Neighborhood-based Hard Negative Mining for Sequential Recommendation

Negative sampling plays a crucial role in training successful sequential recommendation models. Instead of merely employing random negative sample selection, numerous strategies have been proposed to mine informative negative samples to enhance training and performance. However, few of these approaches utilize structural information. In this work, we observe that as training progresses, the distributions of node-pair similarities in different groups with varying degrees of neighborhood overlap change significantly, suggesting that item pairs in distinct groups may possess different negative relationships. Motivated by this observation, we propose a Graph-based Negative sampling approach based on Neighborhood Overlap (GNNO) to exploit structural information hidden in user behaviors for negative mining. GNNO first constructs a global weighted item transition graph using training sequences. Subsequently, it mines hard negative samples based on the degree of overlap with the target item on the graph. Furthermore, GNNO employs curriculum learning to control the hardness of negative samples, progressing from easy to difficult. Extensive experiments on three Amazon benchmarks demonstrate GNNO's effectiveness in consistently enhancing the performance of various state-of-the-art models and surpassing existing negative sampling strategies. The code will be released at \url{https://github.com/floatSDSDS/GNNO}

Combined PD-1 blockade and GITR triggering induce a potent antitumor immunity in murine cancer models and synergizes with chemotherapeutic drugs

BACKGROUND: The coinhibitory receptor Programmed Death-1 (PD-1) inhibits effector functions of activated T cells and prevents autoimmunity, however, cancer hijack this pathway to escape from immune attack. The costimulatory receptor glucocorticoid-induced TNFR related protein (GITR) is up-regulated on activated T cells and increases their proliferation, activation and cytokine production. We hypothesize that concomitant PD-1 blockade and GITR triggering would synergistically improve the effector functions of tumor-infiltrating T cells and increase the antitumor immunity. In present study, we evaluated the antitumor effects and mechanisms of combined PD-1 blockade and GITR triggering in a clinically highly relevant murine ID8 ovarian cancer model. METHODS: Mice with 7 days-established peritoneal ID8 ovarian cancer were treated intraperitoneally (i.p.) with either control, anti-PD-1, anti-GITR or anti-PD-1/GITR monoclonal antibody (mAb) and their survival was evaluated; the phenotype and function of tumor-associated immune cells in peritoneal cavity of treated mice was analyzed by flow cytometry, and systemic antigen-specific immune response was evaluated by ELISA and cytotoxicity assay. RESULTS: Combined anti-PD-1/GITR mAb treatment remarkably inhibited peritoneal ID8 tumor growth with 20% of mice tumor free 90 days after tumor challenge while treatment with either anti-PD-1 or anti-GITR mAb alone exhibited little antitumor effect. The durable antitumor effect was associated with a memory immune response and conferred by CD4(+) cells and CD8(+) T cells. The treatment of anti-PD-1/GITR mAb increased the frequencies of interferon-γ-producing effector T cells and decreased immunosuppressive regulatory T cells and myeloid-derived suppressor cells, shifting an immunosuppressive tumor milieu to an immunostimulatory state in peritoneal cavity. In addition, combined treatment of anti-PD-1/GITR mAb mounted an antigen-specific immune response as evidenced by antigen-specific IFN-γ production and cytolytic activity of spleen cells from treated mice. More importantly, combined treatment of anti-PD-1/GITR mAb and chemotherapeutic drugs (cisplatin or paclitaxel) further increased the antitumor efficacy with 80% of mice obtaining tumor-free long-term survival in murine ID8 ovarian cancer and 4 T1 breast cancer models. CONCLUSIONS: Combined anti-PD-1/GITR mAb treatment induces a potent antitumor immunity, which can be further promoted by chemotherapeutic drugs. A combined strategy of anti-PD-1/GITR mAb plus cisplatin or paclitaxel should be considered translation into clinic

Surface plasmon resonance hydrogen sensor based on metallic grating with high sensitivity

