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BackgroundResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Tripartite motif containing 25 (TRIM25), an E3-ubiquitin ligase, has been reported to play a vital role in tumorigenesis. The present study aimed to explore the function and mechanism of TRIM25 in regulating oxaliplatin resistance in colorectal cancer.MethodsThe expression of TRIM25 in colorectal cancer tissues was examined using publicly available datasets, immunohistochemistry, and western blotting. Further survival analysis was conducted using the Kaplan-Meier method. CCK8 assays, colony-formation assays, Annexin V-FITC /PI staining and xenograft tumor models were used to evaluate the sensitivity of CRC cells to oxaliplatin. Sphere-formation assays, RT-PCR and limiting dilution assays were used to evaluate the influence of TRIM25 on the stem cell properties of CRC cells. Co-immunoprecipitation, polyubiquitination assays and western blotting were used to determine the mechanism by which TRIM25 regulates EZH2.ResultsPatients with high expression of TRIM25 had a significantly higher recurrence rate (28.9% vs. 15.0%, P = 0.012) and worse disease-free survival (P = 0.006) than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after oxaliplatin treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3-ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting oxaliplatin resistance.ConclusionsOur study provided evidence that TRIM25 is a novel epigenetic regulator of oxaliplatin resistance. Targeting TRIM25 might be a promising strategy for CRC treatment.

Background: We evaluated the prognostic value of C-reactive protein/albumin (CAR) and systemic immune-inflammation index (SII), which we calculated as neutrophil × platelet/lymphocyte) in patients with colorectal liver metastasis (CRLM) after curative resection.Methods: We retrospectively enrolled 283 consecutive patients with CRLM who underwent curative resection between 2006 and 2016. We determined the optimal cutoff values of CAR and SII using receiver operating curve (ROC) analysis. Overall survival (OS)- and recurrence-free survival (RFS)-related to CAR and SII were analyzed using the log-rank test and multivariate Cox regression methods.Results: We found that a high CAR was significantly associated with poor OS (P < 0.001) and RFS (P = 0.008) rates compared with a low CAR; a high SII was significantly associated with poor RFS (P = 0.003) rates compared with a low SII. The multivariate analysis indicated that CAR was an independent predictor of OS (hazard ratio [HR] = 2.220; 95% confidence interval [CI] = 1.387–3.550; P = 0.001) and RFS (HR = 1.494; 95% CI = 1.086–2.056; P = 0.014). The SII was an independent predictor of RFS (HR = 1.973; 95% CI = 1.230–3.162; P = 0.005) in patients with CRLM.Conclusion: We proved that CAR was an independent predictor of OS and RFS in patients with CRLM who underwent curative resection, and that the prognostic value of CAR was superior to that of SII.

Photothermal effects can alter the response of an optical cavity, for example, by inducing self-locking behavior or unstable anomalies. The consequences of these effects are often regarded as parasitic and generally cause limited operational performance of the cavity. Despite their importance, however, photothermal parameters are usually hard to characterize precisely. In this work we use an optical cavity strongly coupled to photothermal effects to experimentally observe an optical back-action on the photothermal relaxation rate. This effect, reminiscent of the radiation-pressure-induced optical spring effect in cavity optomechanical systems, uses optical detuning as a fine control to change the photothermal relaxation process. The photothermal relaxation rate of the system can be accordingly modified by more than an order of magnitude. This approach offers an opportunity to obtain precise in-situ estimations of the parameters of the cavity, in a way that is compatible with a wide range of optical resonator platforms. Through this back-action effect we are able to determine the natural photothermal relaxation rate and the effective thermal conductivity of the cavity mirrors with unprecedented resolution., 11 pages, 4 figures

