Chimeric antigen receptor for treatment of T-cell malignancies and HIV-1 cure

Chimeric Antigen Receptors (CARs) T cell therapy has achieved great success in the treatment of B-cell malignancies by targeting B-cell specific antigen CD19. However, a similar approach targeting the CD4 molecule for T cell lymphoma has thus far been unrealised. CD4, a cell surface glycoprotein, is highly expressed in the majority of mature T-cell malignancies, and absent in hematopoietic stem cells. Anti-CD4 monoclonal antibodies have been widely assessed for T-cell leukaemia/lymphoma treatment, but yielded limited efficacy, suggesting more potent therapies targeting CD4 are required. Here T cells were transduced with a third-generation CAR specifically targeting CD4 molecule (CART4) via a two-step retroviral system, incorporating with truncated epidermal growth factor receptor (tEGFR) as tracking marker and inducible caspase-9 (iC9) as safety switch. CART4 transduced T cells showed remarkable cytotoxicity against CD4+ T cells in vitro. Those CART4 cells effectively eliminated CD4+ T tumour cell line and primary tumour cells from patients with adult T-cell leukaemia/lymphoma (ATLL) and cutaneous T-cell lymphoma (CTCL). In a xenograft model bearing T cell leukaemia cell line, CART4 cells efficiently suppressed tumour progression and prolonged mouse survival, suggesting that CART4 T cells could be a promising strategy for T-cell malignancy. Besides, as CD4 as serves the primary receptor for HIV-1 entry, it was hypothesised that the anti-CD4 CAR could be applied for HIV eradication. By in vitro co-culture assays, CART4 cells effectively eliminated target cells, including CD4+ T cells, dendritic cells (DCs), and macrophages. In vivo test utilizing A humanized mouse model of HIV treatment demonstrated that CART4 cells were superior at expanding upon antigen stimulation, eliminating target cells, and controlling HIV rebound after antiretroviral therapy (ART) interruption. Together, these results support the therapeutic potential of CART4 in patients with T-cell malignancies and HIV-1 infection, respectively.Open Acces

Photoconductivity of Single-crystalline Selenium Nanotubes

Photoconductivity of single-crystalline selenium nanotubes (SCSNT) under a range of illumination intensities of a 633nm laser is carried out with a novel two terminal device arrangement at room temperature. It's found that SCSNT forms Schottky barriers with the W and Au contacts, and the barrier height is a function of the light intensities. In low illumination regime below 1.46x10E-4 muWmum-2, the Au-Se-W hybrid structure exhibits sharp switch on/off behavior, and the turn-on voltages decrease with increasing illuminating intensities. In the high illumination regime above 7x10E-4 muWmum-2, the device exhibits ohmic conductance with a photoconductivity as high as 0.59Ohmcm-1, significantly higher that reported values for carbon and GaN nanotubes. This finding suggests that SCSNT is potentially a good photo-sensor material as well we a very effective solar cell material.Comment: 12pages including 5 figures, submitted to Nanotechnolog

Classification with class noises through probabilistic sampling

© 2017 Accurately labeling training data plays a critical role in various supervised learning tasks. Now a wide range of algorithms have been developed to identify and remove mislabeled data as labeling in practical applications might be erroneous due to various reasons. In essence, these algorithms adopt the strategy of one-zero sampling (OSAM), wherein a sample will be selected and retained only if it is recognized as clean. There are two types of errors in OSAM: identifying a clean sample as mislabeled and discarding it, or identifying a mislabeled sample as clean and retaining it. These errors could lead to poor classification performance. To improve classification accuracy, this paper proposes a novel probabilistic sampling (PSAM) scheme. In PSAM, a cleaner sample has more chance to be selected. The degree of cleanliness is measured by the confidence on the label. To accurately estimate the confidence value, a probabilistic multiple voting idea is proposed which is able to assign a high confidence value to a clean sample and a low confidence value to a mislabeled sample. Finally, we demonstrate that PSAM could effectively improve the classification accuracy over existing OSAM methods

Effects of brake pressures on stick-slip bifurcation and chaos of the vehicle brake system

