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The evolution of the cracking pattern of an internally pressurized, circular, brittle ring supported with radial elastic springs is investigated. The ill-posed Griffith-type energy functional is regularized via a sequence of boundary value problems (BVPs). We show, that internal bending in the fragments plays an essential role in the position of the new crack. We also find that the pattern formation is driven by a co-dimension one bifurcation, which leads to the conclusion that in the beginning of the cracking process the new crack emerges in the vicinity of the existing cracks. In the second phase of the evolution the cracking process obeys a halving rule. The critical value of the fragment-length is derived. The results obtained are readily applicable to describe the crack evolution of hemispherical domes.

The literature is still divided about the information asymmetry problems of actively managed mutual funds. This disagreement raises an issue about the conditions behind the existence of this market. Some authors support the existence of market clearing mechanisms, while others estimate that passive funds are a substitute for active funds and the higher fees charged for the latter are not justified. We contribute to this discussion by formalizing these two approaches in price-setting strategies in two subgames. To solve it, we resort to an “external body” with a defined role to coordinate investors and mutual funds. We find that, owing to the actions of the external body and the presence of sophisticated investors and a low-quality mutual fund, there are incentives to deliver high-quality service and the active mutual fund market is preserved.

Background: Aneurysm shrinkage has been proposed as a marker of successful endovascular aneurysm repair (EVAR). We evaluated the impact of sac shrinkage on secondary interventions, on survival and its association with endoleaks, and on compliance with instructions for use (IFU). Methods: This observational retrospective study was conducted on all consecutive patients receiving EVAR for an infrarenal abdominal aortic aneurysm (AAA) using exclusively Endurant II/IIs endograft from 2014 to 2018. Sixty patients were entered in the study. Aneurysm sac shrinkage was defined as decrease ≥5 mm of the maximum aortic diameter. Univariate methods and Kaplan–Meier plots assessed the potential impact of shrinkage. Results: Twenty-six patients (43.3%) experienced shrinkage at one year, and thirty-four (56.7%) had no shrinkage. Shrinkage was not significantly associated with any demographics or morbidity, except hypertension (p = 0.01). No aneurysm characteristics were associated with shrinkage. Non-compliance with instructions for use (IFU) in 13 patients (21.6%) was not associated with shrinkage. Three years after EVAR, freedom from secondary intervention was 85 ± 2% for the entire series, 92.3 ± 5.0% for the shrinkage group and 83.3 ± 9% for the no-shrinkage group (Logrank: p = 0.49). Survival at 3 years was not significantly different between the two groups (85.9 ± 7.0% vs. 79.0 ± 9.0%, Logrank; p = 0.59). Strict compliance with IFU was associated with less reinterventions at 3 years (92.1 ± 5.9% vs. 73.8 ± 15%, Logrank: p = 0.03). Similarly, survival at 3 years did not significantly differ between strict compliance with IFU and non-compliance (81.8 ± 7.0% vs. 78.6 ± 13.0%, Logrank; p = 0.32). Conclusion: This study suggests that shrinkage ≥5 mm at 1-year is not significantly associated with a better survival rate or a lower risk of secondary intervention than no-shrinkage. In this series, the risk of secondary intervention regardless of shrinkage seems to be linked more to non-compliance with IFU. Considering the small number of patients, these results must be confirmed by extensive prospective studies.

Background & Aims: Human allogeneic liver-derived progenitor cells (HALPC, HepaStem®; Promethera Biosciences, Mont-Saint-Guibert, Belgium) are an advanced therapy medicinal product that could potentially alleviate systemic inflammation and ameliorate liver function in patients with acute-on-chronic liver failure (ACLF) or acute decompensation of cirrhosis (AD). Methods: This open-label phase II study was conducted in 9 centres in Belgium, Spain, and Bulgaria between 2016 and 2019. The primary objective was to assess the safety of HALPC therapy up to Day 28 and the secondary objectives were to assess its safety and preliminary efficacy up to Month 3. Results: The 24 treated patients (mean age: 51 years) were mostly male with an alcoholic cirrhosis. On pre-infusion Day 1, 15 patients had ACLF and 9 patients had AD. Two of the 3 initial patients treated with high HALPC doses (∼5×106 cells/kg body weight [BW]) had severe adverse bleeding events attributed to treatment. In 21 patients subsequently treated with lower HALPC doses (0.6 or 1.2×106 cells/kg BW, 1 or 2 times 7 days apart), no serious adverse events were related to treatment, and the other adverse events were in line with those expected in patients with ACLF and AD. Overall, markers of systemic inflammation and altered liver function decreased gradually for the surviving patients. The Day-28 and Month-3 survival rates were 83% (20/24) and 71% (17/24), and at Month 3, no patient had ACLF. Conclusions: The treatment of patients with ACLF or AD with up to 2 doses of 1.2×106 HALPC/kg BW appeared safe. The results of this study support the initiation of a proof-of-concept study in a larger cohort of patients with ACLF to further confirm the safety and evaluate the efficacy of HALPC therapy. Clinical Trials Registration: EudraCT 2016-001177-32. Lay summary: Patients with liver cirrhosis may suffer from the rapid onset of organ failure or multiple organ failure associated with a high risk of death in the short term. This clinical study of 24 patients suggests that an advanced therapy based on the intravenous infusion of low doses of human allogeneic liver-derived progenitor cells is safe and supports the next phase of clinical development of this type of therapy., SCOPUS: ar.j, info:eu-repo/semantics/published

