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Kai Chen,1 Yaohui Yu,1 Yishu Wang,1 Yi Zhu,1 Chaoren Qin,1 Jintao Xu,1 Xiangjie Zou,2 Tianqi Tao,1 Yang Li,1 Yiqiu Jiang1 1Department of Sports Medicine and Joint Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yiqiu Jiang, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, People’s Republic of China, Email jyq_3000@163.comBackground: Astragalus membranaceus (AM) shows promise as a therapeutic agent for osteoarthritis (OA), a debilitating condition with high disability rates. OA exacerbation is linked to chondrocyte ferroptosis, yet the precise pharmacological mechanisms of AM remain unclear.Methods: We validated AM’s protective efficacy in an anterior cruciate ligament transection (ACLT) mouse model of OA. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database was utilized to identify AM’s active components and their targets. FerrDb (a database for regulators and markers of ferroptosis and ferroptosis-disease associations) pinpointed ferroptosis-related targets, while GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), Therapeutic Target Database (TTD), and DrugBank sourced OA-related genes. Molecular docking analysis further validated these targets. Ultimately, the validation of the results was accomplished through in vitro experiments.Results: AM exhibited anabolic effects and suppressed catabolism in OA chondrocytes. Network pharmacology identified 19 common genes, and molecular docking suggested quercetin, an AM constituent, interacts with key proteins like HO-1 and NRF2 to inhibit chondrocyte ferroptosis. In vitro experiments confirmed AM’s ability to modulate the NRF2/HO-1 pathway via quercetin, mitigating chondrocyte ferroptosis.Conclusion: This study elucidates how AM regulates chondrocyte ferroptosis, impacting OA progression, providing a theoretical basis and experimental support for AM’s scientific application.Keywords: systematic pharmacology, osteoarthritis, ferroptosis, Astragalus membranaceus, quercetin

Wenmei Zhou,1 Tao Tao,1 Wenfeng Yu,2 Wanfu Wu,3 Zhirong Hui,1 Hongliang Xu,1 Yaqi Li,4 Ying Zhang,5 Xiaohui Yang1,6 1Department of Rehabilitation Medicine, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of China; 2Department of Human Anatomy, Basic Medical College, Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China; 3Department of Biology and Biochemistry, University of Houston, Houston, TX, 77204, USA; 4Emergency Department, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of China; 5Department of Chinese Traditional Medicine, Zunyi Medical and Pharmaceutical College, Zunyi, Guizhou, 563006, People’s Republic of China; 6Department of Rehabilitation Medicine, The Affiliated Hospital Guizhou Medical University, Guiyang, Guizhou, 550001, People’s Republic of ChinaCorrespondence: Tao Tao, Tel +86 13985162824, Email ttdoc915@sina.comBackground: Hypoxia inducible factor-1α (HIF-1α) regulates glucose metabolism during ischemia. This study investigated the effect of recombinant adenovirus HIF-1ɑ on neurological function and energy metabolism in a rat cerebral ischemia-reperfusion model.Methods: Rats were divided into four groups: sham-operated (Sham) group, cerebral ischemia-reperfusion (CIR) group, recombinant adenovirus empty vector (Ad) group, and recombinant adenovirus-mediated HIF-1α (AdHIF-1α) group. The AdHIF-1α group and the Ad group were injected with AdHIF-1α and Ad in the lateral ventricle. The mNSS was performed at post-ischemia day 0 (P0) and P1, P14 and P28. At P14, the cerebral infarct volume was compared. At P28, HE staining, Nissl stains and TUNEL staining were performed. The expression of HIF-1α, GLUT1 and PFKFB3 were evaluated by Western Blot and immunohistochemistry. High performance liquid chromatography (HPLC) was used to determine the expression of GLUT1 and PFKFB3, and the level of energy metabolites: ATP, ADP and AMP.Results: mNSS scores in the AdHIF-1α group were consistently lower than those in the CIR and Ad groups from P14 (P < 0.05) and Ad groups (P < 0.05). The cerebral infarct volume was reduced in the AdHIF-1α group compared with that in CIR group and Ad group (P < 0.05). At P28, HE showed better pathological changes in AdHIF-1α group. The number of Nissl bodies was increased in the AdHIF-1α group compared with the CIR and Ad groups (P < 0.05). The number of apoptotic cells in the AdHIF-1α group was fewer than that in the CIR and Ad groups (P < 0.05). The expression of HIF-1α, GLUT1 and PFKFB3 was significantly higher in the AdHIF-1α group compared with the CIR and Ad groups (P < 0.05). The ATP, ADP and AMP in the ischemic penumbra were also higher in the AdHIF-1α group (P < 0.05).Conclusion: HIF-lα promoted neurological function recovery and decreased cerebral infarct volume in rats after cerebral ischemia-reperfusion injury by improving energy metabolism.Keywords: cerebral ischemia-reperfusion injury, HIF-lα, energy metabolism, glucose transporter protein-1, GLUT1, 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3, PFKFB3

