KB4VA: A Knowledge Base of Visualization Designs for Visual Analytics

Visual analytics (VA) systems have been widely used to facilitate decision-making and analytical reasoning in various application domains. VA involves visual designs, interaction designs, and data mining, which is a systematic and complex paradigm. In this work, we focus on the design of effective visualizations for complex data and analytical tasks, which is a critical step in designing a VA system. This step is challenging because it requires extensive knowledge about domain problems and visualization to design effective encodings. Existing visualization designs published in top venues are valuable resources to inspire designs for problems with similar data structures and tasks. However, those designs are hard to understand, parse, and retrieve due to the lack of specifications. To address this problem, we build KB4VA, a knowledge base of visualization designs in VA systems with comprehensive labels about their analytical tasks and visual encodings. Our labeling scheme is inspired by a workshop study with 12 VA researchers to learn user requirements in understanding and retrieving professional visualization designs in VA systems. The theme extends Vega-Lite specifications for describing advanced and composited visualization designs in a declarative manner, thus facilitating human understanding and automatic indexing. To demonstrate the usefulness of our knowledge base, we present a user study about design inspirations for VA tasks. In summary, our work opens new perspectives for enhancing the accessibility and reusability of professional visualization designs

PAF-Mediated MAPK Signaling Hyperactivation via LAMTOR3 Induces Pancreatic Tumorigenesis

SummaryDeregulation of mitogen-activated protein kinase (MAPK) signaling leads to development of pancreatic cancer. Although Ras-mutation-driven pancreatic tumorigenesis is well understood, the underlying mechanism of Ras-independent MAPK hyperactivation remains elusive. Here, we have identified a distinct function of PCNA-associated factor (PAF) in modulating MAPK signaling. PAF is overexpressed in pancreatic cancer and required for pancreatic cancer cell proliferation. In mouse models, PAF expression induced pancreatic intraepithelial neoplasia with expression of pancreatic cancer stem cell markers. PAF-induced ductal epithelial cell hyperproliferation was accompanied by extracellular signal-regulated kinase (ERK) phosphorylation independently of Ras or Raf mutations. Intriguingly, PAF transcriptionally activated the expression of late endosomal/lysosomal adaptor, MAPK and mTOR activator 3 (LAMTOR3), which hyperphosphorylates MEK and ERK and is necessary for pancreatic cancer cell proliferation. Our results reveal an unsuspected mechanism of mitogenic signaling activation via LAMTOR3 and suggest that PAF-induced MAPK hyperactivation contributes to pancreatic tumorigenesis

Frequency and distribution of AP-1 sites in the human genome

The AP-1-binding sequences are promoter/enhancer elements that play an essential role in the induction of many genes in mammalian cells; however, the number of genes containing AP-1 sites remains unknown. In order to better address the overall effect of AP-1 on expression of genes encoded by the entire genome, a genome-wide analysis of the frequency and distribution of AP-1 sites would be useful; yet to date, no such analysis of AP-1 sites or any other promoter/enhancer elements has been performed. We present here our study of the consensus AP-1 site and two single-bp variants showing that the frequency of AP-1 sites in promoter regions is significantly lower than their average rate of occurrence in the whole genomic sequence, as well as the frequency of a random heptanucleotide suggesting that nature has selected for a decrease in the frequency of AP-1 sites in the regulatory regions of genes. In addition, genes containing multiple AP-1 sites are more prevalent than those containing only one copy of an AP-1 site, which again may have evolved to allow for greater signal amplification or integration in the regulation of AP-1 target genes. However, the number of AP-1-regulated genes identified in various studies is far smaller than the number of genes containing potential AP-1 sites, indicating that not all AP-1 sites are activated in a given cell under a given condition, and is consistent with the prediction by others that cellular context determines which AP-1 sites are targeted by AP-1

Detection of pancreatic cancer tumours and precursor lesions by cathepsin E activity in mouse models.

