Numerical study of transverse position monitor and compensation for x-ray polarization diagnosis.

Diagnosing free electron laser (FEL) polarization is critical for polarization-modulated research such as x-ray FEL diffraction imaging and probing material magnetism. In an electron time-of-flight (eTOF) polarimeter, the flight time and angular distribution of photoelectrons were designed based on x-ray polarimetry for on-site diagnosis. However, the transverse position of x-ray FEL pulses introduces error into the measured photoelectron angular distribution. This work, thus, proposes a method of compensating transverse position jitters for the polarization by the eTOF polarimeter itself without an external x-ray beam-position monitor. A comprehensive numerical model is developed to demonstrate the feasibility of the compensation method, and the results reveal that a spatial resolution of 20 µm and a polarity improved by 0.02 are possible with fully polarized FEL pulses. The impact of FEL pulses and a method to calibrate their linearity are also discussed.

Metastasis Pattern and Survival Analysis in Primary Small Bowel Adenocarcinoma: A SEER-Based Study.

Background: Small bowel adenocarcinoma (SBA) is a rare gastrointestinal tumor with high malignancy. The aim of this study was to comprehensively evaluate the distant metastasis pattern and establish nomograms predicting survival for SBA. Methods: From 2010 to 2015, patients diagnosed with SBA were identified based on the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival analysis was applied to compare survival differences between metastasis patterns. Then, univariate and multivariate cox analyses were applied to screened out independent prognostic factors of cancer-specific survival (CSS) and overall survival (OS), and identify the risk factors for metastasis of SBA. To assess the discrimination and calibration of nomograms, the concordance index (C-index), calibration curves, receiver-operating characteristic curve (ROC), and decision curve analysis (DCA) were calculated. Results: Kaplan-Meier curves revealed that metastasis patterns were significantly correlated with CSS (p < 0.001) and OS (p < 0.001). Then, the metastasis pattern was showed to be an independent prognostic factor of OS and CSS in patients with SBA, as well as age, grade, T stage, N stage, surgery, retrieval of regional lymph nodes, and chemotherapy. Combining these factors, we constructed prognostic nomograms, which suggested that the metastasis pattern made the greatest contribution to the survival of patients with SBA. Nomograms for OS and CSS had a C-index of 0.787 and 0.793, respectively. Calibration curves showed an excellent agreement between probability and actual observation in the training and validation cohort. Decision curve analysis also exhibited its clinical value with an improved net benefit. In addition, the models we constructed had better prognostic accuracy and clinical utility than traditional TNM staging based on C-index and ROC. Further, Cox regression analysis showed that old age, poor differentiation, N2, and not receiving chemotherapy were the risk factors for prognosis in patients with metastatic SBA. Conclusion: As an independent prognostic factor, the metastasis pattern exhibited the greatest predictive effect on OS and CSS for patients with SBA. Adjuvant chemotherapy had a positive effect on the survival of patients with SBA. Nomograms for predicting 3-and 5-year OS and CSS of patients with SBA were constructed, which could identify patients with higher risk and might be superior in predicting the survival of patients with SBA than TNM staging.

Features and futures of X-ray free-electron lasers.

Linear accelerator-based free-electron lasers (FELs) are the leading source of fully coherent X-rays with ultra-high peak powers and ultra-short pulse lengths. Current X-ray FEL facilities have proved their worth as useful tools for diverse scientific applications. In this paper, we present an overview of the features and future prospects of X-ray FELs, including the working principles and properties of X-ray FELs, the operational status of different FEL facilities worldwide, the applications supported by such facilities, and the current developments and outlook for X-ray FEL-based research.

Self-Amplification of Coherent Energy Modulation in Seeded Free-Electron Lasers.

