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1.
Prof. Michael Murray Dr. Ariane Roseblade Dr. Yongjuan Chen Kirsi Bourget Dr. Tristan Rawling 《ChemMedChem》2020,15(2):247-255
Targeting the tumor cell mitochondrion could produce novel anticancer agents. We designed an aryl−urea fatty acid ( 1 g ; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that disrupted the mitochondrion and decreased MDA-MB-231 breast cancer cell viability. To optimize the aryl−ureas the present study evaluated mitochondrial targeting by 1 g analogues containing alkyl chains between 10–17 carbons. Using the dye JC-1, the C12−C17 analogues efficiently disrupted the mitochondrial membrane potential (IC50s 3.5±1.2 to 7.6±1.1 μM) and impaired ATP production; shorter analogues were less active. 7-Aminoactinomycin D/annexin V staining and flow cytometry showed that these agents activated the killing mechanisms of necrosis and apoptosis to varying extents (7-aminoactinomycin D/annexin V staining ratios 4.3–6.0). Indeed, 1 g and its C17 analogue preferentially activated necrosis and apoptosis, respectively (ratios 2.1 and 16). Taken together, alkyl chain length is a determinant of mitochondrial targeting by aryl−ureas and can be varied to develop analogues that activate apoptosis or necrosis in a regulated fashion. 相似文献
2.
Thomas S. Lowry John C. Bright Murray E. Close Christina A. Robb Paul A. White Stewart G. Cameron 《国际水资源开发杂志》2003,19(4):579-592
The primary objective of this project is to identify gaps, whether real or perceived, that hinder effective groundwater management in New Zealand. These gaps show as gaps in information, gaps in implementation, gaps in technological and management tools, and gaps in understanding of fundamental processes. The secondary objective is to propose a management strategy to close the identified gaps. Several methods are used to meet these objectives: surveys distributed to selected staff in each regional council; the review of various written reports; the analysis of land-use databases; and private consultation within each regional council. Results show that groundwater management in New Zealand is generally reactionary with the main gaps being in strategic planning and national guidelines. Most gaps appear to be predominantly information and implementation issues. In some cases there are gaps in the understanding of fundamental processes within an aquifer system, including the long-term effects of land-use on groundwater quality. An adaptive management approach is suggested as a means of closing these gaps. 相似文献
3.
4.
KC Murray 《Canadian Metallurgical Quarterly》1994,87(3):186-187
Primary psoas abscess is a relatively rare disease with highest incidence in children and adolescents. It usually presents with fever, abdominal pain and limp. Limping tends to incriminate musculoskeletal problems below the pelvis, but movement of the hip involves the psoas muscle which is mostly retroperitoneal and intimately related to pelvic and intraperitoneal organs. Although the current tendency is to use abdominal sonography, rectal examination is still a valuable step in clinical examination, and may help to assess a pelvic mass or abscess. The following case report describes the elusive nature of psoas abscess and a rare occurrence of abscess rupture and peritonitis, immediately after rectal examination. 相似文献
5.
Reviews the book, Elements of episodic memory by Endel Tulving (1983). Those of us who have followed Tulving's investigations in the somewhat fragmented form of journal articles are very grateful to have his ideas encapsulated, elaborated, and elegantly expounded in his Elements of episodic memory. Tulving spends the initial third of the book driving home the evidence that the distinction between episodic and semantic memory is not just that episodic is time-lagged and semantic is not: it is more far-ranging, and his new work on amnesia is leading to the conclusion that for some forms of this disorder either type of memory may be attacked but not necessarily both. The first vista that opens from Tulving's vantage point is that "systems" and "schemata" are collections of connections that derive a certain autonomy from being only loosely connected to other collections. The second vista that emerges is a psychology in which the use of numbers is rich and strange. A third vista that opens up is shielded at first by a spectre of opposition. The spectre seizes on the passage on "free radicals," in which Tulving claims that certain thoughts cannot be unambiguously assigned to either episodic or semantic memory. Perhaps the most heartening aspect of this book is that Tulving could never have written this monograph without the foundations of his experiments. It is a great relief to see experimentation validated in so invigorating a form. Nevertheless, the most difficult chapters of the book, on recognition and recall, are built on experimental findings that are not yet properly understood. I am glad Tulving did not delay in writing this book until he felt more secure about the questions raised in these last chapters: the work thereby remains a challenge rather than a fait accompli. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
6.