Vibrations and noises induced by vehicle braking at low speeds are problems that have always blocked the development of the automotive industry, which the stick-slip vibrations of brake system are the major reason that causes the vibration and noise. Ref. [19] predicts chaotic stick-slip vibrations by introducing a torsional model. Additionally, in this article, we have established a four degree of freedom torsional braking model under pure braking, which is based on that reference. Since the chaotic stick-slip motions have been found based on a proper friction model through numerical method, from the bifurcation diagram of the relative velocity between the rotor and pad to corresponding brake pressure, we also found the dynamic characteristics of the system changing from doubling periodic bifurcation to chaos just by increasing the brake pressures. Any further numerical study showed that the doubling periodic bifurcation occurs both in stick phase and slip phase, which composed of the upper and lower bifurcation of the global bifurcation diagram. Thus, chaos and periodic motions in it can be identified by calculating Lyapunov exponents with ‘CLDYN’ method. At last, the effects of friction model parameters on bifurcation and chaos were studied, which provides important evidence theoretically showing that the decrease in braking vibrations and noises at low speed and the matching control of braking pressures

Connecting Researchers with Companies for University-Industry Collaboration

Nowadays, companies are spending more time and money to enhance their innovation ability to respond to the increasing market competition. The pressure makes companies seek help from external knowledge, especially those from academia. Unfortunately, there is a gap between knowledge seekers (companies) and suppliers (researchers) due to the scattered and asymmetric information. To facilitate shared economy, various platforms are designed to connect the two parties. In this context, we design a researcher recommendation system to promote their collaboration (e.g. patent license, collaborative research, contract research and consultancy) based on a research social network with complete information about both researchers and companies. In the recommendation system, we evaluate researchers from three aspects, including expertise relevance, quality and trustworthiness. The experiment result shows that our system performs well in recommending suitable researchers for companies. The recommendation system has been implemented on an innovation platform, InnoCity.

The response of human induced pluripotent stem cells to cyclic temperature changes explored by BIO-AFM

Human induced pluripotent stem cells (hiPSCs) are highly sensitive to extrinsic physical and biochemical signals from their extracellular microenvironments. In this study, we analyzed the effect of cyclic temperature changes on hiPSCs behaviors, especially by means of scanning force microscopy (BIO-AFM). The alternation in cellular mechanics, as well as the secretion and pattern of deposition of extracellular matrix (ECM) protein in hiPSCs were evaluated. The arrangement of the actin cytoskeleton changed with the variation of the temperature. The rearranged cytoskeleton architecture led to the subsequent changes in cell mechanics (Young's modulus of hiPSCs). With the exposure to the cyclic cold stimuli, an increase in the average surface roughness (Ra) and roughness mean square (RMS) was detected. This observation might be at least in part due to the upregulated secretion of Laminin α5 during repeated temporary cooling. The expression of pluripotent markers, NANOG and SOX2, was not impaired in hiPSCs, when exposed to the cyclic cold stimuli for 24 h. Our findings provide an insight into the effect of temperature on the hiPSC behaviors, which may contribute to a better understanding of the application of locally controlled therapeutic hypothermia

A Dual-view Attention Neural Network for Assigning Industrial Categories to Academic Patents

Industrial technology matching events are held by governmental institutions worldwide to promote patent transfer from universities to industries. When collecting academic patents for the matching events, governmental institutions lack professional knowledge for identifying academic patents suitable for various industries. Therefore, previous studies adopted International Patent Classification (IPC) codes assigned by patent examiners to represent patents and mined the industry-related cues through the mapping link between IPC codes and industry categories. However, IPC codes are too general to specifically represent the complex patents, leading to inaccurate tagging. The view of patent inventors (e.g., patent titles and abstracts) contains rich industry-related cues that benefit assigning industrial categories to academic patents. Therefore, we propose a dual-view attention neural network that learns low-dimensional patent representations from the views of patent examiners and inventors and merges the representations for classifying academic patents into suitable industrial categories. Experiments show that the proposed method outperforms benchmark methods

A Significant Increase of RNAi Efficiency in Human Cells by the CMV Enhancer with a tRNAlys Promoter

RNA interference (RNAi) is the process of mRNA degradation induced by double-stranded RNA in a sequence-specific manner. Different types of promoters, such as U6, H1, tRNA, and CMV, have been used to control the inhibitory effect of RNAi expression vectors. In the present study, we constructed two shRNA expression vectors, respectively, controlled by tRNAlys and CMV enhancer-tRNAlys promoters. Compared to the vectors with tRNAlys or U6 promoter, the vector with a CMV enhancer-tRNAlys promoter silenced pokemon more efficiently on both the mRNA and the protein levels. Meanwhile, the silencing of pokemon inhibited the proliferation of MCF7 cells, but the induction of apoptosis of MCF7 cells was not observed. We conclude that the CMV enhancer-tRNAlys promoter may be a powerful tool in driving intracellular expression of shRNA which can efficiently silence targeted gene