Recent developments in the fabrication of micro-electro-mechanical systems (MEMS) are moving away from the deposition/mask/etch paradigm and instead exploiting useful properties of polymers. Many polymeric insulating materials, such as Parylene, PMMA, HSQ, SU-8 and KMPR, have attracted attention in microfabrication lately, because of their low cost and significantly easy processing procedures [1,2]. Metallization of these polymers is required for their integration in MEMS technology. While conventional microfabrication methods for preparing metallic thin films on insulating substrates are limited to vapor deposition techniques, it has recently demonstrated that electroless deposition can be considered as an alternative and efficient approach [3,4]. Presently used process of electroless plating onto plastics requires a pretreatment based on chromic acid etching for oxidizing the surface. This pretreatment increases the surface energy and wettability for the subsequent step of surface activation with noble metal catalysts. Thus, the development of simple, cost-effective and environment friendly strategies, such as avoiding chromic acid etching and/or minimizing the gravimetric use of noble metal, to metallize the surface of insulating substrates is of huge interest. Here, we report a simple one step covalent amination of the surface of commercial structural polymers employing diazonium-based aqueous chemistry. These amine-terminated functionalities allow minimizing the quantity of palladium cations used as catalyst for the subsequent electroless nickel deposition, as well as offer excellent adhesion between the polymer substrate and the nickel film. X-ray photoelectron spectroscopy is carried out to elucidate the mechanism of surface functionalization with amine groups. We then focus our attention on the comprehensive characterization of the metallic thin film through scanning electron microscopy, energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy techniques. Keywords: Metallization of plastics, diazonium chemistry, covalent grafting, environment plating process, MEMS fabrication Reference W. Dai et al., Sensors and Actuators A 135 (2007) 300–307. Y. Liu et al., Progress in Polymer Science 52 (2016) 79–106. Y. Shacham-Diamand et al. Microelectron. Eng. 132 (2015) 35–45. G. Zeb et al., Applied Surface Science 407 (2017) 518–525.

Cell-penetrating peptides (CPPs) allow intracellular delivery of bioactive cargo molecules. The mechanisms allowing CPPs to enter cells are ill-defined. Using a CRISPR/Cas9-based screening, we discovered that KCNQ5, KCNN4, and KCNK5 potassium channels positively modulate cationic CPP direct translocation into cells by decreasing the transmembrane potential (Vm). These findings provide the first unbiased genetic validation of the role of Vm in CPP translocation in cells. In silico modeling and live cell experiments indicate that CPPs, by bringing positive charges on the outer surface of the plasma membrane, decrease the Vm to very low values (–150 mV or less), a situation we have coined megapolarization that then triggers formation of water pores used by CPPs to enter cells. Megapolarization lowers the free energy barrier associated with CPP membrane translocation. Using dyes of varying dimensions in CPP co-entry experiments, the diameter of the water pores in living cells was estimated to be 2 (–5) nm, in accordance with the structural characteristics of the pores predicted by in silico modeling. Pharmacological manipulation to lower transmembrane potential boosted CPP cellular internalization in zebrafish and mouse models. Besides identifying the first proteins that regulate CPP translocation, this work characterized key mechanistic steps used by CPPs to cross cellular membranes. This opens the ground for strategies aimed at improving the ability of cells to capture CPP-linked cargos in vitro and in vivo., eLife digest Before a drug can have its desired effect, it must reach its target tissue or organ, and enter its cells. This is not easy because cells are surrounded by the plasma membrane, a fat-based barrier that separates the cell from its external environment. The plasma membrane contains proteins that act as channels, shuttling specific molecules in and out of the cell, and it also holds charge, with its inside surface being more negatively charged than its outside surface. Cell-penetrating peptides are short sequences of amino acids (the building blocks that form proteins) that carry positive charges. These positive charges allow them to cross the membrane easily, but it is not well understood how. To find out how cell-penetrating peptides cross the membrane, Trofimenko et al. attached them to dyes of different sizes. This revealed that the cell-penetrating peptides enter the cell through temporary holes called water pores, which measure about two nanometres across. The water pores form when the membrane becomes ‘megapolarized’, this is, when the difference in charge between the inside and the outside of the membrane becomes greater than normal. This can happen when the negative charge on the inside surface or the positive charge on the outer surface of the membrane increase. Megapolarization depends on potassium channels, which transport positive potassium ions outside the cell, making the outside of the membrane positive. When cell-penetrating peptides arrive at the outer surface of the cell near potassium channels, they make it even more positive. This increases the charge difference between the inside and the outside of the cell, allowing water pores to form. Once the peptides pass through the pores, the charge difference between the inside and the outside of the cell membrane dissipates, and the pores collapse. Drug developers are experimenting with attaching cell-penetrating peptides to drugs to help them get inside their target cells. Currently there are several experimental medications of this kind in clinical trials. Understanding how these peptides gain entry, and what size of molecule they could carry with them, provides solid ground for further drug development.