The spectroscopic techniques for time-resolved fine analysis of matter require coherent x-ray radiation with femtosecond duration and high average brightness. Seeded free-electron lasers (FELs), which use the frequency up-conversion of an external seed laser to improve temporal coherence, are ideal for providing fully coherent soft x-ray pulses. However, it is difficult to operate seeded FELs at a high repetition rate due to the limitations of present state-of-the-art laser systems. Here, we report a novel self-modulation method for enhancing laser-induced energy modulation, thereby significantly reducing the requirement of an external laser system. Driven by this scheme, we experimentally realize high harmonic generation in a seeded FEL using an unprecedentedly small external laser-induced energy modulation. An electron beam with a laser-induced energy modulation as small as 1.8 times the slice energy spread is used for lasing at the seventh harmonic of a 266-nm seed laser in a single-stage high-gain harmonic generation (HGHG) setup and the 30th harmonic of the seed laser in a two-stage HGHG setup. The results mark a major step toward a high-repetition-rate, fully coherent x-ray FEL.

A novel UBE2T inhibitor suppresses Wnt/ß-catenin signaling hyperactivation and gastric cancer progression by blocking RACK1 ubiquitination.

Dysregulation of the Wnt/ß-catenin signaling pathway is critically involved in gastric cancer (GC) progression. However, current Wnt pathway inhibitors being studied in preclinical or clinical settings for other cancers such as colorectal and pancreatic cancers are either too cytotoxic or insufficiently efficacious for GC. Thus, we screened new potent targets from ß-catenin destruction complex associated with GC progression from clinical samples, and found that scaffolding protein RACK1 deficiency plays a significant role in GC progression, but not APC, AXIN, and GSK3ß. Then, we identified its upstream regulator UBE2T which promotes GC progression via hyperactivating the Wnt/ß-catenin signaling pathway through the ubiquitination and degradation of RACK1 at the lysine K172, K225, and K257 residues independent of an E3 ligase. Indeed, UBE2T protein level is negatively associated with prognosis in GC patients, suggesting that UBE2T is a promising target for GC therapy. Furthermore, we identified a novel UBE2T inhibitor, M435-1279, and suggested that M435-1279 acts inhibit the Wnt/ß-catenin signaling pathway hyperactivation through blocking UBE2T-mediated degradation of RACK1, resulting in suppression of GC progression with lower cytotoxicity in the meantime. Overall, we found that increased UBE2T levels promote GC progression via the ubiquitination of RACK1 and identified a novel potent inhibitor providing a balance between growth inhibition and cytotoxicity as well, which offer a new opportunity for the specific GC patients with aberrant Wnt/ß-catenin signaling.

Research progress in Lamins in malignant tumors. / æ ¸çº¤å±‚è›‹ç™½å®¶æ—åœ¨æ¶æ€§è‚¿ç˜¤ä¸­çš„ç ”ç©¶è¿›å±•.

Changes in nuclear morphology are common in malignant tumors, but the underlying molecular mechanisms remain poorly understood. Lamins is involved in supporting nuclear structure, and the expression of Lamins is the molecular basis for nuclear morphological changes during tumor progression. In recent years, the research on the relationship between Lamins and malignant tumors has made great progress. Lamins is of great value in the diagnosis, treatment, and prognosis of various malignant tumors.

Superior mesenteric artery first approach can improve the clinical outcomes of pancreaticoduodenectomy: A meta-analysis.

BACKGROUND AND AIM: Superior mesenteric artery (SMA) first approach was a new improvement for pancreaticoduodenectomy (PD), but there is no evidence whether this approach is advantageous to PD. This meta-analysis aimed to determine the effects of the superior mesenteric artery (SMA) first approach on outcomes of pancreaticoduodenectomy (PD). METHODS: Literature searches were conducted on PubMed, The Cochrane Library, EMBASE, Web of Science, Clinical Trials Registry and China Biology Medicine disc. We completed a meta-analysis of the SMA first approach in PD, assessing overall survival, R0 resection, blood loss, postoperative complications, operation time and postoperative stay. The odds ratios and weighted mean differences with 95% confidence intervals (CIs) were pooled. RESULTS: Eighteen studies comprising 1483 participants were included. Patients who received SMA-PD had significantly lower overall complication rate (OR 0.62, 95% CI 0.47 to 0.81, P = 0.001) and less blood loss (WMD -264.84, 95% CI -336.1 to -193.58, P < 0.001). The obviously increased R0 resection rate (OR 2.92, 95% CI 1.72 to 4.96, P < 0.001) and 3-year OS (OR 2.15, 95% CI 1.34 to 3.43, P = 0.001) were found in the SMA-PD group. CONCLUSION: The SMA-PD group had better clinical outcomes, particularly in long-term survival of pancreatic cancer patients; furthermore, the patients acquired superior clinical efficacy via the posterior approach in SMA-PD.

