Inflammation and host-microbe signaling in the development and progression of colorectal carcinoma

Gut microbiota play an integral role in the postnatal development and maturation of the intestinal epithelium as well as the innate and adaptive immune system. Gut microbes communicate to the host via pattern recognition receptors (PRRs) which regulate intestinal homeostasis during health and disease. My thesis has elucidated the role of gut microflora and PRR-mediated signaling during inflammation, infection and tumor development. I have examined the relevant contributions of host-microbe crosstalk in the regulation of intestinal tumorigenesis (Paper I and II) and innate immune responses to enteric pathogens (Paper III), as well as the transcriptional regulation of gene expression during inflammation and cancer development (Paper IV). In Paper I, the role of microbiota-derived signals in promoting tumor growth in APCMin/+ mice, a mouse model of colorectal cancer (CRC) was examined. Our data showed that germ-free APCMin/+ mice have a reduced tumor load compared to that observed in APCMin/+ mice harboring gut microbiota. Further in-depth characterization studies suggested a role for c-Jun/JNK and myeloid cell-dependent STAT3 activation pathways in the acceleration of tumor growth. Thus, gut microbiota can accelerate tumor growth. In Paper II, the role of PRR-mediated signaling in intestinal tumorigenesis was studied. By introduction of a constitutively active Toll-like-receptor 4 transgene (CD4-TLR4) to the intestinal epithelium of APCMin/+ mice, we found a marked reduction of intestinal tumor burden in CD4-TLR4-APCMin/+ mice. This tumor suppression was likely due to the observed Cox-2 down-regulation and IFNβ induction which resulted in increased apoptosis of tumor cells. These results unravel a previously unrecognized role of TLR4 signaling in modulating the balance between proliferative and apoptotic signals. In Paper III, the regulation of host innate immune responses during Salmonella Typhimurium induced colitis was studied. Our data demonstrated an aggravated colitis in infected mice lacking the innate immune regulator gene - PPAR in the intestinal epithelium. This increased tissue damage correlated with the elevation of lipocalin-2 (Lcn2) expression, which promoted the stabilization of tissue degrading enzyme, matrix metalloproteinase 9 (MMP-9). Interestingly, Lcn2-deficient mice were markedly protected from S. Typhimurium induced colitis. These findings therefore illustrate how enteric pathogens can exploit the host’s mucosal defense mechanisms to disrupt normal host-microbe homeostasis, in order to ensure colonization and survival in the host. In Paper IV, I have examined the significance of histone modifications and chromatinbinding proteins in the transcriptional regulation of T lymphocytes. Our results demonstrate that the bromodomain-containing protein, BRD4, is important in regulating Pol II Ser2-mediated transcriptional elongation in human CD4+ T cells. In conclusion, my thesis work further underscores the significant impact of gut microbiota mediated signaling in the regulation of intestinal homeostasis and tumorigenesis

Intense keV isolated attosecond pulse generation by orthogonally polarized multicycle midinfrared two-color laser field

We theoretically investigate the generation of intense keV attosecond pulses in an orthogonally polarized multicycle midinfrared two-color laser field. It is demonstrated that multiple continuum-like humps, which have a spectral width of about twenty orders of harmonics and an intensity of about one order higher than adjacent normal harmonic peaks, are generated under proper two-color delays, owing to the reduction of the number of electron-ion recollisions and suppression of inter-half-cycle interference effect of multiple electron trajectories when the long wavelength midinfrared driving field is used. Using the semiclassical trajectory model, we have revealed the two-dimensional manipulation of the electron-ion recollision process, which agrees well with the time frequency analysis. By filtering these humps, intense isolated attosecond pulses are directly generated without any phase compensation. Our proposal provides a simple technique to generate intense isolated attosecond pulses with various central photon energies covering the multi-keV spectral regime by using multicycle driving pulses with high pump energy in experiment.Comment: 11 pages,5 figures, research articl

Cochylimorpha Razowski (Lepidoptera: Tortricidae: Cochylini) in China: one new species, three newly recorded species and description of the female of three species

Cochylimorpha subnomadana sp. n., from Mt. Liupan, Ningxia, China is described as new. Cochylimorpha declivana (Kennel, 1901), C. halophilana clavana (Constant, 1888), and C. meridiolana (Ragonot, 1894) are newly recorded for China. The previously unknown females of C. conankinensis (Ge, 1992), C. maleropa (Meyrick, 1937), and C. razowskiana Kuznetzov, 2005 are described for the first time. Photographs of the adults and genitalia are provided, along with a key to all the described Chinese Cochylimorpha species

