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Knowledge graph reasoning plays an important role in data mining, AI, Web, and social science. These knowledge graphs serve as intuitive repositories of human knowledge, allowing for the inference of new information. However, traditional symbolic reasoning, while powerful in its own right, faces challenges posed by incomplete and noisy data in the knowledge graphs. In contrast, recent years have witnessed the emergence of Neural Symbolic AI, an exciting development that fuses the capabilities of deep learning and symbolic reasoning. It aims to create AI systems that are not only highly interpretable and explainable but also incredibly versatile, effectively bridging the gap between symbolic and neural approaches. Furthermore, with the advent of large language models, the integration of LLMs with knowledge graph reasoning has emerged as a prominent frontier, offering the potential to unlock unprecedented capabilities. This tutorial aims to comprehensively review different aspects of knowledge graph reasoning applications and also introduce the recent advances about Neural Symbolic reasoning and combining knowledge graph reasoning with large language models. It is intended to benefit researchers and practitioners in the fields of data mining, AI, Web, and social science. © 2024 Copyright held by the owner/author(s). Publication rights licensed to ACM.

Recent advancements in contrastive learning have revolutionized self-supervised representation learning and achieved state-of-the-art performance on benchmark tasks. While most existing methods focus on applying contrastive learning to input data modalities such as images, natural language sentences, or networks, they overlook the potential of utilizing outputs from previously trained encoders. In this paper, we introduce SIMSKIP, a novel contrastive learning framework that specifically refines input embeddings for downstream tasks. Unlike traditional unsupervised learning approaches, SIMSKIP takes advantage of the output embeddings of encoder models as its input. Through theoretical analysis, we provide evidence that applying SIMSKIP does not result in larger upper bounds on downstream task errors than those of the original embeddings, which serve as SIMSKIP's input. Experimental results on various open datasets demonstrate that the embeddings produced by SIMSKIP improve performance on downstream tasks.

Despite the superb performance in many tasks, large language models (LLMs) bear the risk of generating hallucination or even wrong answers when confronted with tasks that demand the accuracy of knowledge. The issue becomes even more noticeable when addressing logic queries that require multiple logic reasoning steps. On the other hand, knowledge graph (KG) based question answering methods are capable of accurately identifying the correct answers with the help of knowledge graph, yet its accuracy could quickly deteriorate when the knowledge graph itself is sparse and incomplete. It remains a critical challenge on how to integrate knowledge graph reasoning with LLMs in a mutually beneficial way so as to mitigate both the hallucination problem of LLMs as well as the incompleteness issue of knowledge graphs. In this paper, we propose 'Logic-Query-of-Thoughts' (LGOT) which is the first of its kind to combine LLMs with knowledge graph based logic query reasoning. LGOT seamlessly combines knowledge graph reasoning and LLMs, effectively breaking down complex logic queries into easy to answer subquestions. Through the utilization of both knowledge graph reasoning and LLMs, it successfully derives answers for each subquestion. By aggregating these results and selecting the highest quality candidate answers for each step, LGOT achieves accurate results to complex questions. Our experimental findings demonstrate substantial performance enhancements, with up to 20% improvement over ChatGPT.

Objective: Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1/ligand-1 (PD-1/PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), and lymphocyte-activation gene-3 (LAG-3) have been widely studied and applied throughout the course of cancer treatment. This study aimed to provide a comprehensive profile of ICI-associated toxicity and elucidate the toxicity patterns of ICIs across different treatment lines. Methods: In total, 155 cohorts comprising 24 539 eligible patients were included in the safety analysis. Trial name, registration number, cancer type, trial phase, clinical setting, trial design, regimen, dosing schedule, age, sex and ethnicity distributions, number of patients, number of treatment-related adverse events (trAEs), and number of treatment-related death were extracted. We defined a timeline from the neoadjuvant setting to the third-line setting. We also introduced a synthesizing principle for adverse event rates (SPAER) of immunotherapy to ensure the comparability and reliability across different treatment lines. The study protocol was registered and approved by the PROSPERO protocol review committee (CRD42021242368). Results: After excluding the neoadjuvant setting group, we observed a distinct reduction in the incidence of treatment-related adverse events (trAEs) with an advancement of the line of ICI treatment. The incidence of trAEs was negatively correlated with the line of treatment, irrespective of whether monotherapy or dual-ICI combination therapy was administered. Sensitivity analyses also confirmed the coincident negative correlations. Conclusion: In summary, using a timeline-based concept centered around treatment lines, we revealed the dynamic landscape of ICI-associated toxicity and found that patients treated with ICIs during later lines of therapy may have a lower risk of trAEs.

Immunophenotyping of the tumor microenvironment (TME) is essential for enhancing immunotherapy effi-cacy. However, strategies for characterizing the TME exhibit significant heterogeneity. Here, we show that endoplasmic reticular oxidoreductase-1a (ERO1A) mediates an immune-suppressive TME and attenuates the response to PD-1 blockade. Ablation of ERO1A in tumor cells substantially incites anti-tumor T cell im-munity and promotes the efficacy of aPD-1 in therapeutic models. Single-cell RNA-sequencing analyses confirm that ERO1A correlates with immunosuppression and dysfunction of CD8+ T cells along anti-PD-1 treatment. In human lung cancer, high ERO1A expression is associated with a higher risk of recurrence following neoadjuvant immunotherapy. Mechanistically, ERO1A ablation impairs the balance between IRE1a and PERK signaling activities and induces lethal unfolded protein responses in tumor cells undergoing endoplasmic reticulum stress, thereby enhancing anti-tumor immunity via immunogenic cell death. These findings reveal how tumor ERO1A induces immunosuppression, highlighting its potential as a therapeutic target for cancer immunotherapy.

