Starting Time Point Research Articles

A knowledge guided deep learning framework for underground natural gas micro-leaks detection from hyperspectral imagery

Detecting natural gas (NG) micro-leaks is critical for NG transport and storage. In the event of underground NG leaks in vegetation covered areas, a priori knowledge derived from analyzing vegetation growth mechanisms can effectively describe the degree of vegetation response to NG stress, which is of theoretical importance for the quantitative detection of NG leaks. This study proposed a knowledge-guided deep learning framework and use it for underground NG leaks detection, in which an image and spectrum combined multi-branching deep learning (DL) network (Img-Spec-PGE model) was used to estimate the leaf area index (LAI) of NG-stressed plants, and an improved physical model for describing plant NG stress mechanisms was proposed, then assimilating the SAFY-NG model with LAI as an intermediate variable to obtain an accurate NG stress factor (Ka). The results showed that the Img-Spec-PGE model with the NIR-RE-R spectral bands' combination had the highest LAI estimation accuracy (R2 = 0.867, RMSE = 0.312) among the three designed DL models. The assimilated SAFY-NG model can accurately simulate the wheat LAI growth curve under NG leaks, and the calibration results of environmental parameters for NG leaks (leak start time and leak point depth) were consistent with the realistic experimental settings. Ka is sensitive to NG leaks in all experimental periods (p < 0.05). Enabling distinction between leak and non-leak scenarios as early as 1 day after NG leaks. 30 days after NG leaks, Ka can distinguish between 1 L min−1 and 1.5 L min−1 gas flow. The proposed approach provides a reference for detecting micro-leaks in NG transit and storage.

Rehabilitation with intensive attention training early after acquired brain injury promotes better long-term status on health-related quality of life, daily activities, work ability and return to work.

To describe long-term effects on activity, participation, and quality of life (i) at different post-injury starting time points of attention training and (ii) of two different types of rehabilitation with attention training in patients after stroke or traumatic brain injury; and to describe their functioning level. 2 years after rehabilitation intervention, comparisons were made in one cohort receiving attention training subacute (< 4 months) or post-acute (4-12 months) and in one cohort with two different training methods, a process-based and an activity-based method respectively. 100 patients were recruited from our earlier RCT study. They had mild to moderate stroke or traumatic brain injury with relatively limited symptomatology, and all had moderate to severe attention impairment. A questionnaire-based interview: EuroQol 5 dimensions, Occupational Gaps Questionnaire, Work Ability Index, self-assessed work status, self-reported employment conditions, sick leave, and experienced cognitive limitations in work performance. An advantage for patients receiving subacute attention training regarding daily activities, work ability and returning to work. The results indicate that subacute rehabilitation with attention training (< 4 months) is preferable compared to post-acute intervention (4-12 months). There were only minor differences between the training methods.

