Transient mitochondrial permeability transition pore opening mediates preconditioning-induced protection

Background - Transient (low-conductance) opening of the mitochondrial permeability transition pore (mPTP) may limit mitochondrial calcium load and mediate mitochondrial reactive oxygen species (ROS) signaling. We hypothesize that transient mPTP opening and ROS mediate the protection associated with myocardial preconditioning and mitochondrial uncoupling.Methods and Results - Isolated perfused rat hearts were subjected to 35 minutes of ischemia/ 120 minutes of reperfusion, and the infarct-risk-volume ratio was determined by tetrazolium staining. Inhibiting mPTP opening during the preconditioning phase with cyclosporine-A (CsA, 0.2 mumol/L) or sanglifehrin-A (SfA, 1.0 mumol/L) abolished the protection associated with ischemic preconditioning (IPC) ( 20.2 +/- 3.6% versus 45.9 +/- 2.5% with CsA, 49.0 +/- 7.1% with SfA; P < 0.001); and pharmacological preconditioning with diazoxide (Dzx, 30 mu mol/L) (22.1 +/- 2.7% versus 46.3 +/- 3.0% with CsA, 48.4 +/- 5.5% with SfA; P < 0.001), CCPA ( the adenosine A1-receptor agonist, 200 nmol/L) (24.9 +/- 4.5% versus 54.4 +/- 6.6% with CsA, 42.6 +/- 9.0% with SfA; P < 0.001), or 2,4-dinitrophenol (DNP, the mitochondrial uncoupler, 50 mu mol/L) (15.7 +/- 2.7% versus 40.8 +/- 5.5% with CsA, 34.3 +/- 3.1% with SfA; P < 0.001), suggesting that mPTP opening during the preconditioning phase is required to mediate protection in these settings. Inhibiting ROS during the preconditioning protocols with N-mercaptopropionylglycine (MPG, 1 mmol/L) also abolished the protection associated with IPC (20.2 +/- 3.6% versus 47.1 +/- 3.8% with MPG; P < 0.001), diazoxide (22.1 +/- 2.7% versus 56.3 +/- 3.8% with MPG; P < 0.001), and DNP (15.7 +/- 2.7% versus 50.7 +/- 6.6% with MPG; P < 0.001) but not CCPA (24.9 +/- 4.5% versus 26.5 +/- 8.4% with MPG; P = NS). Further experiments in adult rat myocytes demonstrated that diazoxide induced CsA-sensitive, low-conductance transient mPTP opening (represented by a 28 +/- 3% reduction in mitochondrial calcein fluorescence compared with control; P < 0.01).Conclusions - We report that the protection associated with IPC, diazoxide, and mitochondrial uncoupling requires transient mPTP opening and ROS

The consumer price index

The consumer price index (CPI) is probably the most closely watched indicator of inflation in the U.S. economy. In this article, Mark Wynne and Fiona Sigalla explain the construction of the CPI and evaluate some of its potential shortcomings as a measure of inflation. Specifically, they examine the discrepancies that arise between the CPI and the true cost- of-living index as a result of improvements in the quality of goods, the introduction of new goods, substitution on the part of consumers between different goods and retail outlets, and the difficulty of measuring the prices actually paid by consumers for the goods they purchase. ; The authors review the literature that quantifies these discrepancies, with the objective of estimating the magnitude of the overall bias in the CPI. Wynne and Sigalla argue that, in fact, remarkably little is known about the extent or significance of the overall bias in the CPI. They conclude that biases in the CPI cause it to overstate inflation by no more than 1 percent a year, and probably less.Consumer price indexes ; Prices

The Desert Shall Blossom as the Rose

IRRIGATION AGRICULTURE has not received attention commensurate with its significance in either ancient or modem times. Although most ancient civilizations depended on irrigation for their very existence, one can consult volume after volume of history only to find irrigation scarcely mentioned. To the agricultural specialist the great challenge and the strength and weakness of irrigation agriculture is not in constructing Boulder Dams nor in planning winding canals and syphons to carry water from the Columbia River to California. The critical point is on the farms where water is applied to the soil and crops are harvested. There the real battles are being waged. This lecture has been prepared to emphasize some of these on-the-farm problems, particularly those involved in the relationships among irrigation water, soils, and the growth of crop plants. I appreciate this honor of being the Faculty Research Lecturer for 1950-51. In preparing the material presented here I have drawn freely on the ideas and data of my colleagues, often without proper credit. In many instances I have no way of knowing just where concepts originated. To the many who have aided me directly and indirectly, I express my deep appreciation

The Path out of Washington\u27s Takings Quagmire: The Case for Adopting the Federal Takings Analysis

