Deregulating America’s Big Banks and What It Means for You (with transcript)

David Skeel and Kevin Cirilli examine how the U.S. government will regulate America’s big banks in the wake of changes to Dodd-Frank, and what this means for Wall St. and Main St

Design, synthesis and biological activity of selective hCAs inhibitors based on 2-(benzylsulfinyl)benzoic acid scaffold

A large library of derivatives based on the scaffold of 2-(benzylsulfinyl)benzoic acid were synthesised and tested as atypical inhibitors against four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). The exploration of the chemical space around the main functional groups led to the discovery of selective hCA IX inhibitors in the micromolar/nanomolar range, thus establishing robust structure-activity relationships within this versatile scaffold. HPLC separation of some selected chiral compounds and biological evaluation of the corresponding enantiomers was performed along with molecular modelling studies on the most active derivatives

Latest Triassic onset of the Central Atlantic Magmatic Province (CAMP) volcanism in the Fundy Basin (Nova Scotia): New stratigraphic constraints

In this paper we investigate the stratigraphic relationship between the emplacement of the CAMP basalts and the Triassic–Jurassic (Tr–J) boundary in the Fundy Basin (Nova Scotia, Canada). This is one of the best exposed of the synrift basins of eastern North America (ENA) formed as a consequence of the rifting that led to the formation of the Atlantic Ocean. The Triassic palynological assemblages found in the sedimentary rocks below (uppermost Blomidon Formation) and just above the North Mountain Basalt (Scots Bay Member of the McCoy Brook Formation) indicate that CAMP volcanism, at least in Nova Scotia, is entirely of Triassic age, occurred in a very short time span, and may have triggered the T–J boundary biotic and environmental crisis. The palynological assemblage from the Blomidon Formation is characterised by the dominance of the Circumpolles group (e.g. Gliscopollis meyeriana, Corollina murphyae, Classopollis torosus) which crosses the previously established Tr–J boundary.The Triassic species Patinasporites densus disappears several centimetres below the base of the North Mountain basalt, near the previously interpreted Tr–J boundary. The lower strata of the Scots Bay Member yielded a palynological assemblage dominated by Triassic bisaccate pollens (e.g Lunatisporites acutus, L. rhaeticus Lueckisporites sp., Alisporites parvus) with minor specimens of the Circumpolles group. Examination of the state of preservation and thermal alteration of organic matter associated with the microfloral assemblages precludes the possibility of recycling of the Triassic sporomorphs from the older strata. Our data argue against the previous definition of the Tr–J boundary in the ENA basins, which was based mainly on the last occurrence of P. densus. Consequently, it follows that the late Triassic magnetostratigraphic correlations should be revised considering that chron E23r, which is correlated with the last occurrence of P. densus in the Newark basin, does not occur at the Tr–J boundary but marks rather a late Triassic (probably Rhaetian) reversal

Cystic Fibrosis Mortality in Childhood : Data from European Cystic Fibrosis Society Patient Registry

Data collected in the European Cystic Fibrosis Society Patient Registry (ECFSPR) database were used to investigate whether risk factors for death in childhood and adolescents CF patients have different impact in countries of different income. In this way, it is possible to recognize where interventions could improve the quality of care and survival in these patients. We matched deceased and alive patients by age, country, year of follow-up. Multivariable logistic models were developed. In the years of this study, the ECFSPR collected information on 24,416 patients younger than 18 years: 7830 patients were from countries with low/middle income and 16,586 from countries with high income; among these the dead are 102 and 107 (p 60%). Evaluation of mortality in pediatric age may reflect the availability of resources for CF diagnosis and treatment in some countries

40Ar/39Ar ages of CAMP in North America: implications for the Triassic-Jurassic boundary and the 40K decay constant bias