483. Pharmacokinetics of Nirmatrelvir and Ritonavir in COVID-19 Patients with Hemodialysis

Abstract Background Nirmatrelvir/ritonavir (Paxlovid) is one of the few therapeutic options for COVID-19. It is not recommended to use in patients with end-stage renal disease (ESDR), and large-scale clinical trials are needed to support its application in this population. We investigated the pharmacokinetics of nirmatrelvir/ritonavir (150 mg/100 mg twice a day) in COVID-19 patients with hemodialysis (HD). Methods SARS-Cov-2 tested positive patients with HD were included and given treatment with nirmatrelvir/ritonavir (150 mg/100 mg twice a day) for 5 days. For most patients, a 4 h-HD started 2 h after the morning dose on day 2. Blood samples were collected 4 h and 12 h after the first dose on day 1 to obtain peak and trough concentrations, respectively. And the blood samples at the start and finish time points of HD were drawn to observe the effect of dialysis on drug clearance. A tandem mass spectrometry (LC-MS/MS) method was conducted to quantify the nirmatrelvir and ritonavir concentrations. Results A total of 14 COVID-19 patients undergoing dialysis were enrolled, with 4 females and 10 males. The age was 66.6 ± 8.0 years and the body mass index (BMI) was 22.3 ± 3.5. The peak concentration of nirmatrelvir after the first dose was 4960 ± 1889 ng/mL. And the trough concentration was 2940 ± 1305 ng/mL, which was approximately 10 times above the EC90 (292 ng/mL). Nirmatrelvir concentration fell by 42% from 10426 ± 3191 ng/mL to 6035 ± 2402 ng/mL during 4 h-HD. The peak and trough concentrations of ritonavir were 816 ± 445 ng/mL and 326±201 ng/mL after the first dose, respectively. And the concentration fell by 17% during 4 h-HD. Based on the assumption of a first-order elimination kinetic, nirmatrelvir/ritonavir 150 mg/100 mg, once a day dose regimen was simulated which showed that the plasma concentration of nirmatrelvir could also achieve the target EC90 value.Figure 1.Plasma concentration of nirmatrelvir (blue circles) and ritonavir (orange circles) in COVID-19 patients with hemodialysis during the course of 150 mg/100 mg twice a day treatment. 4 h- hemodialysis was performed at 26 - 30 h after the first dose. Data are presented as the mean ± standard deviation. The open circles indicate the individual concentration data.Figure 2.Simulated plasma concentration data in dialysis patients following a single dose of 150 mg/100 mg nirmatrelvir/ritonavir. Long dashed line represents patients not on dialysis. Short dashed line represents patients receiving a 4 h - dialysis. Conclusion 150 mg/100 mg twice a day dose regimen of nirmatrelvir/ritonavir produced sufficient concentrations to reach the effective target in COVID-19 patients with HD. Simulation data suggested that a modified dose with 150 mg/100 mg once a day could also reach effective concentration. Our data provide evidence for the application of nirmatrelvir/ritonavir in patients with ESRD and further validation in large-scale investigation was needed. Disclosures All Authors: No reported disclosures

Design and Optimization of Low Impact Shift Control Strategy for Aviation Transmission Power System Based on Response Surface Methodology

The utilization of a variable-speed power system significantly improves the forward flight speed and cruising range of the helicopter. Nevertheless, the shock of speed and torque during the shift process brings stability and safety problems that cannot be ignored. Thus, swift and stable shift control is a key issue in the research on aviation power systems. This study focuses on the design and optimization of low-impact shift control strategies for a variable-speed power system, which involves multiple control variables, long adjustment times, and uncontrollable risks due to the nonsteady state. A comprehensive power system model that integrates the engine, a two-speed dual-clutch transmission system, and the main rotor was proposed. By selecting the engine fuel flow, friction clutch hydraulic pressure, and rotor pitch angle as input signals, regression fitting models between the input signals’ starting time points and speed or torque shock were obtained using Response Surface Methodology (RMS). The interaction effect of multiple time series was analyzed, and four kinds of low-impact nonlinear programming multi-objective optimized models for speed or torque are proposed. The results indicate that the P values of the RMS fitting models at upshift and downshift are less than 0.0001 and 0.05, respectively, which are highly significant and can effectively predict the shift dynamic response; under the optimized upshift and downshift control strategy, the speed and torque shock are reduced by 5–10%.

Comprehensive numerical study of sequential injection of SiO2-nanofluids for enhanced oil recovery

Improving the efficiency of oil production is an important element in reducing the carbon footprint of the oil industry. One of the methods for increasing the efficiency of oil recovery is the use of oil flooding using solutions of various chemical reagents. The paper presents a computational investigation of the oil recovery from a porous micromodel using a nanofluid during sequential injection of water-SiO2 nanofluid-water. The effect of the nanosuspension concentration, duration of injection of the nanosuspension, the starting time point of nanosuspension injection, as well as the influence of oil viscosity on the oil recovery during sequential injection of main displacement fluid and nanosuspensions was investigated. Such a systematic study was performed for the first time. It was found that injection of three pore volumes of nanosuspension increases oil recovery factor by 1.5 times compared to injection of three pore volumes of water. It has been established that, from a practical point of view, it is most effective to increase oil recovery by starting the injection of nanosuspension after injecting two pore volumes of water. This case leads to an increase in recovery factor by 1.35 times compared to the injection of three pore volumes of water. As a result, it was shown that employing sequential injection allows obtaining an oil recovery factor comparable to that corresponding to oil recovery by nanosuspension. Thus, sequential injection makes it possible to significantly reduce the amount of nanoparticles during injection of nanosuspensions, while maintaining a high beneficial effect on the ORF. This is an important positive fact for the further development of this method of increasing oil recovery.