Optical levitation of mechanical oscillators has been suggested as a promising way to decouple the environmental noise and increase the mechanical quality factor. Here, we investigate the dynamics of a free-standing mirror acting as the top reflector of a vertical optical cavity, designed as a testbed for a tripod cavity optical levitation setup. To reach the regime of levitation for a milligram-scale mirror, the optical intensity of the intracavity optical field approaches 3 MW cm$^{-2}$. We identify three distinct optomechanical effects: excitation of acoustic vibrations, expansion due to photothermal absorption, and partial lift-off of the mirror due to radiation pressure force. These effects are intercoupled via the intracavity optical field and induce complex system dynamics inclusive of high-order sideband generation, optical bistability, parametric amplification, and the optical spring effect. We modify the response of the mirror with active feedback control to improve the overall stability of the system., 11 pages, 6 figures

Background Gastric cancer (GC) is the third most common cause of cancer deaths worldwide. In the present study, we aimed to identify novel GC biomarkers by integrating isobaric tags of relative and absolute quantitation (iTRAQ) for aberrantly expressed proteins in GC patients. Methods Using stable isotope tags, we labeled an initial discovery group comprising four paired gastric cancer and adjacent gastric tissue samples, and subjected them to LC‐ESI‐MS/MS. We used a validation set comprising 129 paired gastric cancer and adjacent gastric tissues from patients and benign healthy controls to validate the candidate targets. Results We identified two proteins, NAD(P)‐dependent steroid dehydrogenase‐like (NSDHL) and neutral cholesterol ester hydrolase 1 (NCEH1), that were significantly overexpressed in GC tissues. The sensitivity and specificity of NSDHL were 80.6% and 74.4%, respectively, in GC compared with a sensitivity of 25.6% in adjacent tissues and 24% in benign healthy controls. The area under the ROC curve (AUC) for NSDHL was 0.810 for GC detection. Overexpression of NSDHL in GC was significantly correlated with local tumor invasion. The sensitivity and specificity of NCEH1 were 77.5% and 73.6%, respectively, in GC compared with a sensitivity of 26.4% in adjacent tissues and 20% in benign controls. The AUC for NSDHL was 0.792. Overexpression of NCEH1 was significantly associated with tumor histological classification and local invasion. Moreover, a combined analysis of NSDHL and NCEH1 achieved a sensitivity and specificity of 85.7% and 83%, respectively, and the AUC was 0.872. The combined analysis of NSDHL and NCEH1 was significantly correlated with histological grade and TNM Ⅱ‐Ⅳ staging. Conclusions iTRAQ‐labeled quantitative proteomics represents a powerful method to identify novel cancer biomarkers. The present study identified NSDHL and NCEH1 as useful biomarkers for screening, diagnosis, and prognosis of patients with gastric cancer., In the present study, The AUCs for NSDHL and NCEH1 were 0.810 and 0.792. A combined analysis of NSDHL and NCEH1 achieved a sensitivity and specificity of 85.7% and 83%, and the AUC was 0.872. The combined analysis of NSDHL and NCEH1 significantly improved the AUC for detecting gastric cancer.

We analyse the dynamics of a one-dimensional vertical Fabry-P\'erot cavity, where the upper mirror levitates due to intra-cavity radiation pressure force. A perturbative approach is used based around separation of timescales, which allows us to calculate the physical quantities of interest. Due to the dynamics of the cavity field, we find that the upper mirror's motion will always be unstable for levitation performed using only a single laser. Stability can be achieved for two lasers, where one provides the trapping potential and the other a damping effect, and we locate and characterise all parameter regimes where this can occur. Finally we analyse photothermal effects due to heating of the mirror substrate. We show that this can stabilise the system, even with only a single input laser, if it acts to increase the optical path length of the cavity. This work serves as a foundation for understanding how levitated optical cavity schemes can be used as stable metrological platforms., Comment: 14 pages, 7 figures. Code & data available for download at github.com/ruvilecamwasam/lmdynamics

