Repurposing Albendazole: new potential as a chemotherapeutic agent with preferential activity against HPV-negative head and neck squamous cell cancer.

Albendazole is an anti-helminthic drug that has been shown to exhibit anti-cancer properties, however its activity in head and neck squamous cell cancer (HNSCC) was unknown. Using a series of in vitro assays, we assessed the ability of albendazole to inhibit proliferation in 20 HNSCC cell lines across a range of albendazole doses (1 nM-10 μM). Cell lines that responded to treatment were further examined for cell death, inhibition of migration and cell cycle arrest. Thirteen of fourteen human papillomavirus-negative HNSCC cell lines responded to albendazole, with an average IC50 of 152 nM. In contrast, only 3 of 6 human papillomavirus-positive HNSCC cell lines responded. Albendazole treatment resulted in apoptosis, inhibition of cell migration, cell cycle arrest in the G2/M phase and altered tubulin distribution. Normal control cells were not measurably affected by any dose tested. This study indicates that albendazole acts to inhibit the proliferation of human papillomavirus-negative HNSCC cell lines and thus warrants further study as a potential chemotherapeutic agent for patients suffering from head and neck cancer

A case report and genetic characterization of a massive acinic cell carcinoma of the parotid with delayed distant metastases.

We describe the presentation, management, and clinical outcome of a massive acinic cell carcinoma of the parotid gland. The primary tumor and blood underwent exome sequencing which revealed deletions in CDKN2A as well as PPP1R13B, which induces p53. A damaging nonsynonymous mutation was noted in EP300, a histone acetylase which plays a role in cellular proliferation. This study provides the first insights into the genetic underpinnings of this cancer. Future large-scale efforts will be necessary to define the mutational landscape of salivary gland malignancies to identify therapeutic targets and biomarkers of treatment failure

High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines.

Head and neck squamous cell carcinoma (HNSCC) is a common cancer diagnosis worldwide. Despite advances in treatment, HNSCC has very poor survival outcomes, emphasizing an ongoing need for development of improved therapeutic options. The distinct tumor characteristics of human papillomavirus (HPV)-positive vs. HPV-negative disease necessitate development of treatment strategies tailored to tumor HPV-status. High-throughput robotic screening of 1,433 biologically and pharmacologically relevant compounds at a single dose (4 μM) was carried out against 6 HPV-positive and 20 HPV-negative HNSCC cell lines for preliminary identification of therapeutically relevant compounds. Statistical analysis was further carried out to differentiate compounds with preferential activity against cell lines stratified by the HPV-status. These analyses yielded 57 compounds with higher activity in HPV-negative cell lines, and 34 with higher-activity in HPV-positive ones. Multi-point dose-response curves were generated for six of these compounds (Ryuvidine, MK-1775, SNS-032, Flavopiridol, AZD-7762 and ARP-101), confirming Ryuvidine to have preferential potency against HPV-negative cell lines, and MK-1775 to have preferential potency against HPV-positive cell lines. These data comprise a valuable resource for further investigation of compounds with therapeutic potential in the HNSCC

Navigating the Looking Glass:Severing the Lawyer's Head in <i>Arkham Asylum</i>

Reading Arkham Asylum jurisprudentially, we encounter a story of the meeting of reason and unreason in the context of justice – of conscious law and its unconscious threat. Batman’s exploration of the Asylum is symbolic of the legal unconscious, and reflects the processes of repression that can be seen in dominant legal knowledge. A threat to this dominant knowledge can be seen in Two-Face’s reliance on his coin to ‘judge’ his victims. Moreover, Arkham Asylum configures the threat of law’s unconscious as the lawyer’s severed head inside the house of law. Ultimately, Batman’s journey through Arkham Asylum reminds law of the aesthetic and irrational contexts that it strives to deny and from which it seeks to defend itself – and that cultural legal studies explores. It recalls the unreason outside law’s logic, the chaos outside its order, the madness outside its sanity. The lesson of Batman’s encounters in the Asylum is that we should remember the ‘madness’ outside the legal order, and thus recognise that law is always already more than its conscious ‘sanity’ can contain

Bringing 'place' back in: regional clusters, project governance, and new product outcomes