Anal Cancer Prevention Through the Topical Use of Single or Dual PI3K/mTOR Inhibitors

IntroductionAnal dysplasia and anal cancer are major health problems. This study seeks to determine if inhibition of mTOR and/or PI3K pathways is effective at anal cancer prevention in mice with/without established precancerous lesions of the anus (anal dysplasia). MethodsK14E6/E7 mice were entered into the study at 5 wk, 15 wk, or 25 wk of age. Mice were treated with a topical carcinogen, 7,12-Dimethylbenz[a]anthracene (DMBA), which ensures carcinoma development within 20 wk. Treatment groups included: no treatment, DMBA only, topical Pictilisib (PI3K inhibitor) with/without DMBA, topical Sapanisertib (mTOR inhibitor) with/without DMBA, and topical Samotolisib (dual PI3K/mTOR inhibitor) with/without DMBA. Mice underwent weekly observations for anal tumor development (tumor-free survival). After 20 wk of treatment, anal tissue was harvested and evaluated histologically for squamous cell carcinoma (SqCC). ResultsAll topical treatments in conjunction with DMBA increased tumor-free survival in mice that started treatment at 15 wk of age when compared to DMBA-only treatment, except for Pictilisib + DMBA in males. Topical Sapanisertib increased tumor-free survival in mice regardless of starting treatment age. When examining tissue for microscopic evidence of SqCC, only topical Samotolisib in males decreased SqCC in the 15 wk starting mice. ConclusionsSapanisertib, the mTOR inhibitor, had the greatest effect, in terms of increasing tumor-free survival, regardless of starting time point or sex. Unlike the other treatments, Samotolisib, the dual PI3K/mTOR inhibitor, decreased microscopic evidence of SqCC when starting treatment at 15 wk of age but only in male mice.

A Generalized Transformer-Based Pulse Detection Algorithm.

Pulse-like signals are ubiquitous in the field of single molecule analysis, e.g., electrical or optical pulses caused by analyte translocations in nanopores. The primary challenge in processing pulse-like signals is to capture the pulses in noisy backgrounds, but current methods are subjectively based on a user-defined threshold for pulse recognition. Here, we propose a generalized machine-learning based method, named pulse detection transformer (PETR), for pulse detection. PETR determines the start and end time points of individual pulses, thereby singling out pulse segments in a time-sequential trace. It is objective without needing to specify any threshold. It provides a generalized interface for downstream algorithms for specific application scenarios. PETR is validated using both simulated and experimental nanopore translocation data. It returns a competitive performance in detecting pulses through assessing them with several standard metrics. Finally, the generalization nature of the PETR output is demonstrated using two representative algorithms for feature extraction.

Improving mobility in the intensive care unit with a protocolized, early mobilization program: observations of a single center before-and-after the implementation of a multidisciplinary program.

BackgroundEarly intensive care unit (ICU) protocolized rehabilitative programs have been described previously, yet with differing starting time points and mostly on mechanically ventilated patients. We extended the concept to all admitted ICU patients and investigate the efficacy of early mobilization in improving mobility of the critically ill, address issues surrounding the timing and intensity of an early rehabilitative program.MethodsProspective cohorts of patients admitted consecutively before-and-after (control, n=92; intervention, n=90) the introduction of an early mobilization program in a single center, general hospital ICU. Improvement in mobility as assessed by ICU mobility score, on ICU admission and upon ICU discharge, was measured as a primary outcome.ResultsThose receiving early mobilization in the intensive care unit had higher ICU mobility score (2.63; 95% confidence interval, 0.65–4.61; P<0.001) upon discharge from the intensive care, with earlier out of bed mobilization on day 5 compared to the control group of day 21 (P<0.001). No differences were found in terms of mortality, intensive care hospitalization and subsequent hospitalization duration after discharge from ICU. ConclusionsHere, we report that improvement in mobility score earlier in the course of intensive care hospitalization with the introduction of a protocolized early rehabilitative program.

