Assessing Consistency and Fairness in Sentencing: A Comparative Study in Three States

Summarizes a study of sentencing guidelines in Michigan, Minnesota, and Virginia comparing levels of predictability and judicial discretion under different guideline systems, effectiveness in limiting discriminatory disparities, and lessons learned

From farmers' fields to data fields and back: A Synthesis of Participatory Information Systems for Irrigation and other Resources: Proceedings of an International Workshop held at the Institute of Agriculture and Animal Science, Rampur, Nepal, 21-26 March 1993

Irrigation / Forestry / Natural resources / Farmer participation / Participatory rural appraisal / Rapid rural appraisal / GIS / Data collection / Databases / Field tests / Farmers' associations / Training / Water rights / Water law / Institutions / Non-governmental organizations / India / Nepal

Extreme enrichment in atmospheric 15N15N.

Molecular nitrogen (N2) comprises three-quarters of Earth's atmosphere and significant portions of other planetary atmospheres. We report a 19 per mil (‰) excess of 15N15N in air relative to a random distribution of nitrogen isotopes, an enrichment that is 10 times larger than what isotopic equilibration in the atmosphere allows. Biological experiments show that the main sources and sinks of N2 yield much smaller proportions of 15N15N in N2. Electrical discharge experiments, however, establish 15N15N excesses of up to +23‰. We argue that 15N15N accumulates in the atmosphere because of gas-phase chemistry in the thermosphere (>100 km altitude) on time scales comparable to those of biological cycling. The atmospheric 15N15N excess therefore reflects a planetary-scale balance of biogeochemical and atmospheric nitrogen chemistry, one that may also exist on other planets

Activation of Adenylyl Cyclase Reduces TGF-b Profibrotic Response in Osteoarthritic Fibroblast-like Synoviocytes

Purpose: The hallmarks of osteoarthritis (OA) include cartilage degeneration, bone remodeling and synovial fibrosis. Synovial fibrosis is characterized by excessive extracellular matrix (ECM) accumulation due to an imbalance in ECM production, in particular collagen, and its turnover. Transforming growth factor beta (TGF-β) and its associated signaling pathway mediated by ALK5, plays an important role in synovial fibrosis and blocking TGF-β’s effect prevents synovial fibrosis. Increasing intracellular cyclic AMP (cAMP) produces an antifibrotic effect in fibroblasts of multiple origins. Forskolin (FsK) is a naturally occurring diterpene in the roots of the Indian Coleus plant that activates adenylyl cyclase resulting in an elevation in intracellular cAMP levels. We hypothesized that FsK treatment results in an anti-fibrotic effect in TGF-β stimulated fibroblast-like synoviocytes (FLS) from patients with advanced OA. Methods: OA FLS (Cell Applications, USA) were harvested from patients undergoing total knee replacement. Cells were used between the 3rd and 6th passages for all experiments. OA FLS (300,000 cells per well) were treated with TGF-β (1ng/ml; R&D Systems) in the absence or presence of FsK (10μM; Sigma Aldrich) or SB431542, an ALK5 inhibitor (1μM, Sigma Aldrich) for 24 hours followed by RNA extraction using Trizol reagent and RNA concentrations were determined using a NanoDrop ND-2000 spectrophotometer. cDNA was synthesized using iScript Reverse Transcription Supermix for RT-qPCR (Bio-Rad, USA). Quantitative PCR (qPCR) was performed using TaqMan Fast Advanced Master Mix (Lifetechnologies, USA). The cycle threshold (Ct) value of genes of interest were normalized to the Ct value of GAPDH in the same sample, and the relative expression was calculated using the 2−ΔΔCt method. Genes of interest included collagens type 1 (COL1A1) and 3 (COL3A1), α2 smooth muscle actin (ACTA2), proteoglycan-4 (PRG4), matrix metalloproteinases 3, 9 and 13 (MMP3, MMP9 and MMP13), tissue inhibitor of metalloproteinase-1 (TIMP1) and aggrecanase-1 (ADAMTS4). Multiple group comparisons were performed by ANOVA or ANOVA on the ranks followed by pairwise group comparisons using Tukey\u27s test. Data is presented as the average ± S.D. of 3–6 independent experiments. Results:FsK treatment significantly reduced TGF-β induced expression of collagen type I (fig. 1A; p Conclusions: Using a model of TGF-β stimulated OA synovial fibroblasts, FsK treatment resulted in a reduction in the expression of collagen type I, a major component of fibrosis and α2 smooth muscle actin, a marker of fibroblast differentiation to myofibroblasts. To this end, FsK\u27s effect was comparable to the inhibition of intracellular TGF-β signaling. PRG4 regulates synovial proliferation and inflammation and FsK treatment enhanced PRG4 expression by OA fibroblasts. FsK reduced expression of matrix degrading enzymes, especially MMP3 and MMP9 involved in synovial proliferation, and MMP13 and ADAMTS4, involved in cartilage degradation. Increasing intracellular levels of cAMP in synovial fibroblasts may result in antifibrotic and chondroprotective effects in the joint