A genome-wide regulatory network identifies key transcription factors for memory CD8+ T-cell development

Memory CD8[superscript +] T-cell development is defined by the expression of a specific set of memory signature genes. Despite recent progress, many components of the transcriptional control of memory CD8[superscript +] T-cell development are still unknown. To identify transcription factors and their interactions in memory CD8[superscript +] T-cell development, we construct a genome-wide regulatory network and apply it to identify key transcription factors that regulate memory signature genes. Most of the known transcription factors having a role in memory CD8[superscript +] T-cell development are rediscovered and about a dozen new ones are also identified. Sox4, Bhlhe40, Bach2 and Runx2 are experimentally verified, and Bach2 is further shown to promote both development and recall proliferation of memory CD8[superscript +] T cells through Prdm1 and Id3. Gene perturbation study identifies the interactions between the transcription factors, with Sox4 positioned as a hub. The identified transcription factors and insights into their interactions should facilitate further dissection of molecular mechanisms underlying memory CD8[superscript +] T-cell development.Singapore-MIT AllianceNational Institutes of Health (U.S.) (Grant AI69208)National Cancer Institute (U.S.) (Koch Institute Support (core) Grant P30-CA14051

Localization of just noticeable difference for image compression

The just noticeable difference (JND) is the minimal difference between stimuli that can be detected by a person. The picture-wise just noticeable difference (PJND) for a given reference image and a compression algorithm represents the minimal level of compression that causes noticeable differences in the reconstruction. These differences can only be observed in some specific regions within the image, dubbed as JND-critical regions. Identifying these regions can improve the development of image compression algorithms. Due to the fact that visual perception varies among individuals, determining the PJND values and JND-critical regions for a target population of consumers requires subjective assessment experiments involving a sufficiently large number of observers. In this paper, we propose a novel framework for conducting such experiments using crowdsourcing. By applying this framework, we created a novel PJND dataset, KonJND++, consisting of 300 source images, compressed versions thereof under JPEG or BPG compression, and an average of 43 ratings of PJND and 129 self-reported locations of JND-critical regions for each source image. Our experiments demonstrate the effectiveness and reliability of our proposed framework, which is easy to be adapted for collecting a large-scale dataset. The source code and dataset are available at https://github.com/angchen-dev/LocJND.</p

Localization of Just Noticeable Difference for Image Compression

The just noticeable difference (JND) is the minimal difference between stimuli that can be detected by a person. The picture-wise just noticeable difference (PJND) for a given reference image and a compression algorithm represents the minimal level of compression that causes noticeable differences in the reconstruction. These differences can only be observed in some specific regions within the image, dubbed as JND-critical regions. Identifying these regions can improve the development of image compression algorithms. Due to the fact that visual perception varies among individuals, determining the PJND values and JND-critical regions for a target population of consumers requires subjective assessment experiments involving a sufficiently large number of observers. In this paper, we propose a novel framework for conducting such experiments using crowdsourcing. By applying this framework, we created a novel PJND dataset, KonJND++, consisting of 300 source images, compressed versions thereof under JPEG or BPG compression, and an average of 43 ratings of PJND and 129 self-reported locations of JND-critical regions for each source image. Our experiments demonstrate the effectiveness and reliability of our proposed framework, which is easy to be adapted for collecting a large-scale dataset. The source code and dataset are available at https://github.com/angchen-dev/LocJND

Subjective assessment of global picture-wise just noticeable difference

The picture-wise just noticeable difference (PJND) for a given image and a compression scheme is a statistical quantity giving the smallest distortion that a subject can perceive when the image is compressed with the compression scheme. The PJND is determined with subjective assessment tests for a sample of subjects. We introduce and apply two methods of adjustment where the subject interactively selects the distortion level at the PJND using either a slider or keystrokes. We compare the results and times required to those of the adaptive binary search type approach, in which image pairs with distortions that bracket the PJND are displayed and the difference in distortion levels is reduced until the PJND is identified. For the three methods, two images are compared using the flicker test in which the displayed images alternate at a frequency of 8 Hz. Unlike previous work, our goal is a global one, determining the PJND not only for the original pristine image but also for a sequence of compressed versions. Results for the MCL-JCI dataset show that the PJND measurements based on adjustment are comparable with those of the traditional approach using binary search, yet significantly faster. Moreover, we conducted a crowdsourcing study with side-by-side comparisons and forced choice, which suggests that the flicker test is more sensitive than a side-by-side comparison

