Extreme Value at Risk and Expected Shortfall during Financial Crisis

This paper investigates Value at Risk and Expected Shortfall for CAC 40, S&P 500, Wheat and Crude Oil indexes during the 2008 financial crisis. We show an underestimation of the risk of loss for the unconditional VaR models as compared with the conditional models. This underestimation is stronger using the historical VaR approach than when using the extreme values theory VaR model. Even in 2008 financial crisis, the conditional EVT model is more accurate and reliable for predicting the asset risk losses. Banks have no interest in using it because the Basel II agreement penalizes banks using accuracy models like the conditional EVT model, and this is the case for the assets being studied in this paper.Market risk; Value at Risk; EVT; GARCH; Financial crisis; Basel requirements

Alignment of leading-edge and peak-picking time of arrival methods to obtain accurate source locations

The location of a radiating source can be determined by time-tagging the arrival of the radiated signal at a network of spatially distributed sensors. The accuracy of this approach depends strongly on the particular time-tagging algorithm employed at each of the sensors. If different techniques are used across the network, then the time tags must be referenced to a common fiducial for maximum location accuracy. In this report we derive the time corrections needed to temporally align leading-edge, time-tagging techniques with peak-picking algorithms. We focus on broadband radio frequency (RF) sources, an ionospheric propagation channel, and narrowband receivers, but the final results can be generalized to apply to any source, propagation environment, and sensor. Our analytic results are checked against numerical simulations for a number of representative cases and agree with the specific leading-edge algorithm studied independently by Kim and Eng (1995) and Pongratz (2005 and 2007)

Relativistic electron beams above thunderclouds

Non-luminous relativistic electron beams above thunderclouds have been detected by the radio signals of low frequency ∼40–400 kHz which they radiate. The electron beams occur ∼2–9 ms after positive cloud-to-ground lightning discharges at heights between ∼22–72 km above thunderclouds. Intense positive lightning discharges can also cause sprites which occur either above or prior to the electron beam. One electron beam was detected without any luminous sprite which suggests that electron beams may also occur independently of sprites. Numerical simulations show that beams of electrons partially discharge the lightning electric field above thunderclouds and thereby gain a mean energy of ∼7 MeV to transport a total charge of ∼−10 mC upwards. The impulsive current ∼3 × 10<sup>−3</sup> Am<sup>−2</sup> associated with relativistic electron beams above thunderclouds is directed downwards and needs to be considered as a novel element of the global atmospheric electric circuit

Thinking like a man? The cultures of science

Culture includes science and science includes culture, but conflicts between the two traditions persist, often seen as clashes between interpretation and knowledge. One way of highlighting this false polarity has been to explore the gendered symbolism of science. Feminism has contributed to science studies and the critical interrogation of knowledge, aware that practical knowledge and scientific understanding have never been synonymous. Persisting notions of an underlying unity to scientific endeavour have often impeded rather than fostered the useful application of knowledge. This has been particularly evident in the recent rise of molecular biology, with its delusory dream of the total conquest of disease. It is equally prominent in evolutionary psychology, with its renewed attempts to depict the fundamental basis of sex differences. Wars over science have continued to intensify over the last decade, even as our knowledge of the political, economic and ideological significance of science funding and research has become ever more apparent

Alterations in the transcriptome and antibiotic susceptibility of Staphylococcus aureus grown in the presence of diclofenac

<p>Abstract</p> <p>Background</p> <p>Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) which has been shown to increase the susceptibility of various bacteria to antimicrobials and demonstrated to have broad antimicrobial activity. This study describes transcriptome alterations in <it>S. aureus </it>strain COL grown with diclofenac and characterizes the effects of this NSAID on antibiotic susceptibility in laboratory, clinical and diclofenac reduced-susceptibility (Dc^RS) <it>S. aureus </it>strains.</p> <p>Methods</p> <p>Transcriptional alterations in response to growth with diclofenac were measured using <it>S. aureus </it>gene expression microarrays and quantitative real-time PCR. Antimicrobial susceptibility was determined by agar diffusion MICs and gradient plate analysis. Ciprofloxacin accumulation was measured by fluorescence spectrophotometry.</p> <p>Results</p> <p>Growth of <it>S. aureus </it>strain COL with 80 μg/ml (0.2 × MIC) of diclofenac resulted in the significant alteration by ≥2-fold of 458 genes. These represented genes encoding proteins for transport and binding, protein and DNA synthesis, and the cell envelope. Notable alterations included the strong down-regulation of antimicrobial efflux pumps including <it>mepRAB </it>and a putative <it>emrAB/qacA</it>-family pump. Diclofenac up-regulated <it>sigB </it>(σ^B), encoding an alternative sigma factor which has been shown to be important for antimicrobial resistance. <it>Staphylococcus aureus </it>microarray metadatabase (SAMMD) analysis further revealed that 46% of genes differentially-expressed with diclofenac are also σ^B-regulated. Diclofenac altered <it>S. aureus </it>susceptibility to multiple antibiotics in a strain-dependent manner. Susceptibility increased for ciprofloxacin, ofloxacin and norfloxacin, decreased for oxacillin and vancomycin, and did not change for tetracycline or chloramphenicol. Mutation to Dc^RSdid not affect susceptibility to the above antibiotics. Reduced ciprofloxacin MICs with diclofenac in strain BB255, were not associated with increased drug accumulation.</p> <p>Conclusions</p> <p>The results of this study suggest that diclofenac influences antibiotic susceptibility in <it>S. aureus</it>, in part, by altering the expression of regulatory and structural genes associated with cell wall biosynthesis/turnover and transport.</p

