QR-CLIP: Introducing Explicit Open-World Knowledge for Location and Time Reasoning

Daily images may convey abstract meanings that require us to memorize and infer profound information from them. To encourage such human-like reasoning, in this work, we teach machines to predict where and when it was taken rather than performing basic tasks like traditional segmentation or classification. Inspired by Horn's QR theory, we designed a novel QR-CLIP model consisting of two components: 1) the Quantity module first retrospects more open-world knowledge as the candidate language inputs; 2) the Relevance module carefully estimates vision and language cues and infers the location and time. Experiments show our QR-CLIP's effectiveness, and it outperforms the previous SOTA on each task by an average of about 10% and 130% relative lift in terms of location and time reasoning. This study lays a technical foundation for location and time reasoning and suggests that effectively introducing open-world knowledge is one of the panaceas for the tasks.Comment: Technical Report. Github: https://github.com/Shi-Wm/QR-CLI

Trans-Regime Structural Transition of (In3+ + Nb5+) Co-Doped Anatase TiO2 Nanocrystals under High Pressure

Chemical co-doping and high pressure reactions have been broadly used to synthesize novel materials or to tune the physicochemical properties of traditional materials. Here, we take In3+ and Nb5+ ions co-doped anatase TiO2 nanocrystals as an example and report that a combination of both a chemical and a high pressure reaction route is more powerful for the preparation of metastable polymorphs. It is experimentally demonstrated that In3+ and Nb5+ co-doping significantly changes the high-pressure reaction behaviors of anatase TiO2 nanocrystals (<10 nm) and leads to their trans-regime structural transition in terms of in situ Raman analysis, from an anatase to a baddeleyite-like phase under compressive pressures and then to an α-PbO2-like structure under decompressive pressures. This abnormal phase transition is attributed to a defect-induced heterogeneous nucleation mechanism. Furthermore, the stiffness of co-doped TiO2 nanocrystals is significantly enhanced due to the synergistic effects of co-dopants. This research not only proposes a potentially effective strategy to synthesize co-doped metastable polymorphic phases but also suggests one feasible method to improve the mechanical properties of anatase TiO2 nanocrystals

Targeting Inhibition of Accumulation and Function of Myeloid-Derived Suppressor Cells by Artemisinin via PI3K/AKT, mTOR, and MAPK Pathways Enhances Anti-PD-L1 Immunotherapy in Melanoma and Liver Tumors

Despite the remarkable success and efficacy of immune checkpoint blockade (ICB) therapy such as anti-PD-L1 antibody in treating cancers, myeloid-derived suppressor cells (MDSCs) that lead to the formation of the protumor immunosuppressive microenvironment are one of the major contributors to ICB resistance. Therefore, inhibition of MDSC accumulation and function is critical for further enhancing the therapeutic efficacy of anti-PD-L1 antibody in a majority of cancer patients. Artemisinin (ART), the most effective antimalarial drug with tumoricidal and immunoregulatory activities, is a potential option for cancer treatment. Although ART is reported to reduce MDSC levels in 4T1 breast tumor model and improve the therapeutic efficacy of anti-PD-L1 antibody in T cell lymphoma-bearing mice, how ART influences MDSC accumulation, function, and molecular pathways as well as MDSC-mediated anti-PD-L1 resistance in melanoma or liver tumors remains unknown. Here, we reported that ART blocks the accumulation and function of MDSCs by polarizing M2-like tumor-promoting phenotype towards M1-like antitumor one. This switch is regulated via PI3K/AKT, mTOR, and MAPK signaling pathways. Targeting MDSCs by ART could significantly reduce tumor growth in various mouse models. More importantly, the ART therapy remarkably enhanced the efficacy of anti-PD-L1 immunotherapy in tumor-bearing mice through promoting antitumor T cell infiltration and proliferation. These findings indicate that ART controls the functional polarization of MDSCs and targeting MDSCs by ART provides a novel therapeutic strategy to enhance anti-PD-L1 cancer immunotherapy

Genetic diversity and selection of Tibetan sheep breeds revealed by whole-genome resequencing

Objective This study aimed to elucidate the underlying gene regions responsible for productive, phenotypic or adaptive traits in different ecological types of Tibetan sheep and the discovery of important genes encoding valuable traits. Methods We used whole-genome resequencing to explore the genetic relationships, phylogenetic tree, and population genetic structure analysis. In addition, we identified 28 representative Tibetan sheep single-nucleotide polymorphisms (SNPs) and genomic selective sweep regions with different traits in Tibetan sheep by fixation index (Fst) and the nucleotide diversity (θπ) ratio. Results The genetic relationships analysis showed that each breed partitioned into its own clades and had close genetic relationships. We also identified many potential breed-specific selective sweep regions, including genes associated with hypoxic adaptability (MTOR, TRHDE, PDK1, PTPN9, TMTC2, SOX9, EPAS1, PDGFD, SOCS3, TGFBR3), coat color (MITF, MC1R, ERCC2, TCF25, ITCH, TYR, RALY, KIT), wool traits (COL4A2, ERC2, NOTCH2, ROCK1, FGF5, SOX9), and horn phenotypes (RXFP2). In particular, a horn-related gene, RXFP2, showed the four most significantly associated SNP loci (g. 29481646 A>G, g. 29469024 T>C, g. 29462010 C>T, g. 29461968 C>T) and haplotypes. Conclusion This finding demonstrates the potential for genetic markers in future molecular breeding programs to improve selection for horn phenotypes. The results will facilitate the understanding of the genetic basis of production and adaptive unique traits in Chinese indigenous Tibetan sheep taxa and offer a reference for the molecular breeding of Tibetan sheep

