Forcing the Whole Video as Background: An Adversarial Learning Strategy for Weakly Temporal Action Localization

With video-level labels, weakly supervised temporal action localization (WTAL) applies a localization-by-classification paradigm to detect and classify the action in untrimmed videos. Due to the characteristic of classification, class-specific background snippets are inevitably mis-activated to improve the discriminability of the classifier in WTAL. To alleviate the disturbance of background, existing methods try to enlarge the discrepancy between action and background through modeling background snippets with pseudo-snippet-level annotations, which largely rely on artificial hypotheticals. Distinct from the previous works, we present an adversarial learning strategy to break the limitation of mining pseudo background snippets. Concretely, the background classification loss forces the whole video to be regarded as the background by a background gradient reinforcement strategy, confusing the recognition model. Reversely, the foreground(action) loss guides the model to focus on action snippets under such conditions. As a result, competition between the two classification losses drives the model to boost its ability for action modeling. Simultaneously, a novel temporal enhancement network is designed to facilitate the model to construct temporal relation of affinity snippets based on the proposed strategy, for further improving the performance of action localization. Finally, extensive experiments conducted on THUMOS14 and ActivityNet1.2 demonstrate the effectiveness of the proposed method.Comment: 9 pages, 5 figures, conferenc

Helicobacter hepaticus cytolethal distending toxin promotes intestinal carcinogenesis in 129Rag2‐deficient mice

Multiple pathogenic Gram-negative bacteria produce the cytolethal distending toxin (CDT) with activity of DNase I; CDT can induce DNA double-strand breaks (DSBs), G2/M cell cycle arrest, and apoptosis in cultured mammalian cells. However, the link of CDT to in vivo tumorigenesis is not fully understood. In this study, 129/SvEv Rag2−/−mice were gavaged with wild-type Helicobacter hepatics 3B1(Hh) and its isogenic cdtB mutant HhcdtBm7, followed by infection for 10 and 20 weeks (WPI). HhCDT deficiency did not affect cecal colonization levels of HhcdtBm7, but attenuated severity of cecal pathology in HhcdtBm7-infected mice. Of importance, preneoplasic dysplasia was progressed to cancer from 10 to 20 WPI in the Hh-infected mice but not in the HhcdtBm7-infected mice. In addition, the loss of HhCDT significantly dampened transcriptional upregulation of cecal Tnfα and Il-6, but elevated Il-10 mRNA levels when compared to Hh at 10 WPI. Furthermore, the presence of HhCDT increased numbers of lower bowel intestinal γH2AX-positive epithelial cells (a marker of DSBs) at both 10 and 20 WPI and augmented phospho-Stat3 foci[superscript +] intestinal crypts (activation of Stat3) at 20 WPI. Our findings suggest that CDT promoted Hh carcinogenesis by enhancing DSBs and activation of the Tnfα/Il-6-Stat3 signaling pathway.National Institutes of Health (U.S.) (Grant R01-OD01141)National Institutes of Health (U.S.) (Grant T32-OD010978)National Institutes of Health (U.S.) (Grant P01 CA28842

Spatial and temporal colonization dynamics of segmented filamentous bacteria is influenced by gender, age and experimental infection with Helicobacter hepaticus in Swiss Webster mice

In this study, we examined colonization dynamics of segmented filamentous bacteria (SFB) in intestine of Swiss Webster (SW) mice infected with Helicobacter hepaticus (Hh). At 8 weeks post-inoculation with Hh (WPI), cecal and colonic SFB levels in the control males were significantly lower compared to those at 16 WPI. Hh infection in both genders did not alter SFB levels in the jejunum and ileum, but increased SFB levels in the cecum and colon of males compared to the controls (P < 0.05) at 8 WPI. At 16 WPI, the Hh-infected females contained lower levels of SFB in the jejunum, cecum and colon compared to the female controls. Irrespective of gender, aging and Hh infection, the Il-17A mRNA levels decreased from the small intestine to the cecum and then to the colon, whereas the Foxp3 mRNA levels were comparable in these intestinal regions. There were significant differences in Il-17A mRNA levels in the ileum (P < 0.05, R2 = 0.31), with females having greater Il-17A mRNA levels than males, and higher SFB colonization levels related to more Il-17A mRNA. These results indicate that aging and gender play an important role in colonization dynamics of intestinal SFB and ileal SFB-associated Th17 response.United States. National Institutes of Health (P30-ES002109)United States. National Institutes of Health (R01OD11141)United States. National Institutes of Health (R01-CA067529

Author Manuscript Published OnlineFirst on

Abstract Helicobacter pylori infection promotes male-predominant gastric adenocarcinoma in humans. Estrogens reduce gastric cancer risk and previous studies demonstrated that prophylactic 17ɴ-estradiol (E2) in INS-GAS mice decreases H. pylori-induced carcinogenesis. We examined the effect of E2 and Tamoxifen, on H. pylori-induced gastric cancer in male and female INS-GAS mice. After confirming robust gastric pathology at 16 weeks post-infection (WPI), mice were implanted with E2

Helicobacter hepaticus infection in mice: models for understanding lower bowel inflammation and cancer

