A deep learning model to identify gene expression level using cobinding transcription factor signals.

Gene expression is directly controlled by transcription factors (TFs) in a complex combination manner. It remains a challenging task to systematically infer how the cooperative binding of TFs drives gene activity. Here, we quantitatively analyzed the correlation between TFs and surveyed the TF interaction networks associated with gene expression in GM12878 and K562 cell lines. We identified six TF modules associated with gene expression in each cell line. Furthermore, according to the enrichment characteristics of TFs in these TF modules around a target gene, a convolutional neural network model, called TFCNN, was constructed to identify gene expression level. Results showed that the TFCNN model achieved a good prediction performance for gene expression. The average of the area under receiver operating characteristics curve (AUC) can reach up to 0.975 and 0.976, respectively in GM12878 and K562 cell lines. By comparison, we found that the TFCNN model outperformed the prediction models based on SVM and LDA. This is due to the TFCNN model could better extract the combinatorial interaction among TFs. Further analysis indicated that the abundant binding of regulatory TFs dominates expression of target genes, while the cooperative interaction between TFs has a subtle regulatory effects. And gene expression could be regulated by different TF combinations in a nonlinear way. These results are helpful for deciphering the mechanism of TF combination regulating gene expression.

Predictive value of the controlling nutritional status (CONUT) score to assess long-term mortality (10 Years) in patients with hypertension.

BACKGROUND AND AIMS: Malnutrition is associated with poor outcomes in patients with chronic diseases. The aim of this study is to investigate the prevalence of malnutrition in patients with hypertension and relationship between malnutrition severity and long-term mortality in these patients. METHODS AND RESULTS: The study included 11,278 patients with hypertension from the National Health and Nutrition Examination Survey database. The degree of malnutrition was assessed using the Controlled Nutritional Status score, with patients divided into normal, mild, and moderate-to-severe groups. After 10 years of follow-up, the results showed that patients who died had higher CONUT scores, poorer nutritional status, and lower albumin, total cholesterol, and lymphocytes than those who survived (P < 0.05). The Kaplan-Meier analysis revealed that patients with poor nutritional status had a significantly higher risk of all-cause death. In the Non-Lipid Lowering Drugs group, the CONUT score (hazard ratio (HR): 1.225; 95% confidence interval (CI): 1.162-1.292; P < 0.0001), as well as mild (HR: 1.532; 95% CI 1.340-1.751; P < 0.0001) and moderate-to-severe malnutrition (HR: 2.797; 95% CI: 1.441-5.428; P = 0.0024), were independent predictors of long-term mortality. The competing risk regression models showed that cardiovascular and cerebrovascular mortality increased with increasing CONUT scores. The results were robust in both subgroup and sensitivity analyses. CONCLUSIONS: Malnutrition significantly impacts long-term mortality in hypertensive patients. The CONUT score may be a useful tool for assessing the nutritional status of patients with hypertension in the non-lipid-lowering population and for predicting their long-term mortality.

Direct femtosecond laser ablation of large-area TaSe2, SnS2, and TiS2 thick films by a back ablation procedure.

Direct ablation of large-area graphene-like two-dimensional (2D) materials, i.e., tantalum diselenide (TaSe2), stannic disulfide (SnS2), and titanium disulfide (TiS2), by the back ablation method with a femtosecond laser with a repetition rate of 50 MHz and pulse width of 200 fs is studied for the first time to our knowledge. The ablation thresholds of the three kinds of materials are discussed. In addition, the optimization and ablation of narrow grooves on the films are demonstrated. Our work demonstrates the direct femtosecond laser ablation processing of the graphene-like 2D-material films and the potential of 2D-material-film-based devices.

Pulse dynamics manipulation by the phase bias in a nonlinear fiber amplifying loop mirror.

Pulse dynamics controlling is of great importance for high quality pulse generation in ultra-short pulse fiber lasers. The pulse quality characteristics in terms of pulse duration, energy, chirp profile, tunability, as well as noise feature substantially depend on intracavity pulse propagation dynamics. Here we found that a nonlinear amplifying loop mirror mode-locked thulium-doped fiber laser can switch among enabling operation conventional soliton, stretched-pulse soliton and dissipative soliton regimes only by manipulating an intracavity phase bias device. This provides a simple approach to tailoring ultra-short laser characteristics to different applications.

