Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Linear Real-time Rate Control

Most existing rate control schemes in the literature calculated quantisation parameters of the macro-blocks (MB) based on the standard deviation of the residue before quantisation. We found that some factors after quantisation (eg probability of non-zero quantised coefficients, standard deviation of quantised coefficients, mean absolute difference of quantised coefficients (MAD') divided by standard deviation before quantisation, Context-based Adaptive Variable Length Coding (CAVLC)) were new factors, having an interesting property that the rate tended to be linear with those factors. This work investigated the relationship of bit rate and distortion with MB quantisation step size and these factors. Then we established rate and distortion models with MB quantisation step size and these factors. By Lagrange optimisation, the distortion model was minimised subject to the target bit constraint, resulting in obtaining the closed-form formulas of optimal quantisation parameters. Interestingly, our proposed algorithm had low quantisation overhead, low computation complexity and was independent of the distortion factors. The experimental results suggested that our scheme achieved PSNR gain over TMN8 and He schemes

Serum and endometrial markers

Endometriosis is a benign but aggressive disease. It occurs when shed endometrium from the female reproductive tract grows at a site outside the uterus. The physiological changes in endometriosis-abnormal tissue growth, invasion, and adhesion phenomena-are similar to those seen in tumorous tissues. Although the etiology of endometriosis is not well understood, the disease is widely accepted to result from the ectopic implantation of refluxed menstrual tissues. In addition, immunologic changes, genetic factors, and environmental factors might also affect a woman's susceptibility to develop endometriosis. Thus far, laparoscopic examination is required to confirm the presence of endometriosis; there is no reliable marker for its diagnosis. Many studies are therefore focusing on identifying markers for the diagnosis and follow-up of endometriosis. This chapter provides a systematic review of these studies, including recent findings from our group on the identification of molecules, in serum and/or endometrium, which are associated with the development of endometriosis at different stages. From this research, we hope to be able to suggest how to approach the potential markers. The identification of highly sensitive and specific markers of endometriosis should facilitate the development of accurate and non-invasive techniques for diagnosis and prognosis

Transcriptome analysis in blastocyst hatching by cDNA microarray

BACKGROUND: Hatching is an important process for early embryo development, differentiation and implantation. However, little is known about its regulatory mechanisms. By integrating the technologies of RNA amplification and cDNA microarrays, it has become possible to study the gene expression profile at this critical stage. METHODS: Pre-hatched and hatched ICR mouse embryos (25 blastocysts in each group were used in the triplicate experiments) were collected for RNA extraction, amplification, and microarray analysis (the mouse cDNA microarray, 6144 genes, including expressed sequence tags). RESULTS: According to cDNA microarray data, we have identified 85 genes that were expressed at a higher level in hatched blastocyst than in pre-hatched blastocysts. In this study, 47 hatching-related candidate genes were verified via re-sequencing. Some of these genes have been selected and confirmed by real-time quantitative RT-PCR. These hatching-specific genes were also expressed at a lower level in the delayed growth embryos (morula or blastocyst without hatching at day 6 post hCG). These genes included: cell adhesion and migration molecules [E-cadherin, neuronal cell adhesion molecule (NCAM), lectin, galactose binding, soluble 7 (Lgals7), vanin 3 and biglycan], epigenetic regulators (Dnmt1, and SIN3 yeast homolog A), stress response regulators (heme oxygenase 1) and immunoresponse regulators [interleukin (IL)-2-inducible T-cell kinase, IL-4R, interferon-gamma receptor 2, and neurotrophin]. The immunostaining of E-cadherin and NCAM showed strong and specific localization in hatched blastocyst. CONCLUSIONS: This work provides important information for studying the mechanisms of blastocyst hatching and implantation. These hatching-specific genes may have potential as new drug targets for controlling fertility

Sensory processes

An online survey system provides a convenient way for people to conduct surveys. It removes the necessity of human resources to hold paper surveys or telephone interviews and hence reduces the cost significantly. Nevertheless, accuracy and privacy remain as the major obstacles that need additional attention. To conduct an accurate survey, privacy maybe lost, and vice versa. In this paper, we provide new insight to preserve these two seeming contradictory issues in online survey systems especially suitable in big data era. We propose a secure system, which is shown to be efficient and practical by simulation data. Our analysis further shows that the proposed solution is desirable not only in online survey systems but also in several potential applications, including E-Voting, Smart-Grid and Vehicular Ad Hoc Networks.Department of Computin