This paper aims to analyze the determinants of cash usage in a selection of European Union (EU) countries over the 2003–2016 period, based on a set of technological, socioeconomic, and socio-cultural indicators and cost components. Our results reveal the existence of both common and region-specific determinants for the EU advanced and Central and Eastern European (CEE) countries. In both groups cash usage is determined by payment system characteristics. Additionally, in the EU advanced countries cash usage can also be explained by the level of economic development and income inequalities and proliferation of Internet. In contrast, cash usage in CEE countries is negatively associated with consumer confidence and is inversely related to the technological progress, expressed in terms of mobile users.

Arenaviruses are a large family of emerging enveloped negative-strand RNA viruses that include several causative agents of viral hemorrhagic fevers. For cell entry, human-pathogenic arenaviruses use different cellular receptors and endocytic pathways that converge at the level of acidified late endosomes, where the viral envelope glycoprotein mediates membrane fusion. Inhibitors of arenavirus entry hold promise for therapeutic antiviral intervention and the identification of “druggable” targets is of high priority. Using a recombinant vesicular stomatitis virus pseudotype platform, we identified the clotrimazole-derivative TRAM-34, a highly selective antagonist of the calcium-activated potassium channel KCa3.1, as a specific entry inhibitor for arenaviruses. TRAM-34 specifically blocked entry of most arenaviruses, including hemorrhagic fever viruses, but not Lassa virus and other enveloped viruses. Anti-arenaviral activity was likewise observed with the parental compound clotrimazole and the derivative senicapoc, whereas structurally unrelated KCa3.1 inhibitors showed no antiviral effect. Deletion of KCa3.1 by CRISPR/Cas9 technology did not affect the antiarenaviral effect of TRAM-34, indicating that the observed antiviral effect of clotrimazoles was independent of the known pharmacological target. The drug affected neither virus-cell attachment, nor endocytosis, suggesting an effect on later entry steps. Employing a quantitative cell-cell fusion assay that bypasses endocytosis, we demonstrate that TRAM-34 specifically inhibits arenavirus-mediated membrane fusion. In sum, we uncover a novel antiarenaviral action of clotrimazoles that currently undergo in vivo evaluation in the context of other human diseases. Their favorable in vivo toxicity profiles and stability opens the possibility to repurpose clotrimazole derivatives for therapeutic intervention against human-pathogenic arenaviruses. IMPORTANCE Emerging human-pathogenic arenaviruses are causative agents of severe hemorrhagic fevers with high mortality and represent serious public health problems. The current lack of a licensed vaccine and the limited treatment options makes the development of novel antiarenaviral therapeutics an urgent need. Using a recombinant pseudotype platform, we uncovered that clotrimazole drugs, in particular TRAM-34, specifically inhibit cell entry of a range of arenaviruses, including important emerging human pathogens, with the exception of Lassa virus. The antiviral effect was independent of the known pharmacological drug target and involved inhibition of the unusual membrane fusion mechanism of arenaviruses. TRAM-34 and its derivatives currently undergo evaluation against a number of human diseases and show favorable toxicity profiles and high stability in vivo. Our study provides the basis for further evaluation of clotrimazole derivatives as antiviral drug candidates. Their advanced stage of drug development will facilitate repurposing for therapeutic intervention against human-pathogenic arenaviruses.

