Target Mutations

Since its emergence, CRISPR/Cas9-mediated base editors (BEs) with cytosine deaminase activity have been used to precisely and efficiently introduce single-base mutations in genomes, including those of human cells, mice, and crop species. Most production traits in livestock are induced by point mutations, and genome editing using BEs without homology-directed repair of double-strand breaks can directly alter single nucleotides. The p.96R > C variant of Suppressor cytokine signaling 2 (SOCS2) has profound effects on body weight, body size, and milk production in sheep. In the present study, we successfully obtained lambs with defined point mutations resulting in a p.96R > C substitution in SOCS2 by the co-injection of BE3 mRNA and a single guide RNA (sgRNA) into sheep zygotes. The observed efficiency of the single nucleotide exchange in newborn animals was as high as 25%. Observations of body size and body weight in the edited group showed that gene modification contributes to enhanced growth traits in sheep. Moreover, targeted deep sequencing and unbiased family trio-based whole genome sequencing revealed undetectable off-target mutations in the edited animals. This study demonstrates the potential for the application of BE-mediated point mutations in large animals for the improvement of production traits in livestock species

Current management of intracerebral haemorrhage in China: a national, multi-centre, hospital register study

<p>Abstract</p> <p>Background</p> <p>We aimed to examine current practice of the management and secondary prevention of intracerebral haemorrhage (ICH) in China where the disease is more common than in Western populations.</p> <p>Methods</p> <p>Data on baseline characteristics, management in-hospital and post-stroke, and outcome of ICH patients are from the ChinaQUEST (QUality Evaluation of Stroke Care and Treatment) study, a multi-centre, prospective, 62 hospital registry in China during 2006-07.</p> <p>Results</p> <p>Nearly all ICH patients (n = 1572) received an intravenous haemodiluting agent such as mannitol (96%) or a neuroprotectant (72%), and there was high use of intravenous traditional Chinese medicine (TCM) (42%). Neurosurgery was undertaken in 137 (9%) patients; being overweight, having a low Glasgow Coma Scale (GCS) score on admission, and Total Anterior Circulation Syndrome (TACS) clinical pattern on admission, were the only baseline factors associated with this intervention in multivariate analyses. Neurosurgery was associated with nearly three times higher risk of death/disability at 3 months post-stroke (odd ratio [OR] 2.60, p < 0.001). Continuation of antihypertensives in-hospital and at 3 and 12 months post-stroke was reported in 732/935 (78%), 775/935 (83%), and 752/935 (80%) living patients with hypertension, respectively.</p> <p>Conclusions</p> <p>The management of ICH in China is characterised by high rates of use of intravenous haemodiluting agents, neuroprotectants, and TCM, and of antihypertensives for secondary prevention. The controversial efficacy of these therapies, coupled with the current lack of treatments of proven benefit, is a call for action for more outcomes based research in ICH.</p

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Horizontal Vibration of Pile in Transversely Isotropic Saturated Soil Based on Saturated Porous Medium Theory

In order to consider the influence of liquid phase and soil anisotropy, the soil around the pile is considered a transversely isotropic saturated porous medium, and a horizontal dynamic model of transversely isotropic saturated soil-pile is established. Based on Beor’s saturated porous medium theory and the constitutive equation of transversely isotropic media, the horizontal dynamic control equation of transversely isotropic saturated soil is obtained without considering the vertical displacement. The horizontal vibration of transversely isotropic soil layers was solved using the potential function and separation of the variable method, and the horizontal and radial displacements of the solid soil skeleton of transversely isotropic saturated soil were obtained. The horizontal force of transversely isotropic saturated soil on a single pile was also obtained. On this basis, the horizontal dynamic equation of a single pile in transversely isotropic saturated soil was established, and the horizontal vibration of the pile foundation was solved using the initial parameter method, and the horizontal dynamic impedance of a single pile in transversely isotropic saturated soil is obtained. The influence of soil anisotropy parameter, liquid-solid coupling coefficient, diameter-length ratio, and modulus ratio on the horizontal dynamic impedance of a single pile in transversely isotropic saturated soil was analyzed through numerical examples. The analysis results show that the anisotropy parameters δ1, diameter-length ratio r0/H, and modulus ratio Ep/C66 have a significant impact on the horizontal dynamic impedance of pile foundation in transversely isotropic saturated soil, and the influence of anisotropy on the horizontal vibration of pile foundation should not be ignored. The influence of the liquid-solid coupling coefficient on the horizontal dynamic impedance factor is related to frequency to a certain extent

