Carbon Chain Length Modulates MDA-MB-231 Breast Cancer Cell Killing Mechanisms by Mitochondrially Targeted Aryl−Urea Fatty Acids

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.     

Management gaps analysis: a case study of groundwater resource management in New Zealand

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.     

Dedicated defense team strengthens liability protection

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.     

Review of Elements of episodic memory.

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)     

Pulse-stream VLSI neural networks mixing analog and digitaltechniques

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.     

你实现碳平衡了吗

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，     

The significance of spinal cord compression as the initial manifestation of lymphoma

Sex hormones have profound effects on immune responses and may influence the outcome of autoimmune diseases such as rheumatoid arthritis (RA). We investigated the effect of gonadal steroids on the production of interleukin-1 (IL-1) and IL-6, cytokines believed to be important in the pathogenesis of RA. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy male donors and male patients with RA, and were stimulated with lipopolysaccharide (LPS) in the presence of different concentrations of 17-beta-estradiol, progesterone or testosterone. In studies of cells from normal male donors, 17-beta-estradiol at pharmacological concentrations (> or = 10(-6) M) enhanced IL-1 and IL-6 secretion as well as the production of cell-associated IL-1. Progesterone and testosterone at similar concentrations inhibited IL-1 secretion but had no significant effect on IL-6 secretion or on the production of cell-associated IL-1. In studies of male RA donors, 17-beta-estradiol failed to enhance IL-1 or IL-6 secretion and progesterone failed to inhibit IL-1 secretion. The inhibitory effects of testosterone, however, appeared to be similar to that in normal donors. It is suggested that 17-beta-estradiol may promote IL-1 and IL-6 production and release, while gestation hormone, progesterone, and testosterone may inhibit IL-1 release in vivo. These data may partly explain the gender and age differences in the incidence of RA and the development of the disease in men with low and androgen levels.     

Superplasticity in a high strength powder aluminum

The superplastic properties of a rapidly solidified, high strength P/M Al alloy and the same alloy reinforced with SiC particulates (SiC _p ) have been studied. To prepare superplastic test materials, a matrix alloy powder of composition 7.2Zn-2.4Mg-2Cu-0.2Zr-0.12Cr-0.2Co (Kaiser PM-64) and the powder mixed with 10 to 20 vol pct SiC _p (~5 μm diameter) were thermomechanically processed to very fine equiaxed grain structures of ~6 μm and ~8 μm, respectively. Superplasticity in these materials was evaluated by characterizing (1) high temperature stability, (2) dynamic grain growth, (3) strain rate sensitivity, (4) flow stress behavior, (5) cavitation and cavitation control, and (6) total superplastic strain. It was observed that the PM-64 alloy could achieve a total elongation of over 800 pct, while the SiC_p reinforced alloy could attain an elongation greater than 500 pct before failure. Also, it was shown that with the use of hydrostatic pressure during superplastic flow, cavitation could be controlled. Observations were made of the effect SiC _p reinforcement particles had on the superplastic flow stress behavior. Interpretations are proposed to explain the role of particulates during superplastic straining.     

Pulse arithmetic in VLSI neural networks

This review explores the use of biological signaling methods to build silicon networks. Recent designs using a technique called `pulse stream', which employs fully analog, dynamic weight storage, are described. The pulse-stream concept is explained, and a comparison is made with conventional analog neural networks. An analog synapse based on the pulse-stream approach is presented. Chip details and simulation results are given