The detuning effect of crystal monochromator in self-seeding and oscillator free electron laser.

Self-amplified spontaneous emission (SASE) free electron laser (FEL) is capable of generating ultra-short, high power and high brightness X-ray pulses, but its temporal coherence is poor. Self-seeding scheme is an approach to improve the temporal coherence by employing a crystal monochromator. The crystal detuning effect is the phenomenon that the Bragg angle deviates from the middle of the reflection domain due to the refraction effect, and can affect the seed power of hard X-ray self-seeding (HXRSS) FEL. In this paper, we introduce a novel idea to maximize the seed power by tuning the incident angle off the Bragg condition where the Bragg photon energy is corresponding to the central photon energy of the input X-ray pulse. We present the numerical analysis of the detuning effect in different reflecting atomic planes and different asymmetry angles of diamond crystal. Moreover, we analyze how the detuning affects the seed efficiency of HXRSS FEL, and discuss the application to X-ray FEL oscillator (XFELO). We find when the detuning is much smaller than the bandwidth of input X-ray pulse, we can neglect the detuning effect. However, if the detuning is much larger than or comparable with the bandwidth of input X-ray pulse, the detuning effect can not be ignored. This work can give a guidance to HXRSS FEL and XFELO commissioning for high efficiency FEL output.

Slippage boosted spectral cleaning in a seeded free-electron laser.

The realization of fully coherent light sources at extreme ultraviolet to x-ray region has been a long-standing challenge for laser technologies. While modern single pass free-electron lasers (FELs) hold the ability to produce very intense x-ray radiation on few-femtosecond timescale, the output radiation pulses usually have noisy spectra and limited temporal coherence since the amplification starts from electron noise. A promising way for producing stable transform-limited pulses is based on the harmonic up-conversion techniques with a conventional laser as the seed. However, it is found that the insignificant phase error in the seed laser may be eventually multiplied by the harmonic number, leading to a degradation of the output temporal coherence at x-ray wavelength. Here, we report for the first time on the demonstration of a slippage boosted spectral cleaning technique to mitigate the impact of seed laser induced phase errors and to significantly improve the temporal coherence of a seeded FEL with large phase errors in the seed laser. Experimental results indicate the possibility of generating fully coherent x-ray radiation pulses with this technique.

Proposal of X-ray absorption spectroscopy and magnetic circular dichroism using broadband free-electron lasers.

X-ray free-electron lasers (XFELs) have been widely used for applications such as X-ray crystallography and magnetic spin probes because of their unprecedented performance. Recently, time-resolved X-ray magnetic circular dichroism (XMCD) with ultrafast XFEL pulses have made it possible to achieve an instantaneous view of atomic de-excitation. However, owing to the narrow bandwidth and coherence of XFELs, X-ray absorption spectroscopy (XAS) and XMCD are time- and effort-consuming for both machine scientists and users of XFELs. In this work, an efficient scheme using a broadband XFEL pulse and single-shot X-ray spectrometer is proposed, in which the XAS and XMCD measurements can be accomplished with the same machine conditions. An evolutionary multi-objective optimization algorithm is used to maximize the XFEL bandwidth offered by the Shanghai Soft X-ray FEL user facility without additional hardware. A numerical example using MnO is demonstrated, showing that, by using approximately 1000 consecutive XFEL shots with a central photon energy of 650 eV and full bandwidth of 4.4%, precise spectral measurements for XAS and XMCD can be achieved. Additional considerations related to single-shot XAS and XMCD are discussed.