Objective: Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1/ligand-1 (PD-1/PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), and lymphocyte-activation gene-3 (LAG-3) have been widely studied and applied throughout the course of cancer treatment. This study aimed to provide a comprehensive profile of ICI-associated toxicity and elucidate the toxicity patterns of ICIs across different treatment lines. Methods: In total, 155 cohorts comprising 24 539 eligible patients were included in the safety analysis. Trial name, registration number, cancer type, trial phase, clinical setting, trial design, regimen, dosing schedule, age, sex and ethnicity distributions, number of patients, number of treatment-related adverse events (trAEs), and number of treatment-related death were extracted. We defined a timeline from the neoadjuvant setting to the third-line setting. We also introduced a synthesizing principle for adverse event rates (SPAER) of immunotherapy to ensure the comparability and reliability across different treatment lines. The study protocol was registered and approved by the PROSPERO protocol review committee (CRD42021242368). Results: After excluding the neoadjuvant setting group, we observed a distinct reduction in the incidence of treatment-related adverse events (trAEs) with an advancement of the line of ICI treatment. The incidence of trAEs was negatively correlated with the line of treatment, irrespective of whether monotherapy or dual-ICI combination therapy was administered. Sensitivity analyses also confirmed the coincident negative correlations. Conclusion: In summary, using a timeline-based concept centered around treatment lines, we revealed the dynamic landscape of ICI-associated toxicity and found that patients treated with ICIs during later lines of therapy may have a lower risk of trAEs.

Immunophenotyping of the tumor microenvironment (TME) is essential for enhancing immunotherapy effi-cacy. However, strategies for characterizing the TME exhibit significant heterogeneity. Here, we show that endoplasmic reticular oxidoreductase-1a (ERO1A) mediates an immune-suppressive TME and attenuates the response to PD-1 blockade. Ablation of ERO1A in tumor cells substantially incites anti-tumor T cell im-munity and promotes the efficacy of aPD-1 in therapeutic models. Single-cell RNA-sequencing analyses confirm that ERO1A correlates with immunosuppression and dysfunction of CD8+ T cells along anti-PD-1 treatment. In human lung cancer, high ERO1A expression is associated with a higher risk of recurrence following neoadjuvant immunotherapy. Mechanistically, ERO1A ablation impairs the balance between IRE1a and PERK signaling activities and induces lethal unfolded protein responses in tumor cells undergoing endoplasmic reticulum stress, thereby enhancing anti-tumor immunity via immunogenic cell death. These findings reveal how tumor ERO1A induces immunosuppression, highlighting its potential as a therapeutic target for cancer immunotherapy.

Objective: Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1/ligand-1 (PD-1/PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), and lymphocyte-activation gene-3 (LAG-3) have been widely studied and applied throughout the course of cancer treatment. This study aimed to provide a comprehensive profile of ICI-associated toxicity and elucidate the toxicity patterns of ICIs across different treatment lines. Methods: In total, 155 cohorts comprising 24 539 eligible patients were included in the safety analysis. Trial name, registration number, cancer type, trial phase, clinical setting, trial design, regimen, dosing schedule, age, sex and ethnicity distributions, number of patients, number of treatment-related adverse events (trAEs), and number of treatment-related death were extracted. We defined a timeline from the neoadjuvant setting to the third-line setting. We also introduced a synthesizing principle for adverse event rates (SPAER) of immunotherapy to ensure the comparability and reliability across different treatment lines. The study protocol was registered and approved by the PROSPERO protocol review committee (CRD42021242368). Results: After excluding the neoadjuvant setting group, we observed a distinct reduction in the incidence of treatment-related adverse events (trAEs) with an advancement of the line of ICI treatment. The incidence of trAEs was negatively correlated with the line of treatment, irrespective of whether monotherapy or dual-ICI combination therapy was administered. Sensitivity analyses also confirmed the coincident negative correlations. Conclusion: In summary, using a timeline-based concept centered around treatment lines, we revealed the dynamic landscape of ICI-associated toxicity and found that patients treated with ICIs during later lines of therapy may have a lower risk of trAEs.

Immunophenotyping of the tumor microenvironment (TME) is essential for enhancing immunotherapy effi-cacy. However, strategies for characterizing the TME exhibit significant heterogeneity. Here, we show that endoplasmic reticular oxidoreductase-1a (ERO1A) mediates an immune-suppressive TME and attenuates the response to PD-1 blockade. Ablation of ERO1A in tumor cells substantially incites anti-tumor T cell im-munity and promotes the efficacy of aPD-1 in therapeutic models. Single-cell RNA-sequencing analyses confirm that ERO1A correlates with immunosuppression and dysfunction of CD8+ T cells along anti-PD-1 treatment. In human lung cancer, high ERO1A expression is associated with a higher risk of recurrence following neoadjuvant immunotherapy. Mechanistically, ERO1A ablation impairs the balance between IRE1a and PERK signaling activities and induces lethal unfolded protein responses in tumor cells undergoing endoplasmic reticulum stress, thereby enhancing anti-tumor immunity via immunogenic cell death. These findings reveal how tumor ERO1A induces immunosuppression, highlighting its potential as a therapeutic target for cancer immunotherapy.