A quagmire awaits anyone attempting to understand the analysis Washington courts employ to determine whether government action constitutes a “taking” of property for which compensation is due under the U.S. Constitution. The Washington takings analysis is complex and confounding, especially when compared to the relatively straightforward takings analysis established by the U.S. Supreme Court. This Article argues that the Washington State Supreme Court should reject the Washington takings analysis and adopt the federal analysis. Comparing the federal and Washington analyses underscores how, as a matter of form, the Washington analysis easily stymies those who must work with it. Substantively, the Washington analysis is unfounded on three key levels: (1) the existence of differences between the two analyses fatally undermines the Washington analysis; (2) the nature of those differences renders the Washington analysis constitutionally insufficient by lowering the floor of protection that property owners enjoy under the federal analysis; and (3) the differences do not enhance the federal analysis. Rejecting the Washington takings analysis in favor of the federal analysis would be consistent with the doctrine of stare decisis because the Washington State Supreme Court originally intended to harmonize Washington and federal takings law, even though the Court failed to implement that intent. When embracing the federal takings analysis, the Court should avoid mischaracterizations of the federal takings analysis and the temptation to justify the Washington analysis on independent state constitutional grounds for the first tim

Defining Green : Toward Regulation of Environmental Marketing Claims

This Note joins a rising chorus calling for government regulation of green marketing claims. It attempts to encourage and add a sense of urgency to a burgeoning regulatory movement by highlighting some of the legal issues that such regulation entails. Part I identifies a gap in the law: the inability of current truth-in-advertising laws to clarify the legality of green marketing claims. Part II urges bridging that gap quickly; it examines the costs of continued nonregulation and describes some of the forms regulation is taking. Part III attempts to allay any fears that such regulations might be challenged on first amendment grounds. Part IV distinguishes the goals toward which green marketing regulations should strive from those that motivate so-called environmental seal of approval programs

Enrichment Procedures for Soft Clusters: A Statistical Test and its Applications

Clusters, typically mined by modeling locality of attribute spaces, are often evaluated for their ability to demonstrate ‘enrichment’ of categorical features. A cluster enrichment procedure evaluates the membership of a cluster for significant representation in pre-defined categories of interest. While classical enrichment procedures assume a hard clustering definition, in this paper we introduce a new statistical test that computes enrichments for soft clusters. We demonstrate an application of this test in refining and evaluating soft clusters for classification of remotely sensed images

The Path out of Washington\u27s Takings Quagmire: The Case for Adopting the Federal Takings Analysis

A quagmire awaits anyone attempting to understand the analysis Washington courts employ to determine whether government action constitutes a “taking” of property for which compensation is due under the U.S. Constitution. The Washington takings analysis is complex and confounding, especially when compared to the relatively straightforward takings analysis established by the U.S. Supreme Court. This Article argues that the Washington State Supreme Court should reject the Washington takings analysis and adopt the federal analysis. Comparing the federal and Washington analyses underscores how, as a matter of form, the Washington analysis easily stymies those who must work with it. Substantively, the Washington analysis is unfounded on three key levels: (1) the existence of differences between the two analyses fatally undermines the Washington analysis; (2) the nature of those differences renders the Washington analysis constitutionally insufficient by lowering the floor of protection that property owners enjoy under the federal analysis; and (3) the differences do not enhance the federal analysis. Rejecting the Washington takings analysis in favor of the federal analysis would be consistent with the doctrine of stare decisis because the Washington State Supreme Court originally intended to harmonize Washington and federal takings law, even though the Court failed to implement that intent. When embracing the federal takings analysis, the Court should avoid mischaracterizations of the federal takings analysis and the temptation to justify the Washington analysis on independent state constitutional grounds for the first tim

Washington\u27s Vested Rights Doctrine: How We Have Muddled a Simple Concept and How We Can Reclaim It

The article explores many of the problems with the details of the vested rights doctrine and outlines a statutory solution to them.\u27 Part I examines the inconsistent rationales that underlie the various manifestations of the doctrine. The differences between the mandamus and fairness/certainty rationales help explain some of the confusion that has become a fixture of the doctrine. Part II discusses a host of issues that the doctrine fails to resolve adequately. It groups these issues into four fundamental questions, the divergent answers to which often form the key dispute in any vested rights case: (1) to which types of land use permit applications is the doctrine applicable; (2) what types of laws does the doctrine freeze in time; (3) when does the doctrine begin to freeze those laws in time; and (4) for how long, and for what purpose, does the doctrine apply in the context of development projects that require more than one permit? Part III makes the case for adopting a statutory rule that replaces the muddled common-law doctrine in a way that reestablishes certainty and at least strives for fairness in the law\u27s details

Calculation of transonic steady and oscillatory pressures on a low aspect ratio model and comparison with experiment

Pressure data measured by the British Royal Aircraft Establishment for the AGARD SMP tailplane are compared with results calculated using the transonic small perturbation code XTRAN3S. A brief description of the analysis is given and a recently developed finite difference grid is described. Results are presented for five steady and nine harmonically oscillating cases near zero angle of attack and for a range of subsonic and transonic Mach numbers

An SMP Soft Classification Algorithm for Remote Sensing

This work introduces a symmetric multiprocessing (SMP) version of the continuous iterative guided spectral class rejection (CIGSCR) algorithm, a semiautomated classification algorithm for remote sensing (multispectral) images. The algorithm uses soft data clusters to produce a soft classification containing inherently more information than a comparable hard classification at an increased computational cost. Previous work suggests that similar algorithms achieve good parallel scalability, motivating the parallel algorithm development work here. Experimental results of applying parallel CIGSCR to an image with approximately 10^8 pixels and six bands demonstrate superlinear speedup. A soft two class classification is generated in just over four minutes using 32 processors