ALTERNATIVE METHODS FOR DISTRIBUTING STATE AID TO LOCAL GOVERNMENTS IN NEW YORK

This paper simulates alternative distributions of general purpose state aid to local governments under different combinations of criteria: tax capacity, effort, and revenue needs. Revenue needs are based on Tobit estimates of the costs of providing average levels of 16 categories of services. Segmenting the sample into high and low population jurisdictions provided a more realistic set of cost estimates. Available revenues or capacity are determined by multiplying each jurisdiction's tax bases by standard tax rates. A Need-Capacity gap, the difference between needed revenues and available revenues, is used as a needs-based distribution strategy for general purpose aid. Finally an effort gap, based on above average tax efforts was added to the Need-Capacity gap to define a Need-Capacity-Effort strategy.Public Economics,

Measurement of the SOC State Specific Heat in ^4He

When a heat flux Q is applied downward through a sample of liquid 4He near the lambda transition, the helium self organizes such that the gradient in temperature matches the gravity induced gradient in Tlambda. All the helium in the sample is then at the same reduced temperature tSOC = ((T[sub SOC] - T[sub lambda])/T[sub lambda]) and the helium is said to be in the Self-Organized Critical (SOC) state. We have made preliminary measurements of the 4He SOC state specific heat, C[del]T(T(Q)). Despite having a cell height of 2.54 cm, our results show no difference between C[del]T and the zero-gravity 4He specific heat results of the Lambda Point Experiment (LPE) [J.A. Lipa et al., Phys. Rev. B, 68, 174518 (2003)] over the range 250 to 450 nK below the transition. There is no gravity rounding because the entire sample is at the same reduced temperature tSOC(Q). Closer to Tlambda the SOC specific heat falls slightly below LPE, reaching a maximum at approximately 50 nK below Tlambda, in agreement with theoretical predictions [R. Haussmann, Phys. Rev. B, 60, 12349 (1999)]

Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation

The cyclic AMP-specific phosphodiesterase PDE8 has been shown to play a pivotal role in important processes such as steroidogenesis, T cell adhesion, regulation of heart beat and chemotaxis. However, no information exists on how the activity of this enzyme is regulated. We show that under elevated cAMP conditions, PKA acts to phosphorylate PDE8A on serine 359 and this action serves to enhance the activity of the enzyme. This is the first indication that PDE8 activity can be modulated by a kinase, and we propose that this mechanism forms a feedback loop that results in the restoration of basal cAMP levels. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserve

Phosphorylation-dependent assembly and coordination of the DNA damage checkpoint apparatus by Rad4TopBP1

The BRCT-domain protein Rad4(TopBP1) facilitates activation of the DNA damage checkpoint in Schizosaccharomyces pombe by physically coupling the Rad9-Rad1-Hus1 clamp, the Rad3(ATR) -Rad26(ATRIP) kinase complex, and the Crb2(53BP1) mediator. We have now determined crystal structures of the BRCT repeats of Rad4(TopBP1), revealing a distinctive domain architecture, and characterized their phosphorylation-dependent interactions with Rad9 and Crb2(53BP1). We identify a cluster of phosphorylation sites in the N-terminal region of Crb2(53BP1) that mediate interaction with Rad4(TopBP1) and reveal a hierarchical phosphorylation mechanism in which phosphorylation of Crb2(53BP1) residues Thr215 and Thr235 promotes phosphorylation of the noncanonical Thr187 site by scaffolding cyclin-dependent kinase (CDK) recruitment. Finally, we show that the simultaneous interaction of a single Rad4(TopBP1) molecule with both Thr187 phosphorylation sites in a Crb2(53BP1) dimer is essential for establishing the DNA damage checkpoint

Fermi Surface of the Electron-doped Cuprate Superconductor Nd_{2-x}Ce_xCuO_{4} Probed by High-Field Magnetotransport

