Diffuse large B-cell lymphoma: sub-classification by massive parallel quantitative RT-PCR.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity with remarkably variable clinical outcome. Gene expression profiling (GEP) classifies DLBCL into activated B-cell like (ABC), germinal center B-cell like (GCB), and Type-III subtypes, with ABC-DLBCL characterized by a poor prognosis and constitutive NF-κB activation. A major challenge for the application of this cell of origin (COO) classification in routine clinical practice is to establish a robust clinical assay amenable to routine formalin-fixed paraffin-embedded (FFPE) diagnostic biopsies. In this study, we investigated the possibility of COO-classification using FFPE tissue RNA samples by massive parallel quantitative reverse transcription PCR (qRT-PCR). We established a protocol for parallel qRT-PCR using FFPE RNA samples with the Fluidigm BioMark HD system, and quantified the expression of the COO classifier genes and the NF-κB targeted-genes that characterize ABC-DLBCL in 143 cases of DLBCL. We also trained and validated a series of basic machine-learning classifiers and their derived meta classifiers, and identified SimpleLogistic as the top classifier that gave excellent performance across various GEP data sets derived from fresh-frozen or FFPE tissues by different microarray platforms. Finally, we applied SimpleLogistic to our data set generated by qRT-PCR, and the ABC and GCB-DLBCL assigned showed the respective characteristics in their clinical outcome and NF-κB target gene expression. The methodology established in this study provides a robust approach for DLBCL sub-classification using routine FFPE diagnostic biopsies in a routine clinical setting.The research in Du lab was supported by research grants (LLR10006 & LLR13006) from Leukaemia & Lymphoma Research, U.K. XX was supported by a visiting fellowship from the China Scholarship Council, Ministry of Education, P.R. China.This is the accepted manuscript. The final version is available from NPG at http://www.nature.com/labinvest/journal/v95/n1/full/labinvest2014136a.html

Exact dipole solitary wave solution in metamaterials with higher-order dispersion

We present an exact dipole solitary wave solution in a mutual modulation form of bright and dark solitons for a higher-order nonlinear Schrödinger equation with third- and fourth-order dispersion in metamaterials (MMs) using an ansatz method. Based on the Drude model, the formation conditions, existence regions and propagation properties are discussed. The results reveal that the solitary wave may exist in a few parameter regions of MMs, different from those in optical fibres, and its propagation properties can be controlled by adjusting the frequency of incident waves in each existence region

Blockchain for Transparent Data Management Toward 6G

The wealth of user data acts as a fuel for network intelligence toward the sixth generation wireless networks (6G). Due to data heterogeneity and dynamics, decentralized data management (DM) is desirable for achieving transparent data operations across network domains, and blockchain can be a promising solution. However, the increasing data volume and stringent data privacy-preservation requirements in 6G bring significantly technical challenge to balance transparency, efficiency, and privacy requirements in decentralized blockchain-based DM. In this paper, we investigate blockchain solutions to address the challenge. First, we explore the consensus protocols and scalability mechanisms in blockchains and discuss the roles of DM stakeholders in blockchain architectures. Second, we investigate the authentication and authorization requirements for DM stakeholders. Third, we categorize DM privacy requirements and study blockchain-based mechanisms for collaborative data processing. Subsequently, we present research issues and potential solutions for blockchain-based DM toward 6G from these three perspectives. Finally, we conclude this paper and discuss future research directions.Huawei Technologies Canada || Natural Sciences and Engineering Research Council of Canad

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A Posteriori Fractional Tikhonov Regularization Method for the Problem of Analytic Continuation

In this paper, the numerical analytic continuation problem is addressed and a fractional Tikhonov regularization method is proposed. The fractional Tikhonov regularization not only overcomes the difficulty of analyzing the ill-posedness of the continuation problem but also obtains a more accurate numerical result for the discontinuity of solution. This article mainly discusses the a posteriori parameter selection rules of the fractional Tikhonov regularization method, and an error estimate is given. Furthermore, numerical results show that the proposed method works effectively

Poly(Lactic Acid) Hemodialysis Membranes with Poly(Lactic Acid)-block-Poly(2-Hydroxyethyl Methacrylate) Copolymer As Additive: Preparation, Characterization, and Performance

Poly(lactic acid) (PLA) hemodialysis membranes with enhanced antifouling capability and hemocompatibility were developed using poly(lactic acid)-block-poly(2-hydroxyethyl methacrylate) (PLA-PHEMA) copolymers as the blending additive. PLA-PHEMA block copolymers were synthesized via reversible addition-fragmentation (RAFT) polymerization from aminolyzed PLA. Gel permeation chromatography (GPC) and 1H-nuclear magnetic resonance (1H NMR) were applied to characterize the synthesized products. By blending PLA with the amphiphilic block copolymer, PLA/PLA-PHEMA membranes were prepared by nonsolvent induced phase separation (NIPS) method. Their chemistry and structure were characterized with X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM) and atomic force microscopy (AFM). The results revealed that PLA/PLA-PHEMA membranes with high PLA-PHEMA contents exhibited enhanced hydrophilicity, water permeability, antifouling and hemocompatibility. Especially, when the PLA-PHEMA concentration was 15 wt %, the water flux of the modified membrane was about 236 L m(-2) h(-1). Its urea and creatinine clearance was more than 0.70 mL/min, lysozyme clearance was about 0.50 mL/min, BSA clearance was as less as 0.31 mL/min. All the results suggest that PLA-PHEMA copolymers had served as effective agents for optimizing the property of PLA-based membrane for hemodialysis applications

Full-term live birth in a woman with 17α-hydroxylase and 17,20-lyase deficiency with assisted reproductive technology: a case report

Abstract Background 17α-hydroxylase deficiency, which is caused by a CYP17A1 gene mutation, is a rare type of congenital adrenocortical hyperplasia that mainly manifests as hypertension, hypokalaemia and sexual dysplasia. To date, few pregnancies associated with this syndrome have been reported. Case presentation We describe a 35-year-old Chinese woman with nonclassical congenital adrenal hyperplasia (NCCAH) due to 17α-hydroxylase/17,20-lyase deficiency who achieved pregnancy after in vitro fertilization (IVF) and frozen-thawed embryo transfer. She had secondary amenorrhea since she was 27, and subsequently, high level of progesterone in the follicular phase was found during a blood test. A compound heterozygous mutation was found in the CYP17A1 gene, c.1263G > A and c.985_987delinsAA. The patient was given standardized treatment with dexamethasone. Due to ovulation disorder, IVF was performed. She underwent whole embryo vitrification freezing. Frozen-thawed embryo transplantation was performed following the artificial cycle protocol of endometrium preparation, resulting in a singleton pregnancy. At 39 weeks and 1 day of gestation, caesarean section was performed due to the breech position of the foetus. Conclusion A high level of progesterone reduces endometrial receptivity. Standardized treatment with dexamethasone and frozen-thawed embryo transfer with an artificial cycle protocol of endometrium preparation should be the choice for infertile female patients with CYP17A1 deficiency