Tingting Tao, Junnan Zheng, Yu Han, Qiqi Yang, Yiming Ni, Liang Ma Department of Cardiovascular Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Liang Ma, Department of Cardiovascular Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79#, Qingchun Road, Hangzhou, Zhejiang, 310003, People’s Republic of China, Tel +86 571 87236841, Fax +86 571 87236843, Email ml1402@zju.edu.cnObjective: Calcific aortic valve disease (CAVD) is a prevalent type of valvular heart disease, its association with dyslipidemia remains controversial.Methods: Of 449 CAVD patients who underwent aortic valve replacement, 228 formed the aortic valve calcification (AVC) group, and 221 were the non-calcification group. We retrospectively reviewed the preoperative and one-year postoperative plasma lipoprotein levels of both and performed a logistic regression to evaluate the factors associated with AVC.Results: Preoperatively, AVC patients had significantly higher coronary heart disease (43.0% vs 24.9%, p< 0.001), peripheral vascular disease (41.7% vs 26.2%, p< 0.001), and heart failure rates (63.6% vs 47.1%, p< 0.001), and a higher level of total cholesterol (4.1± 0.9 vs 3.9± 0.8 mmol/L, p=0.032) and very low-density cholesterol (0.6 (0.4– 0.7) vs 0.5 (0.3– 0.7) mmol/L, p=0.054). Echocardiography revealed a significant difference of aortic stenosis in both AVC and non-AVC groups (p< 0.05), and also identified aortic regurgitation (AR) with a significant difference between these two groups (p=0.003). The peak transaortic jet velocity, peak transaortic gradient, and mean transaortic gradient were significantly higher in the calcification group (all p< 0.001), but the aortic valve area (0.7 (0.5– 1.0) vs 4 (0.9– 4.5) cm2; p< 0.001) was smaller. Age (OR=1.023), total cholesterol (OR=1.272), and mean transaortic gradient (OR=1.182) were AVC risk factors. A larger aortic valve area (OR=0.010) were protective factors. The one-year mortality and perivalvular leakage rates were significantly higher in the calcification group.Conclusion: Total cholesterol was significantly higher in AVC patients and may be an AVC risk factor along with age and mean transaortic gradient. AVC patients had a relatively poorer outcome within one year.Keywords: aortic valve calcification, total cholesterol, plasma lipoprotein levels, low-density lipoprotein, aortic valve replacement