Tumor cell resistance to apoptosis, which is triggered by many anti-tumor therapies, remains a major clinical problem. Therefore, development of more efficient therapies is a priority to improve cancer prognosis. We have previously shown that a cell-permeable peptide derived from the p120 Ras GTPase-activating protein (RasGAP), called TAT-RasGAP317-326, bears anti-malignant activities in vitro and in vivo, such as inhibition of metastatic progression and tumor cell sensitization to cell death induced by various anti-cancer treatments. Recently, we discovered that this RasGAP-derived peptide possesses the ability to directly kill some cancer cells. TAT-RasGAP317-326 can cause cell death in a manner that can be either partially caspase-dependent or fully caspase-independent. Indeed, TAT-RasGAP317-326-induced toxicity was not or only partially prevented when apoptosis was inhibited. Moreover, blocking other forms of cell death, such as necroptosis, parthanatos, pyroptosis and autophagy did not hamper the killing activity of the peptide. The death induced by TAT-RasGAP317-326 can therefore proceed independently from these modes of death. Our finding has potentially interesting clinical relevance because activation of a death pathway that is distinct from apoptosis and necroptosis in tumor cells could lead to the generation of anti-cancer drugs that target pathways not yet considered for cancer treatment.

Resumen Con base en las teorías de Hall, Hofstede y el estudio Globe, este artículo analiza, de un lado, la manera de negociar de los franceses y una interpretación de por qué negocian así, y de otro, los retos que afrontan personas de otras culturas al negociar con ellos. Se utilizan metodologías cualitativas inductivas y comparativas, sobre experiencias concretas de negociación con franceses: un grupo focal y tres estudios con entrevistas semiestructuradas con 244 negociadores de cinco continentes. A quienes van a negociar con los franceses, se recomienda preparar la negociación con datos y argumentos sólidos, buscar un acercamiento gradual, ser asertivo pero flexible y mantener la formalidad y las buenas maneras. Abstract Based on theories developed by Hall, Hofstede, and the Globe project, this article analyzes, on one hand, the patterns of French negotiators, and on the other hand, the challenges that people from other cultures face when they negotiate with the French. Inductive, comparative and qualitative methodologies are used about specific negotiation experiences with the French: a focus group and three studies with semi-structured interviews with 244 negotiators from five continents. To those negotiating with the French, it is advised to prepare negotiations with facts, figures and solid arguments, to look for a gradual approach, to be assertive but flexible, and to maintain formality and good manners at the negotiation table. Résumé Basé sur les théories de Hall, Hofstede, et l’étude Globe, cet article analyse, d’une part, la manière de négocier des Français et les raisons pour lesquelles ils négocient ainsi, et, d’autre part, les défis culturels auxquels sont confrontés les individus qui négocient avec eux. Il applique des méthodologies qualitatives inductives et comparatives à des expériences concrètes de négociation avec des Français, à savoir : un groupe de discussion, et trois études comportant des entretiens semi-structurés avec 244 négociateurs des cinq continents. A ceux qui vont négocier avec les Français, il est recommandé de préparer la négociation avec des données et arguments solides, de rechercher une approche progressive, d’être assertif mais flexible, et de maintenir la formalité et les bonnes manières.

This paper examines the return on recent venture capital (VC) investment and its impact on the long–run stock market performance of initial public offerings (IPOs). Firms with higher return on recent VC investment underperform firms with lower return on recent VC investment by 32 to 43% in the 3–year period following the offer. This effect is robust to various risk–adjustment procedures. Market conditions at the time of the VC valuation and changes in these market conditions thereafter are the main drivers of this result, suggesting that investors are too optimistic or do not properly understand the informational content of the recent return on VC investment.

Macroautophagy has important physiological roles and its cytoprotective or detrimental function is compromised in various diseases such as many cancers and metabolic diseases. However, the importance of autophagy for cell responses has also been demonstrated in many other physiological and pathological situations. In this review, we discuss some of the recently discovered mechanisms involved in specific and unspecific autophagy related to mitochondrial dysfunction and organelle degradation, lipid metabolism and lipophagy as well as recent findings and evidence that link autophagy to unconventional protein secretion.