Objective: Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1/ligand-1 (PD-1/PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), and lymphocyte-activation gene-3 (LAG-3) have been widely studied and applied throughout the course of cancer treatment. This study aimed to provide a comprehensive profile of ICI-associated toxicity and elucidate the toxicity patterns of ICIs across different treatment lines. Methods: In total, 155 cohorts comprising 24 539 eligible patients were included in the safety analysis. Trial name, registration number, cancer type, trial phase, clinical setting, trial design, regimen, dosing schedule, age, sex and ethnicity distributions, number of patients, number of treatment-related adverse events (trAEs), and number of treatment-related death were extracted. We defined a timeline from the neoadjuvant setting to the third-line setting. We also introduced a synthesizing principle for adverse event rates (SPAER) of immunotherapy to ensure the comparability and reliability across different treatment lines. The study protocol was registered and approved by the PROSPERO protocol review committee (CRD42021242368). Results: After excluding the neoadjuvant setting group, we observed a distinct reduction in the incidence of treatment-related adverse events (trAEs) with an advancement of the line of ICI treatment. The incidence of trAEs was negatively correlated with the line of treatment, irrespective of whether monotherapy or dual-ICI combination therapy was administered. Sensitivity analyses also confirmed the coincident negative correlations. Conclusion: In summary, using a timeline-based concept centered around treatment lines, we revealed the dynamic landscape of ICI-associated toxicity and found that patients treated with ICIs during later lines of therapy may have a lower risk of trAEs.

Immunophenotyping of the tumor microenvironment (TME) is essential for enhancing immunotherapy effi-cacy. However, strategies for characterizing the TME exhibit significant heterogeneity. Here, we show that endoplasmic reticular oxidoreductase-1a (ERO1A) mediates an immune-suppressive TME and attenuates the response to PD-1 blockade. Ablation of ERO1A in tumor cells substantially incites anti-tumor T cell im-munity and promotes the efficacy of aPD-1 in therapeutic models. Single-cell RNA-sequencing analyses confirm that ERO1A correlates with immunosuppression and dysfunction of CD8+ T cells along anti-PD-1 treatment. In human lung cancer, high ERO1A expression is associated with a higher risk of recurrence following neoadjuvant immunotherapy. Mechanistically, ERO1A ablation impairs the balance between IRE1a and PERK signaling activities and induces lethal unfolded protein responses in tumor cells undergoing endoplasmic reticulum stress, thereby enhancing anti-tumor immunity via immunogenic cell death. These findings reveal how tumor ERO1A induces immunosuppression, highlighting its potential as a therapeutic target for cancer immunotherapy.

Objective: Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1/ligand-1 (PD-1/PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), and lymphocyte-activation gene-3 (LAG-3) have been widely studied and applied throughout the course of cancer treatment. This study aimed to provide a comprehensive profile of ICI-associated toxicity and elucidate the toxicity patterns of ICIs across different treatment lines. Methods: In total, 155 cohorts comprising 24 539 eligible patients were included in the safety analysis. Trial name, registration number, cancer type, trial phase, clinical setting, trial design, regimen, dosing schedule, age, sex and ethnicity distributions, number of patients, number of treatment-related adverse events (trAEs), and number of treatment-related death were extracted. We defined a timeline from the neoadjuvant setting to the third-line setting. We also introduced a synthesizing principle for adverse event rates (SPAER) of immunotherapy to ensure the comparability and reliability across different treatment lines. The study protocol was registered and approved by the PROSPERO protocol review committee (CRD42021242368). Results: After excluding the neoadjuvant setting group, we observed a distinct reduction in the incidence of treatment-related adverse events (trAEs) with an advancement of the line of ICI treatment. The incidence of trAEs was negatively correlated with the line of treatment, irrespective of whether monotherapy or dual-ICI combination therapy was administered. Sensitivity analyses also confirmed the coincident negative correlations. Conclusion: In summary, using a timeline-based concept centered around treatment lines, we revealed the dynamic landscape of ICI-associated toxicity and found that patients treated with ICIs during later lines of therapy may have a lower risk of trAEs.

Immunophenotyping of the tumor microenvironment (TME) is essential for enhancing immunotherapy effi-cacy. However, strategies for characterizing the TME exhibit significant heterogeneity. Here, we show that endoplasmic reticular oxidoreductase-1a (ERO1A) mediates an immune-suppressive TME and attenuates the response to PD-1 blockade. Ablation of ERO1A in tumor cells substantially incites anti-tumor T cell im-munity and promotes the efficacy of aPD-1 in therapeutic models. Single-cell RNA-sequencing analyses confirm that ERO1A correlates with immunosuppression and dysfunction of CD8+ T cells along anti-PD-1 treatment. In human lung cancer, high ERO1A expression is associated with a higher risk of recurrence following neoadjuvant immunotherapy. Mechanistically, ERO1A ablation impairs the balance between IRE1a and PERK signaling activities and induces lethal unfolded protein responses in tumor cells undergoing endoplasmic reticulum stress, thereby enhancing anti-tumor immunity via immunogenic cell death. These findings reveal how tumor ERO1A induces immunosuppression, highlighting its potential as a therapeutic target for cancer immunotherapy.

Graph Neural Networks (GNNs) have been widely applied on a variety of real-world applications, such as social recommendation. However, existing GNN-based models on social recommendation suffer from serious problems of generalization and oversmoothness, because of the underexplored negative sampling method and the direct implanting of the off-the-shelf GNN models. In this paper, we propose a succinct multi-network GNN-based neural model (NeMo) for social recommendation. Compared with the existing methods, the proposed model explores a generative negative sampling strategy, and leverages both the positive and negative user-item interactions for users' interest propagation. The experiments show that NeMo outperforms the state-of-the-art baselines on various real-world benchmark datasets (e.g., by up to 38.8% in terms of NDCG@15).