We report on the study of the Fermi surface of the electron-doped cuprate superconductor Nd$_{2-x}$Ce$_x$CuO$_{4}$ by measuring the interlayer magnetoresistance as a function of the strength and orientation of the applied magnetic field. We performed experiments in both steady and pulsed magnetic fields on high-quality single crystals with Ce concentrations of $x=0.13$ to 0.17. In the overdoped regime of $x > 0.15$ we found both semiclassical angle-dependent magnetoresistance oscillations (AMRO) and Shubnikov-de Haas (SdH) oscillations. The combined AMRO and SdH data clearly show that the appearance of fast SdH oscillations in strongly overdoped samples is caused by magnetic breakdown. This observation provides clear evidence for a reconstructed multiply-connected Fermi surface up to the very end of the overdoped regime at $x\simeq 0.17$. The strength of the superlattice potential responsible for the reconstructed Fermi surface is found to decrease with increasing doping level and likely vanishes at the same carrier concentration as superconductivity, suggesting a close relation between translational symmetry breaking and superconducting pairing. A detailed analysis of the high-resolution SdH data allowed us to determine the effective cyclotron mass and Dingle temperature, as well as to estimate the magnetic breakdown field in the overdoped regime.Comment: 23 pages, 8 figure

Artemisinin resistance in Plasmodium falciparum malaria.

BACKGROUND: Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease. There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border, historically a site of emerging antimalarial-drug resistance. METHODS: In two open-label, randomized trials, we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin, western Cambodia, and Wang Pha, northwestern Thailand: oral artesunate given at a dose of 2 mg per kilogram of body weight per day, for 7 days, and artesunate given at a dose of 4 mg per kilogram per day, for 3 days, followed by mefloquine at two doses totaling 25 mg per kilogram. We assessed in vitro and in vivo Plasmodium falciparum susceptibility, artesunate pharmacokinetics, and molecular markers of resistance. RESULTS: We studied 40 patients in each of the two locations. The overall median parasite clearance times were 84 hours (interquartile range, 60 to 96) in Pailin and 48 hours (interquartile range, 36 to 66) in Wang Pha (P<0.001). Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients (30%) receiving artesunate monotherapy and 1 of 20 (5%) receiving artesunate-mefloquine therapy in Pailin, as compared with 2 of 20 (10%) and 1 of 20 (5%), respectively, in Wang Pha (P=0.31). These markedly different parasitologic responses were not explained by differences in age, artesunate or dihydroartemisinin pharmacokinetics, results of isotopic in vitro sensitivity tests, or putative molecular correlates of P. falciparum drug resistance (mutations or amplifications of the gene encoding a multidrug resistance protein [PfMDR1] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [PfSERCA]). Adverse events were mild and did not differ significantly between the two treatment groups. CONCLUSIONS: P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thailand. Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing. Containment measures are urgently needed. (ClinicalTrials.gov number, NCT00493363, and Current Controlled Trials number, ISRCTN64835265.

Trust and Public Health Emergency Events:A Mixed-Methods Systematic Review

The systematic review examined the phenomenon of trust during public health emergency events. The literature reviewed was field studies done with people directly affected or likely to be affected by such events and included quantitative, qualitative, mixed-method, and case study primary studies in English (N = 38) as well as Arabic, Chinese, French, Russian, and Spanish (all non-English N = 30). Studies were mostly from high-and middle-income countries, and the event most covered was infectious disease. Findings from individual studies were first synthesized within methods and evaluated for certainty/confidence, and then synthesized across methods. The final set of 11 findings synthesized across methods identified a set of activities for enhancing trust and showed that it is a multi-faceted and dynamic concept

Identification of new DNA i-motif binding ligands through a fluorescent intercalator displacement assay

i-Motifs are quadruplex DNA structures formed from sequences rich in cytosine and held together by intercalated, hemi-protonated cytosine–cytosine base pairs. These sequences are prevalent in gene promoter regions and may play a role in gene transcription. Targeting these structures with ligands could provide a novel way to target genetic disease but there are very few ligands which have been shown to interact with i-motif DNA. Fluorescent intercalator displacement (FID) assays are a simple way to screen ligands against DNA secondary structures. Here we characterise how thiazole orange interacts with i-motif DNA and assess its ability for use in a FID assay. Additionally, we report FID-based ligand screening using thiazole orange against the i-motif forming sequence from the human telomere to reveal new i-motif binding compounds which have the potential for further development