A controlled regulation of mitochondrial mass through either the production (biogenesis) or the degradation (mitochondrial quality control) of the organelle represents a crucial step for proper mitochondrial and cell function. Key steps of mitochondrial biogenesis and quality control are overviewed, with an emphasis on the role of mitochondrial chaperones and proteases that keep mitochondria fully functional, provided the mitochondrial activity impairment is not excessive. In this case, the whole organelle is degraded by mitochondrial autophagy or "mitophagy". Beside the maintenance of adequate mitochondrial abundance and functions for cell homeostasis, mitochondrial biogenesis might be enhanced, through discussed signalling pathways, in response to various physiological stimuli, like contractile activity, exposure to low temperatures, caloric restriction and stem cells differentiation. In addition, mitochondrial dysfunction might also initiate a retrograde response, enabling cell adaptation through increased mitochondrial biogenesis. Although the examples cited above suggest that the control of mitochondrial mass, through biogenesis or quality control, is beneficial to the cell/organism demands, the data generated from diverse pathologies suggest that modulations in mitochondrial abundance/functions may participate to the pathogenesis. Increased mitochondrial abundance is generally described to characterize mitochondrial myopathies as well as most cancers, and is generally accompanied by qualitative modifications of mitochondria, thereby affecting programmed cells death susceptibility. On the contrary, in ageing, obesity and type 2 diabetes, mitochondrial biogenesis and functions are generally down-regulated. The development of insulin resistance, favoured by an impaired mitochondrial function, tends to reduce the abundance of the organelle, through a vicious circle. J. Cell. Physiol. © 2011 Wiley-Liss, Inc.

Mutations in the mitochondrial DNA can lead to the development of mitochondrial diseases such as Myoclonic Epilepsy with Ragged Red Fibers (MERRF) or Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes (MELAS). We first show that human 143B-derived cybrid cells harboring either the A8344G (MERRF) or the A3243G (MELAS) mutation, are more prone to undergo apoptosis then their wild-type counterpart, when challenged with various apoptotic inducers such as staurosporine, etoposide and TRAIL. In addition, investigating the mechanisms underlying A8344G cybrid cells hypersensitivity to staurosporine-induced cell death, we found that staurosporine treatment activates caspases independently of cytochrome c release in both wild-type and mutated cells. Caspases are activated, at least partly, through the activation of calcium-dependent calpain proteases, a pathway that is more strongly activated in mutated cybrid cells than in wild-type cells exposed to staurosporine. These results suggest that calcium homeostasis perturbation induced by mitochondrial dysfunction could predispose cells to apoptosis, a process that could take part into the progressive cell degeneration observed in MERRF syndrome, and more generally in mitochondrial diseases.

Mitochondria-to-nucleus communication, known as retrograde signaling, is important to adjust the nuclear gene expression in response to organelle dysfunction. Among the transcription factors described to respond to mitochondrial stress, CHOP-10 is activated by respiratory chain inhibition, mitochondrial accumulation of unfolded proteins and mtDNA mutations. In this study, we show that altered/impaired expression of mtDNA induces CHOP-10 expression in a signaling pathway that depends on the eIF2α/ATF4 axis of the integrated stress response rather than on the mitochondrial unfolded protein response.

I hypothesize that the stock market overreacts to management earnings forecasts. I find that negative management forecast surprises lead to a -5.9% abnormal return around the forecast and a 1.9% correction in the 2-month period after earnings are announced. Positive surprises work in the opposite direction, with a 1.9% abnormal return and a -1.7% correction. The level of the stock market overreaction varies depending on forecast and firm characteristics, but the marginal impact remains the same: a 1% change in the stock market reaction around the forecast is associated with a 0.4% correction. These findings are consistent with the idea that investors overweight their recent experience in situation of increased uncertainty, leading to stock market overreaction.

The author documents analysts' reliance on the company-issued guidance range as a frame of reference in making their EPS forecasts. Analysts who use the guidance range as a reference may limit information diffusion to market participants by keeping their true beliefs private. The author therefore analyzes the stock market's reaction to analyst forecasting decisions, and finds that investors overreact to forecasts that are exactly equal to the minimum or maximum of the guidance range, but do not overreact to other types of forecasts. The evidence presented is most consistent with overreaction driven by overconfident investors who trade too much in the face of information uncertainty.

This paper finds that about one-quarter of analyst forecast dispersion and one-half of the dispersion-return relationship between 1985 and 2012 are explained by analyst overconfidence. In particular, the firm’s analyst overconfidence mean and analyst overconfidence dispersion are the two most significant determinants of analyst forecast dispersion. Together, these two variables capture 77% of the explained variation in analyst forecast dispersion when all known determinants are considered. With respect to the dispersion-return relationship, the analyst forecast dispersion predicted by analyst overconfidence leads to a monthly hedging portfolio profit of 0.35% compared to a profit of 0.37% for the analyst forecast dispersion not predicted by analyst overconfidence.

