1,393 research outputs found

    Stress‐response balance drives the evolution of a network module and its host genome

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    Stress response genes and their regulators form networks that underlie drug resistance. These networks often have an inherent tradeoff: their expression is costly in the absence of stress, but beneficial in stress. They can quickly emerge in the genomes of infectious microbes and cancer cells, protecting them from treatment. Yet, the evolution of stress resistance networks is not well understood. Here, we use a two‐component synthetic gene circuit integrated into the budding yeast genome to model experimentally the adaptation of a stress response module and its host genome in three different scenarios. In agreement with computational predictions, we find that: (i) intra‐module mutations target and eliminate the module if it confers only cost without any benefit to the cell; (ii) intra‐ and extra‐module mutations jointly activate the module if it is potentially beneficial and confers no cost; and (iii) a few specific mutations repeatedly fine‐tune the module's noisy response if it has excessive costs and/or insufficient benefits. Overall, these findings reveal how the timing and mechanisms of stress response network evolution depend on the environment

    French Experience of 2009 A/H1N1v Influenza in Pregnant Women

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    BACKGROUND: The first reports on the pandemic influenza 2009 A/H1N1v from the USA, Mexico, and Australia indicated that this disease was associated with a high mortality in pregnant women. The aim of this study was to describe and compare the characteristics of severe critically ill and non-severe pregnant women with 2009 A/H1N1v-related illness in France. METHODOLOGY/PRINCIPAL FINDINGS: A national registry was created to screen pregnant women with laboratory-confirmed 2009 A/H1N1v influenza. Three hundred and fifteen patients from 46 French hospitals were included: 40 patients were admitted to intensive care units (severe outcomes), 111 were hospitalized in obstetric or medical wards (moderate outcomes), and 164 were outpatients (mild outcomes). The 2009 A/H1N1v influenza illness occurred during all pregnancy trimesters, but most women (54%), notably the severe patients (70%), were in the third trimester. Among the severe patients, twenty (50%) underwent mechanical ventilation, and eleven (28%) were treated with extracorporeal membrane oxygenation. Three women died from A/H1N1v influenza. We found a strong association between the development of a severe outcome and both co-existing illnesses (adjusted odds ratio [OR], 5.1; 95% confidence interval [CI], 2.2-11.8) and a delay in oseltamivir treatment after the onset of symptoms (>3 or 5 days) (adjusted OR, 4.8; 95% CI, 1.9-12.1 and 61.2, 95% CI; 14.4-261.3, respectively). Among the 140 deliveries after 22 weeks of gestation known to date, 19 neonates (14%) were admitted to a neonatal intensive care unit, mainly for preterm delivery, and two neonates died. None of these neonates developed 2009 A/H1N1v infection. CONCLUSIONS: This series confirms the high incidence of complications in pregnant women infected with pandemic A/H1N1v observed in other countries but depicts a lower overall maternal and neonatal mortality and morbidity than indicated in the USA or Australia. Moreover, our data demonstrate the benefit of early oseltamivir treatment in this specific population

    Effect of clay type on dispersion and barrier properties of hydrophobically modified poly(vinyl alcohol)-bentonite nanocomposites

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    The oxygen and water vapor permeability at high relative humidity was studied for composite films formed by incorporation of three different bentonites (MMT) into an ethylene-modified, water-soluble poly(vinyl alcohol), EPVOH. The oxygen permeability decreased linearly with an increased addition of hydrophilic MMTs. X-ray diffraction and Fourier transform infrared spectroscopy suggested a homogeneous distribution in the thickness direction with disordered and probably exfoliated structures for hydrophilic MMTs. In contrast, organophilic modified clay showed an intercalated structure with the clay preferentially located at the lower film surface, a combination which was however efficient in reducing the water vapor- and oxygen permeabilities at low addition levels. Composite films of EPVOH and Na+-exchanged MMT resulted in high resistance to dissolution in water, which was ascribed to strong interactions between the components resulting from matching polarities. Annealing the films at 120°C resulted in enhanced resistance to water dissolution and a further reduction in oxygen permeabilit

