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Background-Endothelial progenitor cells (EPCs) promote neovascularization and endothelial repair. Renal artery stenosis (RAS) may impair renal function by inducing intrarenal microvascular injury and remodeling. We investigated whether replenishment with EPCs would protect the renal microcirculation in chronic experimental renovascular disease. Methods and Results-Single-kidney hemodynamics and function were assessed with the use of multidetector computed tomography in vivo in pigs with RAS, pigs with RAS 4 weeks after intrarenal infusion of autologous EPCs, and controls. Renal microvascular remodeling and angiogenic pathways were investigated ex vivo with the use of micro-computed tomography, histology, and Western blotting. EPCs increased renal expression of angiogenic factors, stimulated proliferation and maturation of new vessels, and attenuated renal microvascular remodeling and fibrosis in RAS. Furthermore, EPCs normalized the blunted renal microvascular and filtration function. Conclusions-The present study shows that a single intrarenal infusion of autologous EPCs preserved microvascular architecture and function and decreased microvascular remodeling in experimental chronic RAS. It is likely that restoration of the angiogenic cascade by autologous EPCs involved not only generation of new vessels but also acceleration of their maturation and stabilization. This contributed to preserving the blood supply, hemodynamics, and function of the RAS kidney, supporting EPCs as a promising therapeutic intervention for preserving the kidney in renovascular disease. (Circulation. 2009;119:547-557.)Key Words: blood flow Ⅲ kidney Ⅲ progenitor cells Ⅲ renal artery stenosis Ⅲ hypertension, renal E ndothelial progenitor cells (EPCs) mobilized endogenously in response to ischemia play a crucial role in augmenting neovascularization of ischemic tissues and endothelial replacement after vascular injury. Replenishment of such cells may limit vascular injury through reconstitution of the luminal barrier and cellular secretion of paracrine factors, providing a novel therapeutic option. 1,2 Indeed, growing experimental and clinical evidence underscores the critical role that circulating cells play in healing the endothelium when the intrinsic system is unable to adequately support tissue repair. Targeted delivery of EPCs has been shown to improve the function of the infarcted myocardium, 3 decrease hindlimb ischemia, 4,5 rescue the kidney from acute ischemia injury, 6 and participate in glomerular endothelial repair in glomerulonephritis. 7 Clinical Perspective p 557Ischemic nephropathy secondary to renal artery stenosis (RAS) represents an important cause of renovascular disease and hypertension that may induce renal injury and lead to end-stage renal disease. The presence of renovascular disease also constitutes an independent predictor for increased morbidity and mortality in cardiovascular disease and cardiac events. 8 We have shown previously that the kidney exposed to chronic RAS shows significant functional deteriorati...

This paper analyzes incentive compatible (truthful) mechanisms over restricted domains of preferences, the leading example being combinatorial auctions. Our work generalizes the characterization of Roberts (1979) who showed that truthful mechanisms over unrestricted domains with at least 3 possible outcomes must be "affine maximizers". We show that truthful mechanisms for combinatorial auctions (and related restricted domains) must be "almost affine maximizers" if they also satisfy an additional requirement of "independence of irrelevant alternatives". This requirement is without loss of generality for unrestricted domains as well as for auctions between two players where all goods must be allocated. This implies unconditional results for these cases, including a new proof of Roberts' theorem. The computational implications of this characterization are severe, as reasonable "almost affine maximizers" are shown to be as computationally hard as exact optimization. This implies the near-helplessness of such truthful polynomial-time auctions in all cases where exact optimization is computationally intractable.

We give a general technique to obtain approximation mechanisms that are truthful in expectation. We show that for packing domains, any α-approximation algorithm that also bounds the integrality gap of the LP relaxation of the problem by α can be used to construct an α-approximation mechanism that is truthful in expectation. This immediately yields a variety of new and significantly improved results for various problem domains and furthermore, yields truthful (in expectation) mechanisms with guarantees that match the best-known approximation guarantees when truthfulness is not required. In particular, we obtain the first truthful mechanisms with approximation guarantees for a variety of multiparameter domains. We obtain truthful (in expectation) mechanisms achieving approximation guarantees of O( √ m) for combinatorial auctions (CAs), (1 + ) for multiunit CAs with B = (log m) copies of each item, and 2 for multiparameter knapsack problems (multi-unit auctions).Our construction is based on considering an LP relaxation of the problem and using the classic VCG mechanism to obtain a truthful mechanism in this fractional domain. We argue that the (fractional) optimal solution scaled down by α, where α is the integrality gap of the problem, can be represented as a convex combination of integer solutions, and by viewing this convex combination as specifying a probability distribution over integer solutions, we get a randomized, truthful in expectation mechanism. Our construction can be seen as a way of exploiting VCG in a computational tractable way even when the underlying social-welfare maximization problem is NP-hard. ACM Reference Format:Lavi, R. and Swamy, C. 2011. Truthful and near-optimal mechanism design via linear programming.

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Background-From animal studies it emerged that nitric oxide is important for the modulation of CO 2 -mediated cerebral blood flow (CBF chemoregulation) but not for the pressor-dependent mechanism (mechanoregulation). This hypothesis was tested in 18 healthy subjects. Methods and Results-Peak velocity (PV), diastolic velocity (DV), and mean velocity (MV) were measured by transcranial Doppler of the middle cerebral artery. Chemoregulation was assessed during normocapnia, hypocapnia, and after inhaled mixture of 95% O 2 ϩ5% CO 2 . Mechanoregulation was evaluated by incremental doses of phenylephrine. Measurements were repeated during infusion of sodium nitroprusside (SNP). Regional cerebrovascular resistance (CVR) was calculated as mean blood pressure (BP)/MV. SNP infusion decreased mean BP by 7 mm Hg and CVR decreased from 1.38Ϯ0.08 to 1.29Ϯ0.09 mm Hg/cm ⅐ s Ϫ1 ; Pϭ0.01, resulting in unaffected CBF. Phenylephrine (25 to 250 g) caused a similar increase in BP in a dose-response fashion before and during SNP infusion. Despite the increments in BP and CVR, CBF remained unaffected. During hyperventilation (end-tidal CO 2 Ϸ24 mm Hg), CVR increased by 75Ϯ3% and PV and DV decreased by 27Ϯ2% and 43Ϯ2%, respectively (PϽ0.001 for all). SNP infusion blunted the vasoconstrictive effect of hypocapnia; CVR increased only by 57Ϯ5%, and PV and DV decreased by 23Ϯ2% and 35Ϯ3%, respectively, (PϽ0.05 for all). Similarly, SNP augmented the vasodilatory effect of hypercapnia. Conclusions-Exogenous nitric oxide donor affects the basal cerebral vascular tone without affecting the CBF mechanoregulation. However, it selectively affects only the chemoregulatory mechanism (CO 2 -dependent). Thus, the CO 2 -NO axis is a cardinal pathway for CBF regulation in humans.

We characterize dominant-strategy incentive compatibility with multidimensional types. A deterministic social choice function is dominant-strategy incentive compatible if and only if it is weakly monotone (W-Mon). The W-Mon requirement is the following: If changing one agent's type (while keeping the types of other agents fixed) changes the outcome under the social choice function, then the resulting difference in utilities of the new and original outcomes evaluated at the new type of this agent must be no less than this difference in utilities evaluated at the original type of this agent.