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Unlike the better-studied aberrant epigenome in the tumor, the clinicopathologic impact of DNA methylation in the tumor microenvironment (TME), especially the contribution from cancer-associated fibroblasts (CAFs), remains elusive. CAFs exhibit profound patient-to-patient tumorigenic heterogeneity. We asked whether such heterogeneity may be exploited to quantify the level of TME malignancy. We developed a robust and efficient methylome/transcriptome co-analytical system for CAFs and paired normal fibroblasts (NFs) from non-small-cell lung cancer patients. We found 14,781 CpG sites of CAF/NF differential methylation, of which 3,707 sites showed higher methylation changes in ever-smokers than in nonsmokers. Concomitant CAF/NF differential gene expression analysis pointed to a subset of 54 smoking-associated CpG sites with strong methylation-regulated gene expression. A methylation index that summarizes the [beta] values of these CpGs was built for NF/CAF discrimination (MIND) with high sensitivity and specificity. The potential of MIND in detecting premalignancy across individual patients was shown. MIND succeeded in predicting tumor recurrence in multiple lung cancer cohorts without reliance on patient survival data, suggesting that the malignancy level of TME may be effectively graded by this index. Precision TME grading may provide additional pathological information to guide cancer prognosis and open up more options in personalized medicine., Introduction The multistep process of tumor development accompanies the coevolution of the tumor microenvironment (TME) that engages critical participants during tumorigenesis through direct and indirect interaction with tumors (1, 2). [...]

The Al-Si-Cu alloy system is considered to be a promising choice of filler metal for aluminium alloys brazing due to its high strength and low melting point. The greatest obstacle is its lack of plastic forming ability and being difficult to be processed by conventional methods. This disadvantage is ascribed to the considerable amount of brittle CuAl2 intermetallic compound which forms when alloy composition is around the ternary eutectic point. In order to overcome this deficiency, authors of this article proposed to synthesize Al-Si-Cu filler metal by using in situ synthesis method, and the structure and properties of brazing joints were studied. The results show that AlSi alloy is used as the wrap layer, and CuAl alloy is used as the powder core in the composite brazing wire, the two alloys have similar melting points. The machinability of the composite brazing wire is much superior to the traditional Al-Si-Cu filler metal. During the induction brazing of 3A21 alloy, when using AlSi-CuAl composite filler wire, AlSi and CuAl alloys melt almost simultaneously, then after short time holding, Al-Si-Cu braze filler is obtained, the brazing seam has uniform composition and good bonding interface, also, the shearing strength of the brazing joints is higher than the joint brazed by conventional Al-Si-Cu filler metal.

Dengue haemorrhagic fever and dengue shock syndrome, the most severe responses to dengue virus (DV) infection, are characterized by plasma leakage (due to increased vascular permeability) and low platelet counts [...]

Research reveals heat shock induced heat shock regulons, including those controlled by the sigma (sup)B regulon, along with many operons not reported to be heat inducible in Bacillus subtilis. Among the new operons those of arginine biosynthesis and transport and some additional members of the sigma (sup)B regulon are prominent.

A method for generating two-variable 3D FDs directly from a striped lighting system is developed. An iterative algorithm is proposed to compute the two-variable 3D FDs for both axisymmetric and nonaxisymmetric objects and a formula for convergence test is derived. Experiments conducted for a set of 3D objects show that the iterative algorithm converges very quickly and the two-variable 3D FD representations are attained accurately. Index Terms - Two-variable 3D Fourier descriptor, surface reconstruction, shape representation, striped lighting.