Antibiotics induce polarization of pleural macrophages to M2-like phenotype in patients with tuberculous pleuritis

Pleural macrophages play critical roles in pathogenesis of tuberculous pleuritis, but very little is known about their response to anti-tuberculosis antibiotics treatment. Here, we examined whether and how pleural macrophages change in phenotype, transcription and function following antibiotics treatment in patients with tuberculous pleuritis. Results show pro-inflammatory cytokines were down-regulated significantly post antibiotic treatment in the pleural effusions and pleural macrophages up-regulated markers characteristic of M2 macrophages such as CD163 and CD206. Differential expression analysis of transcriptomes from four paired samples before and after treatment identified 230 treatment-specific responsive genes in pleural macrophages. Functional analysis identified interferon-related pathway to be the most responsive genes and further confirmed macrophage polarization to M2-like phenotype. We further demonstrate that expression of a significant fraction of responsive genes was modulated directly by antibiotics in pleural macrophages in vitro. Our results conclude that pleural macrophages polarize from M1-like to M2-like phenotype within a mean of 3.5 days post antibiotics treatment, which is dependent on both pleural cytokine environment and direct modulatory effects of antibiotics. The treatment-specific genes could be used to study the roles of pleural macrophages in the pathogenesis of tuberculous pleuritis and to monitor the response to antibiotics treatment

The Natural Compound Myricetin Effectively Represses the Malignant Progression of Prostate Cancer by Inhibiting PIM1 and Disrupting the PIM1/CXCR4 Interaction

Background/Aims: Natural compounds are a promising resource for anti-tumor drugs. Myricetin, an abundant flavonoid found in the bark and leaves of bayberry, shows multiple promising anti-tumor functions in various cancers. Methods: The cytotoxic, pro-apoptotic, and anti-metastatic effects of myricetin on prostate cancer cells were investigated in both in vitro and in vivo studies. Short-hairpin RNA knockdown of the proviral integration site for Moloney murine leukemia virus-1 (PIM1), pull-down and co-immunoprecipitation assays, and an intracellular Ca2+ flux assay were used to investigate the potential underlying mechanism of myricetin. ONCOMINE database data mining and immunohistochemical analysis of prostate cancer tissues were used to evaluate the expression of PIM1 and CXCR4, as well as the correlation between PIM1 and CXCR4 expression and the clinicopathologic characteristics and prognoses of prostate cancer patients. Results: Myricetin exerted selective cytotoxic, pro-apoptotic, and anti-metastatic effects on prostate cancer cells by inhibiting PIM1 and disrupting the PIM1/CXCR4 interaction. Moreover, PIM1 and CXCR4 were coexpressed and associated with aggressive clinicopathologic traits and poor prognosis in prostate cancer patients. Conclusion: These results offer preclinical evidence for myricetin as a potential chemopreventive and therapeutic agent for precision medicine tailored to prostate cancer patients characterized by concomitant elevated expression of PIM1 and CXCR4

LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation.