Conversational question answering (convQA) over knowledge graphs (KGs) involves answering multi-turn natural language questions about information contained in a KG. State-of-the-art methods of ConvQA often struggle with inexplicit question-answer pairs. These inputs are easy for human beings to understand given a conversation history, but hard for a machine to interpret, which can degrade ConvQA performance. To address this problem, we propose a reinforcement learning (RL) based model, CornNet, which utilizes question reformulations generated by large language models (LLMs) to improve ConvQA performance. CornNet adopts a teacher-student architecture where a teacher model learns question representations using human writing reformulations, and a student model to mimic the teacher model's output via reformulations generated by LLMs. The learned question representation is then used by an RL model to locate the correct answer in a KG. Extensive experimental results show that CornNet outperforms state-of-the-art convQA models.

Reasoning is a fundamental capability for harnessing valuable insight, knowledge and patterns from knowledge graphs. Existing work has primarily been focusing on point-wise reasoning, including search, link predication, entity prediction, subgraph matching and so on. This paper introduces comparative reasoning over knowledge graphs, which aims to infer the commonality and inconsistency with respect to multiple pieces of clues. We envision that the comparative reasoning will complement and expand the existing point-wise reasoning over knowledge graphs. In detail, we develop KompaRe, the first of its kind prototype system that provides comparative reasoning capability over large knowledge graphs. We present both the system architecture and its core algorithms, including knowledge segment extraction, pairwise reasoning and collective reasoning. Empirical evaluations demonstrate the efficacy of the proposed KompaRe., Comment: 9 pages, 8 figures

[EN] Gut development is stimulated by exposure to microorganisms, especially early-life microbial exposure. This study aimed to investigate whether doe-litter separation, which is performed in many rabbit farms, affects this exposure and therefore inhibits the development of intestinal system in suckling rabbits. Immediately after parturition, Rex rabbit does (n=16) were adjusted to 8 kits per litter and divided into doe-litter separation (DLS) group and doe-litter together (DLT) group based on the conditions of the does. One healthy kit per litter was selected and sacrificed at 7 d, 14 d, 21 d and 28 d of age, and the number of total bacteria, Escherichia coli and Bacteroides-Prevotella, expression of interleukin 6 (IL-6) and interleukin 10 (IL-10) in duodenum and caecum were investigated by real-time polymerase chain reaction. The morphological parameters of duodenum and vermiform appendix were also measured. Our results showed that doe-litter separation affected the number of intestinal bacteria. At 7 d of age, except for caecal Escherichia coli, the number of the investigated bacteria was decreased by doe-litter separation (P<0.05). But 1 wk later, only the number of total bacteria and Bacteroides-Prevotella in caecal content (P<0.05) and Escherichia coli in duodenal content from DLS kits (P<0.05) were still lower than those from DLT kits. After being provided with supplementary food for 7 d, DLS kits had fewer total bacteria in caecal content (P<0.05) and fewer E. coli in duodenal content (P<0.01) than DLT kits. After growing to 28 d of age, kits in DLS group still tended to have fewer total bacteria in caecal content, and expression of IL-10 and secretion of secretory IgA (sIgA) in vermiform appendix in DLS group was obviously lower than kits in DLT group (P<0.05). The villus height:crypt depth ratio in duodenum at 3rd wk and 4th wk was decreased by DLS (P<0.05). Kits in DLS group had shorter villus height (P<0.05), higher crypt depth (P<0.05) and shorter verm

[EN] Gut development is stimulated by exposure to microorganisms, especially early-life microbial exposure. This study aimed to investigate whether doe-litter separation, which is performed in many rabbit farms, affects this exposure and therefore inhibits the development of intestinal system in suckling rabbits. Immediately after parturition, Rex rabbit does (n=16) were adjusted to 8 kits per litter and divided into doe-litter separation (DLS) group and doe-litter together (DLT) group based on the conditions of the does. One healthy kit per litter was selected and sacrificed at 7 d, 14 d, 21 d and 28 d of age, and the number of total bacteria, Escherichia coli and Bacteroides-Prevotella, expression of interleukin 6 (IL-6) and interleukin 10 (IL-10) in duodenum and caecum were investigated by real-time polymerase chain reaction. The morphological parameters of duodenum and vermiform appendix were also measured. Our results showed that doe-litter separation affected the number of intestinal bacteria. At 7 d of age, except for caecal Escherichia coli, the number of the investigated bacteria was decreased by doe-litter separation (P<0.05). But 1 wk later, only the number of total bacteria and Bacteroides-Prevotella in caecal content (P<0.05) and Escherichia coli in duodenal content from DLS kits (P<0.05) were still lower than those from DLT kits. After being provided with supplementary food for 7 d, DLS kits had fewer total bacteria in caecal content (P<0.05) and fewer E. coli in duodenal content (P<0.01) than DLT kits. After growing to 28 d of age, kits in DLS group still tended to have fewer total bacteria in caecal content, and expression of IL-10 and secretion of secretory IgA (sIgA) in vermiform appendix in DLS group was obviously lower than kits in DLT group (P<0.05). The villus height:crypt depth ratio in duodenum at 3rd wk and 4th wk was decreased by DLS (P<0.05). Kits in DLS group had shorter villus height (P<0.05), higher crypt depth (P<0.05) and shorter verm

