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A glance of p53 functions in brain development, neural stem cells, and brain cancer
Get PDFp53 is one of the most intensively studied tumor suppressors. It transcriptionally regulates a broad range of genes to modulate a series of cellular events, including DNA damage repair, cell cycle arrest, senescence, apoptosis, ferroptosis, autophagy, and metabolic remodeling, which are fundamental for both development and cancer. This review discusses the role of p53 in brain development, neural stem cell regulation and the mechanisms of inactivating p53 in gliomas. p53 null or p53 mutant mice show female biased exencephaly, potentially due to X chromosome inactivation failure and/or hormone-related gene expression. Oxidative cellular status, increased PI3K/Akt signaling, elevated ID1, and metabolism are all implicated in p53-loss induced neurogenesis. However, p53 has also been shown to promote neuronal differentiation. In addition, p53 mutations are frequently identified in brain tumors, especially glioblastomas. Mechanisms underlying p53 inactivation in brain tumor cells include disruption of p53 protein stability, gene expression and transactivation potential as well as p53 gene loss or mutation. Loss of p53 function and gain-of-function of mutant p53 are both implicated in brain development and tumor genesis. Further understanding of the role of p53 in the brain may provide therapeutic insights for brain developmental syndromes and cancer
Phase 2 study of vismodegib, a hedgehog inhibitor, combined with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic adenocarcinoma
Get PDFBackground: The Hedgehog (Hh) signalling pathway is overexpressed in pancreatic ductal adenocarcinoma (PDA). Preclinical studies have shown that Hh inhibitors reduce pancreatic cancer stem cells (pCSC), stroma and Hh signalling. Methods: Patients with previously untreated metastatic PDA were treated with gemcitabine and nab-paclitaxel. Vismodegib was added starting on the second cycle. The primary endpoint was progression-free survival (PFS) as compared with historical controls. Tumour biopsies to assess pCSC, stroma and Hh signalling were obtained before treatment and after cycle 1 (gemcitabine and nab-paclitaxel) or after cycle 2 (gemcitabine and nab-paclitaxel plus vismodegib). Results: Seventy-one patients were enrolled. Median PFS and overall survival (OS) were 5.42 months (95% confidence interval [CI]: 4.37–6.97) and 9.79 months (95% CI: 7.85–10.97), respectively. Of the 67 patients evaluable for response, 27 (40%) had a response: 26 (38.8%) partial responses and 1 complete response. In the tumour samples, there were no significant changes in ALDH + pCSC following treatment. Conclusions: Adding vismodegib to chemotherapy did not improve efficacy as compared with historical rates observed with chemotherapy alone in patients with newly diagnosed metastatic pancreatic cancer. This study does not support the further evaluation of Hh inhibitors in this patient population. Trial registration: ClinicalTrials.gov Identifier: NCT01088815
Simulation Studies of Combustion in Spark Ignition Engine using Openfoam
Get PDFThe open source Field Operation and Manipulation (OpenFOAM) software was used to investigate the performance of a fully premixed, modern high-performance 4-valve, iso-octane, dual overhead cam (DOHC) engine with quasi-symmetric pent roof combustion chamber running at 1500 revolutions per minute. The peak pressure occurred at the TDC and had a value of about 30 bar. The results from this study show that the maximum combustion temperature occurred at approximately 95 degrees crank angle ATDC and has a volume averaged value of about 2700° K, whereas the actual computed peak temperature was found to be about 3000° K and it occurred at grid point 12630. The other temperatures which were found to be higher than the volume averaged temperature were found to be in the range 2968.81° K to 2974.01° K and correspond to grid point positions 12630 to 12633. The flame-wrinkling factor, Ξ = St / Su was found to be in the range 1.0 ≤ Ξ ≤ 3.8. The dynamics of the regress variable b was accurately predicted
What Motivates Drivers to Comply with Speed Guidance Information at Signalized Intersections?