Graph Homomorphism Revisited for Graph Matching

In a variety of emerging applications one needs to decide whether a graph G matches another G p , i.e. , whether G has a topological structure similar to that of G p . The traditional notions of graph homomorphism and isomorphism often fall short of capturing the structural similarity in these applications. This paper studies revisions of these notions, providing a full treatment from complexity to algorithms. (1) We propose p-homomorphism (p -hom) and 1-1 p -hom, which extend graph homomorphism and subgraph isomorphism, respectively, by mapping edges from one graph to paths in another, and by measuring the similarity of nodes . (2) We introduce metrics to measure graph similarity, and several optimization problems for p -hom and 1-1 p -hom. (3) We show that the decision problems for p -hom and 1-1 p -hom are NP-complete even for DAGs, and that the optimization problems are approximation-hard. (4) Nevertheless, we provide approximation algorithms with provable guarantees on match quality. We experimentally verify the effectiveness of the revised notions and the efficiency of our algorithms in Web site matching, using real-life and synthetic data. </jats:p

Swing Leg Motion Strategy for Heavy-load Legged Robot Based on Force Sensing

The heavy-load legged robot has strong load carrying capacity and can adapt to various unstructured terrains. But the large weight results in higher requirements for motion stability and environmental perception ability. In order to utilize force sensing information to improve its motion performance, in this paper, we propose a finite state machine model for the swing leg in the static gait by imitating the movement of the elephant. Based on the presence or absence of additional terrain information, different trajectory planning strategies are provided for the swing leg to enhance the success rate of stepping and save energy. The experimental results on a novel quadruped robot show that our method has strong robustness and can enable heavy-load legged robots to pass through various complex terrains autonomously and smoothly

MixEdit: Revisiting Data Augmentation and Beyond for Grammatical Error Correction

Data Augmentation through generating pseudo data has been proven effective in mitigating the challenge of data scarcity in the field of Grammatical Error Correction (GEC). Various augmentation strategies have been widely explored, most of which are motivated by two heuristics, i.e., increasing the distribution similarity and diversity of pseudo data. However, the underlying mechanism responsible for the effectiveness of these strategies remains poorly understood. In this paper, we aim to clarify how data augmentation improves GEC models. To this end, we introduce two interpretable and computationally efficient measures: Affinity and Diversity. Our findings indicate that an excellent GEC data augmentation strategy characterized by high Affinity and appropriate Diversity can better improve the performance of GEC models. Based on this observation, we propose MixEdit, a data augmentation approach that strategically and dynamically augments realistic data, without requiring extra monolingual corpora. To verify the correctness of our findings and the effectiveness of the proposed MixEdit, we conduct experiments on mainstream English and Chinese GEC datasets. The results show that MixEdit substantially improves GEC models and is complementary to traditional data augmentation methods.Comment: Accepted to Findings of EMNLP 202

Nanostructured graphite/Li-N-H based composite materials for hydrogen storage

Ball-milled hydrogenated graphite and LiNH2+LiH are considered potential materials for solid state hydrogen storage. This work investigates the structural and dehydrogenation properties of ball-milled graphite and composites of 2graphite+LiNH2, LiNH2+1.2LiH and 2graphite+LiNH2+1.2LiH. Characterization of the as-milled materials showed the formation of a nanocrystalline/amorphous mixture in the composites. A higher ball-milling rotation speed led to a smaller crystallite size for graphite. Decomposition of the as-milled graphite was performed by heating to 950 °C at 2 °C /min. Graphite milled for 10 h released 2.2 wt. % H2 at onset temperature of 350 °C, indicates the presence of C-H bond in the hydrogenated graphite. A large amount of H2 was released during the heating of graphite+LiNH2, as opposed to the release of NH3 during the decomposition of as-received LiNH2. Dehydrogenation of 2graphite+LiNH2+1.2LiH was performed by heating to 500 °C at 2 °C /min. The onset temperature of hydrogen decomposition was reduced to 80 °C-95 °C. In-situ XRD shows the presence of Li2NCN above 350 °C, with no Li2C2 or Li2NH detected. The formation pathway of this new phase is not clear, but it presumably must involve a reaction between graphite and a Li-N-H compound