ABSTRACT Background and Aims Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA. Surgical resection is the only effective treatment; however, only 20% of patients are candidates for surgery. The ability to detect early PDAC would increase the availability of surgery and improve patient survival. This study assessed the feasibility of using the enzymatic activity of cathepsin E (Cath E), a protease highly and specifically expressed in PDAC, as a novel biomarker for the detection of pancreas-bearing pancreatic intraepithelial neoplasia (PanIN) lesions and PDAC. Methods Pancreas from normal, chronic pancreatitis and PDAC patients was assessed for Cath E expression by quantitative real-time PCR and immunohistochemistry. Human PDAC xenografts and genetically engineered mouse models (GEMM) of PDAC were injected with a Cath E activity selective fluorescent probe and imaged using an optical imaging system. Results The specificity of Cath E expression in PDAC patients and GEMM of pancreatic cancer was confirmed by quantitative real-time PCR and immunohistochemistry. The novel probe for Cath E activity specifically detected PDAC in both human xenografts and GEMM in vivo. The Cath E sensitive probe was also able to detect pancreas with PanIN lesions in GEMM before tumour formation. Conclusions The elevated Cath E expression in PanIN and pancreatic tumours allowed in-vivo detection of human PDAC xenografts and imaging of pancreas with PanIN and PDAC tumours in GEMM. Our results support the usefulness of Cath E activity as a potential molecular target for PDAC and early detection imaging. Despite great efforts to help patients with pancreatic ductal adenocarcinoma (PDAC) in the past few years, this disease remains devastating with the worst outcome of all major cancers. In the USA, PDAC ranks 10th in terms of incidence, but for both men and women, it is fourth in terms of cancer deaths. Although many molecular biomarker candidates of PDAC have been identified, 3 biomarkers with the necessary sensitivity and specificity for early detection are still lacking. 4e6 The most widely utilised blood-based biomarker is CA 19-9, which is not expressed in all patients, is not highly specific as it is elevated in other gastrointestinal cancers, and is not useful for the detection of early disease. 7 8 Furthermore, CA 19-9 levels do not provide information about the localisation of the disease nor the existence of metastases. The most sensitive diagnosis of PDAC currently requires invasive imaging procedures such as endoscopic ultrasonography, which Significance of this study What is already known about this subject? < No highly specific and sensitive biomarkers are clinically available for the detection of PDAC at an early stage. < Cath E is highly overexpressed in many cancers including PDAC. < A Cath E selective peptide was recently identified that specifically detects its enzymatic activity. What are the new findings? < We demonstrate that the elevated levels of Cath E expression in early pancreatic cancer lesions and pancreatic tumours could be exploited for PDAC detection. < We illustrate that the detection and localisation of PDAC in mouse xenografts and GEMM was possible utilising the outstanding specificity of a novel Cath E-activatable imaging probe. How might it impact on clinical practice in the foreseeable future? < The ability to detect and visualise pancreatic tumours and PanIN in PDAC by virtue of Cath E activity sensitive probes in preclinical mouse models suggests that modifications of this approach will be useful for the early detection and management of this deadly cancer in patients. < The specificity of Cath E activity for PDAC suggests that this enzymatic activity will be useful in the future for the development of novel therapeutics or theranostics. Cruz-Monserrate Z, Abd-Elgaliel WR, Grote T, et al. Gut (2011)

Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma differentiation and progression

<p>Abstract</p> <p>Purpose</p> <p>Cell division cycle 20 (CDC20) homolog is an anaphase-promoting complex activator that is essential for cell division, but whether its expression in pancreatic ductal adenocarcinoma (PDAC) is significant is unknown. In this retrospective study, we determined whether aberrant CDC20 expression can be used as a biomarker in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis and whether its expression reflects clinical progression.</p> <p>Experimental design</p> <p>We compared CDC20 expression levels in normal, cancerous, and inflamed pancreatic tissues from stage II PDAC patients with clinical outcomes and determined CDC20 levels in seven PDAC cell lines. CDC20 was identified using a cDNA microarray database containing gene expression profiles for PDAC tissues and cell lines and chronic pancreatitis and normal pancreas tissues. Its expression was confirmed by real-time quantitative reverse-transcriptase-polymerase chain reaction (qRT-PCR). An immunohistochemical analysis of tissue microarrays from resected PDAC tumors and paired benign pancreatic tissues was done and CDC20 levels were correlated with clinical outcome.</p> <p>Results</p> <p>Fifty-six patients were included in this study. A microarray analysis revealed 5-fold higher CDC20 expression in PDAC tissue than in chronic pancreatitis tissue. A qRT-PCR analysis confirmed a mean 20-fold higher CDC20 level in PDAC tissue than in normal pancreas and pancreatitis tissue. RNA and protein CDC20 expression was detected in several PDAC cell lines. An immunohistochemical analysis revealed higher CDC20 protein expression levels in PDAC tissue than in normal pancreas tissue, and high CDC20 expression was associated with poor differentiation (<it>P </it>= 0.020) and a significantly lower 5-year recurrence-free survival rate (<it>P </it>= 0.039); we also found a trend toward a shorter overall survival duration.</p> <p>Conclusions</p> <p>Aberrant CDC20 expression may play an important role in PDAC tumorigenesis and progression and may thus be useful as a marker of disease progression and prognosis and as a therapeutic target.</p