Some plant metabolites from Petasítes sp. and their effect on cancer cells motility in vitro.

e15077 Background: Plant metabolites are traditionally a valuable source of anticancer drugs. The huge variety of molecular structures found in plants makes it possible to isolate substances that possess not only antimitotic, but also anti-migratory properties on cancer cells. The objective of this study was to evaluate the anti-migratory activity of selected metabolites from Petasítes sp. plants. Methods: Cells of cancer cell cultures PC3 (prostate cancer), A431 (skin cancer), CaCo-2 (colorectal cancer), HeLa (cervical cancer) and T98G (glioma) were seeded in an amount of 15*104 cells per well of a 24-well plate (Biofil, China) in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA). After cell adhesion the test substances at a concentration of 40 µM were added, and a wound healing assay was performed according to the standard procedure. The study included the following metabolites: 1) substance 1 (S1) - 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one; 2) substance 2 (S2) - 5-(hydroxymethyl)furan-2-carbaldehyde; 3) substance 3 (S3) - corynan. The wound area was measured using a Lionheart FX imager (BioTek, USA) at starting time point and after 48 hours of cultivation. Data are presented as mean±95% confidence interval (n = 12). Results: The studied cultures were found to be differently sensitive to the tested substances. Cells of CaCo-2 and PC3 cultures did not demonstrate a significant decrease in mobility, as the degree of scratch overgrowth did not decrease compared to the control without the addition of substances (α = 0.05, df = 22) in all variants of the experiment. However, the A431 skin cancer culture showed reduced motility in all three trials compared to the no-substance control. Namely, the wound area reduction was 81.52 ± 9.6% in the control, 63.77 ± 8.4% in S1 variant, 62.42 ± 6.3% in S2 variant, and 12.05 ± 7.1% in S3 variant. Also, a slowdown in cell motility was observed in HeLa (28.92±5.1% compared to 37.0±6.3% in control) and T98G cells (82.41±9.1% compared to with 97.35±1.9% in control) when incubated with S1. Taking into account the correction for multiple comparisons, only the results for A431 turned out to be significant, but the results obtained for HeLa and T98G cultures were not significant at a corrected significance level (α = 0.003, df = 22). Conclusions: Further studies of 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one anti-migratory properties are of particular interest, since it showed promising results in three of the five studied cancer cell cultures.

Skeletal maturation in different anteroposterior and vertical skeletal growth patterns in female subjects.

The aim of the present work was to study the sequence of skeletal maturation in the various anteroposterior and vertical skeletal growth patterns and to detect whether differences existed between them. Cephalograms of 861 growing and adolescent female patients were traced to categorize the subjects into 9skeletal patterns. Each subject was assigned askeletal maturational stage. Analysis of variance (ANOVA) followed by Bonferroni test were used to detect differences in the onset of the three growth stages (prepubertal, pubertal and postpubertal) between the 9groups. The same statistical methods were used to detect differences between the mean ages at the three growth stages within each group. No statistically significant differences were found between the mean ages of pubertal and postpubertal growth stages between the 9skeletal patterns. However, classIII growers had asignificantly earlier onset of prepubertal growth (10.25 ± 1.56years) when compared to that of classII high angle cases (11.11 ± 1.67years; P < 0.01). Also, significant differences were found between the mean ages at the three growth stages within the groups. Amap was created defining the sequence of skeletal maturation for each skeletal growth pattern. This map defines clinically relevant differences in the starting time points and the optimum intervals of growth modification for each skeletal growth pattern.