[EN] Gut development is stimulated by exposure to microorganisms, especially early-life microbial exposure. This study aimed to investigate whether doe-litter separation, which is performed in many rabbit farms, affects this exposure and therefore inhibits the development of intestinal system in suckling rabbits. Immediately after parturition, Rex rabbit does (n=16) were adjusted to 8 kits per litter and divided into doe-litter separation (DLS) group and doe-litter together (DLT) group based on the conditions of the does. One healthy kit per litter was selected and sacrificed at 7 d, 14 d, 21 d and 28 d of age, and the number of total bacteria, Escherichia coli and Bacteroides-Prevotella, expression of interleukin 6 (IL-6) and interleukin 10 (IL-10) in duodenum and caecum were investigated by real-time polymerase chain reaction. The morphological parameters of duodenum and vermiform appendix were also measured. Our results showed that doe-litter separation affected the number of intestinal bacteria. At 7 d of age, except for caecal Escherichia coli, the number of the investigated bacteria was decreased by doe-litter separation (P<0.05). But 1 wk later, only the number of total bacteria and Bacteroides-Prevotella in caecal content (P<0.05) and Escherichia coli in duodenal content from DLS kits (P<0.05) were still lower than those from DLT kits. After being provided with supplementary food for 7 d, DLS kits had fewer total bacteria in caecal content (P<0.05) and fewer E. coli in duodenal content (P<0.01) than DLT kits. After growing to 28 d of age, kits in DLS group still tended to have fewer total bacteria in caecal content, and expression of IL-10 and secretion of secretory IgA (sIgA) in vermiform appendix in DLS group was obviously lower than kits in DLT group (P<0.05). The villus height:crypt depth ratio in duodenum at 3rd wk and 4th wk was decreased by DLS (P<0.05). Kits in DLS group had shorter villus height (P<0.05), higher crypt depth (P<0.05) and shorter verm

[EN] Gut development is stimulated by exposure to microorganisms, especially early-life microbial exposure. This study aimed to investigate whether doe-litter separation, which is performed in many rabbit farms, affects this exposure and therefore inhibits the development of intestinal system in suckling rabbits. Immediately after parturition, Rex rabbit does (n=16) were adjusted to 8 kits per litter and divided into doe-litter separation (DLS) group and doe-litter together (DLT) group based on the conditions of the does. One healthy kit per litter was selected and sacrificed at 7 d, 14 d, 21 d and 28 d of age, and the number of total bacteria, Escherichia coli and Bacteroides-Prevotella, expression of interleukin 6 (IL-6) and interleukin 10 (IL-10) in duodenum and caecum were investigated by real-time polymerase chain reaction. The morphological parameters of duodenum and vermiform appendix were also measured. Our results showed that doe-litter separation affected the number of intestinal bacteria. At 7 d of age, except for caecal Escherichia coli, the number of the investigated bacteria was decreased by doe-litter separation (P<0.05). But 1 wk later, only the number of total bacteria and Bacteroides-Prevotella in caecal content (P<0.05) and Escherichia coli in duodenal content from DLS kits (P<0.05) were still lower than those from DLT kits. After being provided with supplementary food for 7 d, DLS kits had fewer total bacteria in caecal content (P<0.05) and fewer E. coli in duodenal content (P<0.01) than DLT kits. After growing to 28 d of age, kits in DLS group still tended to have fewer total bacteria in caecal content, and expression of IL-10 and secretion of secretory IgA (sIgA) in vermiform appendix in DLS group was obviously lower than kits in DLT group (P<0.05). The villus height:crypt depth ratio in duodenum at 3rd wk and 4th wk was decreased by DLS (P<0.05). Kits in DLS group had shorter villus height (P<0.05), higher crypt depth (P<0.05) and shorter verm

[EN] Gut development is stimulated by exposure to microorganisms, especially early-life microbial exposure. This study aimed to investigate whether doe-litter separation, which is performed in many rabbit farms, affects this exposure and therefore inhibits the development of intestinal system in suckling rabbits. Immediately after parturition, Rex rabbit does (n=16) were adjusted to 8 kits per litter and divided into doe-litter separation (DLS) group and doe-litter together (DLT) group based on the conditions of the does. One healthy kit per litter was selected and sacrificed at 7 d, 14 d, 21 d and 28 d of age, and the number of total bacteria, Escherichia coli and Bacteroides-Prevotella, expression of interleukin 6 (IL-6) and interleukin 10 (IL-10) in duodenum and caecum were investigated by real-time polymerase chain reaction. The morphological parameters of duodenum and vermiform appendix were also measured. Our results showed that doe-litter separation affected the number of intestinal bacteria. At 7 d of age, except for caecal Escherichia coli, the number of the investigated bacteria was decreased by doe-litter separation (P<0.05). But 1 wk later, only the number of total bacteria and Bacteroides-Prevotella in caecal content (P<0.05) and Escherichia coli in duodenal content from DLS kits (P<0.05) were still lower than those from DLT kits. After being provided with supplementary food for 7 d, DLS kits had fewer total bacteria in caecal content (P<0.05) and fewer E. coli in duodenal content (P<0.01) than DLT kits. After growing to 28 d of age, kits in DLS group still tended to have fewer total bacteria in caecal content, and expression of IL-10 and secretion of secretory IgA (sIgA) in vermiform appendix in DLS group was obviously lower than kits in DLT group (P<0.05). The villus height:crypt depth ratio in duodenum at 3rd wk and 4th wk was decreased by DLS (P<0.05). Kits in DLS group had shorter villus height (P<0.05), higher crypt depth (P<0.05) and shorter verm

