Coronary artery calcification in male and female subjects with and without type 1 diabetes mellitus: A pharmacological dissection of the role of the L-arginine: nitric oxide: cGMP pathway.

Background: Defective nitric oxide (NO) release/response may contribute to increased risk in coronary heart disease (CHD) and the loss of sex difference in CHD in diabetes. Evidence for defective NO release/response in type 1 diabetes has been conflicting possibly due to the small sample sizes in previous studies. We conducted a large study to determine whether (1) NO release/response is impaired in type 1 diabetes, (2) whether there is a sex difference in NO release/response in the general population that is altered in diabetes and (3) whether defective NO release/response is associated with coronary artery calcification (CAC). Methods and Results: Forearm blood flow response was assessed by plethysmography in 88 diabetic and 69 non-diabetic subjects aged 30-53 years without clinical CHD. All participants had CAC measured by electron beam computed tomography. Acetylcholine (ACh) and bradykinin (BK) were used to assess agonist-stimulated NO release. Glyceryl trinitrate (GTN) was used to assess vascular smooth muscle cell (VSMC) response. NG-monomethyl-L-arginine (L-NMMA) was used to assess basal NO release and noradrenaline as vasoconstrictor control. In diabetic patients, vascular response was reduced by 18% for ACh (p=0.0008); 7% for BK (p=0.042) and 17% for GTN (p=0.0001). No difference in response to L-NMMA (p=0.49) or noradrenaline (p=0.55) was observed. Women did not have a greater response than men to all drugs after adjusting for sex differences in basal flow and forearm volume. The effect of diabetes on vasodilator response was the same in men and women. There was no association between CAC and drug responses. Conclusions: The primary defect in type 1 diabetes is impaired response to exogenous NO donor. The effect of diabetes on vascular function is the same in men and women and does not underlie the loss of the sex difference in CAC in diabetic patients. Vascular dysfunction is not associated with coronary atheroma

Vowels in Malacca Portuguese Creole

This paper examines the vowel system of present day Malacca Portuguese Creole (MPC) or Kristang, based on recordings from interviews with five female native speakers of MPC. A total of 1083 monophthongs were extracted from the recordings. The first and second formants of these vowels were measured and analysed. Considerable variation was found within and between the speakers in the way each of the vowels was produced. There were also noticeable overlaps between /i/ and /e/ suggesting that they were being used interchangeably. The quality of some of the vowels found in this study was also found to be different from those previously described. Based on the reduced vowel inventory, the variation in the way that vowels are produced, and the overlaps between vowels, the findings suggest the possibility of phonological instability of this endangered language

(2+1)-Dimensional Black Hole with Coulomb-like Field

A (2+1)-static black hole solution with a nonlinear electric field is derived. The source to the Einstein equations is a nonlinear electrodynamics, satisfying the weak energy conditions, and it is such that the energy momentum tensor is traceless. The obtained solution is singular at the origin of coordinates. The derived electric field E(r) is given by $E(r)=q/r^2$, thus it has the Coulomb form of a point charge in the Minkowski spacetime. This solution describes charged (anti)--de Sitter spaces. An interesting asymptotically flat solution arises for $\Lambda=0$.Comment: 6 pages, Latex, Phys. Lett. B. 484, 154 (2000

Properties of the circumgalactic medium in cosmic ray-dominated galaxy haloes

We investigate the impact of cosmic rays (CRs) on the circumgalactic medium (CGM) in FIRE-2 simulations, for ultra-faint dwarf through Milky Way (MW)-mass haloes hosting star-forming (SF) galaxies. Our CR treatment includes injection by supernovae, anisotropic streaming and diffusion along magnetic field lines, and collisional and streaming losses, with constant parallel diffusivity κ∼3×10²⁹ cm² s⁻¹ chosen to match γ-ray observations. With this, CRs become more important at larger halo masses and lower redshifts, and dominate the pressure in the CGM in MW-mass haloes at z ≲ 1–2. The gas in these ‘CR-dominated’ haloes differs significantly from runs without CRs: the gas is primarily cool (a few ∼10⁴), and the cool phase is volume-filling and has a thermal pressure below that needed for virial or local thermal pressure balance. Ionization of the ‘low’ and ‘mid’ ions in this diffuse cool gas is dominated by photoionization, with O VI columns ≳10^(14.5) cm⁻² at distances ≳150kpc⁠. CR and thermal gas pressure are locally anticorrelated, maintaining total pressure balance, and the CGM gas density profile is determined by the balance of CR pressure gradients and gravity. Neglecting CRs, the same haloes are primarily warm/hot (⁠T≳10⁵) with thermal pressure balancing gravity, collisional ionization dominates, O VI columns are lower and Ne VIII higher, and the cool phase is confined to dense filaments in local thermal pressure equilibrium with the hot phase

The effects of mood and judgmental heuristics on decision making under uncertainty

