248 research outputs found
Race and Policing: An Agenda for Action
This paper is organized into two parts -- Strategic Voice and Tactical Agency. Strategic Voice argues that problems of race in policing cannot be resolved by the police alone. Other people must help by understanding and ameliorating the social conditions that cause race to be associated with crime and hence become a dilemma for American policing. Rather than accepting these conditions as givens, police leaders with their powerful collective voice should actively call attention to what needs to be changed. Tactical Agency outlines what the police can do on their own initiative to deal with the operational dilemmas of race -- in the communities they serve and in their own organizations
The Local Role in Homeland Security
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73848/1/j.1540-5893.2005.00236.x.pd
Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.
Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies
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The Internal-External Security Nexus and EU Police/Rule of Law Missions in the Western Balkans
Common Security and Defence Policy (CSDP) police/rule of law missions in the Western Balkans are increasingly guided by externally imposed normative agendas that respond primarily to EU internal security needs rather than functional imperatives or local realities. In line with these needs, EU police reform efforts tend to prioritise effectiveness and crime fighting over longer- term democratic policing and good governance reforms. In practice this means that police reform initiatives are technocratically oriented, yet value ridden fitting EU security concerns and needs. As a result, the police reform process can be—and often is—disconnected from the political and socio-economic reforms necessary for long-term stability and sustainable peace. Police assistance in Bosnia and Herzegovina has been shaped by a determined albeit questionable focus on organised crime and corruption. The focus of EU police reform in Macedonia on primarily crime-fighting aspects of policing has compromised the functioning of the Macedonian police. Similarly, the politics of (non-)recognition of Kosovo's self-proclaimed independence and the intrusiveness of EULEX Kosovo's executive mandate contravene meeting local challenges
Long-term prognosis of patients with pediatric pheochromocytoma
A third of patients with paraganglial tumors, pheochromocytoma, and paraganglioma, carry germline mutations in one of the susceptibility genes, RET, VHL, NF1, SDHAF2, SDHA, SDHB, SDHC, SDHD, TMEM127, and MAX. Despite increasing importance, data for long-term prognosis are scarce in pediatric presentations. The European-American-Pheochromocytoma-Paraganglioma-Registry, with a total of 2001 patients with confirmed paraganglial tumors, was the platform for this study. Molecular genetic and phenotypic classification and assessment of gene-specific long-term outcome with second and/or malignant paraganglial tumors and life expectancy were performed in patients diagnosed at <18 years. Of 177 eligible registrants, 80% had mutations, 49% VHL, 15% SDHB, 10% SDHD, 4%NF1, and one patient each in RET, SDHA, and SDHC. A second primary paraganglial tumor developed in 38% with increasing frequency over time, reaching 50% at 30 years after initial diagnosis. Their prevalence was associated with hereditary disease (P=0.001), particularly in VHL and SDHD mutation carriers (VHL vs others, P=0.001 and SDHD vs others, P=0.042). A total of 16 (9%) patients with hereditary disease had malignant tumors, ten at initial diagnosis and another six during follow-up. The highest prevalence was associated with SDHB (SDHB vs others, P<0.001). Eight patients died (5%), all of whom had germline mutations. Mean life expectancy was 62 years with hereditary disease. Hereditary disease and the underlying germline mutation define the long-term prognosis of pediatric patients in terms of prevalence and time of second primaries, malignant transformation, and survival. Based on these data, gene-adjusted, specific surveillance guidelines can help effective preventive medicine.publishersversionPeer reviewe
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