Simulation-Based Exact Tests for Jump-Diffusions with Unidentified Nuisance Parameters. An Application to Commodities Spot Prices

In this paper, we propose to use the Monte-Carlo (MC) test technique to obtain valid p-values when testing for the presence of discontinuities in jump-diffusion models. Indeed, the LR statistic used to test for discontinuities has typically a complex non-standard distribution, for at least two reasons: the jump frequency parameter lies on the boundary of its domain, and unidentified nuisance parameters intervene under the null hypothesis. We show that, if no other (identified) nuisance parameters are present (e.g. the geometric Brownian motion case), the proposed p-value is finite sample exact. Otherwise, we derive nuisance-parameter free bounds on the null distribution of the LR and obtain exact bounds p-values. We illustrate our approach with four classes of jump diffusion models (geometric Brownian motion and logarithmic Ornstein-Uhlenbeck, with and without a GARCH(1,1) error structure), which we apply to weekly and monthly spot prices of non-precious metals, gold, and crude oil. We find significant jumps in all weekly time series, but only in a few monthly time series.

Derivation of Del180 from sediment core log data\u27 Implications for millennial-scale climate change in the Labrador Sea

Sediment core logs from six sediment cores in the Labrador Sea show millennial-scale climate variability during the last glacial by recording all Heinrich events and several major Dansgaard-Oeschger cycles. The same millennial-scale climate change is documented for surface water δ18O records of Neogloboquadrina pachyderma (left coiled); hence the surface water δ18O record can be derived from sediment core logging by means of multiple linear regression, providing a paleoclimate proxy record at very high temporal resolution (70 years). For the Labrador Sea, sediment core logs contain important information about deepwater current velocities and also reflect the variable input of ice-rafted debris from different sources as inferred from grain-size analysis, the relation of density and P wave velocity, and magnetic susceptibility. For the last glacial, faster deepwater currents, which correspond to highs in sediment physical properties, occurred during iceberg discharge and lasted from several centuries to a few millennia. Those enhanced currents might have contributed to increased production of intermediate waters during times of reduced production of North Atlantic Deep Water. Hudson Strait might have acted as a major supplier of detrital carbonate only during lowered sea level (greater ice extent). During coldest atmospheric temperatures over Greenland, deepwater currents increased during iceberg discharge in the Labrador Sea, then surface water freshened shortly thereafter, while the abrupt atmospheric temperature rise happened after a larger time lag of ≥ 1 kyr. The correlation implies a strong link and common forcing for atmosphere, sea surface, and deep water during the last glacial at millennial timescales but decoupling at orbital timescales

NMR strategies to support medicinal chemistry workflows for primary structure determination.

International audienceCentral to drug discovery is the correct characterization of the primary structures of compounds. In general, medicinal chemists make great synthetic and characterization efforts to deliver the intended compounds. However, there are occasions which incorrect compounds are presented, such as those reported for Bosutinib and TIC10. This may be due to a variety of reasons such as uncontrolled reaction schemes, reliance on limited characterization techniques (LC-MS and/or 1D 1H NMR spectra), or even the lack of availability or knowledge of characterization strategies. Here, we present practical NMR approaches that support medicinal chemist workflows for addressing compound characterization issues and allow for reliable primary structure determinations. These strategies serve to differentiate between regioisomers and geometric isomers, distinguish between N- versus O-alkyl analogues, and identify rotamers and atropisomers. Overall, awareness and application of these available NMR methods (e.g. HMBC/HSQC, ROESY and VT experiments, to name only a few) should help practicing chemists to reveal chemical phenomena and avoid mis-assignment of the primary structures of compounds

Fragment-Based Phenotypic Lead Discovery: Cell-Based Assay to Target Leishmaniasis

International audienceA rapid and practical approach for the discovery of new chemical matter for targeting pathogens and diseases is described. Fragment-based phenotypic lead discovery (FPLD) combines aspects of traditional fragment-based lead discovery (FBLD), which involves the screening of small-molecule fragment libraries to target specific proteins, with phenotypic lead discovery (PLD), which typically involves the screening of drug-like compounds in cell-based assays. To enable FPLD, a diverse library of fragments was first designed, assembled, and curated. This library of soluble, low-molecular-weight compounds was then pooled to expedite screening. Axenic cultures of Leishmania promastigotes were screened, and single hits were then tested for leishmanicidal activity against intracellular amastigote forms in infected murine bone-marrow-derived macrophages without evidence of toxicity toward mammalian cells. These studies demonstrate that FPLD can be a rapid and effective means to discover hits that can serve as leads for further medicinal chemistry purposes or as tool compounds for identifying known or novel targets

CONNECT-EURE Contribution des vestiges du Canal Louis XIV aux continuités écologiques actuelles et passées

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Modified polysulfones. VI. Preparation of polymer membrane materials containing benzimine and benzylamine groups as precursors for molecularly imprinted sensor devices

A modified polysulfone containing benzylamine groups was synthesized as a reactive membrane material. Polysulfone was activated at the ortho-sulfone site by direct lithiation with n-butyllithium, and the resulting lithiated polysulfone was then reacted with benzonitrile; this yielded a polymer with pendant benzimine groups. The structure was confirmed by NMR and IR spectroscopy and by the transformation of imine to ketone by acid hydrolysis. The polymeric benzimine was also reduced to benzylamine with sodium cyanoborohydride in an acidic medium. The structure and degree of substitution of both benzylamine derivatives were determined by NMR and IR spectroscopy. The modified polysulfone containing benzylamine groups initiated the polymerization of N-carboxyanhydride of gamma-benzyl-L-glutamate [Glu(OBzl)-NCA]. The side-chain oligopeptide of Glu(OBzl)-NCA attached to polysulfone was converted into molecular recognition sites.NRC publication: Ye

Neuromuscular fatigue induced by alternating isometric contractions of the ankle plantar and dorsiflexors

Ankle muscle activity is important in regulating postural control as well as more complex movement tasks. Fatigue of these muscles clearly influences postural stability; however, the mechanisms responsible for this change have not been well characterized. In this study the fatigue produced in the plantar (PF) and dorsiflexors (DF) during intermittent, isometric contractions was examined and the recovery process was monitored for ten minutes post-fatigue. Fifteen healthy participants alternated between isometric PF and DF contractions until the torque was reduced to >50% of the pre-fatigue maximal voluntary contraction level in both directions. Peripheral fatigue was identified by measuring the change in the twitch torque and M-wave amplitude pre and post-fatigue. Central fatigue was determined by comparing the level of voluntary activation in the PF and DF between pre and post-fatigue. The fatigue protocol decreased the torque production in PF and DF to similar levels; however, the characteristics and recovery of the fatigue were different for the two muscle groups. This study demonstrates that although the torque produced by two antagonist muscles can be reduced to the same level, the mechanisms responsible for this change may not be similar and therefore may not impact motor tasks in the same way