Interval-censored Hawkes processes

Interval-censored data solely records the aggregated counts of events during specific time intervals - such as the number of patients admitted to the hospital or the volume of vehicles passing traffic loop detectors - and not the exact occurrence time of the events. It is currently not understood how to fit the Hawkes point processes to this kind of data. Its typical loss function (the point process log-likelihood) cannot be computed without exact event times. Furthermore, it does not have the independent increments property to use the Poisson likelihood. This work builds a novel point process, a set of tools, and approximations for fitting Hawkes processes within interval-censored data scenarios. First, we define the Mean Behavior Poisson process (MBPP), a novel Poisson process with a direct parameter correspondence to the popular self-exciting Hawkes process. We fit MBPP in the interval-censored setting using an interval-censored Poisson log-likelihood (IC-LL). We use the parameter equivalence to uncover the parameters of the associated Hawkes process. Second, we introduce two novel exogenous functions to distinguish the exogenous from the endogenous events. We propose the multi-impulse exogenous function - for when the exogenous events are observed as event time - and the latent homogeneous Poisson process exogenous function - for when the exogenous events are presented as interval-censored volumes. Third, we provide several approximation methods to estimate the intensity and compensator function of MBPP when no analytical solution exists. Fourth and finally, we connect the interval-censored loss of MBPP to a broader class of Bregman divergence-based functions. Using the connection, we show that the popularity estimation algorithm Hawkes Intensity Process (HIP) is a particular case of the MBPP. We verify our models through empirical testing on synthetic data and real-world data

Tetramethylpyrazine ameliorates acute lung injury by regulating the Rac1/LIMK1 signaling pathway

Acute lung injury (ALI) is a respiratory disorder characterized by severe inflammation of the alveoli and lung parenchyma. Tetramethylpyrazine (TMP), the main active compound in Ligusticum chuanxiong Hort (LC), can protect against lipopolysaccharide (LPS)-induced ALI. Our study aimed to investigate how TMP protects the endothelial cell barrier in pulmonary capillaries. We administered TMP intraperitoneally at different doses and found that acute lung injury in mice was improved, but not in a dose-dependent manner. TMP toxicity was tested in vitro. We observed that LPS-induced cytoskeletal remodeling was inhibited by TMP. Murine ALI was induced as follows: For the 1st hit, LPS (2 mg/kg) was injected intraperitoneally; after 16 h, for the 2nd hit, LPS (4 mg/kg) was instilled intratracheally. The mice in treatment groups had TMP or dexamethasone administered intraperitoneally 30 min prior to the 1st hit and 30 min past the 2nd hit. Mice were euthanized 24 h after the last injecting. We measured protein and mRNA levels using enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase real-time PCR (RT-qPCR), respectively. The ultrastructural analysis was performed with transmission electron microscopy (TEM) and the cytoskeleton was observed by immunofluorescence. Immunohistochemistry and Western blotting were used to detect protein expression in the Rac1/LIMK1/ZO-1/occludin signal pathway. The results showed that TMP treatment decreased inflammatory cell infiltration and alleviated LPS-induced damage in lung tissue. Also, TMP significantly inhibited the Rac1/LIMK1/ZO-1/occludin signaling pathway. Our findings show that using TMP during sepsis can protect the pulmonary microvascular endothelial cell barrier and suppress inflammation. Therefore, TMP may have a promising therapeutic role in preventing acute lung injury from sepsis

Micro/Nanostructures and Mechanical Properties of Trabecular Bone in Ovariectomized Rats

Bone mechanical properties encompass both geometric and material factors, while the effects of estrogen deficiency on the material and structural characteristics of bone at micro- to nanoscales are still obscure. We performed a series of combined methodological experiments, including nanoindentation assessment of intrinsic material properties, atomic force microscopy (AFM) characterization of trabecular (Tb) nanostructure, and Tb microarchitecture and 2D BMD. At 15 weeks after surgery, we found significantly less Tb bone mineral density (BMD) at organ (−27%) and at tissue level (−12%), Tb bone volume fraction (−29%), Tb thickness (−14%), and Tb number (−17%) in ovariectomy (OVX) rats than in sham operated (SHAM) rats, while the structure model index (+91%) and Tb separation (+19%) became significantly greater. AFM images showed lower roughness Tb surfaces with loosely packed large nodular structures and less compacted interfibrillar space in OVX than in SHAM. However, no statistically significant changes were in the Tb intrinsic material properties—nanoindentation hardness, elastic modulus, and plastic deformation—nanoindentation depths, and residual areas. Therefore, estrogen deprivation results in a dramatic deterioration in Tb micro/nanoarchitectures, 3D volumetric BMD at both organ and tissue levels, and 2D BMD, but not in the nanomechanical properties of the trabeculae per se