Abstract: High sensitivity is obtained at larger resonant incident angle if negative diffraction order of metallic grating is used to excite the surface plasmon. A highly sensitive grating-based surface plasmon resonance (SPR) sensor is designed for the hydrogen detection. A thin palladium (Pd) film deposited on the grating surface is used as transducer. The influences of grating period and the thickness of Pd on the performance of sensor are investigated using rigorous coupled-wave analysis (RCWA) method. The sensitivity as well as the width of the SPR curves and reflective amplitude is considered simultaneously for designing the grating-based SPR hydrogen sensor, and a set of optimized structural parameters is presented. The performance of grating-based SPR sensor is also compared with that of conventional prism-based SPR sensor. 12． M. J. Jory, P. S. Vukusic, and J. R. Sambles, "Development of a prototype gas sensor using surface plasmon resonance on gratings," Sens. Actuators B 17, 203-209 (1994). 13． C. R. Lawrence, N. J. Geddes, D. N. Furlong, and J. R. Sambles, "Surface plasmon resonance studies of immunoreactions utilizing disposable diffraction gratings," Biosens. Bioelectron. 11, 389-400 (1996). 14． D. Zhang, P. Wang, X. Jiao, G. Yuan, J. Zhang, C. Chen, H. Ming, and R. Rao, "Investigation of the sensitivity of H-shaped nano-grating surface plasmon resonance biosensors using rigorous coupled wave analysis," Appl. Phys. A 89, 407-411(2007 5056-5070 (1974). 18． D. R. Shankaran, K. V. Gobi, T. Sakai, K. Matsumoto, K. Toko, and N. Miura, "Surface plasmon resonance immunosensor for highly sensitive detection of 2, 4, 6-trinitrotoluene," Biosens. Bioelectron. 20, 1750-1756 (2005). 19． B. Chadwick, J. Tann, M. Brungs, and M. Gal, "A hydrogen sensor based on the optical generation of surface plasmons in a palladium alloy," Sens. Actuators B 17, 215-220 (1994)

Role of histone methyltransferase SETDB1 in regulation of tumourigenesis and immune response

Epigenetic alterations are implicated in tumour immune evasion and immune checkpoint blockade (ICB) resistance. SET domain bifurcated histone methyltransferase 1 (SETDB1) is a histone lysine methyltransferase that catalyses histone H3K9 di- and tri-methylation on euchromatin, and growing evidence indicates that SETDB1 amplification and abnormal activation are significantly correlated with the unfavourable prognosis of multiple malignant tumours and contribute to tumourigenesis and progression, immune evasion and ICB resistance. The main underlying mechanism is H3K9me3 deposition by SETDB1 on tumour-suppressive genes, retrotransposons, and immune genes. SETDB1 targeting is a promising approach to cancer therapy, particularly immunotherapy, because of its regulatory effects on endogenous retroviruses. However, SETDB1-targeted therapy remains challenging due to potential side effects and the lack of antagonists with high selectivity and potency. Here, we review the role of SETDB1 in tumourigenesis and immune regulation and present the current challenges and future perspectives of SETDB1 targeted therapy

Global hybrid simulations of soft X-ray emissions in the Earth’s magnetosheath

Earth’s magnetopause is a thin boundary separating the shocked solar wind plasma from the magnetospheric plasmas, and it is also the boundary of the solar wind energy transport to the magnetosphere. Soft X-ray imaging allows investigation of the large-scale magnetopause by providing a two-dimensional (2-D) global view from a satellite. By performing 3-D global hybrid-particle-in-cell (hybrid-PIC) simulations, we obtain soft X-ray images of Earth’s magnetopause under different solar wind conditions, such as different plasma densities and directions of the southward interplanetary magnetic field. In all cases, magnetic reconnection occurs at low latitude magnetopause. The soft X-ray images observed by a hypothetical satellite are shown, with all of the following identified: the boundary of the magnetopause, the cusps, and the magnetosheath. Local X-ray emissivity in the magnetosheath is characterized by large amplitude fluctuations (up to 160%); however, the maximum line-of-sight-integrated X-ray intensity matches the tangent directions of the magnetopause well, indicating that these fluctuations have limited impact on identifying the magnetopause boundary in the X-ray images. Moreover, the magnetopause boundary can be identified using multiple viewing geometries. We also find that solar wind conditions have little effect on the magnetopause identification. The Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) mission will provide X-ray images of the magnetopause for the first time, and our global hybrid-PIC simulation results can help better understand the 2-D X-ray images of the magnetopause from a 3-D perspective, with particle kinetic effects considered

Three-dimensional network of filamentary currents and super-thermal electrons during magnetotail magnetic reconnection

Magnetic reconnection is a fundamental plasma process by which magnetic field lines on two sides of the current sheet flow inward to yield an X-line topology. It is responsible for producing energetic electrons in explosive phenomena in space, astrophysical, and laboratorial plasmas. The X-line region is supposed to be the important place for generating energetic electrons. However, how these energetic electrons are generated in such a limited region is still poorly understood. Here, using Magnetospheric multiscale mission data acquired in Earth&rsquo;s magnetotail, we present direct evidence of super-thermal electrons up to 300&thinsp;keV inside an X-line region, and the electrons display a power-law spectrum with an index of about 8.0. Concurrently, three-dimensional network of dynamic filamentary currents in electron scale is observed and leads to electromagnetic turbulence therein. The observations indicate that the electrons are effectively accelerated while the X-line region evolves into turbulence with a complex filamentary current network. &nbsp;</p