The Central Atlantic magmatic province (CAMP) is one of the largest igneous provinces on Earth (>107 km²) and spanning four continents. Recent high-precision 40Ar/39Ar dating of mineral separates has provided important constraints on the age, duration, and geodynamic history of CAMP. Yet, the North American CAMP is strikingly under-represented in this dating effort. Here we present 13 new statistically robust plateau, mini-plateau and isochron ages obtained on plagioclase and sericite separates from lava flows from the Fundy (n = 10; Nova Scotia, Canada) and Hartford and Deerfield (n = 3; U.S.A.) basins. Ages mostly range from 198.6 ± 1.1 to 200.1 ± 1.4 Ma (2σ), with 1 date substantially younger at 190.6 ± 1.0 Ma. Careful statistical regression shows that ages from the upper (199.7.0 ± 1.5 Ma) and bottom (200.1 ± 0.9 Ma) units of the lava pile in the Fundy basin are statistically indistinguishable, confirming a short duration emplacement (<< 1.8 Ma; ≤1 Ma). Three ages obtained on the Hartford (198.6 ± 2.0 Ma and 199.8 ± 1.1 Ma) and Deerfield (199.3 ± 1.2 Ma) basins were measured on sericite from the upper lava flow units. We interpret these dates as reflecting synemplacement hydrothermal activity within these units. Collectively, CAMP ages gathered so far suggest a short duration of the main magmatic activity (2-3 Ma), but also suggest the possibility of a temporal migration of the active magmatic centers from north to south. Such a migration challenges a plume model that would postulate a radial outward migration of the magmatism and is more compatible with other models such as the supercontinent global warming hypothesis. When compared to the age of the Triassic-Jurassic boundary, the filtered CAMP age database suggests that the onset of the magmatic activity precedes the limit by at least few hundred thousand years, therefore suggesting a causal relationship between CAMP and the end of Triassic mass extinction. An age at 191 Ma possibly suggests a minor CAMP late tailing activity (190-194 Ma) which has already observed for dykes and sills in Africa and Brazil. We speculate that, if real, this late activity can be due to a major extensional event, possibly heralding the oceanisation process at ~190 Ma. Comparison between high quality U/Pb and 40Ar/39Ar ages of pegmatite lenses from the North Mountain basalts confirms a ~1% bias between the two chronometers. This discrepancy is likely attributed to the miscalibration of the 40K decay constants, in particular the electron capture branch

Cystic Fibrosis Defective Response to Infection Involves Autophagy and Lipid Metabolism

Cystic fibrosis (CF) is a hereditary disease, with 70% of patients developing a proteinopathy related to the deletion of phenylalanine 508. CF is associated with multiple organ dysfunction, chronic inflammation, and recurrent lung infections. CF is characterized by defective autophagy, lipid metabolism, and immune response. Intracellular lipid accumulation favors microbial infection, and autophagy deficiency impairs internalized pathogen clearance. Myriocin, an inhibitor of sphingolipid synthesis, significantly reduces inflammation, promotes microbial clearance in the lungs, and induces autophagy and lipid oxidation. RNA-seq was performed in Aspergillusfumigatus-infected and myriocin-treated CF patients' derived monocytes and in a CF bronchial epithelial cell line. Fungal clearance was also evaluated in CF monocytes. Myriocin enhanced CF patients' monocytes killing of A. fumigatus. CF patients' monocytes and cell line responded to infection with a profound transcriptional change; myriocin regulates genes that are involved in inflammation, autophagy, lipid storage, and metabolism, including histones and heat shock proteins whose activity is related to the response to infection. We conclude that the regulation of sphingolipid synthesis induces a metabolism drift by promoting autophagy and lipid consumption. This process is driven by a transcriptional program that corrects part of the differences between CF and control samples, therefore ameliorating the infection response and pathogen clearance in the CF cell line and in CF peripheral blood monocytes

How many chronic myeloid leukemia patients who started a frontline second-generation tyrosine kinase inhibitor have to switch to a second-line treatment? A retrospective analysis from the monitoring registries of the italian medicines agency (AIFA)

The frequency of patients who switch to a second-line therapy from a frontline second-generation (2gen) tyrosine kinase inhibitor (TKI) such as dasatinib and nilotinib, is still substantially unknown. We retrospectively investigated a large series of chronic phase chronic myeloid leukemia (CP-CML) patients initially treated with 2gen TKIs monitored through the Italian Medicines Agency (AIFA Agenzia Italiana del farmaco) registries. Overall, 2420 patients were analyzed over a period of 6&nbsp;years. One hundred and fifty-seven patients (16.3%) treated with dasatinib and 164 treated with nilotinib (11.3%) have switched to another drug, with an overall frequency of 13.2%. In the dasatinib cohort, 39.4% of patients changed treatment for failure and 36.3% for intolerance as compared to 45.7% and 27.4% respectively in the nilotinib cohort. Overall, the median time to switch due to resistance was 293&nbsp;days, whereas it was 317&nbsp;days in case of intolerance. Resistance was observed mainly in younger male patients with high-risk features, while intolerance was not related to any baseline parameter. After resistance/intolerance to nilotinib, the majority of patients switched to dasatinib (53.8%) whereas in case of frontline dasatinib to ponatinib (43.2%). To the best of our knowledge these data provide the first report on the frequency of discontinuation of frontline 2gen TKIs and on the main causes and pattern of choice to a second-line therapy in the real-life setting