Background: A comprehensive investigation into immune cell infiltration provides more accurate and reliable prognostic information for patients with colorectal liver oligometastases (CLO) after liver metastasectomy. Methods: Simultaneous detection of the immune constituents CD3+, CD8+, Foxp3+ T, and &alpha, SMA+ cells in the liver oligometastasis of 133 patients was conducted using a four-colour immunohistochemical multiplex technique. Immune cells were quantified, and tumour-infiltrating lymphocyte (TIL) ratios were subsequently calculated. Correlation analysis was performed using Pearson&rsquo, s correlation. Recurrence-free survival (RFS) and overall survival (OS) for TIL ratios were analysed using the Kaplan&ndash, Meier method and Cox regression models. Results: Significantly fewer CD3+, CD8+, and Foxp3+ T cells were observed in the intratumoural region than in the peritumoural region of liver metastases. CD3+, CD8+, Foxp3+ T, and &alpha, SMA+ cells showed significantly positive correlations with each other both in the intratumoural and peritumoural regions of liver metastases. Only the CD8/CD3 TIL ratio demonstrated a positive correlation between intratumoural and peritumoural regions of liver metastases (r = 0.541, p &lt, 0.001). Patients with high intratumoural CD8/CD3 ratios had significantly longer 3-year RFS (59.0% vs. 47.4%, p = 0.035) and 3-year OS rates (83.3% vs. 65.8%, p = 0.007) than those with low intratumoural CD8/CD3 ratios. Multivariate analyses revealed that the intratumoural CD8/CD3 ratio was independently associated with RFS (HR = 0.593, 95% CI = 0.357&ndash, 0.985, p = 0.043) and OS (HR = 0.391, 95% CI = 0.193&ndash, 0.794, p = 0.009). Conclusion: These findings offer a better understanding of the prognostic value of immune cell infiltration on liver oligometastasis from colorectal cancer.

Background: The overview of the tumor microenvironment on liver oligometastasis from colorectal cancer remains largely unclear. A comprehensive investigation on the immune cell infiltration and its constituent ratio might provide a more accurate and reliable prognostic information for the patients with colorectal liver oligometastasis (CLO) after liver metastasectomy. Methods: A simultaneous detection of immune constituents CD3+, CD8+, Foxp3+ T cells, and α-SMA fibroblast on the liver oligometastasis of 133 patients were conducted by using a five-color immunohistochemical multiplex technique. The immune cells were quantified and tumor-infiltrating lymphocytes (TILs) ratios were subsequently calculated. Correlation analysis was performed using Pearson's correlation. Recurrence-free survival (RFS) and overall survival (OS) for TIL ratios were analyzed using the Kaplan-Meier method and Cox regression models. Results: The number of CD3+, CD8+, and Foxp3+ T cells were significantly fewer in the intratumoral subsection by compared to the peritumoral subsection of metastases. CD3+, CD8+, Foxp3+ T cells, and α-SMA+ fibroblast showed a significantly positive correlation between each other both in the intratumoral and peritumoral subsection of liver metastases. As to the correlation of TIL ratios, only the CD8/CD3 ratio demonstrated a positive correlation in intratumoral and peritumoral metastases (r=0.541, P

Detections of gravitational waves (GW) in the frequency band 35 Hz to 500 Hz have led to the birth of GW astronomy. Expected signals above 500 Hz, such as the quasinormal modes of lower mass black holes and neutron star mergers signatures are currently not detectable due to increasing quantum shot noise at high frequencies. Squeezed vacuum injection has been shown to allow broadband sensitivity improvement, but this technique does not change the slope of the noise at high frequency. It has been shown that white light signal recycling using negative dispersion optomechanical filter cavities with strong optical dilution for thermal noise suppression can in principle allow broadband high frequency sensitivity improvement. Here we present detailed modelling of AlGaAs/GaAs optomechanical filters to identify the available parameter space in which such filters can achieve the low thermal noise required to allow useful sensitivity improvement at high frequency. Material losses, the resolved sideband condition and internal acoustic modes dictate the need for resonators substantially smaller than previously suggested. We identify suitable resonator dimensions and show that a 30 $\mu$m scale cat-flap resonator combined with optical squeezing allows 8 fold improvement of strain sensitivity at 2 kHz compared with Advanced LIGO. This corresponds to a detection volume increase of a factor of 500 for sources in this frequency range., Comment: 20 pages, 4 figures