THz polarization-sensitive characterization of a large-area multilayer rhenium diselenide nanofilm.

Recently, rhenium diselenide (ReSe2) has attracted considerable attention due to its high anisotropy in the layer plane, which makes it a promising candidate for wide applications in electronics and optoelectronics. In this paper, we focus on the polarization-sensitive characteristics of a large-area multilayer ReSe2 nanofilm in the terahertz (THz) region under passive and active conditions by means of THz time-domain spectroscopy. We demonstrate the passive ReSe2 nanofilm with intrinsic THz polarization anisotropy. Maximum transmittance occurs only when the polarization direction of the incident THz wave is along the Re-chains direction. More importantly, THz polarization properties of the active ReSe2 nanofilm by an external electric field applied in a selected directions are also demonstrated. The modulation depth of the THz transmission is up to 16% and the response time is on the order of picoseconds. In addition, a comparative experiment is performed on three kinds of THz polarizers, i.e., ReSe2 nanofilm, carbon nanotubes (CNTs) and wire-gird, respectively. The results prove that the performance of the polarizer based on the active ReSe2 nanofilm is comparable with those of CNTs and the THz wire-gird polarizer. Based on these studies, we believe that the polarization-sensitive ReSe2 nanofilm can find important applications in ultrafast switches, filters and modulation devices in the THz region.

Geographical distribution of the P-R interval reference value of Chinese healthy adults.

To explore the relationship between the geographical factors and P-R interval reference value of healthy adults, and to elucidate the geographical distribution of the P-R interval reference value in Chinese adults, to provide the basis for the standard of P-R interval reference value in different regions. The P-R interval reference value of 64,753 healthy adults in 341 cities (counties) level hospitals, research institutes, and universities in China was collected, and 15 geographical data and P-R interval reference value of healthy people were studied, and then 10 geographical factors with correlation were extracted for further analysis. Using spatial autocorrelation analysis to determine the autocorrelation of data space, using backward regression and ridge regression to construct forecast model, and the optimal prediction model is selected by comparing and evaluating the prediction effect of each model, the spatial distribution map of P-R interval reference value of Chinese healthy adults was constructed by statistical analysis. There was a significant correlation between normal reference value of adult P-R interval reference value and geographical factors. The regression model of normal reference value and geographical factors of adult P-R interval reference value was established by ridge regression analysis method: [Formula: see text] =149.2 + 0.02590X2 + 0.0005000X3 + 0.02634X5-0.05890X6 + 0.0008400X7 + 0.01606X8 + 0.2592X9-0.03638X12 + 5.888X13-0.2126X15 ± 8.6, and ArcGIS10.2. In the software interpolation method, the distribution chart of normal reference value of Chinese adult P-R interval reference value was inserted. Knowing the geographical factors of some places in China, we can use this model to estimate the P-R interval reference value in this region, and to obtain the normal P-R interval reference value between adults anywhere in China.

Downregulation of Long Non-Coding RNA Kcnq1ot1: An Important Mechanism of Arsenic Trioxide-Induced Long QT Syndrome.

BACKGROUND/AIMS: Arsenic trioxide (ATO) is a known anti-acute promyelocytic leukemia (APL) reagent, whose clinical applications are limited by its serious cardiac toxicity and fatal adverse effects, such as sudden cardiac death resulting from long QT syndrome (LQTS). The mechanisms of cardiac arrhythmia due to ATO exposure still need to be elucidated. Long non-coding RNAs (lncRNAs) are emerging as major regulators of various pathophysiological processes. This study aimed to explore the involvement of lncRNAs in ATO-induced LQTS in vivo and in vitro. METHODS: For in vivo experiments, mice were administered ATO through the tail vein. For in vitro experiments, ATO was added to the culture medium of primary cultured neonatal mouse cardiomyocytes. To evaluate the effect of lncRNA Kcnq1ot1, siRNA and lentivirus-shRNA were synthesized to knockdown lncRNA Kcnq1ot1. RESULTS: After ATO treatment, the Kcnq1ot1 and Kcnq1 expression levels were down regulated. lncRNA Kcnq1ot1 knockdown prolonged the action potential duration (APD) in vitro and exerted LQTS in vivo. Correspondingly, Kcnq1 expression was decreased after silencing lncRNA Kcnq1ot1. However, the knockdown of Kcnq1 exerted no effect on lncRNA Kcnq1ot1 expression. CONCLUSIONS: To our knowledge, this report is the first to demonstrate that lncRNA Kcnq1ot1 downregulation is responsible for QT interval prolongation induced by ATO at least partially by repressing Kcnq1 expression. lncRNA Kcnq1ot1 has important pathophysiological functions in the heart and could become a novel antiarrhythmic target.