We examine new product outcomes in the context of regional clusters. Based on past research on marketing relationships, clusters, and social networks, we propose that the overall configuration of a cluster helps promote particular governance practices among its members. These practices have distinct value-creating properties, and when they are brought to bear on a specific new product development project within a cluster, they promote performance outcomes like product novelty and speed to market. Ultimately, these performance effects are reinforced by the configuration of the cluster itself. In general, we propose that new product outcomes follow from complex interactions between a cluster's macro-level configuration and its micro-level governance processes. More broadly, our framework points to the importance of geographical variables and to the role of “place” in marketing decision-making

Relational Contracting In A Digital Age; Panel Discussion

If, as it has sometimes been argued, changes in contract rules and theory are strongly affected by changes in economic conditions, we should note that the world has changed a good deal since the early 1960s when relational contract theory began to bloom. The economic world of 2004 is very different from the world of 1964. Modern relational contract theory was born about the same time as its great theoretical competitor, the rational choice approach of the legal economists. It came before the vast changes wrought by the information revolution and the increased globalization of the economy. What has relational theory taught us over the past forty years? How has it changed and adapted in light of those great economic changes? Where is it going in the future? Those were the general topics at a panel discussion which took place June 8, 2004, at the Oxstalls campus of the University of Gloucestershire in Gloucester, England. It was part of a conference entitled, The Common Law of Contracts as a World Force in Two Ages of Revolution, which marked the 150th anniversary of one of the most famous contracts cases of all time, Hadley v. Baxendale, and is the theme of the present Symposium. The Conference\u27s object was to explore how the common law adapts to and influences the kind of revolutionary changes that have swept over our society in the past forty years, and which swept over England in the forty years before Hadley v. Baxendale

The occurrence of ionospheric signatures of plasmaspheric plumes over different longitudinal sectors

Plasmaspheric plumes have ionospheric signatures and are observed as storm-enhanced density (SED) in global positioning system (GPS) total electron content (TEC). These ionospheric signatures have been primarily observed over the American sector and in a few limited examples over the European sector. This study examines the longitudinal occurrence frequency of plasmaspheric plumes. We analyzed all images from the Imager for Magnetopause-to-Aurora Global Exploration (IMAGE) Extreme Ultraviolet Imager (EUV) databases for the first half of 2001 and identified a total of 31 distinct plume intervals observed during different storm events. Out of the total IMAGE EUV plumes that we identified, 12 were projected over North America, 10 over Asia, and the remaining 9 were over Europe and the Atlantic Ocean. Using ground-based GPS TEC from MIT\u27s Madrigal database, we searched for corresponding SED/TEC plumes at different longitudinal sector and found 12 ionospheric SED plume signatures over North America, 4 over Europe, and 2 over Asia. This indicates that the observation probability of an ionospheric SED plume when a plasmaspheric plume is seen is 100% in the American sector, 50% in the European sector, and 20% in the Asian sector. This could be due to the fact that the plumes may be either positioned beyond the limit of the ground-based GPS field of view, which happens mainly when there is less plasmaspheric erosion, or are too weak to be detected by the sparse number of GPS receivers over Asia. The in situ plasma densities from the available coincident defense metrological satellite program (DMSP) satellites were also used to study the characteristics of SED/TEC plume at DMSP orbiting altitude (i.e., ∼870 km). The TOPographic EXplorer (TOPEX) altimeter TEC also is used to identify the conjugate SED/plume signature over the Southern Hemisphere

Anomaly Detection in Social Media Using Recurrent Neural Network

© 2019, Springer Nature Switzerland AG. In today’s information environment there is an increasing reliance on online and social media in the acquisition, dissemination and consumption of news. Specifically, the utilization of social media platforms such as Facebook and Twitter has increased as a cutting edge medium for breaking news. On the other hand, the low cost, easy access and rapid propagation of news through social media makes the platform more sensitive to fake and anomalous reporting. The propagation of fake and anomalous news is not some benign exercise. The extensive spread of fake news has the potential to do serious and real damage to individuals and society. As a result, the detection of fake news in social media has become a vibrant and important field of research. In this paper, a novel application of machine learning approaches to the detection and classification of fake and anomalous data are considered. An initial clustering step with the K-Nearest Neighbor (KNN) algorithm is proposed before training the result with a Recurrent Neural Network (RNN). The results of a preliminary application of the KNN phase before the RNN phase produces a quantitative and measureable improvement in the detection of outliers, and as such is more effective in detecting anomalies or outliers against the test dataset of 2016 US Presidential Election predictions