Five experiments investigated the effects of mood and judgmental heuristics on decision making under uncertainty. According to the mood-and-general-knowledge model (Bless, 2000), the assimilation-accommodation model (Fiedler, 2000) and the numeric-priming account of anchoring (Jacowitz & Kahneman, 1995; Wong & Kwong, 2000), happy individuals should rely more on the anchoring heuristic in decision making under uncertainty. However, the semantic-priming account of anchoring (Strack & Mussweiler, 1997) and the processing account of mood (Bless, 2000; Fiedler, 2000) predict that it is sad individuals who should be more susceptible to the anchoring bias. Experiment 1 used a new methodological paradigm, which captures the key methodologies of past mood and anchoring studies to test these two competing hypotheses. The overall results of Experiment 1 found that neither positive nor negative mood influenced the reliance on the anchoring heuristic, but a post-hoc analysis suggests that happy participants relied more on the anchoring heuristic in making decisions for low personal relevance, low familiarity scenarios whereas sad participants were more susceptible to the anchoring heuristic in making high personal relevance, high familiarity decisions. Experiment 2 tested this suggestion and confirmed that personal relevance significantly moderated the effects of mood on the use of the anchoring heuristic. Experiment 3 replicated this result and showed that sad participants processed longer in the high personal relevance condition whereas happy participants were comparably fast in making high and low personal relevance decisions. These findings support the suggestion that it was changes in processing styles that were responsible for the effects of mood and personal relevance on the reliance of the anchoring heuristic. In addition, Experiment 3 found no evidence that familiarity moderated the effects of mood on anchoring. Experiment 4 extended these results to the domain of general knowledge questions but failed to show that an individual difference variable, the Need for Cognition (Cacioppo & Petty, 1982) moderated these effects. The fifth and final experiment extended these findings to a different kind of heuristic, the representativeness heuristic. It was predicted and found that, contrary to the previous results, happy participants relied more on the representativeness heuristic in the high personal relevance condition. These findings have important implications for the theories of mood, judgmental heuristics and decision making under uncertainty

The SO2 Allowance Trading System and the Clean Air Act Amendments of 1990: Reflections on Twenty Years of Policy Innovation

The introduction of the U.S. SO2 allowance-trading program to address the threat of acid rain as part of the Clean Air Act Amendments of 1990 is a landmark event in the history of environmental regulation. The program was a great success by almost all measures. This paper, which draws upon a re¬search workshop and a policy roundtable held at Harvard in May 2011, investigates critically the design, enactment, implementation, performance, and implications of this path-breaking application of economic thinking to environmental regulation. Ironically, cap and trade seems especially well suited to addressing the problem of climate change, in that emitted greenhouse gases are evenly distributed throughout the world’s atmosphere. Recent hostility toward cap and trade in debates about U.S. climate legislation may reflect the broader political environment of the climate debate more than the substantive merits of market-based regulation

Comparative transcriptomics of multidrug-resistant Acinetobacter baumannii in response to antibiotic treatments

Abstract Multidrug-resistant Acinetobacter baumannii, a major hospital-acquired pathogen, is a serious health threat and poses a great challenge to healthcare providers. Although there have been many genomic studies on the evolution and antibiotic resistance of this species, there have been very limited transcriptome studies on its responses to antibiotics. We conducted a comparative transcriptomic study on 12 strains with different growth rates and antibiotic resistance profiles, including 3 fast-growing pan-drug-resistant strains, under separate treatment with 3 antibiotics, namely amikacin, imipenem, and meropenem. We performed deep sequencing using a strand-specific RNA-sequencing protocol, and used de novo transcriptome assembly to analyze gene expression in the form of polycistronic transcripts. Our results indicated that genes associated with transposable elements generally showed higher levels of expression under antibiotic-treated conditions, and many of these transposon-associated genes have previously been linked to drug resistance. Using co-expressed transposon genes as markers, we further identified and experimentally validated two novel genes of which overexpression conferred significant increases in amikacin resistance. To the best of our knowledge, this study represents the first comparative transcriptomic analysis of multidrug-resistant A. baumannii under different antibiotic treatments, and revealed a new relationship between transposons and antibiotic resistance

Influence of transport and ocean ice extent on biogenic aerosol sulfur in the Arctic atmosphere

The recent decline in sea ice cover in the Arctic Ocean could affect the regional radiative forcing via changes in sea ice-atmosphere exchange of dimethyl sulfide (DMS) and biogenic aerosols formed from its atmospheric oxidation, such as methanesulfonic acid (MSA). This study examines relationships between changes in total sea ice extent north of 70 degrees N and atmospheric MSA measurement at Alert, Nunavut, during 1980-2009; at Barrow, Alaska, during 1997-2008; and at Ny-Alesund, Svalbard, for 1991-2004. During the 1980-1989 and 1990-1997 periods, summer (July-August) and June MSA concentrations at Alert decreased. In general, MSA concentrations increased at all locations since 2000 with respect to 1990 values, specifically during June and summer at Alert and in summer at Barrow and Ny-Alesund. Our results show variability in MSA at all sites is related to changes in the source strengths of DMS, possibly linked to changes in sea ice extent as well as to changes in atmospheric transport patterns. Since 2000, a late spring increase in atmospheric MSA at the three sites coincides with the northward migration of the marginal ice edge zone where high DMS emissions from ocean to atmosphere have previously been reported. Significant negative correlations are found between sea ice extent and MSA concentrations at the three sites during the spring and June. These results suggest that a decrease in seasonal ice cover influencing other mechanisms of DMS production could lead to higher atmospheric MSA concentrations