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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.
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
4.
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
5.
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
6.
The intermetallic compound Mg2Ni has been prepared by the vapour exchange/diffusion reaction of the elements sealed in a stainless steel container. The product has been characterised by powder X-ray diffractometry with Mo-Kα radiation, using step-scanning and profile refinement techniques. The hexagonal unit cell has constants a = 5.2117(4), . 相似文献
7.
DL Ellies DW Stock G Hatch G Giroux KM Weiss M Ekker 《Canadian Metallurgical Quarterly》1997,45(3):580-590
To understand the relationship between the expression and the genomic organization of the zebrafish dlx genes, we have determined the genomic structure of the dlx2 and dlx4 loci. This led to the identification of the zebrafish dlx1 and dlx6 genes, which are closely linked to dlx2 and dlx4, respectively. Therefore, the inverted convergent configuration of Dlx genes is conserved among vertebrates. Analysis of the expression patterns of dlx1 and dlx6 showed striking similarities to those of dlx2 and dlx4, respectively, the genes to which they are linked. Furthermore, the expression patterns of dlx3 and dlx7, which likely constitute a third pair of convergently transcribed genes, are indistinguishable. Thus, the overlapping expression patterns of linked Dlx genes during embryonic development suggest that they share cis-acting sequences that control their spatiotemporal expression. The evolutionary conservation of the genomic organization and combinatorial expression of Dlx genes in distantly related vertebrates suggest tight control mechanisms that are essential for their function during development. 相似文献
8.
Paraquat (1,1'-dimethyl-4,4'-dipyridylium) is an herbicide associated with both accidental and intentional ingestion, leading to severe and often fatal toxicity. Prognosis is largely dependent on the amount of paraquat absorbed. Rapid identification of the symptoms of paraquat toxicity (burns or ulceration at the site of ingestion or injection, acute respiratory distress, and renal failure) can facilitate early treatment intervention to limit absorption. We report a case of a 71-year-old man with a suicidal ingestion of paraquat 2 days prior to presentation. Serum paraquat levels, time elapsed since ingestion, and clinical symptoms all indicated poor prognosis. The patient developed severe respiratory distress and progressive renal failure, and died 6 days after admission to the hospital. 相似文献
9.
KM Shokat 《Canadian Metallurgical Quarterly》1995,2(8):509-514
Cytoplasmic tyrosine kinases are composed of modular domains; one (SH1) has catalytic activity, the other two (SH2 and SH3) do not. Kinase specificity is largely determined by the binding preferences of the SH2 domain. Attaching the SH1 domain to a new SH2 domain, via protein-protein association or mutation, can thus dramatically change kinase function. 相似文献
10.
Close to three-fourths of patients with chronic obstructive pulmonary disease (COPD) suffer from weight loss. Identifying a single cause for this is difficult, as several factors-including chronic mouth breathing, dyspnea, aerophagia, certain medications, and depression-often act in concert. Malnutrition can exacerbate symptoms of COPD by decreasing ventilatory muscle strength, exercise tolerance, and immunocompetence, and by increasing the risk of depression and anxiety. Goals of nutrition intervention are to prevent or reverse malnutrition without worsening the disease process and to improve respiratory function, thereby reducing morbidity and delaying mortality. Recommendations for intake of fats, carbohydrates, protein, and water must be individualized. 相似文献