This paper focuses on the next detectors for gravitational wave astronomy which will be required after the current ground based detectors have completed their initial observations, and probably achieved the first direct detection of gravitational waves. The next detectors will need to have greater sensitivity, while also enabling the world array of detectors to have improved angular resolution to allow localisation of signal sources. Sect. 1 of this paper begins by reviewing proposals for the next ground based detectors, and presents an analysis of the sensitivity of an 8 km armlength detector, which is proposed as a safe and cost-effective means to attain a 4-fold improvement in sensitivity. The scientific benefits of creating a pair of such detectors in China and Australia is emphasised. Sect. 2 of this paper discusses the high performance suspension systems for test masses that will be an essential component for future detectors, while sect. 3 discusses solutions to the problem of Newtonian noise which arise from fluctuations in gravity gradient forces acting on test masses. Such gravitational perturbations cannot be shielded, and set limits to low frequency sensitivity unless measured and suppressed. Sects. 4 and 5 address critical operational technologies that will be ongoing issues in future detectors. Sect. 4 addresses the design of thermal compensation systems needed in all high optical power interferometers operating at room temperature. Parametric instability control is addressed in sect. 5. Only recently proven to occur in Advanced LIGO, parametric instability phenomenon brings both risks and opportunities for future detectors. The path to future enhancements of detectors will come from quantum measurement technologies. Sect. 6 focuses on the use of optomechanical devices for obtaining enhanced sensitivity, while sect. 7 reviews a range of quantum measurement options.

Three mode parametric instability has been predicted in Advanced gravitational wave detectors. Here we present the first observation of this phenomenon in a large scale suspended optical cavity designed to be comparable to those of advanced gravitational wave detectors. Our results show that previous modelling assumptions that transverse optical modes are stable in frequency except for frequency drifts on a thermal deformation time scale is unlikely to be valid for suspended mass optical cavities. We demonstrate that mirror figure errors cause a dependence of transverse mode offset frequency on spot position. Combined with low frequency residual motion of suspended mirrors, this leads to transverse mode frequency modulation which suppresses the effective parametric gain. We show that this gain suppression mechanism can be enhanced by laser spot dithering or fast thermal modulation. Using Advanced LIGO test mass data and thermal modelling we show that gain suppression factors of 10-20 could be achieved for individual modes, sufficient to greatly ameliorate the parametric instability problem.

Cavities with extremely narrow linewidth of 10-100 Hz are required for realizing frequency dependent squeezing to enable gravitational wave detectors to surpass the free mass standard quantum limit over a broad frequency range. Hundred-meter-scale high finesse cavities have been proposed for this purpose. Optomechanically induced transparency (OMIT) enables the creation of optomechanical cavities in which the linewidth limit is set by the extremely narrow linewidth of a high Q factor mechanical resonator. Using an 85mm OMIT cavity with a silicon nitride membrane, we demonstrate a tunable linewidth from 3Hz up to several hundred Hz and frequency dependent noise ellipse rotation using classical light with squeezed added noise to simulate quantum squeezed light. The frequency dependent noise ellipse angle is rotated in close agreement with predictions., 5 pages + 5 figures, +1 supplementary material, submitted to Phys.Rev.A (2014)

The fast increasing Internet applications need accurate, high performance and scalable packet classification in traffic control systems. Although there are several designs of packet classification implemented on heterogeneous hardware platforms, accurate and ultra-speed packet classification remains elementary. The disparity arises because traditional packet classification algorithms with imprecise port-based method and packet processing have unacceptably memory access latency. This paper discusses an efficient hybrid packet classification in gigabits traffic control systems using second-generation programmable network processor. Firstly, we address the problem of inaccurate packet classification and analyze the payload of applications. Secondly, we present the packet classification using not only packet header but the first 64-bit payload. Finally, we describe the software pipeline architecture and hardware design for our approach with network processor. Compared with traditional solutions, the hybrid packet classification has 93% accuracy and speed up to 7.6Gbps in a real network environment.