Overview of long non-coding RNA and mRNA expression in response to methamphetamine treatment in vitro.

Long non-coding RNAs (lncRNAs) display multiple functions including regulation of neuronal injury. However, their impact in methamphetamine (METH)-induced neurotoxicity has rarely been reported. Here, using microarray analysis, we investigated the expression profiling of lncRNAs and mRNAs in primary cultured prefrontal cortical neurons after METH treatment. We observed a difference in lncRNA and mRNA expression between the experimental and sham control groups. Using bioinformatics, we analyzed the highest enriched gene ontology (GO) terms of biological process, cellular component, and molecular function, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and pathway network analysis. Furthermore, an lncRNA-mRNA co-expression sub-network for aberrantly expressed terms revealed possible interactions of lncRNA NR_110713 and NR_027943 with their related genes. Afterwards, three lncRNAs (NR_110713, NR_027943, GAS5) and two mRNAs (Ddit3, Casp12) were targeted to validate the microarray data by qRT-PCR. This presented an overview of lncRNA and mRNA expression profiling and indicated that lncRNA might participate in METH-induced neuronal apoptosis by regulating the coding genes of neurons.

Intrauterine fetal death in triplet gestation caused by feto-fetal transfusion syndrome - a case report.

Feto-fetal transfusion syndrome (FFTS) severely affects monochorionic (MC) multiple pregnancies and affects 1 in 1600 pregnancies overall. The number of increasing disputed obstetrics cases in China is related to unavailability of prompt diagnosis of FFTS. We present here a woman with a MC triplet pregnancy with intrauterine fetal death at 33 weeks of gestation due to FFTS. Subsequent pathological anatomy showed that the MC placenta contained vascular anastomoses, including arterio-arterial anastomosis and arterio-venous anastomosis. These anastomoses led to unidirectional blood flow with the absence of adequate compensatory counter-transfusion and bi-directional flow. When encountering such challenging conditions, medical practitioners should discreetly compare the fetuses' characteristics with features of placental blood vessels and consult morphological and pathological findings. Furthermore, they should perform ultrasound examinations, particularly focussing on fetal size differences and the maximum vertical pocket in the diagnosis of FFTS, especially in MC multiple pregnancies with abdominal symptoms.

Inhibition of calpain on oxygen glucose deprivation-induced RGC-5 necroptosis.

The purpose of this study was to investigate the effect of inhibition of calpain on retinal ganglion cell-5 (RGC-5) necroptosis following oxygen glucose deprivation (OGD). RGC-5 cells were cultured in Dulbecco's-modified essential medium and necroptosis was induced by 8-h OGD. PI staining and flow cytometry were performed to detect RGC-5 necrosis. The calpain expression was detected by Western blotting and immunofluorescence staining. The calpain activity was tested by activity detection kit. Flow cytometry was used to detect the effect of calpain on RGC-5 necroptosis following OGD with or without N-acetyl-leucyl-leucyl-norleucinal (ALLN) pre-treatment. Western blot was used to detect the protein level of truncated apoptosis inducing factor (tAIF) in RGC-5 cells following OGD. The results showed that there was an up-regulation of the calpain expression and activity following OGD. Upon adding ALLN, the calpain activity was inhibited and tAIF was reduced following OGD along with the decreased number of RGC-5 necroptosis. In conclusion, calpain was involved in OGD-induced RGC-5 necroptosis with the increased expression of its downstream molecule tAIF.

Generating intense fully coherent soft x-ray radiation based on a laser-plasma accelerator.

Laser-plasma based accelerator has the potential to dramatically reduce the size and cost of future x-ray light sources to the university-laboratory scale. However, the large energy spread of the laser-plasma accelerated electron beam may hinder the way for short wavelength free-electron laser generation. In this paper, we propose a novel method for directly imprinting strong coherent micro-bunching on the electron beam with large intrinsic energy spread by using a wavefront-tilted conventional optical laser beam and a weak dipole magnet. Theoretical analysis and numerical simulations demonstrate that this technique can be used for the generation of fully coherent femtosecond soft x-ray radiation at gigawatts level with a very short undulator.