The frame synchronization robust to low signal power in underwater acoustic communications

In underwater acoustic communications, it is difficult to find the starting time of received signals because of noise, multipath, transmission time delay, and Doppler frequency. In this paper, we solve the problem by using 2-STEP frame synchronization in the receiver. The transmitted signal is modulated by using burst PSK. The frame is composed of preamble of PN code and random data. The 2-STEP frame synchronization consist of non-coherent correlation, sliding FFT, and coherent correlation. First, in the STEP 1, the non-coherent correlation and sliding FFT are simultaneously performed to obtain an approximate start time of a frame in time domain and a Doppler frequency in frequency domain. However, through the results of the marine experiments, we can see that it is difficult to guarantee the starting time point in STEP 1 when the received signal power is weak and there is high Doppler frequency. Therefore, in the STEP 2, we use the coherent correlation to get more accurate start time stably after compensating the Doppler frequency of FFT in STEP 1. Finally, we can assure that the performance of the proposed 2-STEP frame synchronization is robust to low power of received signal and high Doppler frequency through marine experiments.

Preloaded D-methionine protects from steady state and impulse noise-induced hearing loss and induces long-term cochlear and endogenous antioxidant effects.

ObjectiveDetermine effective preloading timepoints for D-methionine (D-met) otoprotection from steady state or impulse noise and impact on cochlear and serum antioxidant measures.DesignD-met started 2.0-, 2.5-, 3.0-, or 3.5- days before steady-state or impulse noise exposure with saline controls. Auditory brainstem response (ABRs) measured from 2 to 20 kHz at baseline and 21 days post-noise. Samples were then collected for serum (SOD, CAT, GR, GPx) and cochlear (GSH, GSSG) antioxidant levels.Study sampleTen Chinchillas per group.ResultsPreloading D-met significantly reduced ABR threshold shifts for both impulse and steady state noise exposures but with different optimal starting time points and with differences in antioxidant measures.For impulse noise exposure, the 2.0, 2.5, and 3.0 day preloading start provide significant threshold shift protection at all frequencies. Compared to the saline controls, serum GR for the 3.0 and 3.5 day preloading groups was significantly increased at 21 days with no significant increase in SOD, CAT or GPx for any impulse preloading time point. Cochlear GSH, GSSG, and GSH/GSSG ratio were not significantly different from saline controls at 21 days post noise exposure.For steady state noise exposure, significant threshold shift protection occurred at all frequencies for the 3.5, 3.0 and 2.5 day preloading start times but protection only occurred at 3 of the 6 test frequencies for the 2.0 day preloading start point. Compared to the saline controls, preloaded D-met steady-state noise groups demonstrated significantly higher serum SOD for the 2.5–3.5 day starting time points and GPx for the 2.5 day starting time but no significant increase in GR or CAT for any preloading time point. Compared to saline controls, D-met significantly increased cochlear GSH concentrations in the 2 and 2.5 day steady-state noise exposed groups but no significant differences in GSSG or the GSH/GSSG ratio were noted for any steady state noise-exposed group.ConclusionsThe optimal D-met preloading starting time window is earlier for steady state (3.5–2.5 days) than impulse noise (3.0–2.0). At 21 days post impulse noise, D-met increased serum GR for 2 preloading time points but not SOD, CAT, or GpX and not cochlear GSH, GSSG or the GSH/GSSG ratio. At 21 days post steady state noise D-met increased serum SOD and GPx at select preloading time points but not CAT or GR. However D-met did increase the cochlear GSH at select preloading time points but not GSSG or the GSH/GSSG ratio.