The role of HIV Tat protein in HIV-related cardiovascular diseases.

The human immunodeficiency virus (HIV) is a major global public health issue. HIV-related cardiovascular disease remains a leading cause of morbidity and mortality in HIV positive patients. HIV Tat is a regulatory protein encoded by tat gene of HIV-1, which not only promotes the transcription of HIV, but it is also involved in the pathogenesis of HIV-related complications. This review is aimed at summarizing the current understanding of Tat in HIV-related cardiovascular diseases.

Dual-comb spectroscopy with a single free-running thulium-doped fiber laser.

We demonstrate dual-comb spectroscopy in the vicinity of 2 µm wavelength based on a single dual-wavelength dual-comb Thulium-doped fiber laser. The shared laser cavity ensures passively maintained mutual coherence between the two combs due to common mode environmental noise rejection. In a proof-of-principle experiment, the absorption characteristics caused by the water in the optical path that composes the dual-comb spectrometer are measured. The retrieved spectral positions of the water absorption dips match with the HITRAN database.

Femtosecond laser pulse generation with self-similar amplification of picosecond laser pulses.

Compressing picosecond laser pulses to the femtosecond level is an attractive shortcut for obtaining femtosecond laser pulses. However, dechirped pulses generated by nonlinear compression with self-phase modulation (SPM) show obvious pedestals, which are induced by nonlinear chirp accumulation in spectral broadening process and cannot be easily suppressed. Here, we report systematic numerical simulations and experimental studies on self-similar amplification of picosecond pulses in a short gain fiber for obtaining ~100-fs laser pulses with nearly transform-limited (TL) temporal quality. It is demonstrated that self-similar amplification with picosecond seed pulses is only sensitive to pulse duration and pulse energy. Based on this optimization guideline, we built a compact self-similar amplification fiber system with a picosecond fiber laser as the seed source. This system outputs 66-fs pulses with 6.1-W average power at a repetition rate of 30 MHz. Due to the linear chirp produced in self-similar evolution process, compressed pulses show nearly TL temporal quality. It promises an efficient way of obtaining high-quality femtosecond laser pulses from a picosecond laser source.

Dielectric-mirror-less femtosecond optical parametric oscillator with ultrabroad-band tunability.

We demonstrate a high average power, widely tunable, dielectric-mirror-less optical parametric oscillator (OPO) based on MgO:PPLN (MgO-doped periodically poled lithium niobate), which is synchronously pumped by a 1040 nm femtosecond fiber laser. The OPO does not require any dielectric coating mirrors. By exploiting the four-prism sequence system, combined with the gold mirrors, the oscillating laser pulses could span the spectral regions in both the signal and idler, and the output pulses of OPO can be tuned across 1367-1914 nm in the signal, and 2152-4480 nm in the idler as well. This device can deliver as much as 1.2 W of average power at 1482 nm in the signal and up to 411 mW at 3487 nm in the idler, respectively. The ultrabroad-band spectra tunability, along with the high average output property, makes the dielectric-mirror-less OPO an attractive alternative to conventional OPOs.

Generation of 3.9-cycle pulses from the coherent synthesis of two continuous-wave injection seeded optical parametric amplifiers at 53 MHz.

