Bo Pang - Academia.edu (original) (raw)

Papers by Bo Pang

Chemical Research in Toxicology, 2006

Toxicity induced by nitric oxide (NO • ) has been extensively investigated in many in vitro and i... more Toxicity induced by nitric oxide (NO • ) has been extensively investigated in many in vitro and in vivo experimental models. Recently, our laboratories found that both concentration and cumulative total dose are critical determinants of cell death caused by NO • . Here, we report results of studies designed to define total dose thresholds and threshold effects for several NO • -induced toxicity and cellular responses and to determine impacts of p53 on them. We exposed human lymphoblastoid TK6 cells harboring wildtype p53 and isogenic p53-null NH32 cells to NO • delivered by a membrane delivery system. Cells were exposed at a steady state concentration of 0.6 µM for varying lengths of time to deliver increasing cumulative doses (expressed in units of µM min), and several end points of cytotoxicity and mutagenesis were quantified. Threshold doses for NO • -induced cytotoxicity were 150 µM min in TK6 cells and 300 µM min in NH32 cells, respectively. Threshold doses for NO • -induced apoptosis were identical to those for cytotoxicity, but mitochondrial depolarization thresholds were lower than those for cytotoxicity and apoptosis in both cell types. To gain insight into underlying mechanisms, cells of both types were exposed to sublethal (33% of cytotoxicity threshold), cytotoxicity threshold, or toxic (twice the cytotoxicity threshold) doses of NO • . In TK6 cells (p53), the sublethal threshold dose induced DNA double-strand breaks, but nucleobase deamination products (xanthine, hypoxanthine, and uracil) in DNA were increased only modestly (<50%) by toxic doses. Increased mutant fraction at the thymidine kinase gene (TK1) locus was observed only at the toxic dose of NO • . Treatment of NH32 cells with NO • at the threshold or toxic dose elevated mutagenesis of the TK1 gene, but did not cause detectable levels of DNA doublestrand breaks. At similar levels of cell viability, the frequency of DNA recombinational repair was higher in p53-null NH32 cells than in wild-type TK6 cells. NO • treatment induced p53-independent cell cycle arrest predominately at the S phase. Akt signaling pathway and antioxidant proteins were involved in the modulation of toxic responses of NO • . These findings indicate that exposure to doses of NO • at or above the cytotoxicity threshold dose induces DNA double-strand breaks, mutagenesis, and protective cellular responses to NO • damage. Furthermore, recombinational repair of DNA may contribute to resistance to NO • toxicity and potentially increase the risk of mutagenesis. The p53 plays a central role in these responses in human lymphoblastoid cells. Figure 8. Schematic summary of NO • -induced toxicity pathways in human lymphoblastoid cells, in which p53 plays a central role.

Proceedings of The National Academy of Sciences, 2009

Reactive oxygen species (ROS) appear to play a role in limiting both cellular and organismic life... more Reactive oxygen species (ROS) appear to play a role in limiting both cellular and organismic lifespan. However, because of their pleiotropic effects, it has been difficult to ascribe a specific role to ROS in initiating the process of cellular senescence. We have studied the effects of oxidative DNA damage on cell proliferation, believing that such damage is of central importance to triggering senescence. To do so, we devised a strategy to decouple levels of 8-oxoguanine, a major oxidative DNA lesion, from ROS levels. Suppression of MTH1 expression, which hydrolyzes 8-oxo-dGTP, was accompanied by increased total cellular 8-oxoguanine levels and caused early-passage primary and telomerase-immortalized human skin fibroblasts to rapidly undergo senescence, doing so without altering cellular ROS levels. This senescent phenotype recapitulated several salient features of replicative senescence, notably the presence of senescence-associated beta-galactosidase (SA beta-gal) activity, apparently irreparable genomic DNA breaks, and elevation of p21 Cip1 , p53, and p16 INK4A tumor suppressor protein levels. Culturing cells under low oxygen tension (3%) largely prevented the shMTH1-dependent senescent phenotype. These results indicate that the nucleotide pool is a critical target of intracellular ROS and that oxidized nucleotides, unless continuously eliminated, can rapidly induce cell senescence through signaling pathways very similar to those activated during replicative senescence.

Journal of Clinical Investigation, 2008

Chronic inflammation increases cancer risk. While it is clear that cell signaling elicited by inf... more Chronic inflammation increases cancer risk. While it is clear that cell signaling elicited by inflammatory cytokines promotes tumor development, the impact of DNA damage production resulting from inflammation-associated reactive oxygen and nitrogen species (RONS) on tumor development has not been directly tested. RONS induce DNA damage that can be recognized by alkyladenine DNA glycosylase (Aag) to initiate base excision repair. Using a mouse model of episodic inflammatory bowel disease by repeated administration of dextran sulfate sodium in the drinking water, we show that Aag-mediated DNA repair prevents colonic epithelial damage and reduces the severity of dextran sulfate sodium-induced colon tumorigenesis. Importantly, DNA base lesions expected to be induced by RONS and recognized by Aag accumulated to higher levels in Aag-deficient animals following stimulation of colonic inflammation. Finally, as a test of the generality of this effect we show that Aag-deficient animals display more severe gastric lesions that are precursors of gastric cancer after chronic infection with Helicobacter pylori. These data demonstrate that the repair of DNA lesions formed by RONS during chronic inflammation is important for protection against colon carcinogenesis.