SETA++: Real-Time Scalable Encrypted Traffic Analytics in Multi-Gbps Networks

The security and privacy of the end-users are a few of the most important components of a communication network. Though end-to-end encryption (e.g., TLS/SSL) fulfils this requirement, it makes inspecting network traffic with legacy solutions such as Deep Packet Inspection difficult. Recent Machine Learning techniques have shown outstanding performance in encrypted traffic classification. Nevertheless, such approaches require efficient flow sampling at real enterprise-scale networks due to the sheer volume of transferred data. Through this paper, we propose a holistic architecture to extract flow information of encrypted data at multi Gbps line rate using sampling and sketching mechanisms, enabling network operators to estimate flow size distribution accurately and understand the behavior of VPN-obfuscated traffic. Using over 6000 video traffic traces, under three main evaluation scenarios based on trace duration and starting time point, we show that it is possible to achieve 99% accuracy for service provider classification and over 90% accuracy for content classification for a given service provider in the best case. We also deploy our solution at an operational enterprise-scale network leveraging kernel bypassing to demonstrate its capability to efficiently sample live traffic for analytics.

High-volume hemofiltration reduces short-term mortality with no influence on the incidence of MODS, hospital stay, and hospitalization cost in patients with severe-acute pancreatitis: A meta-analysis.

This study aimed to investigate the efficiency, safety and cost-efficiency of blood purification (BP) in treating patients with severe-acute pancreatitis (SAP). A literature search was conducted using PubMed, OVID, International Clinical Trials Register (ICTRP), and Cochrane Central Register of Controlled Trials (CENTRAL). A total of 11 prospective studies and 6 retrospective studies, which reported the mortality of 1279 SAP patients, were included for analysis. Decreased short-term mortality and incidence rate of infection were observed in the high-volume hemofiltration (HVHF) group, but not in patients treated with other types of BP. There was no significant difference in the incidence of multiple-organ dysfunction (MODS), duration of hospital stay, or cost of hospitalization between the BP and non-BP groups. The starting time point, substitution fluid flow rate, filter membrane type, hemofilter change interval, anticoagulation, and sustaining times of BP varied across studies. In conclusion, HVHF may reduce the short-term mortality (<4weeks), not long-term mortality, of SAP patients by decreasing the incidence of infection, while other types of BP did not show a significant beneficial effect. Neither HVHF nor other BP patterns affect the duration of hospital stay, cost of hospitalization, or incidence of MODS in SAP patients.

Mechanical and Microstructural Characteristics of Calcium Sulfoaluminate Cement Exposed to Early-Age Carbonation Curing.

The early-age carbonation curing technique is an effective way to improve the performance of cement-based materials and reduce their carbon footprint. This work investigates the early mechanical properties and microstructure of calcium sulfoaluminate (CSA) cement specimens under early-age carbonation curing, considering five factors: briquetting pressure, water–binder (w/b) ratio, starting point of carbonation curing, carbonation curing time, and carbonation curing pressure. The carbonization process and performance enhancement mechanism of CSA cement are analyzed by mercury intrusion porosimetry (MIP), thermogravimetry and derivative thermogravimetry (TG-DTG) analysis, X-ray diffraction (XRD), and scanning electron microscope (SEM). The results show that early-age carbonation curing can accelerate the hardening speed of CSA cement paste, reduce the cumulative porosity of the cement paste, refine the pore diameter distribution, and make the pore diameter distribution more uniform, thus greatly improving the early compressive strength of the paste. The most favorable w/b ratio for the carbonization reaction of CSA cement paste is between 0.15 and 0.2; the most suitable carbonation curing starting time point is 4 h after initial hydration; the carbonation curing pressure should be between 3 and 4 bar; and the most appropriate time for carbonation curing is between 6 and 12 h.

New tropolone derivative to inhibit cell motility in colorectal cancer cells.