Image Reconstruction Technology for Voidage Measurement in Two-phase Flow

Image reconstruction technology based on electrical resistance tomography (ERT) is one of the most critical voidage measurement techniques in two-phase flow because of the technology’s merits, such as visualization, non-intrusiveness, and minimal effect on the environment. However, the reconstruction accuracy of ERT usually presents an enormous challenge because of its ill-posed problems in complexity. A new reconstructed algorithm based on forgetting factor-H∞ filter (FF-H∞ filter) for voidage measurement was developed in this study. The H∞ filter was applied to calculate the filter gain and error matrices for state variable formulation. The forgetting factor was then adaptively adjusted by the residual error of two adjacent times to increase the weight of real-time data and update the status variables with the gain matrix. To reduce the noise information and imaging artifacts, the fuzzy threshold de-noising method was implemented in the data processing. Simulated and practical experiments were combined to contribute to the image reconstruction study. The experiments show that compared with the traditional H∞ filter, the FF-H∞ filter can make better use of the three evaluation indexes, improve the reconstructed quality, and significantly reduce boundary artifacts. This method can obtain highly accurate voidage for online measurement because of its strong real-time data availability and antijamming capacity

Estimation of the Wenchuan Earthquake Rupture Sequence Utilizing Teleseismic Records and Coseismic Displacements

For the 12 May 2008 Mw 7.9 Wenchuan earthquake, two imbricate faults, Beichuan fault and Pengguan fault, have ruptured simultaneously. Special attention should be paid to the point of 40 km northeast of the epicenter, in which the Xiaoyudong fault intersects the above two faults, creating a complex fault structure. Surface rupture data from field surveys and previous research of dynamics studies indicate that an important transformation may take place at the intersection. But, few studies about inversion of source rupture process have focused on this issue. We establish a multiple-segment, variable-slip, finite-fault model to reproduce the rupture process and distinguish rupture sequence. Based on the nonnegative least square method and multiple-time-window approach, the spatial and temporal distribution of slip for three rupture sequences are exhibited, using teleseismic records and coseismic displacements. The conformity between synthetic and observed teleseismic records as well as the slip value of the shallowest subfaults and the coseismic displacements is utilized to calibrate the model. The results are as follows: (1) The teleseismic records inversion alone could not distinguish different rupture sequences. However, in order to make the slip of the Hongkou and Yingxiu area coincide with the field investigation, only the Beichuan fault has a bilateral rupture on the point of intersection of Xiaoyudong fault. So the possible rupture sequence is that the earthquake started at the low dip angle part of southern Beichuan fault, and then it propagated to the Pengguan fault, which caused the rupture of Xiaoyudong fault. Then the southern part of Beichuan fault with high dip angle is triggered by the Xiaoyudong fault. (2) The coseismic displacements constraint can control the slip of subfaults near the surface and has little impact on the deeper subfaults. (3) The maximum slip on the fault is located near the Yingxiu and Beichuan area; moreover, the slip is mainly distributed at the shallow region rather than at the deep, which led to serious disasters. Meanwhile, majority of the aftershocks occur in the periphery of large slip

miR-18a-5p derived from mesenchymal stem cells-extracellular vesicles inhibits ovarian cancer cell proliferation, migration, invasion, and chemotherapy resistance

Abstract Objective Ovarian cancer (OC) is a major threat to women’s health. Mesenchymal stem cells (MSCs) are key regulators in cellular communication by secreting extracellular vesicles (EVs) that are involved in OC. This study probed into the mechanism of human MSCs derived-EVs (hMSC-EVs) in regulating OC cell growth and chemotherapy resistance. Methods hMSCs and EVs were isolated and identified. After adding EVs, the uptake of EVs by OC CAOV3/ES2 cells (for in vitro studies), and cell proliferation, migration, and invasion were detected. Downregulated miRNAs in hMSC-EVs were screened and miR-18a-5p expression in OC patients was detected. The prognosis of OC patients was analyzed. Binding sites of miR-18a-5p and NACC1 were predicted and validated. NACC1 expression in OC tissues was measured by RT-qPCR, and its correlation with miR-18a-5p was analyzed by Pearson method. AKT/mTOR pathway activation was assessed by WB. The cisplatin sensitivity of EVs-treated CAOV3 cells was evaluated via MTT assay and tested by tumor formation assay in nude mice. Results hMSC-EVs suppressed OC cell proliferation, migration, and invasion. miR-18a-5p was downregulated in OC and miR-18a-5p low expression was associated with a poor prognosis. EV-encapsulated miR-18a-5p targeted NACC1. NACC1 was upregulated in OC tissues. miR-18a-5p knockdown and NACC1 overexpression both annulled the inhibition of hMSC-EVs on OC cell growth. AKT and mTOR were elevated in OC and NACC1 activated the AKT/mTOR pathway in OC cells. hMSC-EVs promoted cisplatin sensitivity of OC cells by carrying miR-18a-5p. Conclusion hMSC-EVs-derived miR-18a-5p inhibits OC cell proliferation, migration, invasion, and chemotherapy resistance