Despite advances in identifying the key immunoregulatory roles of many of the human leukocyte immunoglobulin-like receptor (LILR) family members, the function of the inhibitory molecule LILRB3 (ILT5, CD85a, LIR3) remains unclear. Studies indicate a predominant myeloid expression; however, high homology within the LILR family and a relative paucity of reagents have hindered progress toward identifying the function of this receptor. To investigate its function and potential immunomodulatory capacity, a panel of LILRB3-specific monoclonal antibodies (mAbs) was generated. LILRB3-specific mAbs bound to discrete epitopes in Ig-like domain 2 or 4. LILRB3 ligation on primary human monocytes by an agonistic mAb resulted in phenotypic and functional changes, leading to potent inhibition of immune responses in vitro, including significant reduction in T cell proliferation. Importantly, agonizing LILRB3 in humanized mice induced tolerance and permitted efficient engraftment of allogeneic cells. Our findings reveal powerful immunosuppressive functions of LILRB3 and identify it as an important myeloid checkpoint receptor

Vitamin D₃-vitamin D receptor axis suppresses pulmonary emphysema by maintaining alveolar macrophage homeostasis and function

Background: Chronic obstructive pulmonary disease (COPD) is characterized by emphysema and/or obstructive bronchiolitis. Deficiency in vitamin D3 (VD3), which regulates gene expression through binding to vitamin D receptor (VDR), is associated with high risks of COPD susceptibility. Alveolar macrophages (AM), which are generated during early ontogeny and maintained in alveoli by self-renewal in response to cytokine GM-CSF, are positively correlated with severity of emphysema. However, whether and how VD3, VDR and AM interact to contribute to COPD pathogenesis at the molecular and cellular levels are largely unknown. Methods: We used systems biology approaches to analyze gene expression in mouse macrophages from different tissues to identify key transcription factors (TF) for AM and infer COPD disease genes. We used RNA-seq and ChIP-seq to identify genes that are regulated by VD3 in AM. We used VDR-deficient (Vdr−/−) mice to investigate the role of VD3-VDR axis in the pathogenesis of COPD and characterized the transcriptional and functional alterations of Vdr−/− AM. Findings: We find that VDR is a key TF for AM and a COPD disease gene. VDR is highly expressed in AM and in response to VD3 inhibits GM-CSF-induced AM proliferation. In Vdr−/− AM, genes involved in proliferation and immune response are upregulated. Consistently, Vdr−/− mice progressively accumulate AM and concomitantly develop emphysema without apparent infiltration of immune cells into the lung tissue. Intratracheal transfer of Vdr−/− AM into wildtype mice readily induces emphysema. The production of reactive oxygen species at basal level and in response to heme or lipopolysaccharide is elevated in Vdr−/− AM and suppressed by VD3 in wildtype AM. Interpretation: These results show that the VD3-VDR axis is critical to counteract GM-CSF-induced AM proliferation and defect in this regulation leads to altered AM homeostasis and function. Our findings identify that VD3 deficiency contributes to emphysema by altering AM function without contributing to bronchiolitis. Our findings also suggest possibilities of modulating the VD3-VDR axis for inhibiting emphysema in COPD patients.National Institutes of Health (U.S.) (Grant AI69208)National Institutes of Health (U.S.) (Grant CA197605)National Institutes of Health (U.S.) (Grant NS104315)National Cancer Institute (U.S.) (Grant P30-CA14051

Multi-view 3D reconstruction for construction site monitoring

Monitoring construction sites is pivotal in effective construction management. Building Information Modeling (BIM) is vital for creating detailed building models and comparing actual construction with planned designs. For this comparison, a 3D model of the building is often generated using images captured by handheld cameras or Unmanned Aerial Vehicles. However, this approach does not provide real-time spatial monitoring of on-site activities within the BIM model. To address this challenge, our study utilizes fixed cameras placed at predetermined locations within an actual construction site. We captured images from these fixed viewpoints and used classical multi-view stereo techniques to create a 3D point cloud representing the as-built building. This point cloud is then aligned with the as-planned BIM model through point cloud registration. In addition, we proposed an algorithm to convert SfM reprojection error into a value with metric units, resulting in a mean SfM reprojection err or of 4.17cm. We also created voxel volumes to track and visualize construction activities within BIM coordinate system, enhancing real-time site monitoring and improving construction management