e15043 Background: Tropolones are small, naturally occurring organic compounds that have anti-cancer effects in a variety of cancer cell lines. Among proposed mechanisms of tropolone derivatives anti-cancer activity are caspase activation, matrix metalloproteinases and histone deacetylases inhibition and other actions. Since matrix metalloproteinases are the major proteins that contribute to tumor cell tissue invasion and migration their blockers are extensively studied as prospective anti metastatic agents. We assumed that tropolones may also have potential as metastases prevention drugs. The aim of the study was to investigate the influence of new tropolone derivative 2-(6,8-dimethyl-5-nitro-4-chloroquinolin-2-yl)-5,6,7-trichloro-1,3-tropolone on the cell migration capacity in colorectal cancer cells. Methods: Cell migration in permanent colorectal cancer cell lines HT29, Caco2 and HCT116 was studied using the standard wound healing assay with automated image acquisition and analysis on Lionheart FX (BioTek) cell imager. Cell cultures were maintained in DMEM medium with L-glutamine (1 μM) (Gibco) and 10% FBS (Gibco) at 37C0 and 5.0% CO2. The day before assay establishment cells were seeded at 250 000 cells per well on 24-well plates. After attachment of cells, a vertical wound in cell layer was made manually in each well, and then medium with studied tropolone derivative (5 μM) was added. Plates with cells were continuously incubated and photographed in cell imager at 37C0 and 5.0% CO2. The extent of cells migration was measured as the percent of wound area decrease after 48 hours of incubation in relation to starting time point. Data are given as: Mean ± 95% confidence interval. Results: The new tropolone derivative under study exhibited pronounced anti migratory activity in all studied colorectal cancer cell cultures. The most prominent effect was observed in HCT116 cell line: after 48 hours of incubation relative wound area decrease was 48.2%±5.7% in control and 7.2%±3.15% in experimental groups. In Caco2 cell line cell migration inhibition was the least with 65%± 6.9% relative wound area decrease in control and 51.5%± 7.7% in experimental groups. The moderate effect was observed in HT29 cell line (measured parameter was 63.6%±7.6% and 36.9%±11.6% in control and experimental groups accordingly). The obtained difference between control and experimental groups was significant in all tested cell cultures at 0.05 level (df = 30). Conclusions: Results of the present study prove tropolone derivative to be prospective candidates for anti-metastatic drug development. Further investigations are needed to reveal the exact mechanisms of tropolones anti-migratory activity.

Antimigratory effect of berberine in T98G, U87MG and primary glioma cell culture.

e15045 Background: Berberine is an alkaloid compound with a structure that is highly similar to that of intercalating agents. It affects numerous cell signaling pathways and is widely studied as potential anticancer drug. It is known that berberine affects cancer cells migration through metalloproteinase-2 inhibition, but this effect was never studied on glioma cells. Anti-migratory drugs are of special interest in brain cancer therapy since glioma's highly invasive nature makes total surgical removal of tumor practically impossible. The aim of the study was to evaluate berberine anti-migratory activity on glioma cells. Methods: Cell migration capacity of T98G and U87MG cell lines, as well as primary glioma cell culture established in our laboratory, was assessed via standard wound healing assay with automated image acquisition and analysis on Lionheart FX (BioTek) cell imager. Prior to assay setting up cell cultures were maintained in DMEM medium with L-glutamine (1 μM) (Gibco) and 10% FBS (Gibco) at 37C0 and 5.0% CO2. Cells were seeded at 250 000 cells per well on 24-well plates and incubated overnight in order to attach to plate bottom. After that a vertical wound was made manually in each well, and berberine was added to experimental wells to final concentration 50 mg/L. Plates with cells were continuously incubated and photographed in cell imager at 37C0 and 5.0% CO2. The extent of cells migration was measured as the percent of wound area decrease after 24 hours of incubation in relation to starting time point. Data are given as: Mean ± 95% confidence interval. Results: In our study we berberine exhibited anti-migratory activity in all cell cultures under study. In rather fast growing primary cell culture wound area decrease was 99.23%±0.62% in control sample and 91.75%±0.28% in experimental sample. The difference was small but significant at p &lt; 0.001 level (df = 30). Popular permanent glioma cell lines T98G and U87MG showed more prominent decrease in studied parameter with higher degree of variance at the same time. In T98G wound area decrease was 71.6%±12.3% in control and 48.8%± 7.6% in experimental samples after 24 hours of cultivation in presence of 50 mg/L berberine. While U87MG demonstrated 60.28%±5.13% and 37.5%± 8.34% wound area decrease accordingly. The obtained difference between control and experimental groups in permanent cell cultures was statistically significant at the 0.05 level (df = 30). Conclusions: Our preliminary research proved berberine to be potent anti-migratory agent in glioma treatment. Further investigations are needed to evaluate its ability to inhibit glioma cell expansion in vivo.

