The N-Vortex Problem on a Symmetric Ellipsoid: A Perturbation Approach

We consider the N-vortex problem on a ellipsoid of revolution. Applying standard techniques of classical perturbation theory we construct a sequence of conformal transformations from the ellipsoid into the complex plane. Using these transformations the equations of motion for the N-vortex problem on the ellipsoid are written as a formal series on the eccentricity of the ellipsoid's generating ellipse. First order equations are obtained explicitly. We show numerically that the truncated first order system for the three-vortices system on the symmetric ellipsoid is non-integrable.Comment: 14 pages, 1 figur

Production of Zika virus-like particles (VLPs) by perfusion processes

Zika virus (ZIKV) emerged as a major international public health concern in 2015 and rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection has been shown to cause Guillain-Barré syndrome in adults, as well as severe congenital malformations in fetuses from as much as 42% of infected mothers (Brasil et al., 2016, doi:10.1056/NEJMoa1602412). While no ZIKV vaccine becomes approved for human use, periodic outbreaks will continue to occur in endemic regions and the risk of spreading to non-endemic regions will continue to exist, especially because ZIKV persists in body fluids for very long time after infection and can be transmitted via the sexual route. Among many different vaccine platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since three-dimensional structures, constituted by recombinant structural proteins of the virus but lacking the viral genome, are able to display the antigen in a repetitive pattern, triggering a robust immune response. In this work, we investigated the production of Zika virus-like particles by both intermittent and continuous perfusion processes, using a recombinant HEK293 cell pool previously generated in our laboratory, which constitutively expresses the VLPs. In order to improve production levels, we first enriched the recombinant cell pool for high producers by means of fluorescence-activated cell sorting (FACS). Using this FACS-enriched cell pool, small-scale shake flask studies showed that intermittent perfusion (also known as pseudoperfusion) with daily medium exchange enhanced viable cell density by 3.5 fold and VLP titer by 4 fold when compared to batch cultures. Continuous perfusion in a controlled stirred-tank bioreactor was carried out using an ATF-2 unit as cell retention device. A steady-state viable cell concentration of 25-30 × 106 cells/mL was maintained at a cell-specific perfusion rate (CSPR) of 50-60 pL/cell/day. VLP titers inside the bioreactor were higher than in the harvest, evidencing product retention by the ATF hollow fiber, especially from day 14 of cultivation on. Our results show that the use of cell lines constitutively expressing zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. This process could potentially be more cost-effective than traditional viral vaccine platforms based on batch production of whole viruses, especially considering that VLPs can be produced in lower biosafety level plants, and that perfusion systems are characterized by higher volumetric productivities, reduced bioreactor sizes, smaller plant footprint and lower investment costs when compared to batch processes

Restoring observed classical behavior of the carbon nanotube field emission enhancement factor from the electronic structure

Experimental Fowler-Nordheim plots taken from orthodoxly behaving carbon nanotube (CNT) field electron emitters are known to be linear. This shows that, for such emitters, there exists a characteristic field enhancement factor (FEF) that is constant for a range of applied voltages and applied macroscopic fields $F_\text{M}$. A constant FEF of this kind can be evaluated for classical CNT emitter models by finite-element and other methods, but (apparently contrary to experiment) several past quantum-mechanical (QM) CNT calculations find FEF-values that vary with $F_\text{M}$. A common feature of most such calculations is that they focus only on deriving the CNT real-charge distributions. Here we report on calculations that use density functional theory (DFT) to derive real-charge distributions, and then use these to generate the related induced-charge distributions and related fields and FEFs. We have analysed three carbon nanostructures involving CNT-like nanoprotrusions of various lengths, and have also simulated geometrically equivalent classical emitter models, using finite-element methods. We find that when the DFT-generated local induced FEFs (LIFEFs) are used, the resulting values are effectively independent of macroscopic field, and behave in the same qualitative manner as the classical FEF-values. Further, there is fair to good quantitative agreement between a characteristic FEF determined classically and the equivalent characteristic LIFEF generated via DFT approaches. Although many issues of detail remain to be explored, this appears to be a significant step forwards in linking classical and QM theories of CNT electrostatics. It also shows clearly that, for ideal CNTs, the known experimental constancy of the FEF value for a range of macroscopic fields can also be found in appropriately developed QM theory.Comment: A slightly revised version has been published - citation below - under a title different from that originally used. The new title is: "Restoring observed classical behavior of the carbon nanotube field emission enhancement factor from the electronic structure

In vitro screening and chemometrics analysis on a series of azole derivatives with fungicide activity against moniliophthora perniciosa

Moniliophthora perniciosa, the causal agent of witches' broom disease in Theobroma cacao, significantly decreased cacao production, especially in Bahia State, the largest cocoa producing of the American continent. Control programs developed so far have low efficiency. Azole derivatives are active both in vitro and in loco against M. perniciosa, however there is no comprehensive study on the activity of azoles against this phytopatogen. Standardized in vitro biological data were employed to develop supervised and unsupervised chemometric models that highlight physicochemical and structural features that are crucial for azole's fungicidal activity against M. perniciosa. Thus, PCA and SIMCA models suggest that electronegativity (BEHe3) and dipolar moment (JGI4), as well as H-bonding to M. pernciosa's lanosterol 14α-desmethylase active site and lack of Cl atoms 6 to 8 bonds from the azole's nitrogen atoms play a major role to azoles' fungicide activity

Perfusion process for the production of a new, VLP-based yellow fever vaccine candidate