Recent results of Hartle-Hawking wave functions on asymptotic dS boundaries show non-normalizability, while the bulk origin is not clear. This paper attempts to addresse this problem by studying (Kerr-)dS_3 cosmology in Einstein gravity deformed by a minimally coupled scalar field. Various saddle-point contributions exp[i(saddle-point action)] to the Hartle-Hawking wave functions are computed with mini-superspace formalism. The saddle-point actions are first obtained in the spacetime bulks by direct computation, then on the asymptotic dS boundary by holographic renormalization. It is found that the imaginary part of the saddle-point actions, as functions of scalar field deformation, are generally bounded in the bulk, but can diverge to -infty on the boundary. This can probably be a source of the scalar field-related non-normalizability of the boundary Hartle-Hawking wave functions. For Kerr-dS_3 cosmology, some saddle-point actions have imaginary parts diverging to -infty both in the bulk and on the boundary, when the boundary T^2 is stretched to infinitely long. This can be an origin of non-normalizability of the boundary Hartle-Hawking wave functions related to temperature divergence. Finally the holographic renormalization is extended to scalar-deformed dS_{d+1} (d>= 3) cosmologies for the imaginary part of the saddle-point actions. The result is tested on a 5d example, and saddle points leading to divergent contribution to the boundary Hartle-Hawking wave function are shown to exist., Comment: 68 pages 32 figures; In v2: typos eliminated; a misjudge of mass range in 3d corrected, related contents revised in Sec.2.3, Sec.7 and appendix B; the 4d example in Sec.6.2 is replaced by a 5d one, due to possible author right clash with another paper in preparation; references added or updated

In these lecture notes I give a pedagogical introduction to the thermodynamics of ideal string gases. The computation of thermodynamic quantities in the canonical ensemble formalism will be shown in detail with explicit examples. Attention will be given mainly to the thermodynamical consequences of string degrees of freedom, where I will especially address i) the Hagedorn temperature, a critical temperature above which the canonical ensemble description breaks down, which can be the onset point of some instability of the string gas; ii) the phase structure arising from compactification, embodied in the moduli-dependence of the Helmholtz free energy, which corrects the tree-level vacuum and can provide mechanism for moduli stabilization. Then I will briefly explain the implementation of string gas thermodynamics in cosmology, showing a simple example which gives rise to a radiation-dominated early universe. Further phenomenological issues and open questions will be discussed qualitatively with references indicated, including the Hagedorn instability in the resolution of the initial singularity, moduli stabilization, generation of hierarchy, radiative symmetry breaking and primordial cosmological fluctuations., Comment: 54 pages, 1 figure, based on lectures given at the Eighth Modave Summer School in Mathematical Physics on 29th and 30th August 2012, Modave, Belgium Published in PoS in 2013: http://pos.sissa.it/archive/conferences/195/002/Modave%20VIII_002.pdf Minor difference from the published version. The work in progress indicated by Ref[58] is published: R.Brandenberger et al, [arXiv:1312.2524]

Recent results of Hartle-Hawking wave functions on asymptotic dS boundaries show non-normalizability, while the bulk origin is not clear. This paper attempts to addresse this problem by studying (Kerr-)dS_3 cosmology in Einstein gravity deformed by a minimally coupled scalar field. Various saddle-point contributions exp[i(saddle-point action)] to the Hartle-Hawking wave functions are computed with mini-superspace formalism. The saddle-point actions are first obtained in the spacetime bulks by direct computation, then on the asymptotic dS boundary by holographic renormalization. It is found that the imaginary part of the saddle-point actions, as functions of scalar field deformation, are generally bounded in the bulk, but can diverge to -infty on the boundary. This can probably be a source of the scalar field-related non-normalizability of the boundary Hartle-Hawking wave functions. For Kerr-dS_3 cosmology, some saddle-point actions have imaginary parts diverging to -infty both in the bulk and on the boundary, when the boundary T^2 is stretched to infinitely long. This can be an origin of non-normalizability of the boundary Hartle-Hawking wave functions related to temperature divergence. Finally the holographic renormalization is extended to scalar-deformed dS_{d+1} (d>= 3) cosmologies for the imaginary part of the saddle-point actions. The result is tested on a 5d example, and saddle points leading to divergent contribution to the boundary Hartle-Hawking wave function are shown to exist., Comment: 68 pages 32 figures; In v2: typos eliminated; a misjudge of mass range in 3d corrected, related contents revised in Sec.2.3, Sec.7 and appendix B; the 4d example in Sec.6.2 is replaced by a 5d one, due to possible author right clash with another paper in preparation; references added or updated

In these lecture notes I give a pedagogical introduction to the thermodynamics of ideal string gases. The computation of thermodynamic quantities in the canonical ensemble formalism will be shown in detail with explicit examples. Attention will be given mainly to the thermodynamical consequences of string degrees of freedom, where I will especially address i) the Hagedorn temperature, a critical temperature above which the canonical ensemble description breaks down, which can be the onset point of some instability of the string gas; ii) the phase structure arising from compactification, embodied in the moduli-dependence of the Helmholtz free energy, which corrects the tree-level vacuum and can provide mechanism for moduli stabilization. Then I will briefly explain the implementation of string gas thermodynamics in cosmology, showing a simple example which gives rise to a radiation-dominated early universe. Further phenomenological issues and open questions will be discussed qualitatively with references indicated, including the Hagedorn instability in the resolution of the initial singularity, moduli stabilization, generation of hierarchy, radiative symmetry breaking and primordial cosmological fluctuations., Comment: 54 pages, 1 figure, based on lectures given at the Eighth Modave Summer School in Mathematical Physics on 29th and 30th August 2012, Modave, Belgium Published in PoS in 2013: http://pos.sissa.it/archive/conferences/195/002/Modave%20VIII_002.pdf Minor difference from the published version. The work in progress indicated by Ref[58] is published: R.Brandenberger et al, [arXiv:1312.2524]

