Effect of aging on colonic chemoprevention by dietary curcumin

The incidence of cancer is highly dependent on age. The hypothesis of this thesis was that aging may alter the efficacy of dietary chemoprevention. This hypothesis was tested by evaluating the effect of age on inhibition of colonic aberrant crypt foci (ACF) by dietary curcumin. Three different ages of male F344 rats were fed either the control diet or diet containing 0.6% curcumin and given injections of a colon carcinogen, azoxymethane (AOM). Curcumin reduced the number of colonic ACF in young and old, but not middle-aged rats. Resistance of middle-aged rats to colonic chemoprevention by curcumin seems to be due to age-related differences in colon carcinogensis rather than curcumin metabolism. Liver cyclooxygenase-2 mRNA expression, measured as an indicator of biological activity of curcumin, was similarly affected by curcumin regardless of ages. Also, curcumin similarly affected arachidonic acid metabolism, which is regarded as one of chemopreventive mechanisms of curcumin, in the colon of young and middle-aged rats. The involvement of apoptosis was investigated as a potential mechanism responsible for age-related differences in curcumin chemoprevention. A time course study of colonic apoptosis following AOM injections demonstrated that older animals were more susceptible to AOM-induced apoptosis. The effect of aging on curcumin-induced apoptosis in the colon was evaluated at 0, 8, and 16 hours after AOM injection. Curcumin increased both basal and AOM-induced apoptosis in young and old but not in middle-aged rats. Activation of caspase-9 only in young rats fed curcumin indicates that curcumin-induced apoptotic pathway is mediated by mitochondria in young but not in old. AOM may also induce apoptosis by a mitochondrial-independent pathway. In conclusion, these studies support the hypothesis that aging modulates colonic chemoprevention by curcumin. This dissertation represents the first documentation of an age-related difference in efficacy of dietary chemoprevention. The differential response to curcumin-induced apoptosis is proposed as a mechanism. Further study is needed to confirm whether this phenomenon occurs in humans and contributes to the lack of agreement between efficacy of dietary chemoprevention in preclinical studies with young animals and clinical studies with adult humans

The Effect Of Abnormal Pay Dispersion On Earnings Management

This study examines the effect of the abnormal pay dispersion on earnings management. Prior studies find that pay dispersion among top executives affect firm performance and executive turnover. We expect that abnormal pay dispersion among top executives affects financial reporting practice as well as firm performance and turnover and provide evidence of positive association between abnormal pay dispersion and earnings management. This result suggests that executives are more likely to be engaged in earnings management to increase their compensation when they feel unfairness from the relative level of compensation. This finding helps financial statement users interpret firm performance and anticipate future outcomes by implying that additional managerial incentives for financial reporting are derived from internal pay dispersion. Our finding that abnormal pay dispersion leads to higher agency costs should also be of interest to shareholders

Electroacupuncture Attenuates Ovalbumin-Induced Allergic Asthma via Modulating CD4+CD25+ Regulatory T Cells

A mouse pulmonary hypersensitivity experimental model that mimics human asthma was developed, and electroacupuncture (EA) treatment was shown to reduce allergic inflammatory processes. In addition, we also assessed whether the beneficial effects of EA on allergic asthma could be correlated with CD4+CD25+Foxp3+ regulatory T cells (Treg). Cellular profiles and histopathologic analysis demonstrated that peribronchial and perivascular inflammatory cell infiltrates were significantly decreased in the EA-treated groups when compared to the OVA and anti-CD25 Ab-injected (Treg depletion) groups. Furthermore, total BAL cells were reduced in the EA groups when compared to other groups. Interestingly, the population of CD4+CD25+Foxp3+Tregs in pneumonocytes increased in EA-treated group when compared to OVA and Treg depletion groups. These results imply that EA stimulation at ST 36 may affect CD4+CD25+Foxp3+ Treg in an OVA-induced experimental model and may enhance Treg function by suppressing other T cells and limiting the immune response

nuQmm: Quantized MatMul for Efficient Inference of Large-Scale Generative Language Models

The recent advance of self-supervised learning associated with the Transformer architecture enables natural language processing (NLP) to exhibit extremely low perplexity. Such powerful models demand ever-increasing model size and, thus, large amounts of computations and memory footprints. In this paper, we propose an efficient inference framework for large-scale generative language models. As the key to reducing model size, we quantize weights by a non-uniform quantization method. Then, quantized matrix multiplications are accelerated by our proposed kernel, called nuQmm, which allows a wide trade-off between compression ratio and accuracy. Our proposed nuQmm reduces the latency of not only each GPU but also the entire inference of large LMs because a high compression ratio (by low-bit quantization) mitigates the minimum required number of GPUs. Assuming 2-bit quantization, we demonstrate that nuQmm can reduce latency to generate each token for OPT-175B (that requires 8 GPUs without nuQmm) by 47.3% using 8 GPUs or by 23.2% using only 2 GPUs.Comment: 15 pages (including 5 pages of References & Appendix), 14 figures, 7 table

The Howl - Spring 2017

The Howl is a magazine that is planned, researched, written, photographed and designed by Otterbein University\u27s ESL and international students. The magazine serves to give them a safe space in which to use their voice to share their cultures, experiences and lives. If you are interested in submitting to The Howl, please email your writing or photography to [email protected]://digitalcommons.otterbein.edu/the_howl/1002/thumbnail.jp