Immunogenomic Landscape in Breast Cancer Reveals Immunotherapeutically Relevant Gene Signatures

Breast cancer is characterized by some types of heterogeneity, high aggressive behaviour, and low immunotherapeutic efficiency. Detailed immune stratification is a prerequisite for interpreting resistance to treatment and escape from immune control. Hence, the immune landscape of breast cancer needs further understanding. We systematically clustered breast cancer into six immune subtypes based on the mRNA expression patterns of immune signatures and comprehensively depicted their characteristics. The immunotherapeutic benefit score (ITBscore) was validated to be a superior predictor of the response to immunotherapy in cohorts from various datasets. Six distinct immune subtypes related to divergences in biological functions, signatures of immune or stromal cells, extent of the adaptive immune response, genomic events, and clinical prognostication were identified. These six subtypes were characterized as immunologically quiet, chemokine dominant, lymphocyte depleted, wounding dominant, innate immune dominant, and IFN-γ dominant and exhibited features of the tumor microenvironment (TME). The high ITBscore subgroup, characterized by a high proportion of M1 macrophages:M2 macrophages, an activated inflammatory response, and increased mutational burden (such as mutations in TP53, CDH1 and CENPE), indicated better immunotherapeutic benefits. A low proportion of tumor-infiltrating lymphocytes (TILs) and an inadequate response to immune treatment were associated with the low ITBscore subgroup, which was also associated with poor survival. Analyses of four cohorts treated with immune checkpoint inhibitors (ICIs) suggested that patients with a high ITBscore received significant therapeutic advantages and clinical benefits. Our work may facilitate the understanding of immune phenotypes in shaping different TME landscapes and guide precision immuno-oncology and immunotherapy strategies

Study on the Properties of Coated Cutters on Functionally Graded WC-Co/Ni-Zr Substrates with FCC Phase Enriched Surfaces

Currently, the research on mechanical behavior and cutting performance of functionally graded carbides is quite limited, which limits the rapid development of high-performance cemented carbide cutting tools. Based on WC-Co-Zr and WC-Ni-Zr, this study synthesized two kinds of cemented carbide cutters, i.e., the cemented carbide cutters with homogeneous microstructure and functionally graded carbide (FGC) cutters with FCC phase ZrN-enriched surfaces. Furthermore, TiAlN coating has been investigated on these carbide cutters. Mechanical behavior, friction, wear performance, and cutting behavior have been investigated for these coated carbides and their corresponding substrates. It was found that, as compared with coated cutters on WC-Co/Ni-Zr carbide substrates with homogeneous microstructures, the coated cutters on WC-Co/Ni-Zr FGC substrates with FCC phase-enriched surfaces show higher wear resistance and cutting life, and the wear mechanism during cutting is mainly adhesion wear

ROBOT TRAJECTORY LEARNING FOR DYNAMIC TASKS

Ph.DDOCTOR OF PHILOSOPHY (FOE

Cutting Performance of Different Coated Micro End Mills in Machining of Ti-6Al-4V

Tool wear is a significant issue for the application of micro end mills. This can be significantly improved by coating materials on tool surfaces. This paper investigates the effects of different coating materials on tool wear in the micro milling of Ti-6Al-4V. A series of cutting experiments were conducted. The tool wear and workpiece surface morphology were investigated by analyzing the wear of the end flank surface and the total cutting edge. It was found that, without coating, serious tool wear and breakage occurred easily during milling. However, AlTiN-based and AlCrN-based coatings could highly reduce cutting edge chipping and flank wear. Specifically, The AlCrN-based coated mill presented less fracture resistance. For TiN coated micro end mill, only slight cutting edge chipping occurred. Compared with other types of tools, the AlTiN-based coated micro end mill could maximize tool life, bringing about an integrated cutting edges with the smallest surface roughness. In short, the AlTiN-based coating material is recommended for the micro end mill in the machining of Ti-6Al-4V