Alterations In the Transciptome and Antibiotic Susceptibility of \u3ci\u3eStaphylococcus aureus\u3c/i\u3e Grown In the Presence of Diclofenac

Background Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) which has been shown to increase the susceptibility of various bacteria to antimicrobials and demonstrated to have broad antimicrobial activity. This study describes transcriptome alterations in S. aureus strain COL grown with diclofenac and characterizes the effects of this NSAID on antibiotic susceptibility in laboratory, clinical and diclofenac reduced-susceptibility (DcRS) S. aureus strains. Methods Transcriptional alterations in response to growth with diclofenac were measured using S. aureus gene expression microarrays and quantitative real-time PCR. Antimicrobial susceptibility was determined by agar diffusion MICs and gradient plate analysis. Ciprofloxacin accumulation was measured by fluorescence spectrophotometry. Results Growth of S. aureus strain COL with 80 μg/ml (0.2 × MIC) of diclofenac resulted in the significant alteration by ≥2-fold of 458 genes. These represented genes encoding proteins for transport and binding, protein and DNA synthesis, and the cell envelope. Notable alterations included the strong down-regulation of antimicrobial efflux pumps including mepRAB and a putative emrAB/qacA-family pump. Diclofenac up-regulated sigB (σB), encoding an alternative sigma factor which has been shown to be important for antimicrobial resistance. Staphylococcus aureus microarray metadatabase (SAMMD) analysis further revealed that 46% of genes differentially-expressed with diclofenac are also σB-regulated. Diclofenac altered S. aureus susceptibility to multiple antibiotics in a strain-dependent manner. Susceptibility increased for ciprofloxacin, ofloxacin and norfloxacin, decreased for oxacillin and vancomycin, and did not change for tetracycline or chloramphenicol. Mutation to DcRS did not affect susceptibility to the above antibiotics. Reduced ciprofloxacin MICs with diclofenac in strain BB255, were not associated with increased drug accumulation. Conclusions The results of this study suggest that diclofenac influences antibiotic susceptibility in S. aureus, in part, by altering the expression of regulatory and structural genes associated with cell wall biosynthesis/turnover and transport

Some Directions for Performance Improvement of Li-Ion Batteries out of Usual Paths

Recent developments at IMN will be shared on several research directions out of usual paths for performance improvement of Li-ion batteries. We will focus on innovative surface modifications of electrode components, new electrode compositions and architectures, and failure mechanism upon cycling by in-depth characterization through coupled advanced spectroscopic techniques. A molecular grafting approach has been proposed as a way to modify the interfacial chemical reactivity of oxide materials, which is detrimental to their long-term energy storage properties as electrodes of Li-ion batteries. Surface derivatization of powder oxide materials such as Li1.2V3O8 and Li(Mn,Ni)2O4 was accomplished by in situ electrografting of a diazonium salt during Li-ion intercalation, leading to a covalently bonded organic multilayer. Charge transfer is not impeded, while electrolyte decomposition is inhibited thus increasing the cycle life and decreasing the self-discharge. Carbon additives of classical porous electrodes occupy a large volume fraction which is lost for charge storage. Redox functionalization of the surface of some carbon additives has been successfully achieved through non-covalent grafting chemistry using multi-redox pyrene molecules synthesized on purpose. Such functionalized carbon additives have been used to increase the stored energy and power of C-coated LFP porous electrodes. Thicker electrodes are needed for higher energy density Li-ion batteries. We evaluate different directions in order to design new innovative electrode architectures for such a purpose. Our grafting chemistry has been further developed to achieve molecular junctions between non-carbon-coated LFP and multiwall carbon nanotubes (MWCNT) using a designed thiophene-based conjugated molecule. The strategy enables original architecturing of the cathode of Li-ion batteries, with the individual MWCNT being electronically nanocontacted at the surface of LFP grains. This advancement leads to much higher specific capacity and better capacity retention for non calendared thick electrodes, for which the electronic wiring of the electroactive material grains is a critical issue. Another direction followed is the use of conducting polymer additives in porous electrodes, which are able to act as both conducting fillers and mechanical reinforcement materials. We have synthesized a new form of lithium doped PANI, the excellent properties of which in terms of specific capacity, stability on cycling and rate capability will be presented. The coating of bare LFP particles with thin layers of this new Li-doped PANI allows surpassing the performance of commercial carbon coated LFP thick electrodes. The role of this PANI additive into millimetric thick electrodes of NMC material will also be discussed. Future developments of higher energy density Si-based Li-ion batteries depend on the mastering of side reactions at the Si anode. We will compare the SEI composition and morphology at the Si surface upon cycling in half cell and full Li-ion cell configurations using a combination of 7Li, 19F MAS NMR, XPS, TOF-SIMS and STEM-EELS. The origin of the much faster aging of Si-based full cells versus half cells and future directions for improvement will be discusse

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81