We examine the relation between an ex ante measure of IPO growth prospects – the industry-level long-term analyst earnings growth forecast – and short- and long-run IPO returns, using a sample of 7,570 IPOs from 1982 to 2007. The use of an industry-level, rather than firm-level growth measure allows the examination of the fullest set of IPOs. We find that before the Internet bubble period (1999-2000), IPOs in industries with high growth prospects earn high first-day and long-run returns up to three years after the IPO. Industry growth has the largest economic impact on IPO long-run performance among all factors we consider, and this effect is strongest among IPOs with sparse firm-level information. However, during the Internet bubble period, the effect of industry growth on long-run performance dramatically reverses so that IPOs in high-growth industries underperform in the long run. For both the short-run and long-run returns in both periods, the industry growth effects are stronger when returns are value-weighted, suggesting that the effects are stronger for larger IPOs which are more representative of their industries. Our results are most consistent with investors’ tendency to underreact to growth prospects of the IPO in normal times, which leads to superior long-run performance for firms in high-growth industries; and their tendency to overreact to the same information during a pronounced market bubble. In the post-bubble period, there is some evidence that the negative relation between industry growth and long-run performance lingers, with much reduced magnitude. In addition, post-bubble IPO withdrawals are more likely to be observed in high growth industries, in contrast with the negative association between withdrawal and industry growth prior to and during the bubble. Therefore, post-bubble investors appear to have a distaste for IPOs in high growth industries, presumably a spill-over effect of the Internet bubble bursting.

This paper shows that analysts’ herding forecasts are accompanied by significant return reversals of 116 basis points per month, while anti-herding forecasts render reversals insignificant. These results are magnified among illiquid stocks and during high VIX months. Since analyst herding is specific to covered firms, we are also able to examine information spillover from covered to uncovered firms. Among uncovered firms, herding forecasts are accompanied by reversals of 118 basis points, but anti-herding forecasts render reversals insignificant. Our findings suggest that herding forecasts do not contain any private information, while anti-herding forecasts have a much higher informational content that can help reduce the information asymmetry between informed and uninformed investors.

We take advantage of the Raman soliton self-frequen cy shift experienced during the propagation in an a nomalous dispersive photonic crystal fiber in order to conti nuously tune the central frequency of ultrashort pu lses. We discuss the fiber properties to be favored to obtain high power spectral densities and we carry out an extensive e xperimental study of the properties of the frequency shifted pulses in t erms of spectral, autocorrelation, and RF spectrum measurements. Keywords: temporal solitons and pulse propagation, Raman sca ttering, photonic crystal fiber. 1. INTRODUCTION Nonlinear optics in fibers provides a very wide pan el of attractive solutions in order to generate new optical spectral components: self-phase modulation, four wave mixing , Raman Stokes generation or intrapulse Raman scatt ering 1 . This latest phenomenon leads to a progressive shift towa rds lower frequencies of the central frequency of u ltrashort pulses propagating in an anomalous dispersive fiber. There fore this effect known as the Raman soliton self-fr equency shift (SSFS)

International audience; We perform multiplex coherent anti-Stokes Raman scattering (CARS) micro-spectroscopy with a picosecond pulsed laser and a broadband supercontinuum (SC) generated in photonic crystal fiber. CARS signal stability is achieved using an active fiber coupler that avoids thermal and mechanical drifts. We obtain multiplex CARS spectra for test liquids in the 600–2000 cm−1 spectral range. In addition we investigate the polarization dependence of the CARS spectra when rotating the pump beam linear polarization state relative to the linearly polarized broad stokes SC. From these polarization measurements we deduce the Raman depolarization ratio, the resonant versus nonresonant contribution, the Raman resonance frequency, and the linewidth.

We show that mitochondrial DNA (mtDNA)-depleted 143B cells are hypersensitive to staurosporine-induced cell death as evidenced by a more pronounced DNA fragmentation, a stronger activation of caspase-3, an enhanced poly(ADP-ribose) polymerase-1 (PARP-1) cleavage, and a more dramatic cytosolic release of cytochrome c. We also show that B-cell CLL/lymphoma-2 (Bcl-2), B-cell lymphoma extra large (Bcl-XL), and myeloid cell leukemia-1 (Mcl-1) are constitutively less abundant in mtDNA-depleted cells, that the inhibition of Bcl-2 and Bcl-XL can sensitize the parental cell line to staurosporine-induced apoptosis, and that overexpression of Bcl-2 or Bcl-XL can prevent the activation of caspase-3 in ρ0143B cells treated with staurosporine. Moreover, the inactivation of cathepsin B with CA074-Me significantly reduced cytochrome c release, caspase-3 activation, PARP-1 cleavage, and DNA fragmentation in mtDNA-depleted cells, whereas the pan-caspase inhibitor failed to completely prevent PARP-1 cleavage and DNA fragmentation in these cells, suggesting that caspase-independent mechanisms are responsible for cell death even if caspases are activated. Finally, we show that cathepsin B is released in the cytosol of ρ0 cells in response to staurosporine, suggesting that the absence of mitochondrial activity leads to a facilitated permeabilization of lysosomal membranes in response to staurosporine.