Sarcopenia Was a Poor Prognostic Predictor for Patients With Advanced Lung Cancer Treated With Immune Checkpoint Inhibitors

BackgroundIt remains not well known whether skeletal muscle mass (SMM) loss has any impact on the effectiveness of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer. We aimed to evaluate the association between SMM and clinical outcome of patients with advanced lung cancer receiving ICIs as first line or second line.Materials and MethodsFrom March 1st, 2019 to March 31st, 2021 at our hospital, 34 patients with advanced lung cancer treated with first-line or second-line ICIs were enrolled retrospectively. The estimation of skeletal muscle index (SMI) for sarcopenia was assessed at the level of the third lumbar vertebra (L3) on computed tomography (CT) images obtained within 4 weeks before initiation of ICIs treatment. The impact of sarcopenia (low SMI) on progression free survival (PFS) was analyzed using Kaplan-Meier method and log-rank tests. The effect of various variables on PFS was evaluated using Cox proportional hazards regression model with univariate and multivariate analysis. The impact on treatment response including objective response rate (ORR) and disease control rate (DCR) and immunotherapy related adverse events (irAEs) between patients with and without sarcopenia was compared by the chi-squared test. The comparison of SMI value between patients with objective response (OR), disease control (DC) and those without OR and DC was used student t-test or Mann-Whitney U test.ResultsBoth in univariate and multivariate analysis, sarcopenia and treatment lines were the predictive factors for PFS (p &lt; 0.05). Patients with sarcopenia had significantly shorter PFS than that of non-sarcopenic ones [6.57 vs. 16.2 months, hazard ratios (HR) = 2.947 and 3.542, and 95% confidence interval (CI): 1.123–13.183 and 1.11–11.308, p = 0.022 and 0.033]. No significant difference in ORR and irAEs was found. Patients with sarcopenia had lower DCR than those without sarcopenia. The mean SMI value of DCR group and non-DCR group was 32.94 ± 5.49 and 44.77 ± 9.06 cm2/m2, respectively (p = 0.008).ConclusionSarcopenia before immunotherapy might be a significant predictor for poor prognosis including shorter PFS and lower DCR in patients with advanced lung cancer treated with ICIs as first line or second line

Genetic and metabolic links between the murine microbiome and memory.

BackgroundRecent evidence has linked the gut microbiome to host behavior via the gut-brain axis [1-3]; however, the underlying mechanisms remain unexplored. Here, we determined the links between host genetics, the gut microbiome and memory using the genetically defined Collaborative Cross (CC) mouse cohort, complemented with microbiome and metabolomic analyses in conventional and germ-free (GF) mice.ResultsA genome-wide association analysis (GWAS) identified 715 of 76,080 single-nucleotide polymorphisms (SNPs) that were significantly associated with short-term memory using the passive avoidance model. The identified SNPs were enriched in genes known to be involved in learning and memory functions. By 16S rRNA gene sequencing of the gut microbial community in the same CC cohort, we identified specific microorganisms that were significantly correlated with longer latencies in our retention test, including a positive correlation with Lactobacillus. Inoculation of GF mice with individual species of Lactobacillus (L. reuteri F275, L. plantarum BDGP2 or L. brevis BDGP6) resulted in significantly improved memory compared to uninoculated or E. coli DH10B inoculated controls. Untargeted metabolomics analysis revealed significantly higher levels of several metabolites, including lactate, in the stools of Lactobacillus-colonized mice, when compared to GF control mice. Moreover, we demonstrate that dietary lactate treatment alone boosted memory in conventional mice. Mechanistically, we show that both inoculation with Lactobacillus or lactate treatment significantly increased the levels of the neurotransmitter, gamma-aminobutyric acid (GABA), in the hippocampus of the mice.ConclusionTogether, this study provides new evidence for a link between Lactobacillus and memory and our results open possible new avenues for treating memory impairment disorders using specific gut microbial inoculants and/or metabolites. Video Abstract

Measurement of the Inclusive Charm Cross Section at 4.03 GeV and 4.14 GeV

The cross section for charmed meson production at $\sqrt{s} = 4.03$ and 4.14 GeV has been measured with the Beijing Spectrometer. The measurement was made using 22.3 $pb^{-1}$ of $e^+e^-$ data collected at 4.03 GeV and 1.5 $pb^{-1}$ of $e^+e^-$ data collected at 4.14 GeV. Inclusive observed cross sections for the production of charged and neutral D mesons and momentum spectra are presented. Observed cross sections were radiatively corrected to obtain tree level cross sections. Measurements of the total hadronic cross section are obtained from the charmed meson cross section and an extrapolation of results from below the charm threshold.Comment: 11 pages, 13 figures. The top level tex file is paper.tex. It builds the paper from other tex files in this .tar and the .eps file