Touch Modality Identification With Tensorial Tactile Signals: A Kernel-Based Approach

Touch modality identification has attracted increasing attention due to its importance in human&#x2013;robot interactions. There are three issues involved in the tactile perception for the touch modality identification, including the high dimensionality of tactile signals, complex tensor morphology of tactile sensing units, and the misalignment among different tactile time-series samples. In this article, we propose a novel kernel-based approach to deal with these three issues in a unified framework. Specifically, the techniques, including sparse principal component analysis and subsampling, are employed to reduce the feature dimension. Then, a singular value decomposition (SVD)-based kernel is proposed to preserve the spatial information of the tactile sensing elements. The sample misalignment issue is addressed via the employment of a global alignment kernel. Moreover, the merits of these two kernels are fused through an ideal regularized composite kernel, which simultaneously takes the label information of the training set into consideration. The effectiveness of the proposed kernel-based approach is verified on a public touch modality data set with a comprehensive comparison with the competing methods. <i>Note to Practitioners</i>&#x2014;In a wealth of tactile recognition tasks, we are in the face of various challenges. For instance, tactile measurements are commonly tensorial and high-dimensional. The misalignments among tactile measurements prevail, such as different durations of tactile measurements and the misaligned starting time point of tactile measurements. This article presents a kernel-based method using an ideal regularized composite kernel to deal with all challenges in a unified framework. The kernel-based method consists of two key components including the SVD-based kernel and the global alignment kernel. The proposed method may shed new insights on new advances in tactile signal processing particularly in human&#x2013;robot interactions.

Manipulating Single-Trial Motor Performance in Chronic Stroke Patients by Closed-Loop Brain State Interaction

Motor impaired patients performing repetitive motor tasks often reveal large single-trial performance variations. Based on a data-driven framework, we extracted robust oscillatory brain states from pre-trial intervals, which are predictive for the upcoming motor performance on the level of single trials. Based on the brain state estimate, i.e. whether the brain state predicts a good or bad upcoming performance, we implemented a novel gating strategy for the start of trials by selecting specifically suitable or unsuitable trial starting time points. In a pilot study with four chronic stroke patients with hand motor impairments, we conducted a total of 41 sessions. After few initial calibration sessions, patients completed approximately 15 hours of effective hand motor training during eight online sessions using the gating strategy. Patients' reaction times were significantly reduced for suitable trials compared to unsuitable trials and shorter overall trial durations under suitable states were found in two patients. Overall, this successful proof-of-concept pilot study motivates to transfer this closed-loop training framework to a clinical study and to other application fields, such as cognitive rehabilitation, sport sciences or systems neuroscience.

Trend Analysis and Intervention Effect Starting Point Detection of COVID-19 Epidemics Using Recalibrated Time Series Models - Worldwide, 2020.

Objective: This study aimed to identify a model for short-term coronavirus disease 2019 (COVID-19) trend prediction and intervention evaluation. Methods: We compared the autoregressive integrated moving average (ARIMA) model and Holt exponential smoothing (Holt) model on predicting the number of cumulative COVID-19 cases in China. Based on the mean absolute percentage error (MAPE) value, the optimal model was selected and further tested using data from the United States, Italy and Republic of Korea. The intervention effect starting time points and abnormal trend changes were detected by observing the pattern of differences between the predicted and real trends. Results: The recalibrated ARIMA model with a 5-day prediction time span has the best model performance with MAPEs ranged between 2% and 5%. The intervention effects started to show on February 7 in the mainland of China, March 5 in Republic of Korea and April 27 in Italy, but have not been detected in the US as of May 19. Temporary abnormal trends were detected in Korea and Italy, but the overall epidemic trends were stable since the effect starting points. Conclusion: The recalibrated ARIMA model can detect the intervention effects starting points and abnormal trend changes; thus to provide valuable information support for epidemic trend analysis and intervention evaluation.