Qifan Zhang,1,* Zhen Xiao,2,* Shibo Sun,1 Kai Wang,1 Jianping Qian,1 Zhonglin Cui,1 Tao Tao,3 Jie Zhou1 1Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, People’s Republic of China; 2College of Life Sciences, Shanghai Normal University, Shanghai, 200234, People’s Republic of China; 3Department of Anesthesiology, Central People’s Hospital of Zhanjiang, Zhanjiang, Guangdong Province, 524045, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao Tao; Jie Zhou Email taotaomzk@smu.edu.cn; jacky_smu@163.comBackground: Liver hepatocellular carcinoma (HCC) is the third most common cause of death by cancer and has a high mortality world-widely. Approximately 75– 85% of primary liver cancers are caused by HCC. Uncovering novel genes with prognostic significance would shed light on improving the HCC patient’s outcome.Objective: In this research, we aim to identify novel prognostic biomarkers in hepatocellular carcinoma.Methods: Integrated proteomics and bioinformatics analysis were performed to investigate the expression landscape of prognostic biomarkers in 24 paired HCC patients.Results: As a result, eight key genes related to prognosis, including ACADS, HSD17B13, PON3, AMDHD1, CYP2C8, CYP4A11, SLC27A5, CYP2E1, were identified by comparing the weighted gene co-expression network analysis (WGCNA), proteomic differentially expressed genes (DEGs), proteomic turquoise module, The Cancer Genome Atlas (TCGA) cohort DEGs of HCC. Furthermore, we trained and validated eight pivotal genes integrating these independent clinical variables into a nomogram with superior accuracy in predicting progression events, and their lower expression was associated with a higher stage/risk score. The Gene Set Enrichment Analysis (GSEA) further revealed that these key genes showed enrichment in the HCC regulatory pathway.Conclusion: All in all, we found that these eight genes might be the novel potential prognostic biomarkers for HCC and also provide promising insights into the pathogenesis of HCC at the molecular level.Keywords: hepatocellular carcinoma, HCC, proteomics, bioinformatics analysis, prognosis, biomarkers

Mingrui Chen,1 Qiulin Chen,1 Tao Tao2 1Department of Neurosurgery, Chongqing Red Cross Hospital (People’s Hospital of Jiangbei District), Jiangbei, Chongqing 400020, People’s Republic of China; 2Department of Rehabilitation Medicine, Guizhou Provincial People’s Hospital, Guiyang, Guizhou 550002, People’s Republic of ChinaCorrespondence: Tao Tao Tel +86 13985162824Email 13985162824@163.comPurpose: Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Increasing evidence indicates that activated microglia play an important role in the inflammatory response in TBI. Inhibiting M1 and stimulating M2 activated microglia have protective effects in several animal models of central nervous system (CNS) disorders. In the present study, we investigated whether tanshinone IIA (TNA) protects neurons by shifting microglia polarization in a mouse TBI model and further investigated the mechanism in vitro.Materials and Methods: Forty C57BL/6 mice were used to investigate the effect of TNA on microglia polarization in TBI. BV-2 cells were used to examine the mechanism of TNA in regulating microglia polarization.Results: Normal saline (NS), TNA and the combination of TNA with ICI 182,780 (ICI, an estrogen receptor antagonist) were used to treat the TBI mice. After TBI, mice from each group demonstrated functional improvement. The improvement rate in mice treated with TNA was faster than other groups. ICI partially reversed the benefits from TNA treatment. TNA treatment significantly reduced TBI-induced neuronal loss. The number of microglia after TBI was not significantly changed by TNA treatment. However, TNA treatment significantly decreased M1 macrophage markers (iNOS, TNFα and IL-1β) and increased M2 macrophage markers (CD206, arginase 1 and Ym1). This effect was partially abolished by ICI. TNA treatment downregulated M1 macrophage markers and upregulated M2 macrophage markers in BV-2 cells under LPS stimulation. IL-10 was significantly increased by TNA treatment without a significantly change of IL-4 and IL-13 expression. IL-10 knockdown completely abolished the effect of TNA on microglial M2 polarization.Conclusion: Taken together, our data demonstrated that TNA attenuates neuronal loss in mouse TBI model and promotes M2 microglia by ERβ/IL-10 pathway. Thus, TNA could be a potential drug for TBI and/or the disorders that caused by microglial over-activation in CNS.Keywords: tanshinone IIA; TNA, traumatic brain injury; TBI, microglia, interleukins, macrophage polarization