Epidemiology of invasive group B streptococcal disease in infants from urban area of South China, 2011–2014

YesBackground: Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in infants in both developed and developing countries. To our knowledge, only a few studies have been reported the clinical features, treatment and outcomes of the GBS disease in China. The severity of neonatal GBS disease in China remains unclear. Population-based surveillance in China is therefore required. Methods: We retrospectively collected data of <3 months old infants with culture-positive GBS in sterile samples from three large urban tertiary hospitals in South China from Jan 2011 to Dec 2014. The GBS isolates and their antibiotic susceptibility were routinely identified in clinical laboratories in participating hospitals. Serotyping and multi-locus sequence typing (MLST) were also conducted for further analysis of the neonatal GBS disease. Results: Total 70 cases of culture-confirmed invasive GBS infection were identified from 127,206 live births born in studying hospitals, giving an overall incidence of 0.55 per 1000 live births (95% confidence interval [CI] 0.44–0.69). They consisted of 49 with early-onset disease (EOD, 0.39 per 1000 live births (95% CI 0.29–0.51)) and 21 with late-onset disease (LOD, 0.17 per 1000 live births (95% CI 0.11–0.25)). The incidence of EOD increased significantly over the studying period. Five infants (4 EOD and 1 LOD) died before discharge giving a mortality rate of 7.1% and five infants (7.1%, 2 EOD and 3 LOD) had neurological sequelae. Within 68 GBS isolates from GBS cases who born in the studying hospitals or elsewhere, serotype III accounted for 77.9%, followed by Ib (14.7%), V (4.4%), and Ia (2.9%). MLST analysis revealed the presence of 13 different sequence types among the 68 GBS isolates and ST-17 was the most frequent sequence type (63.2%). All isolates were susceptible to penicillin, ceftriaxone, vancomycin and linezolid, while 57.4% and 51.5% were resistant to erythromycin and clindamycin, respectively. Conclusions: This study gains the insight into the spectrum of GBS infection in south China which will facilitate the development of the guidance for reasonable antibiotics usage and will provide evidence for the implementation of potential GBS vaccines in the future.Supported by medical and health science and technology projects of Health and Family Planning Commission of Guangzhou Municipality (grant number 20151A010034) and Guangdong provincial science and technology planning projects (grant number 2014A020212520)

An image-space energy-saving visualization scheme for OLED displays

Current energy-saving color design approaches can be classified into two categories, namely, context-aware dimming and color remapping. The former darkens individual regions with respect to the user interactions, and the latter replaces the color set with a new color set that yields lower energy consumption. Both schemes have drawbacks: color dimming tends to cause loss of perceptual quality, and color remapping is an offline color design process. This paper introduces a novel saliency-guided color dimming scheme for OLED displays in both the context of 3D visualization and 2D visualization. The key idea is to eliminate undesired details while enhancing the visually salient features of each frame on-the-fly by leveraging the color and spatial information. A parallelizable image-space salient region detection algorithm is introduced to make the entire process GPU-friendly and real-time. We apply our approach on several representative visualization scenarios and conduct a preliminary user study. Experimental results demonstrate the effectiveness, efficiency, and quality of our approach. (C) 2013 Elsevier Ltd. All rights reserved

Ras Activity Levels Control the Development of Pancreatic Diseases

Differentiated pancreatic acinar cells expressing endogenous levels of mutant K-Ras do not spontaneously develop pancreatic ductal adenocarcinoma (PDAC). However, we hypothesized that acinar cells would develop PDAC in the presence of Ras activity levels mimicking those of human tumor cells.We measured Ras activity in PDAC cells from mice and humans using a Raf pull-down assay. We compared the effects of acinar cell expression of mutant K-Ras at endogenous and elevated levels on Ras activity and on the development of PDAC