We consider the type II superstring compactified on Calabi-Yau threefolds at finite temperature. The latter is implemented at the string level by a free action on the Euclidean time circle. We show that all Kahler and complex structure moduli involved in the gauge theories geometrically engineered in the vicinity of singular loci are lifted by the stringy thermal effective potential. The analysis is based on the effective gauged supergravity at low energy, without integrating out the BPS states becoming massless at the singular loci. The universal form of the action in the weak coupling regime at low enough temperature is determined in two cases. Namely the conifold locus, as well as a locus where the internal space develops a genus-g curve of A{N-1} singularities, realizing an SU(N) gauge theory coupled to g hypermultiplets in the adjoint. In general, the favored points of stabilization sit at the intersection of several singular loci. Thus the entire vector multiplet moduli space can be lifted, together with hypermultiplet moduli. The scalars are dynamically stabilized during the cosmological evolution induced by the back-reaction of the thermal effective potential. When the universe expands and the temperature T drops, the scalars converge to minima, with damped oscillations. Moreover, they store an energy density that scales as T^4, which never dominates over radiation. The reason for this is that the mass they acquire at one-loop is of order the temperature scale, which is time-dependent. As an example we analyze the type IIA compactification on a Calabi-Yau space with Hodge numbers h{11}=2 and h{12}=128. In this case, both Kahler moduli are stabilized, where the internal space develops a node and an enhanced SU(2) gauge theory coupled to 2 adjoint hypermultiplets. This shows that in the dual thermal heterotic picture on K3xT^2, the torus modulus and the axio-dilaton are stabilized., Comment: 59 pages, comments added in the introduction on how moduli stabilization by thermal effects in the early universe is related to late time moduli stabilization by non-thermal effects

We study moduli stabilization by thermal effects in the cosmological context. The implementation of finite temperature, which spontaneously breaks supersymmetry, induces an effective potential at one loop level. At the points where extra massless states appear in the string spectrum, the potential develops local minima whose depth depends on the temperature. Moduli attracted to these points acquire dynamical masses which decrease with cosmological evolution. This makes the coherent scalar oscillations dilute before nucleosynthesis, and the cosmological moduli problem is avoided. In particular, we study the effective potential induced by a maximally supersymmetric heterotic string gas for spacetime dimension D>=4, and a gas of type II strings compactified on Calabi-Yau three-folds (D=4). In the former case, the local minima of the potential arise at enhanced gauge symmetry points, which can stabilize all moduli but the dilaton. In the latter case, the local minima are reached at the loci where 2-cycles or 3-cycles in the Calabi-Yau space shrink to zero size, accompanied with either conifold transitions or non Abelian gauge symmetries. This stabilizes the type II moduli which characterize the deformation of these shrinking cycles. Moduli stabilization in the dual string models is also investigated by heterotic/type I S-dualities and type II/heterotic dualities., Comment: 13+1 pages. Based on a talk given at the "The Seventh International Conference Quantum Theory and Symmetries", Prague, Czech Republic, on August 7-13, 2011

We consider the cosmological evolution induced by the free energy F of a gas of maximally supersymmetric heterotic strings at finite temperature and weak coupling in dimension D>=4. We show that F, which plays the role of an effective potential, has minima associated to enhanced gauge symmetries, where all internal moduli can be attracted and dynamically stabilized. Using the fact that the heterotic/type I S-duality remains valid at finite temperature and can be applied at each instant of a quasi-static evolution, we find in the dual type I cosmology that all internal NS-NS and RR moduli in the closed string sector and the Wilson lines in the open string sector can be stabilized. For the special case of D=6, the internal volume modulus remains a flat direction, while the dilaton is stabilized. An essential role is played by light D-string modes wrapping the internal manifold and whose contribution to the free energy cannot be omitted, even when the type I string is at weak coupling. As a result, the order of magnitude of the internal radii expectation values on the type I side is (lambda_I alpha')^{1/2}, where lambda_I is the ten-dimensional string coupling. The non-perturbative corrections to the type I free energy can alternatively be described as effects of "thermal E1-instantons", whose worldsheets wrap the compact Euclidean time cycle., Comment: 39 pages, 1 figure