A high repetition-rate, few-cycle light pulse is of great importance due to its potential for a variety of applications, including two-dimensional infrared spectroscopy and time-resolved imaging of molecular structures, which benefit from its ultrabroadband spectrum and ultrashort pulse duration. The generation of an ultrabroadband coherent spectrum is one of the frontiers of ultrafast optics, and accessing such few-cycle pulses is presently under active exploration. Here, we demonstrate a simple yet effective pulse synthesizer. It is based on two continuous-wave (cw) injection-seeded high-repetition-rate optical parametric amplification systems and the following self-phase-modulation dominated spectra-broadening processes. The combined spectrum spans from 1250 to 1670 nm, and a near Fourier-transform-limited 3.9-cycle (19.2 fs) synthesized pulse with a central wavelength of 1470 nm is obtained accordingly.

Noise characteristics of high power fiber-laser pumped femtosecond optical parametric generation.

We study, both numerically and experimentally, the relative intensity noise (RIN) and timing jitter characteristics of optical parametric generation (OPG) process in MgO-doped periodically poled LiNbO3 (MgO:PPLN) pumped by fiber femtosecond laser. We directly characterize the RIN, and measure timing jitter spectral density of the OPG process based on the balanced optical cross-correlator (BOC) technique for the first time as well, which are both in a fairly good agreement with numerical simulation. Both the numerical and experimental study reveals that OPG can suffer from a smaller intensity fluctuation but a lager temporal jitter when it is driven into saturation. Furthermore, we demonstrate that with a 30 mW CW diode laser injection seeding the OPG output results in superior noise performance compared to the vacuum fluctuations seeded OPG.

Practical 24-fs, 1-µJ, 1-MHz Yb-fiber laser amplification system.

We develop a practical femtosecond polarization-maintaining fiber laser amplification system with a standard double-cladding fiber technique, enabling 24-fs transform-limited pulses with 1-µJ pulse energy at a 1-MHz repetition rate. The laser system is based on a hybrid amplification scheme. Chirped-pulse amplification is employed in the pre-amplifier stage to supply high-quality pulses with enough energy for the main-amplifier, where nonlinear amplification is utilized to broaden the output spectrum. To obtain a dechirped pulse with high quality and short duration, a pre-shaper is inserted between the two amplification stages to adjust the pre-chirp, central wavelength, and pulse energy of the signal pulses in the main amplifier for optimizing pulse evolution. As a result, temporal pedestal free sub-ten-cycle high-energy laser pulses can be routinely obtained. In the end, the advantages of this novel laser source are demonstrated in the experiments on enhanced damage effect to cells co-cultured with gold nanorods.

Intensity and temporal noise characteristics in femtosecond optical parametric amplifiers.

We characterize the relative intensity noise (RIN) and relative timing jitter (RTJ) between the signal and pump pulses of optical parametric amplifiers (OPAs) seeded by three different seed sources. Compared to a white-light continuum (WLC) seeded- and an optical parametric generator (OPG) seeded OPA, the narrowband CW seeded OPA exhibits the lowest root-mean-square (RMS) RIN and RTJ of 0.79% and 0.32 fs, respectively, integrated from 1 kHz to the Nyquist frequency of 1.25 MHz. An improved numerical model based on a forward Maxwell equation (FME) is built to investigate the transfers of the pump and seed's noise to the resulting OPAs' intensity and temporal fluctuation. Both the experimental and numerical study indicate that the low level of noise from the narrowband CW seeded OPA is attributed to the elimination of the RIN and RTJ coupled from the noise of seed source, being one of the important contributions to RIN and timing jitter in the other two OPAs. The approach to achieve lower level of noise from this CW seeded OPA by driving it close to saturation is also discussed with the same numerical model.

Programmable controlled mode-locked fiber laser using a digital micromirror device.

A digital micromirror device (DMD)-based arbitrary spectrum amplitude shaper is incorporated into a large-mode-area photonic crystal fiber laser cavity. The shaper acts as an in-cavity programmable filter and provides large tunable dispersion from normal to anomalous. As a result, mode-locking is achieved in different dispersion regimes with watt-level high output power. By programming different filter profiles on the DMD, the laser generates femtosecond pulse with a tunable central wavelength and controllable bandwidth. Under conditions of suitable cavity dispersion and pump power, design-shaped spectra are directly obtained by varying the amplitude transfer function of the filter. The results show the versatility of the DMD-based in-cavity filter for flexible control of the pulse dynamics in a mode-locked fiber laser.