Abstract Background Apoptosis-associated biomarkers are rarely studied, especially their role in predicting the development of tuberculosis (TB) from latent TB infection and in prognostication. Methods Patients with TB and interferon-gamma release assay (IGRA)-positive and IGRA-negative family contacts were evaluated to analyze changes in apoptosis-associated serum biomarkers, which included decoy receptor 3 (DcR3), prostaglandin 2 (PGE2), and lipoxin. The prognostic implications of these serum biomarkers were also analyzed. Results One hundred TB patients and 92 IGRA-negative and 91 IGRA-positive family contacts were recruited. The DcR3 and PGE2 levels decreased from the IGRA-negative group to the IGRA-positive group, and peaked in the TB group. Lipoxin decreased to trough in the TB group. The three apoptosis serum markers and age were independent factors discriminating active TB from latent TB infection. In active TB, older age, co-morbidity, and higher serum DcR3 and monocyte chemotactic protein (MCP)-1 were independently associated with poorer six-month survival. Conclusion Apoptosis-associated serum biomarkers change along with the status of Mycobacterium tuberculosis infection. In close contacts with positive IGRA, high DcR3 and PGE2 and low lipoxin may increase the probability of active TB. Older age, co-morbidity, and high DcR3 and MCP-1 levels might be important prognostic factors that warrant further investigation.

Abstract Background High-intensity focused-ultrasound (HIFU) has been successfully employed for thermal ablation of tumors in clinical settings. Continuous- or pulsed-mode HIFU may also induce a host antitumor immune response, mainly through expansion of antigen-presenting cells in response to increased cellular debris and through increased macrophage activation/infiltration. Here we demonstrated that another form of focused ultrasound delivery, using low-pressure, pulsed-mode exposure in the presence of microbubbles (MBs), may also trigger an antitumor immunological response and inhibit tumor growth. Methods A total of 280 tumor-bearing animals were subjected to sonographically-guided FUS. Implanted tumors were exposed to low-pressure FUS (0.6 to 1.4 MPa) with MBs to increase the permeability of tumor microvasculature. Results Tumor progression was suppressed by both 0.6 and 1.4-MPa MB-enhanced FUS exposures. We observed a transient increase in infiltration of non-T regulatory (non-Treg) tumor infiltrating lymphocytes (TILs) and continual infiltration of CD8+ cytotoxic T-lymphocytes (CTL). The ratio of CD8+/Treg increased significantly and tumor growth was inhibited. Conclusions Our findings suggest that low-pressure FUS exposure with MBs may constitute a useful tool for triggering an anticancer immune response, for potential cancer immunotherapy.

Abstract Background The objective of this retrospective study is to investigate laryngeal preservation and long-term treatment results in hypopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) combined with chemotherapy. Methods Twenty-seven patients with hypopharyngeal carcinoma (stage II-IV) were enrolled and underwent concurrent chemoradiotherapy. The chemotherapy regimens were monthly cisplatin and 5-fluorouracil for six patients and weekly cisplatin for 19 patients. All patients were treated with IMRT with simultaneous integrated boost technique. Acute and late toxicities were recorded based on CTCAE 3.0 (Common Terminology Criteria for Adverse Events). Results The median follow-up time for survivors was 53.0 months (range 36-82 months). The initial complete response rate was 85.2%, with a laryngeal preservation rate of 63.0%. The 5-year functional laryngeal, local-regional control, disease-free and overall survival rates were 59.7%, 63.3%, 51.0% and 34.8%, respectively. The most common greater than or equal to grade 3 acute and late effects were dysphagia (63.0%, 17 of 27 patients) and laryngeal stricture (18.5%, 5 of 27 patients), respectively. Patients belonging to the high risk group showed significantly higher risk of tracheostomy compared to the low risk group (p = 0.014). Conclusions After long-term follow-up, our results confirmed that patients with hypopharyngeal carcinoma treated with IMRT concurrent with platinum-based chemotherapy attain high functional laryngeal and local-regional control survival rates. However, the late effect of laryngeal stricture remains a problem, particularly for high risk group patients.

Research has been conducted on Bacillus subtilis transcriptional responses to peroxide stress. The study of these responses has been carried out via gene expression monitoring in stressed cells using DNA microarrays is presented.