A small molecule that blocks fat synthesis by inhibiting the activation of SREBP

Sterol regulatory element binding proteins (SREBPs) are transcription factors that activate transcription of the genes involved in cholesterol and fatty acid biosynthesis. In the present study, we show that a small synthetic molecule we previously discovered to block adipogenesis is an inhibitor of the SREBP activation. The diarylthiazole derivative, now called fatostatin, impairs the activation process of SREBPs, thereby decreasing the transcription of lipogenic genes in cells. Our analysis suggests that fatostatin inhibits the ER-Golgi translocation of SREBPs through binding to their escort protein, the SREBP cleavage-activating protein (SCAP), at a distinct site from the sterol-binding domain. Fatostatin blocked increases in body weight, blood glucose, and hepatic fat accumulation in obese ob/ob mice, even under uncontrolled food intake. Fatostatin may serve as a tool for gaining further insights into the regulation of SREBP

Comparison of the antibody responses to Plasmodium vivax and Plasmodium falciparum antigens in residents of Mandalay, Myanmar

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate the profile of antibodies against several antigens of <it>Plasmodium vivax </it>and <it>Plasmodium falciparum </it>in Mandalay, Myanmar.</p> <p>Methods</p> <p>Malaria parasites were identified by microscopic examination. To test the antibodies against <it>P. vivax </it>and <it>P. falciparum </it>in sera, an indirect immunofluorescence antibody test (IFAT) was performed using asexual blood parasite antigens. An enzyme-linked immunosorbent assay (ELISA) was performed with circumsporozoite protein (CSP), Pvs25 and Pvs28 recombinant proteins of transmission-blocking vaccine candidates for <it>P. vivax</it>, and liver stage specific antigen-1 and -3 (PfLSA-1, PfLSA-3) for <it>P. falciparum</it>.</p> <p>Results</p> <p>Fourteen patients among 112 were found to be infected with <it>P. vivax </it>and 26 with <it>P. falciparum </it>by thick smear examination. Twenty-three patients were found to be infected with <it>P. vivax</it>, 19 with <it>P. falciparum </it>and five with both by thin smear examination. Blood samples were divided into two groups: Group I consisted of patients who were positive for infection by microscopic examination, and Group II consisted of those who showed symptoms, but were negative in microscopic examination. In <it>P. falciparum</it>, IgG against the blood stage antigen in Group I (80.8%) was higher than in Group II (70.0%). In <it>P. vivax</it>, IgG against the blood stage antigen in Group I (53.8%) was higher than in Group II (41.7%). However, the positivity rate of the PvCSP VK210 subtype in Group II (40.0%) was higher than in Group I (23.1%). Similarly for the PvCSP VK247 subtype, Group II (21.7%) was higher than that for Group I (9.6%). A similar pattern was observed in the ELISA using Pvs25 and Pvs28: positive rates of Group II were higher than those for Group I. However, those differences were not shown significant in statistics.</p> <p>Conclusions</p> <p>The positive rates for blood stage antigens of <it>P. falciparum </it>were higher in Group I than in Group II, but the positive rates for antigens of other stages (PfLSA-1 and -3) showed opposite results. Similar to <it>P. falciparum</it>, the positive rate of pre-blood stage (CSP VK210 and 247 subtype) and post-blood stage (Pvs25 and 28) antigens of <it>P. vivax </it>were higher in Group II than in Group I. Therefore, sero-diagnosis is not helpful to discriminate between malaria patients and symptomatic individuals during the epidemic season in Myanmar.</p

Role of kif2c, A Gene Related to ALL Relapse, in Embryonic Hematopoiesis in Zebrafish

Relapse of acute lymphoblastic leukemia (ALL) is dangerous and it worsens the prognosis of patients; however, prognostic markers or therapeutic targets for ALL remain unknown. In the present study, using databases such as TARGET, GSE60926 and GSE28460, we determined that KIF2C and its binding partner, KIF18B are overexpressed in patients with relapsed ALL compared to that in patients diagnosed with ALL for the first time. As 50% of the residues are exactly the same and the signature domain of KIF2C is highly conserved between human and zebrafish, we used zebrafish embryos as a model to investigate the function of kif2c in vivo. We determined that kif2c is necessary for lymphopoiesis in zebrafish embryos. Additionally, we observed that kif2c is not related to differentiation of HSCs; however, it is important for the maintenance of HSCs as it provides survival signals to HSCs. These results imply that the ALL relapse-related gene KIF2C is linked to the survival of HSCs. In conclusion, we suggest that KIF2C can serve as a novel therapeutic target for relapsed ALL

A pathogen-derived metabolite induces microglial activation via odorant receptors

Microglia (MG), the principal neuroimmune sentinels in the brain, continuously sense changes in their environment and respond to invading pathogens, toxins, and cellular debris, thereby affecting neuroinflammation. Microbial pathogens produce small metabolites that influence neuroinflammation, but the molecular mechanisms that determine whether pathogen-derived small metabolites affect microglial activation of neuroinflammation remain to be elucidated. We hypothesized that odorant receptors (ORs), the largest subfamily of G protein-coupled receptors, are involved in microglial activation by pathogen-derived small metabolites. We found that MG express high levels of two mouse ORs, Olfr110 and Olfr111, which recognize a pathogenic metabolite, 2-pentylfuran, secreted by Streptococcus pneumoniae. These interactions activate MG to engage in chemotaxis, cytokine production, phagocytosis, and reactive oxygen species generation. These effects were mediated through the G(alpha s)-cyclic adenosine monophosphate-protein kinase A-extracellular signal-regulated kinase and G(beta gamma)-phospholipase C-Ca2+ pathways. Taken together, our results reveal a novel interplay between the pathogen-derived metabolite and ORs, which has major implications for our understanding of microglial activation by pathogen recognition. Database Model data are available in the PMDB database under the accession number PM0082389.N