    Revisiting Keccak and Dilithium Implementations on ARMv7-M

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    Keccak is widely used in lattice-based cryptography (LBC) and its impact to the overall running time in LBC scheme can be predominant on platforms lacking dedicated SHA-3 instructions. This holds true on embedded devices for Kyber and Dilithium, two LBC schemes selected by NIST to be standardized as quantumsafe cryptographic algorithms. While extensive work has been done to optimize the polynomial arithmetic in these schemes, it was generally assumed that Keccak implementations were already optimal and left little room for enhancement. In this paper, we revisit various optimization techniques for both Keccak and Dilithium on two ARMv7-M processors, i.e., Cortex-M3 and M4. For Keccak, we improve its efficiency using two architecture-specific optimizations, namely lazy rotation and memory access pipelining, on ARMv7-M processors. These optimizations yield performance gains of up to 24.78% and 21.4% for the largest Keccak permutation instance on Cortex-M3 and M4, respectively. As for Dilithium, we first apply the multi-moduli NTT for the small polynomial multiplication cti on Cortex-M3. Then, we thoroughly integrate the efficient Plantard arithmetic to the 16-bit NTTs for computing the small polynomial multiplications csi and cti on Cortex-M3 and M4. We show that the multi-moduli NTT combined with the efficient Plantard arithmetic could obtain significant speed-ups for the small polynomial multiplications of Dilithium on Cortex-M3. Combining all the aforementioned optimizations for both Keccak and Dilithium, we obtain 15.44% ∼ 23.75% and 13.94% ∼ 15.52% speed-ups for Dilithium on Cortex-M3 and M4, respectively. Furthermore, we also demonstrate that the Keccak optimizations yield 13.35% to 15.00% speed-ups for Kyber, and our Keccak optimizations decrease the proportion of time spent on hashing in Dilithium and Kyber by 2.46% ∼ 5.03% on Cortex-M4

    On the structure-properties relationship in montmorillonite-filled polyamide 6 nanocomposites

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    Polyamide 6/montmorillonite (MMT) nanocomposites were prepared by melt compounding method comprising 1–7.5 wt % of Nanomer I.24 TL or 5 and 10 wt % of Cloisite 15A organically modified nanoclays. The composite samples were characterized by synchrotron X-ray, thermal and FT-IR spectroscopy methods looking for changes in the micro- and nanostructure of both PA6 matrix and MMT reinforcement as a function of the clay content and type. These data were discussed in conjunction with the mechanical properties of the respective nanocomposites. Generally, the Young’s modulus was found to increase proportionally to the clay content being the highest in samples with strong aggregation of MMT at micron length scale. The tensile strength passed through a maximum at 2.5 wt % clay load presenting a homogeneous microstructure with almost no agglomeration. Increasing the amount of MMT produced less crystalline PA6 matrices, richer in gamma-PA6 polymorph and resulted in larger long spacings of PA6 due to expansion of both crystalline and amorphous domains.Fundação para a Ciência e a Tecnologia (FCT), Portugal; HASYALb at DESY, Hamburg, German

    Reparameterization of the REBO-CHO potential for graphene oxide molecular dynamics simulations

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    The reactive empirical bond order (REBO) potential developed by Brenner et al. [Phys. Rev. B 42, 9458 (1990); J. Phys. Condens. Matter 14, 783 (2002)] for molecular dynamics (MD) simulations of hydrocarbons, and recently extended to include interactions with oxygen atoms by Ni et al. [J. Phys. Condens. Matter 16, 7261 (2004)], is modified for graphene-oxide (GO). Based on density-functional-theory (DFT) calculations, we optimized the REBO-CHO potential (in which CHO denotes carbon, hydrogen, and oxygen) to improve its ability to calculate the binding energy of an oxygen atom to graphene and the equilibrium C-O bond distances. In this work, the approach toward the optimization is based on modifying the bond order term. The modified REBO-CHO potential is applied to investigate the properties of some GO samples.close111
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