Ming-Lu Jin, 1–3,* Zhe-Hua Zou, 1, 4,* Tao Tao, 1 Jun Li, 3, 5 Jian Xu, 3 Kai-Jian Luo, 6 Zhi Liu 7 1Department of Rehabilitation Medicine, Guizhou Provincial People’s Hospital, Guiyang, Guizhou 550002, People’s Republic of China; 2Department of Neurology, Qijiang Hospital of the First Affiliated Hospital of Chongqing Medical University, Chongqing 404100, People’s Republic of China; 3Department of Neurology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, People’s Republic of China; 4Department of General Practice, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei 066000, People’s Republic of China; 5Department of Neurology, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, People’s Republic of China; 6Guizhou Cancer Hospital, Guiyang, Guizhou 550000, People’s Republic of China; 7Department of Pharmacy, The Affiliated Hospital Guizhou Medical University, Guiyang, Guizhou 550001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao TaoDepartment of Rehabilitation Medicine, Guizhou Provincial People’s Hospital, Guiyang, Guizhou 550002, People’s Republic of ChinaEmail taotao62824@sina.comObjective: To investigate the effect of recombinant adenovirus-mediated HIF-1 alpha (HIF-1α) on the expression of vascular endothelial growth factor (VEGFA) and HIF-1α in hypoxic brain microvascular endothelial cells (BMEC) in rats.Methods: Primary cultured rat BMEC in vitro were treated without or with either recombinant adenovirus-mediated hypoxia-inducible factor-1 alpha (AdHIF-1α) or recombinant adenovirus empty vector (Ad) in the presence of CoCl 2 (simulating hypoxia conditions), or were grown under normoxia conditions. The expression of VEGFA and HIF-1α was analyzed at 12h, 24h, 48h and 72h incubation time, respectively. We also accessed a GEO dataset of stroke to analyze in vivo the alteration of HIF-1α and VEGFA expression, and the correlations between HIF-1α, VEGFA and CD31 mRNA levels in vascular vessels after stroke.Results: VEGFA and HIF-1α expression were significantly higher in at each time point in the AdHIF-1α than other groups (p< 0.05), whereas the Ad group and hypoxia group, showed no statistically significant difference (p> 0.05). Moreover, VEGFA and HIF-1α levels were significantly higher in BMEC under hypoxia conditions than normoxia conditions (p < 0.05). Both HIF-1α and VEGFA expression significantly increased after stroke in vivo with 1.30 and 1.57 fold-change in log2, respectively. There were significantly positive associations between HIF-1α, VEGFA and CD31 mRNA levels in vivo after stroke.Conclusion: Hypoxia-induced HIF-1α and VEGFA expression in vascular vessels, and recombinant AdHIF-1α could up-regulate VEGFA, and enhance HIF-1ααlevels in BMEC in vitro, which may play an important role in the recovery of stroke.Keywords: AdHIF-1α, brain microvascular endothelial cells, hypoxia, VEGFA, stroke

Yongtian Lin,1,* Shaowei Lin,2,* Jianshun Chen,3 Lici Chen,3 Tao Tao,2 Siying Wu2 1Department of Epidemiology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fu Zhou, People’s Republic of China; 2Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fu Zhou, People’s Republic of China; 3Department of Office, Changle Cancer Research Institute, Fu Zhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Siying WuDepartment of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, No. 1 Xuefu North Road, University Town, Fu Zhou 350122, People’s Republic of ChinaTel +86 591 22862510Fax +86 591 88783929Email fmuwsy@163.comPurpose: Although the incidence of gastric cancer in China has declined over the past decades, they were still much higher than the average of global. This aim of this study was to describe the trends and age-period-cohort effects on gastric cancer incidence from 2003 to 2012 in Changle and to explore the potential reason.Materials and methods: Data on patients with gastric cancer diagnosed between 2003 and 2012 were collected by the population-based Changle cancer registration (n=4111). Age-standardized incidence rates of gastric cancer were calculated and joinpoint regression was used to evaluate the trends of gastric cancer incidence. Time trends in gastric cancer incidence by the period of diagnosis and birth cohort were analyzed by sex. Age-period-cohort analysis was performed to investigate the independent effects of age, period of diagnosis and birth cohort among over 25-year-old residents.Results: A steady downward trend was observed among men, with the incidence ranging from 96.15 per 100,000 in 2003 to 62.6 per 100,000 in 2012 (APC, −5.1%; 95% CI: −6.9 to −3.2%). A similarly declining trend was observed among women with the incidence ranging from 34.5 per 100,000 to 15.7 per 100,000 (APC, −5.7%; 95% CI: −9.3 to −2.0%). Age-period-cohort model of incidence rate showed increasing age effect and decreasing period of diagnosis effects in both men and women. Birth cohorts exhibited a decreasing trend in the incidence among women who were born after 1935 and men after 1940.Conclusion: Recent decreases in the incidence of gastric cancer were due to decreased period of diagnosis and cohort effects, which was attributed to the improvements in their lifestyle and habits.Keywords: gastric cancer, incidence, trend, age-period-cohort model