Demonstration of nonlinear-energy-spread compensation in relativistic electron bunches with corrugated structures.

High quality electron beams with flat distributions in both energy and current are critical for many accelerator-based scientific facilities such as free-electron lasers and MeV ultrafast electron diffraction and microscopes. In this Letter, we report on using corrugated structures to compensate for the beam nonlinear energy chirp imprinted by the curvature of the radio-frequency field, leading to a significant reduction in beam energy spread. By using a pair of corrugated structures with orthogonal orientations, we show that the quadrupole wakefields, which, otherwise, increase beam emittance, can be effectively canceled. This work also extends the applications of corrugated structures to the low beam charge (a few pC) and low beam energy (a few MeV) regime and may have a strong impact in many accelerator-based facilities.

Compensating the electron beam energy spread by the natural transverse gradient of laser undulator in all-optical x-ray light sources.

All-optical ideas provide a potential to dramatically cut off the size and cost of x-ray light sources to the university-laboratory scale, with the combination of the laser-plasma accelerator and the laser undulator. However, the large longitudinal energy spread of the electron beam from laser-plasma accelerator may hinder the way to high brightness of these all-optical light sources. In this paper, the beam energy spread effect is proposed to be significantly compensated by the natural transverse gradient of a laser undulator when properly transverse-dispersing the electron beam. Theoretical analysis and numerical simulations on conventional laser-Compton scattering sources and high-gain all-optical x-ray free-electron lasers with the electron beams from laser-plasma accelerators are presented.

Experimental demonstration of longitudinal beam phase-space linearizer in a free-electron laser facility by corrugated structures.

Removal of the undesired time-energy correlations in the electron beam is of paramount importance for efficient lasing of a high-gain free-electron laser. Recently, it has been theoretically and experimentally demonstrated that the longitudinal wakefield excited by the electrons themselves in a corrugated structure allows for precise control of the electron beam phase space. In this Letter, we report the first utilization of a corrugated structure as a beam linearizer in the operation of a seeded free-electron laser driven by a 140 MeV linear accelerator, where a gain of ∼10 000 over spontaneous emission was achieved at the second harmonic of the 1047 nm seed laser, and a free-electron laser bandwidth narrowing by 50% was observed, in good agreement with the theoretical expectations.

Using off-resonance laser modulation for beam-energy-spread cooling in generation of short-wavelength radiation.

To improve temporal coherence in electron beam based light sources, various techniques employ frequency up conversion of external seed sources via electron beam density modulation; however, the energy spread of the beam may hinder the harmonic generation efficiency. In this Letter, a method is described for cooling the electron beam energy spread by off-resonance seed laser modulation, through the use of a transversely dispersed electron beam and a modulator undulator with an appropriate transverse field gradient. With this novel mechanism, it is shown that the frequency up-conversion efficiency can be significantly enhanced. We present theoretical analysis and numerical simulations for seeded soft x-ray free-electron laser and storage ring based coherent harmonic generation in the extreme ultraviolet spectral region.

Proposal for an x-ray free electron laser oscillator with intermediate energy electron beam.

Harmonic lasing of low-gain free electron laser oscillators has been experimentally demonstrated in the terahertz and infrared regions. Recently, the low-gain oscillator has been reconsidered as a promising candidate for hard x-ray free electron lasers, through the use of high reflectivity, high-resolution x-ray crystals. In this Letter, it is proposed to utilize a crystal-based cavity resonant at a higher harmonic of the undulator radiation, together with phase shifting, to enable harmonic lasing of the x-ray free electron laser oscillator, and hence allow the generation of hard x-ray radiation at a reduced electron beam energy. Results show that fully coherent free electron laser radiation with megawatt peak power, in the spectral region of 10-25 keV, can be generated with a 3.5 GeV electron beam.