Biological phosphorus removal in anoxic-aerobic sequencing batch reactor with starch as sole carbon source.

In traditional biological phosphorus removal (BPR), phosphorus release in anaerobic stage is the prerequisite of phosphorus excessive uptake in aerobic conditions. Moreover, when low molecular weight of the organic substance such as volatile fatty acids (VFAs) is scarce in bulk liquid or anaerobic condition does not exist, phosphate accumulating organisms (PAOs) have difficulty removing phosphorus. However, in this work, phosphorus removal in two anoxic-aerobic sequencing batch reactors (SBRs) was observed when starch was supplied as a sole carbon source. The relations of the BPR with idle period were investigated in the two identical SBRs; the idle times were set to 0.5 hr (R1) and 4 hr (R2), respectively. Results of the study showed that, in the two SBRs, phosphorus concentrations of 0.26-3.11 mg/L in effluent were obtained after aeration when phosphorus concentration in influent was about 8 mg/L. Moreover, lower accumulations/transformations of polyhydroxyalkanoates (PHAs) and higher transformation of glycogen occurred in the SBRs, indicating that glycogen was the main energy source that was different from the traditional mechanism of BPR. Under the different idle time, the phosphorus removal was a little different. In R2, which had a longer idle period, phosphorus release was very obvious just as occurs in a anaerobic-aerobic regime, but there was a special phenomenon of chemical oxygen demand increase, while VFAs had no notable change. It is speculated that PAOs can assimilate organic compounds in the mixed liquor, which were generated from glycolysis by fermentative organisms, coupled with phosphorus release. In R1, which had a very short idle period, anaerobic condition did not exist; phosphorus removal rate reached 63%. It is implied that a new metabolic pathway can occur even without anaerobic phosphorus release when starch is supplied as the sole carbon source.

Ultra-flat supercontinuum generated from high-power, picosecond telecommunication fiber laser source.

An ultra-flat, high-power supercontinuum generated from a picosecond telecommunication fiber laser was presented. The pulse from a carbon nanotube mode-locked oscillator was amplified using an Er-Yb codoped fiber amplifier. The output of the system achieved an average power of 2.7 W, with the center wavelength at 1564 nm and a FWHM of 6 nm in the spectral domain. By passing this amplified high-power pulse through a 4.6 m highly nonlinear photonic crystal fiber, an ultra-flat supercontinuum spanning 1600-2180 nm is generated. And the average power of the supercontinuum achieves 1 W.

95 nJ dispersion-mapped amplifier similariton fiber laser at 8.6 MHz repetition rate with linear cavity configuration.

A high-energy and low repetition rate dispersion-mapped amplifier similariton oscillator with a large net intracavity anomalous dispersion and a linear cavity configuration is demonstrated experimentally at 1 µm. The numerical results confirm that self-similar evolution is accomplished in the gain fiber, and both the parabolic- and Gauss-shaped pulses can be emitted at different ports of the cavity, respectively. The maximum output power of 820 mW at a repetition rate of 8.6 MHz under a pump power of 12.76 W, corresponding to a pulse energy as high as of 95 nJ has been obtained.

Effects of high-repetition-rate femtosecond laser micromachining on the physical and chemical properties of polylactide (PLA).

The effects of femtosecond laser ablation, with 115 fs pulses at 1040 nm wavelength and 57 MHz repetition-rate, on the physical and chemical properties of polylactide (PLA) were studied in air and in water. The surface of the PLA sample ablated by high-repetition-rate femtosecond laser was analysed using field emission scanning electron microscopy, infrared spectroscopy, raman spectroscopy, as well as X-ray photoelectron spectroscopy. Compared with the experiments in the air at ambient temperature, melting resolidification was negligible for the experiments conducted under water. Neither in air nor under water did oxidation and crystallization process take place in the laser ablated surface. In addition, the intensity of some oxygen related peaks increased for water experiments, probably due to the hydrolysis. Meantime, the chemical shift to higher energies appeared in C1s XPS spectrum of laser processing in water. Interestingly, a large amount of defects were observed after laser processing in air, while no significant change was shown under water experiments. This indicates that thermal and mechanical effects by high-repetition-rate femtosecond laser ablation in water are quite limited, which could be even ignored.