Computing Research Repository, 2002

We consider the problem of classifying documents not by topic, but by overall sentiment, e.g., de... more We consider the problem of classifying documents not by topic, but by overall sentiment, e.g., determining whether a review is positive or negative. Using movie reviews as data, we find that standard machine learning techniques definitively outperform human-produced baselines. However, the three machine learning methods we employed (Naive Bayes, maximum entropy classification, and support vector machines) do not perform as well on sentiment classification as on traditional topic-based categorization. We conclude by examining factors that make the sentiment classification problem more challenging. 1

Abstract We explore the use of the landing page content in sponsored search ad selection. Specifi... more Abstract We explore the use of the landing page content in sponsored search ad selection. Specifically, we compare the use of the ad&amp;amp;amp;amp;amp;amp;#x27;s intrinsic content to augmenting the ad with the whole, or parts, of the landing page. We explore two types of extractive summarization ...

The success of "infinite-inventory" retailers such as Amazon.com and Netflix has been ascribed to... more The success of "infinite-inventory" retailers such as Amazon.com and Netflix has been ascribed to a "long tail" phenomenon. To wit, while the majority of their inventory is not in high demand, in aggregate these "worst sellers," unavailable at limited-inventory competitors, generate a significant fraction of total revenue. The long tail phenomenon, however, is in principle consistent with two fundamentally different theories. The first, and more popular hypothesis, is that a majority of consumers consistently follow the crowds and only a minority have any interest in niche content; the second hypothesis is that everyone is a bit eccentric, consuming both popular and specialty products. Based on examining extensive data on user preferences for movies, music, Web search, and Web browsing, we find overwhelming support for the latter theory. However, the observed eccentricity is much less than what is predicted by a fully random model whereby every consumer makes his product choices independently and proportional to product popularity; so consumers do indeed exhibit at least some a priori propensity toward either the popular or the exotic.

IEEE Transactions on Biomedical Engineering, 2004

Tongue diagnosis is an important diagnostic method in traditional Chinese medicine (TCM). However... more Tongue diagnosis is an important diagnostic method in traditional Chinese medicine (TCM). However, due to its qualitative, subjective and experience-based nature, traditional tongue diagnosis has a very limited application in clinical medicine. Moreover, traditional tongue diagnosis is always concerned with the identification of syndromes rather than with the connection between tongue abnormal appearances and diseases. This is not well understood in Western medicine, thus greatly obstruct its wider use in the world. In this paper, we present a novel computerized tongue inspection method aiming to address these problems. First, two kinds of quantitative features, chromatic and textural measures, are extracted from tongue images by using popular digital image processing techniques. Then, Bayesian networks are employed to model the relationship between these quantitative features and diseases. The effectiveness of the method is tested on a group of 455 patients affected by 13 common diseases as well as other 70 healthy volunteers, and the diagnostic results predicted by the previously trained Bayesian network classifiers are reported.

Chinese medicine is difficult due to two special factors: (1) There are a lot of pathological det... more Chinese medicine is difficult due to two special factors: (1) There are a lot of pathological details on the surface of tongue, which have a large influence on edge extraction; (2) The shapes of tongue bodies captured from various diseases or persons are quite different, so they are impossible to be properly described by a predefined deformable template. To address these problems, in this paper, we propose an original technique based on the combination of a bielliptical deformable template and an active contour model, namely Bi-Elliptical Deformable Contour (BEDC). Applying our approach to clinical tongue images, the experimental results indicate that it is superior over both traditional DT (Deformable Templates) and ACM (Active Contour Model or Snakes) with respect to stability and veracity.

IEEE Transactions on Medical Imaging, 2005

Automated tongue image segmentation, in Chinese medicine, is difficult due to two special factors... more Automated tongue image segmentation, in Chinese medicine, is difficult due to two special factors: 1) there are many pathological details on the surface of the tongue, which have a large influence on edge extraction; 2) the shapes of the tongue bodies captured from various persons (with different diseases) are quite different, so they are impossible to describe properly using a predefined deformable template. To address these problems, in this paper, we propose an original technique that is based on a combination of a bi-elliptical deformable template (BEDT) and an active contour model, namely the bi-elliptical deformable contour (BEDC). The BEDT captures gross shape features by using the steepest decent method on its energy function in the parameter space. The BEDC is derived from the BEDT by substituting template forces for classical internal forces, and can deform to fit local details. Our algorithm features fully automatic interpretation of tongue images and a consistent combination of global and local controls via the template force. We apply the BEDC to a large set of clinical tongue images and present experimental results.

Information Sciences, 2005

Medical diagnosis using the tongue is a unique and important diagnostic method of traditional Chi... more Medical diagnosis using the tongue is a unique and important diagnostic method of traditional Chinese medicine (TCM). However, the clinical applications of tongue diagnosis have been limited due to two factors: (1) tongue diagnosis is usually based on the capacity of the eye for detailed discrimination; (2) the correctness of tongue diagnosis depends on the experience of physicians; and (3) traditional tongue diagnosis is always dedicated to the identification of syndromes other than diseases. To address these problems, in this paper, we present a tongue-computing model (TCoM) for the diagnosis of appendicitis based on quantitative measurements that include chromatic and textural metrics. These metrics are computed from true color tongue images by using appropriate techniques of image processing. Applying our approach to clinical tongue images, the experimental results are encouraging.