We consider the type II superstring compactified on Calabi-Yau threefolds at finite temperature. The latter is implemented at the string level by a free action on the Euclidean time circle. We show that all Kahler and complex structure moduli involved in the gauge theories geometrically engineered in the vicinity of singular loci are lifted by the stringy thermal effective potential. The analysis is based on the effective gauged supergravity at low energy, without integrating out the BPS states becoming massless at the singular loci. The universal form of the action in the weak coupling regime at low enough temperature is determined in two cases. Namely the conifold locus, as well as a locus where the internal space develops a genus-g curve of A{N-1} singularities, realizing an SU(N) gauge theory coupled to g hypermultiplets in the adjoint. In general, the favored points of stabilization sit at the intersection of several singular loci. Thus the entire vector multiplet moduli space can be lifted, together with hypermultiplet moduli. The scalars are dynamically stabilized during the cosmological evolution induced by the back-reaction of the thermal effective potential. When the universe expands and the temperature T drops, the scalars converge to minima, with damped oscillations. Moreover, they store an energy density that scales as T^4, which never dominates over radiation. The reason for this is that the mass they acquire at one-loop is of order the temperature scale, which is time-dependent. As an example we analyze the type IIA compactification on a Calabi-Yau space with Hodge numbers h{11}=2 and h{12}=128. In this case, both Kahler moduli are stabilized, where the internal space develops a node and an enhanced SU(2) gauge theory coupled to 2 adjoint hypermultiplets. This shows that in the dual thermal heterotic picture on K3xT^2, the torus modulus and the axio-dilaton are stabilized., Comment: 59 pages, comments added in the introduction on how moduli stabilization by thermal effects in the early universe is related to late time moduli stabilization by non-thermal effects

We study moduli stabilization by thermal effects in the cosmological context. The implementation of finite temperature, which spontaneously breaks supersymmetry, induces an effective potential at one loop level. At the points where extra massless states appear in the string spectrum, the potential develops local minima whose depth depends on the temperature. Moduli attracted to these points acquire dynamical masses which decrease with cosmological evolution. This makes the coherent scalar oscillations dilute before nucleosynthesis, and the cosmological moduli problem is avoided. In particular, we study the effective potential induced by a maximally supersymmetric heterotic string gas for spacetime dimension D>=4, and a gas of type II strings compactified on Calabi-Yau three-folds (D=4). In the former case, the local minima of the potential arise at enhanced gauge symmetry points, which can stabilize all moduli but the dilaton. In the latter case, the local minima are reached at the loci where 2-cycles or 3-cycles in the Calabi-Yau space shrink to zero size, accompanied with either conifold transitions or non Abelian gauge symmetries. This stabilizes the type II moduli which characterize the deformation of these shrinking cycles. Moduli stabilization in the dual string models is also investigated by heterotic/type I S-dualities and type II/heterotic dualities., Comment: 13+1 pages. Based on a talk given at the "The Seventh International Conference Quantum Theory and Symmetries", Prague, Czech Republic, on August 7-13, 2011

We consider the cosmological evolution induced by the free energy F of a gas of maximally supersymmetric heterotic strings at finite temperature and weak coupling in dimension D>=4. We show that F, which plays the role of an effective potential, has minima associated to enhanced gauge symmetries, where all internal moduli can be attracted and dynamically stabilized. Using the fact that the heterotic/type I S-duality remains valid at finite temperature and can be applied at each instant of a quasi-static evolution, we find in the dual type I cosmology that all internal NS-NS and RR moduli in the closed string sector and the Wilson lines in the open string sector can be stabilized. For the special case of D=6, the internal volume modulus remains a flat direction, while the dilaton is stabilized. An essential role is played by light D-string modes wrapping the internal manifold and whose contribution to the free energy cannot be omitted, even when the type I string is at weak coupling. As a result, the order of magnitude of the internal radii expectation values on the type I side is (lambda_I alpha')^{1/2}, where lambda_I is the ten-dimensional string coupling. The non-perturbative corrections to the type I free energy can alternatively be described as effects of "thermal E1-instantons", whose worldsheets wrap the compact Euclidean time cycle., Comment: 39 pages, 1 figure

We study the dynamical stability of the BTZ black string against fermonic and gravitational perturbations. The BTZ black string is not always stable against these perturbations. There exist threshold values for $m^2$ related to the compactification of the extra dimension for fermonic perturbation, scalar part of the gravitational perturbation and the tensor perturbation, respectively. Above the threshold values, perturbations are stable; while below these thresholds, perturbations can be unstable. We find that this non-trivial stability behavior qualitatively agrees with that predicted by a thermodynamical argument, showing that the BTZ black string phase is not the privileged stable phase., Comment: 9 pages, revised version to appear in Phys. Rev. D

We study the dynamical stability of the BTZ black string against fermonic and gravitational perturbations. The BTZ black string is not always stable against these perturbations. There exist threshold values for $m^2$ related to the compactification of the extra dimension for fermonic perturbation, scalar part of the gravitational perturbation and the tensor perturbation, respectively. Above the threshold values, perturbations are stable; while below these thresholds, perturbations can be unstable. We find that this non-trivial stability behavior qualitatively agrees with that predicted by a thermodynamical argument, showing that the BTZ black string phase is not the privileged stable phase., Comment: 9 pages, revised version to appear in Phys. Rev. D

We have studied the wave dynamics and the energy absorption problem for the scalar field as well as the brane-localized gravitational field in the background of a braneworld black hole. Comparing our results with the four-dimensional Schwarzschild black hole, we have observed the signature of the extra dimension in the energy absorption spectrum., Comment: 23 pages, 6 figures, Revised Version, Accepted for publication in PRD

In this paper, we present a noise figure improved double-pass L-band EDFA based on HiBi fiber loop mirror as the ASE suppressor. By utilizing a HiBi fiber loop mirror as the wavelength-dependent reflector, the ASE light has been weakened to a large extend, which increases the inversion ion population at the input end of erbium-doped fiber. Therefore, the noise figure of this double-pass EDFA has been much improved. Compared with that of the conventional double-pass structure based on 3dB fiber loop mirror, the NF of our novel configuration is reduced by 2.06~5.33dB for the ten sampled signal wavelength (1580.84nm~1588.48nm).