Ying Zhu,1,2 Xuehui Li,1 Peiyan Guo,1 Yuhan Chen,3 Jiandong Li,1 Tianzhu Tao41Department of Respiratory Medicine, The Seventh Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai, People’s Republic of China; 3Affiliated BaYi Children’s Hospital, The Seventh Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 4Department of Anesthesiology, Air Force Medical Center, PLA, Beijing, People’s Republic of ChinaObjective: The soluble cluster of differentiation 14 subtype (sCD14-ST) or presepsin has recently been identified as a promising biomarker in sepsis. The present meta-analysis is performed to assess the prognostic value of presepsin in septic patients. Further, we compare the prognostic performance between presepsin and procalcitonin (PCT) in predicting all-cause mortality in these patients.Methods: A systemic and comprehensive search was conducted in PubMed, Embase and Cochrane databases by using Exploded Medical Subject Headings and appropriate corresponding keywords. Studies were eligible if they assessed the prognostic value of presepsin in sepsis and provided sufficient information to construct a 2×2 contingency table. A bivariate meta-analysis model was used to calculate the pooled sensitivity, specificity, positive/negative likelihood ratios and diagnostic odds ratio. The Chi-square and I2, index were used to assess the heterogeneity and inconsistency. The Deek’s funnel plot asymmetry test was used to assess the likelihood of publication bias.Results: Nine publications, comprising 1,561 patients, were included in this study. The overall area under the receiver operating characteristic curve (AUROC) of presepsin was 0.77 (95% CI, 0.73–0.81) with a pooled prognostic sensitivity (SEN) and specificity (SPE) of 0.83 (95% CI, 0.72–0.90) and 0.69 (95% CI, 0.63–0.74), respectively. Additionally, the PLR, NLR and DOR of presepsin were 2.6 (95% CI, 2.1–3.3), 0.25 (95% CI, 0.15–0.44) and 10 (95% CI, 5–22), respectively. The AUROC of PCT was 0.81 (95% CI, 0.78–0.84) with a pooled SEN of 0.76 (95% CI, 0.55–0.89) and SPE of 0.74 (95% CI, 0.33–0.94). There is no statistically significant difference in the performance of pooled SEN and SPE between presepsin and PCT, with a p value of 0.39 and 0.71, respectively.Conclusions: Based on the results of this meta-analysis, both presepsin and PCT are promising biomarkers for the prognosis of mortality in sepsis.Keywords: presepsin, sCD14-ST, procalcitonin, prognostic, sepsis, mortality

Mei Peng,1,2 Jun Deng,2 Sichun Zhou,2 Ting Tao,2 Qiongli Su,2 Xue Yang,1 Xiaoping Yang21Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China; 2Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan 410013, People’s Republic of ChinaAbstract: Clusterin is a conserved glycoprotein that has been characterized from almost all human tissues and fluids and plays a key role in cellular stress response and survival. Recently, research efforts have been contributed to explore the function of Clusterin in cancer metastasis, which is particularly important to design the strategies for treating metastatic patients. Evidence collected has demonstrated that Clusterin is overexpressed in tumor metastatic patients and experimental metastasis models. Specifically, Clusterin has been shown to have the role in anti-apoptotic capacities, development of therapy resistance and induction of epithelial–mesenchymal transition, all associated with cancer metastasis. Inhibition of Clusterin is known to increase the cytotoxic effects of chemotherapeutic agents and improves advanced cancer patients survival in clinical trials. Our unpublished data have demonstrated that Clusterin is overexpressed in bladder cancer and metformin, a well-known metabolism modulator specifically targets Clusterin by inhibiting migration of bladder cancer cells. In this review, we provide a general view of how Clusterin modulates cancer metastasis and update current understanding of detailed molecular mechanisms underlying of Clusterin for developing cancer management in future.Keywords: Clusterin, metastasis, EMT, apoptosis, drug resistance