Pioneering work in the 1990s first linked a novel microaerobic bacterium, Helicobacter hepaticus, with chronic active hepatitis and inflammatory bowel disease in several murine models. Targeted H. hepaticus infection experiments subsequently demonstrated its ability to induce colitis, colorectal cancer, and extraintestinal diseases in a number of mouse strains with defects in immune function and/or regulation. H. hepaticus is now widely utilized as a model system to dissect how intestinal microbiota interact with the host to produce both inflammatory and tolerogenic responses. This model has been used to make important advances in understanding factors that regulate both acquired and innate immune response within the intestine. Further, it has been an effective tool to help define the function of regulatory T cells, including their ability to directly inhibit the innate inflammatory response to gut microbiota. The complete genomic sequence of H. hepaticus has advanced the identification of several virulence factors and aided in the elucidation of H. hepaticus pathogenesis. Delineating targets of H. hepaticus virulence factors could facilitate novel approaches to treating microbially induced lower bowel inflammatory diseases.National Institutes of Health (U.S.) (grant R01-DK052413)National Institutes of Health (U.S.) (grant P01-CA026731)National Institutes of Health (U.S.) (grant R01-CA067529)National Institutes of Health (U.S.) (grant P30-ES02109)National Institutes of Health (U.S.) (grant R01-A1052267)National Institutes of Health (U.S.) (grantR01-CA108854

Helicobacter hepaticus Cholesterol-α-glucosyltransferase is Essential for Establishing Colonization in Male A/JCr Mice

Background Helicobacter pylori cholesterol-α-glucosyltransferase (cgt) is essential for survival of H. pylori in mice. Enterohepatic H. hepaticus, the cause of colonic and hepatocellular carcinoma in susceptible mouse strains, contains an ortholog of the H. pylori cgt. However, the role of cgt in the pathogenesis of H. hepaticus has not been investigated. Materials and Methods Two cgt-deficient isogenic mutants of wild-type H. hepaticus (WT) 3B1 were generated and used to inoculate male A/JCr mice. Cecal and hepatic colonization levels of the mutants and WT 3B1 as well as select inflammation-associated cytokines were measured by qPCR at 4 months postinoculation. Results Both mutants were undetectable in the cecum of any inoculated mice (10 per mutant) but were detected in two livers (one for each mutant); by contrast, 9 and 7 of 10 mice inoculated with WT 3B1 were qPCR positive in the ceca and livers, respectively. The mice inoculated with the mutants developed significantly less severe hepatic inflammation (p < .05) and also produced significantly lower hepatic mRNA levels of proinflammatory cytokines Ifn-γ (p < .01) and Tnf-α (p ≤ .02) as well as anti-inflammatory factors Il10 and Foxp3 compared with the WT 3B1-inoculated mice. Additionally, the WT 3B1-inoculated mice developed significantly higher Th1-associated IgG2a (p < .0001) and Th2-associated IgG1 responses (p < .0001) to H. hepaticus infection than mice dosed with isogenic cgt mutants. Conclusion Our data indicate that the cholesterol-α-glucosyltransferase is required for establishing colonization of the intestine and liver and therefore plays a critical role in the pathogenesis of H. hepaticus.National Institutes of Health (U.S.) (Grant R010D011141)National Institutes of Health (U.S.) (Grant 01CA026731)National Institutes of Health (U.S.) (Grant R01AT004326)National Institutes of Health (U.S.) (Grant P30-ES002109

BiFeO3-BaTiO3: A new generation of lead-free electroceramics

Lead-based electroceramics such as Pb(Zr.Ti)O3 (PZT) and its derivatives have excellent piezoelectric, pyroelectric and energy storage properties and can be used in a wide range of applications. Potential lead-free replacements for PZT such as potassium sodium niobate (KNN) and sodium bismuth titanate (NBT) have a much more limited range of useful properties and have been optimized primarily for piezoelectric applications. Here, we review the initial results on a new generation of lead-free electroceramics based on BiFeO3-BaTiO3 (BF-BT) highlighting the essential crystal chemistry that permits a wide range of functional properties. We demonstrate that with the appropriate dopants and heat treatment, BF-BT can be used to fabricate commercially viable ceramics for applications, ranging from sensors, multilayer actuators, capacitors and high-density energy storage devices. We also assess the potential of BF-BT-based ceramics for electrocaloric and pyroelectric applications

Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice

Iron deficiency anemia (IDA) affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world’s population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group) were dosed with H. pylori (Hp) strain SS1 or sham dosed at 6–9 weeks of age, and were necropsied at 27–29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p < 0.0001). Infected mice had a lower red blood cell count (p<0.0001), hematocrit (p < 0.001), and hemoglobin concentration (p <0.0001) than uninfected mice. Relative expression of gastric hepcidin antimicrobial peptide (Hamp) was downregulated in mice infected with Hp SS1 compared to sham-dosed controls (p<0.001). Expression of bone morphogenic protein 4 (Bmp4), a growth factor upstream of hepcidin, was downregulated in gastric tissue of Hp SS1-infected mice (p<0.001). Hp SS1-infected mice had downregulated brain expression of tyrosine hydroxylase (Th) (p = 0.02). Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp) and proteolipid protein 2 (Plp2)) was downregulated in infected mice (p = 0.001 and p = 0.02). Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3), Psd95 (a membrane associated guanylate kinase), and insulin-like growth factor 1 (Igf1)) was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively). Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use of Hp SS1-infected INS-GAS mice will be an appropriate animal model for further study of the effects of concurrent H. pylori infection and anemia on iron homeostasis and adult iron-dependent brain gene expression