No full textThis study explored the intrinsic motivation of drivers most likely to accept guidance information at signalized intersections by using a mixed model approach. The proposed approach contains a multiple-indicator multiple-cause model (MIMIC) with a latent class analysis (LCA). The MIMIC model was used to quantify intrinsic motivations according to individual heterogeneity. From a group similarity perspective, the LCA was employed for the latent classification of drivers. The features and possibility of accepting guidance information of each class were also analyzed according to the intrinsic motivation of drivers. Data were collected from the stated preference online surveys, in which the questionnaire was designed according to the diffusion of innovation, in 2015 and 2019 in China. Four subjective perceptions of drivers were identified: the perception of innovating guidance information, the perception of convenience regarding guidance information transmission, the perception of surrounding complexity, and the individual innovation. The estimation results show that age, driving experience, education levels, and familiarity with road network are significant factors of compliance behavior. The proportion of conservatives gradually decreased from 2015 to 2019, while the proportion of early followers and late followers increased through market penetration, familiarity with the Internet of vehicles, and social networks in the same period. This prevalence demonstrates that guidance information at signalized intersections is gradually becoming acceptable in China
Intelligence Gathering and Challenges of Insecurity In Nigeria
Get PDFThe insecurity challenges in Nigeria such as ethno-religious conflict, communal clashes, Kidnapping, murder, cultism, militancy etc. have become daily occurrence and these have been compounded by the rising waves of terrorism since the return to democratic rule in 1999.The resultant effects of these, are loss of lives and properties of the citizens. The challenges of insecurity are traceable to lapse of intelligence gathering and its proper utilization. The paper adopts as its theoretical framework, the theory of structural functionalism to examine intelligence gathering and challenges of insecurity in Nigeria. The secondary data method is adopted by use of police records, internets newspapers and academic journal for data collection. The paper argues that there is positive relationship between the effective intelligence gathering and the state of security. The paper recommends among others, the training and retraining of personnel of intelligence community to be able to meet up with current trend and changes in contemporary Nigeria
Resisting Extremist Ideologies: Counterterrorism, Women, and Religious Reform in Morocco
Get PDFThis paper examines Morocco’s manifest and latent use of women in its counterterrorism strategy. The first section provides an overview of terrorism and counterterrorism in Morocco, with a special focus on the escalation of women’s involvement in Islamic terrorist organizations. The second section examines the restructuring of the Moroccan religious sphere as a gendered response to local, regional, and global processes and discourses surrounding the relationship between Islam and terrorism. The third presents a thematic analysis and argues that Morocco’s gendered counterterrorism strategy is effective in using a localized inclusion of women in religious roles of authority. This strategy offers a valuable counter narrative that challenges the patriarchal fundamentalist discourses and centralizes the role of women in the prevention of terrorism. However, as progressive as these policies are for women’s rights and counterterrorism policy, the paper also argues that these strategies are designed to consolidate the monarch’s religious legitimacy and increase Morocco’s regional and international soft power claims
Freeman Honors Newsletter, Fall 2020 Issue
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Import of Laugher in Police-Suspect Interaction in Ibadan, Nigeria: A Multimodal Analysis
Get PDFStudies on police-suspect interaction (PSI) have engaged the textual peculiarities of PSI. Scholarly works on the non-verbal mode of communication in PSI are very scanty. Dearth of studies in this regard has prevented an investigation of the significance of the non-verbal mode as a communicative tool in PSI. This study examines the resourcefulness of laughter as a non-verbal mode in PSI with a view to uncovering the contextual roles of laughter in PSI. The study adopts Norris’ multimodal interaction analysis theory to investigate the motivations behind the deployment of laughter by investigating police officer (IPOs) and suspects during interrogation sessions. Data were collected at the Criminal Investigation Department, Iyaganku, Ibadan, Oyo State. Analysis of data reveals that, with particular attention to social context, IPOs and suspects engage laughter to build rapport, mitigate tension, modify verbal expressions and attitude, orchestrate deception, mock suspects, evade questions and maintain social order. The social actors’ recourse to laughter as a meaning making mode reveals how their identities are co-constructed in the interaction
Legal Brief: Rape as a Penal Offence in the Nigerian Violence Against Persons (Prohibition) Act, 2015: A Forensic Investigative Approac
Get PDFThe Nigeria Violence against Persons (Prohibition) Act prohibits all forms of violence against persons while providing maximum protection and remedies for victims and punishment of offenders. Sections 1, 2, 3 and 4 provides for the offence of rape, defines the offence and punishment for offenders. Interesting as the provisions and severe as the punishment may be, successful investigation and prosecution of rapists are predicated upon standard forensic investigative procedures. However, available statistics reveal discrepancies between the cases reported and the number of convictions. Hence, the contention of this paper that the discrepancies is either that these forensic investigative procedures are hitherto neglected or little attention has been paid to them during investigation of rape cases thereby resulting in loss of cases