Apixaban is indicated for the prevention of ischemic stroke in non-valvular atrial fibrillation (NVAF), as well as for the prevention and treatment of venous thromboembolism (VTE). Dose adjustment is based on age, weight, and serum creatinine in NVAF, while there are no recommended adjustment criteria for VTE. Such adjustment is unconventional compared to other commonly used medications. The objective of this manuscript is to critically analyze each apixaban dosing adjustment criterion and its associated outcomes. PubMed articles from March 2013 to March 2020 were selected with search terms “apixaban,” and “dose adjustment,” “adjustment,” or “adjustment criteria.” Pharmacokinetic studies demonstrated increased apixaban exposure in patients >65 years of age, those with extreme body weights, and those with advanced renal impairment, though post-hemodialysis dosing may off-set the elevated apixaban exposure. However, clinical data show that among patients > 75 years, < 60 kg, and with estimated glomerular filtration rate

Introduction Medical students' professional development includes their role as educators. Despite greater opportunities to join medical education curriculum development, medical students' engagement in these activities remains limited. A recent national study on student leadership in curricular change revealed a formal lack of leadership and training in medical education as significant barriers. Medical students' unawareness of how to disseminate curricula as educational scholarship and its value to their careers also restricts the fullness of their formation as educators. Methods We designed a 3-hour, interactive, project-focused conference workshop for medical students without prior knowledge in curriculum development. Of participants, 64 worked in 10 groups creating medical curricula using Kern's six-step approach in student-facilitated breakout sessions. Completed group projects were presented, including brief action plans for transforming their work into scholarship. The workshop was evaluated using a mixed-methods approach. Results Of survey respondents, 44 mostly medical students, faculty, and administrators from different institutions rated the workshop as a very positive experience, and the pacing of the breakout groups as effective. A notable increase in self-reported mastery, as measured by learning objectives aligned with Kern's six-step model, was recorded from student respondents as compared to faculty. A sense of readiness to participate in curricular decisions either at the home institution or in individual career paths was evident from narrative comments. Discussion Our workshop provided medical students with a foundation in curriculum development and educational scholarship. Session design provided flexibility in the pace of breakout sessions and allowed in-depth discussion of educational topics.

We consider the cubic defocusing nonlinear Schrödinger equation on the two dimensional torus. We exhibit smooth solutions for which the support of the conserved energy moves to higher Fourier modes. This behavior is quantified by the growth of higher Sobolev norms: given any δ≪1,K≫1,s>1, we construct smooth initial data u 0 with $\|u_{0}\|_{{H}^{s}}K$ at some time T. This growth occurs despite the Hamiltonian’s bound on $\|u(t)\|_{\dot{H}^{1}}$ and despite the conservation of the quantity $\|u(t)\|_{L^{2}}$ .The proof contains two arguments which may be of interest beyond the particular result described above. The first is a construction of the solution’s frequency support that simplifies the system of ODE’s describing each Fourier mode’s evolution. The second is a construction of solutions to these simpler systems of ODE’s which begin near one invariant manifold and ricochet from arbitrarily small neighborhoods of an arbitrarily large number of other invariant manifolds. The techniques used here are related to but are distinct from those traditionally used to prove Arnold Diffusion in perturbations of Hamiltonian systems.

Basic questions concerning nonsingular multilinear operators with oscillatory factors are posed and partially answered. L-p norm inequalities are established for multilinear integral operators of Calderon-Zygmund type which incorporate oscillatory factors e(iP), where P is a real-valued polynomial.

This paper investigates the use of Ancient Greek imagery in the marketing of male grooming products. Based on a case study of the cosmetics brand HOMMER, the paper analyses how elements such as scent and product ingredients combined with a visual profile and storytelling, provide consumers with elements for an experientially based identity creation. Based on psychological and archaeological theory, the athour argues that the intersection between product, advertising and consumer constitutes a play with identity and the potential for multisensory "time travel." By identifying the elements of a product poster, the visual narrative of a single product, a beard wipe, is shown to contain all the elements of the dominant Modern Greek national narrative and more, tying Greek notions of ancient and modern history to anglo-saxon sailor symbolism and the Neo-hipster phenomenon.