The pulse-stream technique, which represents neural states as sequences of pulses, is reviewed. Several general issues are raised, and generic methods appraised, for pulsed encoding, arithmetic, and intercommunication schemes. Two contrasting synapse designs are presented and compared. The first is based on a fully analog computational form in which the only digital component is the signaling mechanism itself-asynchronous, pulse-rate encoded digital voltage pulses. In this circuit, multiplication occurs in the voltage/current domain. The second design uses more conventional digital memory for weight storage, with synapse circuits based on pulse stretching. Integrated circuits implementing up to 15000 analog, fully programmable synaptic connections are described. A demonstrator project is described in which a small robot localization network is implemented using asynchronous, analog, pulse-stream devices. 相似文献
7.
BACKGROUND: There is controversy over whether colonization with drug-resistant organisms is a contraindication to lung transplantation. METHODS: We undertook a retrospective review of the results of lung transplantation for patients with cystic fibrosis (CF) at Duke University Medical Center. RESULTS: As of May 1996, 21 patients with CF underwent bilateral lung transplantation. The first patient died within 24 h of transplantation from sepsis due to Stenotrophomonas maltophilia. Of the remaining 20 patients, 17 (85%) are alive and in stable condition. The three deaths were related primarily to bronchiolitis obliterans at 4 and 18 months in two patients and to cytomegalovirus pneumonitis at 5 months in the other patient. The 17 surviving patients have been followed up for a mean of 13 months (range, 0.5 to 34 months). Most of them were colonized and infected with multidrug-resistant organisms before transplantation. Following transplantation, 11 patients had complications from infections. One patient had bacteremia due to a panresistant Burkholderia cepacia and was treated successfully. Two patients had bacteremia and wound infection due to Burkholderia gladioli, previously thought to be pathogenic only in plants. Both patients were treated successfully. Of the six patients with Aspergillus fumigatus isolated from cultures before transplantation, only one had invasive disease following transplantation and responded to treatment. CONCLUSION: The organisms present before transplantation were not the primary cause of mortality in our patient population. Our findings suggest that lung transplantation should be considered in CF patients infected with multidrug-resistant organisms. 相似文献
8.
Ovarian mucinous cystadenocarcinoma with mural nodules of anaplastic carcinoma: report of a case and review of the literature 总被引:1,自引:0,他引:1
A decline of cytosol protein kinase C activity was observed in rat myocardial cells at 4 and 8 h after endotoxin administration, and membrane-associated protein kinase C activity rose at the same time. The activity of membrane protein kinase C in aortic smooth muscle cells at 0.5 and 4 h after endotoxin injection was higher than that in control, while cytosol protein kinase C activity was lower. The results indicate that protein kinase C was activated in myocardial cells and aortic smooth muscle cells during various phases of endotoxemia. 相似文献
9.
Murray Slovick 《今日电子》2008,(7)
石油价格攀升和全球变暖导致了人们对清洁能源的需求,2008年最常搜索的单词就是“绿色”。由于普通美国人每年直接排放的二氧化碳大约是10吨(包括家庭、汽车,以及人们旅行所排放的),而在日常生活中(购买服装、食品等)每年间接排放的大约是23吨,所以公众已经很快表现出了对绿色产品的钟爱, 相似文献
10.
Dapsone has clinical utility as an anti-inflammatory agent but the mechanism of this action remains unknown. We have previously reported that dapsone inhibits beta2 integrin (CD11b/CD18)-mediated adherence of human neutrophils in vitro and now describe studies designed to discover how dapsone-mediated inhibition of this neutrophil function occurs. Results indicate that dapsone interferes with the activation or function of the G-protein (Gi type) that initiates the signal transduction cascade common to chemotactic stimuli. They also show that dapsone-mediated suppression of this pathway inhibits the generation of second messengers essential to the activation of beta2 integrin molecules, as well as respiratory and secretory functions of neutrophils exposed to chemoattractants. We propose that the inhibition of chemoattractant-induced signal transduction by dapsone suppresses neutrophil recruitment and local production of toxic respiratory and secretory products in the affected skin of dermatitis herpetiformis and other neutrophilic dermatoses. 相似文献