Several high-performance polymeric electro-optic modulators have been demonstrated in the last decade. Most of them have been elaborated using specific high-performance electro-optic polymers designed for their exceptional electro-optic response and their thermal stability. In this paper we report the high performance of electro-optic modulators made of a commercial side-chain electro-optic copolymer DR1-PMMA as the active core material and of a passive epoxy polymer NOA73 as cladding material. The electro-optic polymer used in these modulators is a Disperse Red 1- poly-methylmethacrylate (DR1-MMA) side-chain copolymer with relative molar concentrations of DR1-substituted (resp. MMA unsubstituted) groups equal to 30% (resp. 70%). We have designed, elaborated and tested phase modulator and pushpull Mach-Zehnder modulators in order to optimize their figure of merit V π L. A push-pull Mach-Zehnder modulator with 2 cm-long electrodes and an inter-electrode distance of 8.8 μm displays a half-wave voltage of 2.6 V at 1550 nm, corresponding to a figure of merit of 5.2 V.cm. This result was obtained with a moderate poling electric field of 75 V/μm applied to the core of the modulator waveguide. We report here the best figure of merit which has never been observed in a modulator realized with a commercial side-chain electro-optic polymer.

We investigate a compact, stable and broadband multiplex Coherent anti-Stokes Raman Scattering (CARS) source for micro-spectroscopy. By pumping an adapted photonic crystal fiber, we generate the broadband Stokes pulses required for multiplex CARS measurements. The CARS signal stability is provided by an active fiber coupling, avoiding therefore the thermal or mechanical drifts. With only a few nanojoule for pump and Stokes pulses energies, we demonstrate on test liquids the capability of the source to generate multiplex CARS spectra in the 600-2000 cm-1 spectral range.

International audience

Using a sample of debt and seasoned equity issues from 1980-2004 and different proxies of investor optimism and the dispersion in investor beliefs, we empirically analyze, for the first time in the literature, the effect of heterogeneous beliefs among outside investors on the capital structure and security issuance choices made by a firm. The paper consists of three parts: In the first part of the paper, we study how heterogeneous beliefs affect a firm's choice between equity and debt for raising external financing; in the second part of the paper, we study the effect of heterogeneous beliefs on the price impact of a security issue on the firm's equity; and in the third part of the paper, we study the effect of heterogeneous beliefs on the long-term stock performance of equity and debt issuers. Our empirical results can be summarized as follows. First, the probability of a firm issuing equity rather than debt is increasing in both the average level of optimism of outside investors and the dispersion in outsider beliefs. Second, the price impact on the firm's equity is negative for an equity issue and zero for a debt issue; further, the price impact of an equity issue is decreasing (more negative) as the dispersion in outsider beliefs is greater. Finally, while the long-term stock returns to both equity and debt issuers is negative, the stock returns to equity issuers is significantly more negative than that of debt issuers. Further, the more optimistic outsiders are on average about a firm's prospects at the time of an equity issue and the more dispersed their beliefs, the more negative the long-term stock returns to the firm. Overall, our results indicate the importance of heterogeneity in investor beliefs as a determinant of the financing decision of a firm.

We apply an ex ante measure of divergence of investor opinions – industry-level dispersion in analyst earnings forecast – to test the Miller (1977) prediction about IPO overvaluation. Our measure of divergence of opinion is the dispersion in analyst long-term earnings growth forecasts divided by the absolute value of the mean long-term growth forecast averaged at the industry level in the month prior to the IPO. We focus on the effect of divergence of opinion on long-run IPO performance, and test two hypotheses. First, greater divergence of opinion should predict lower long-run performance. Second, since the Miller effect depends on the demand of the offer relative to the supply, we further predict that the effect of belief dispersion should be stronger for offers with high investor demand, as measured by issue overallotment at the time of the offer. Using a sample of about 7,000 IPOs from 1982 to 2005, we find that IPOs in industries with high divergence of opinion have lower long-run returns in the following 3-5 years than IPOs in industries with low divergence of opinion. The effect of belief dispersion on long-run performance primarily exists among IPOs with high demand, as measured by the overallotment at the time of the offer, and this effect remains strong when returns are value-weighted. These findings support Miller’s hypothesis that in markets with restricted short-selling, valuations reflect the most optimistic investor’s appraisal in the short-run, and the initial overvaluation is corrected in the long-run. There is evidence that IPOs with high divergence of opinion also have lower first-day returns, but this association is weakened by the amount of overallotment, suggesting that the correction of initial overvaluation starts shortly after the offer, but the initial correction is dampened by investor demand at the time of the offer.

In a sample of 776 venture capital-backed IPOs, I find that IPOs with more optimistic managers underperform IPOs with less optimistic managers in the long-run. Moreover, the IPOs of the most optimistic managers underperform in the long-run when compared to a benchmark portfolio, while the IPOs of the least optimistic manager do not. In particular, IPOs with more optimistic managers underperform IPOs with less optimistic managers by about 45% (40%) on an equal-weighted (value-weighted) basis in the 5-year period following the offer. Indeed, even relative to their style matched portfolio, the firms of the most optimistic managers underperform by about 43% (72%) on an equal-weighted (value-weighted) basis. These results are confirmed using a calendar-time factor-adjusted portfolio approach. Is the long-run underperformance a result of overinvestment or underinvestment? The evidence suggests that it is driven by underinvestment. In fact, the investment of more optimistic managers is significantly lower than for less optimistic managers for 4 of the 5 fiscal years after the offer. These results are robust to industry-adjusting and the inclusion of additional explanatory variables including cash holdings. I also find some evidence that investment is sensitive to cash flows, with high cash flow IPOs mitigating a portion of the underinvestment in some of the years following the offer. Finally, managerial optimism is significantly and positively associated to first-day returns, suggesting more optimistic managers are more prone to using to the middle of the file price range as a reference point from which they anchor.

We test the Miller (1977) prediction about IPO overvaluation in a sample of 7,212 U.S. IPOs from 1980 to 2003. According to Miller (1977), owing to the lack of short sales prior to the offer, IPO prices are determined by the most optimistic investors, leading to IPO overvaluation; this initial overvaluation is corrected in the years after the offer as the uncertainty of IPO firms subdues. We hypothesize that investors categorize IPOs by their industries, and we use an industry-level uncertainty measure - industry volatility in excess of the market volatility - as an ex ante proxy for investor heterogeneity of beliefs. We therefore predict that IPOs in volatile industries should have high initial returns, followed by low long-run returns. Generally, IPOs in industries with high excess volatility have much higher initial returns and lower long-run returns in the following 2-3 years than IPOs in industries with low volatility. In time-series tests, we find that excess industry volatility explains half of the annual time-series variation in aggregate initial returns. In cross-sectional tests, when we sort IPOs into three portfolios by excess industry volatility, we find that over the full sample period, high excess industry volatility IPOs have 18% (7%) higher mean (median) initial returns, and 18% (31%) lower mean (median) style-adjusted returns over a 1.5-year period after the offer (skipping the initial 6-month aftermarket lockup period) than low excess industry volatility IPOs. These results are robust to various risk-adjustment procedures. The effect of excess industry volatility on initial returns is about four times stronger during the "tech bubble" period (01/1997 - 03/2000) than during other periods, and the extreme bubble-period IPO initial returns in volatile industries are not reversed until about 4 years after the offer, consistent with the late 1990s' market being a market bubble fueled by investor euphoria. We also find that firm age - our firm-level proxy for uncertainty and investor heterogeneity -affects both short- and long-run IPO performance, in coalition with industry volatility. Our results suggest that investor opinions are more diverse among young firms, as well as among firms in volatile industries. Adding age to industry volatility strengthens the return predictability of investor heterogeneity. These findings lend strong support to Miller's hypothesis that in markets with restricted short-selling, valuations tend to reflect the most optimistic investor's appraisal in the short-run, and revert to the average appraisal in the long-run.

To depict the largest picture of a core promoter interactome, we developed a one-step DNA-affinity capture method coupled with an improved mass spectrometry analysis process focused on the identification of low abundance proteins. As a proof of concept, this method was developed through the analysis of 230 bp contained in the 5′long terminal repeat (LTR) of the human immunodeficiency virus 1 (HIV-1). Beside many expected interactions, many new transcriptional regulators were identified, either transcription factors (TFs) or co-regulators, which interact directly or indirectly with the HIV-1 5′LTR. Among them, the homeodomain-containing TF myeloid ectopic viral integration site was confirmed to functionally interact with a specific binding site in the HIV-1 5′LTR and to act as a transcriptional repressor, probably through recruitment of the repressive Sin3A complex. This powerful and validated DNA-affinity approach could also be used as an efficient screening tool to identify a large set of proteins that physically interact, directly or indirectly, with a DNA sequence of interest. Combined with an in silico analysis of the DNA sequence of interest, this approach provides a powerful approach to select the interacting candidates to validate functionally by classical approaches.

The Handbook of Research on IPOs provides a comprehensive review of the emerging trends and directions in the global initial public offerings (IPO) markets. The empirical evidence included in the book covers Europe, the US and the Far East, and presents a truly global perspective of IPO markets around the world and at the different stages of the entire IPO process.