Yellow fever (YF) is an acute viral hemorrhagic disease endemic in tropical areas of Africa, Central and South America, which is transmitted by the bite of infected mosquitoes. It is a “historically devastating disease” (Paules and Fauci, 2017) that killed during outbreaks in past centuries, before the introduction of the current vaccine, approximately 10% of the population of cities like Philadelphia (USA) and Barcelona (Spain). According to Garske et al. (2014), YF caused in 2013 78,000 deaths worldwide, which is a disease burden comparable to influenza. In the past few years, outbreaks in Angola (2016) and in Brazil (2017-2018) led to the depletion of the WHO vaccine stockpile and to the introduction of the emergency use of a fractional dose (1/5). Furthermore, the Angola outbreak in 2016 caused the first cases of YF ever to occur in Asia (11 imported cases to China), rising the concern about approximately 2 billion immunologically naïve people who would be at high risk in Asia in case local transmission of the virus starts to occur (Wilder-Smith et al., 2019). The urgent need for a new YF vaccine becomes evident from two major issues concerning the current vaccine, which consists of a live-attenuated virus propagated in chicken embryos: (i) vaccine shortage due to limitations in the manufacturing technology; (ii) rare, but fatal adverse effects. Therefore, this work focuses on the development of a safe, non-replicating YF vaccine, produced by a high-productivity perfusion process. Stable recombinant HEK293 cell lines constitutively expressing the structural proteins prM (pre-membrane) and E (envelope) of YFV were generated, enabling long-term production and secretion of recombinant virus-like particles (VLPs). FACS (fluorescence activated cell sorting) was used to sort the transfected population for high producer cells and allowed obtaining an enriched cell pool producing significantly higher amounts of VLPs. Small scale kinetic studies under intermittent perfusion (pseudoperfusion) were performed in order to investigate possible feeding strategies and to evaluate the use of short-chain fatty acids as productivity enhancers. Subsequently, perfusion runs were carried out in stirred-tank bioreactors in order to investigate optimal conditions for VLP production, as well as to evaluate different cell retention devices (e.g. inclined lamella settler and ATF-2). Partial retention of the VLPs in the perfusion bioreactor system occurred when the ATF-2 was used. VLPs produced by perfusion were purified by a two-step chromatographic process, and transmission electron microscopy (TEM) images confirmed the expected size and morphology of the VLPs, enabling their use in mouse immunogenicity studies. References: Garske T, Van Kerkhove MD, Yactayo S, Ronveaux O, Lewis RF, Staples JE, Perea W, Ferguson NM, Yellow Fever Expert Committee (2014). Yellow fever in Africa: estimating the burden of disease and impact of mass vaccination from outbreak and serological data. PLoS Medicine 11:e1001638. Paules CI, Fauci AS (2017), Yellow fever - once again on the radar screen in the Americas, N Engl J Med 376: 1397-1399. Wilder-Smith A, Lee V, Gubler DJ (2019), Yellow fever: is Asia prepared for an epidemic? The Lancet 19:241-242

Models of Metal Poor Stars with Gravitational Settling and Radiative Accelerations: I. Evolution and Abundance Anomalies

Evolutionary models have been calculated for Pop II stars of 0.5 to 1.0$M_\odot$ from the pre-main-sequence to the lower part of the giant branch. Rosseland opacities and radiative accelerations were calculated taking into account the concentration variations of 28 chemical species, including all species contributing to Rosseland opacities in the OPAL tables. The effects of radiative accelerations, thermal diffusion and gravitational settling are included. While models were calculated both for Z=0.00017 and 0.0017, we concentrate on models with Z=0.00017 in this paper. These are the first Pop II models calculated taking radiative acceleration into account. It is shown that, at least in a 0.8$M_\odot$ star, it is a better approximation not to let Fe diffuse than to calculate its gravitational settling without including the effects of $g_{rad}(Fe)$. In the absence of any turbulence outside of convection zones, the effects of atomic diffusion are large mainly for stars more massive than 0.7$M_\odot$. Overabundances are expected in some stars with \teff \ge 6000K. Most chemical species heavier than CNO are affected. At 12 Gyr, overabundance factors may reach 10 in some cases (e.g. for Al or Ni) while others are limited to 3 (e.g. for Fe). The calculated surface abundances are compared to recent observations of abundances in globular clusters as well as to observations of Li in halo stars. It is shown that, as in the case of Pop I stars, additional turbulence appears to be present.Comment: 40 pages, 17 color figures, to appear in The Astrophysical Journal, April 2002 (paper with original high resolution figures can be found at http://www.cerca.umontreal.ca/~richer/Fichiersps/popII_1.ps

Driving evaluation methods for able-bodied persons and individuals with lower extremity disabilities: a review of assessment modalities

Assessing the driving abilities of individuals with disabilities is often a very challenging task because each medical condition is accompanied by physical impairments and because relative individual functional performance may vary depending on personal characteristics.We identified existing driving evaluation modalities for able-bodied and lower extremity-impaired subjects (spinal cord injury patients and amputees) and evaluated the potential relationships between driving performance and the motor component of driving.An extensive scoping review of the literature was conducted to identify driving assessment tools that are currently used for able-bodied individuals and for those with spinal cord injury or lower extremity amputation. The literature search focused on the assessment of the motor component of driving. References were electronically obtained via Medline from the PubMed, Ovid, Web of Science and Google Scholar databases.This article compares the current assessments of driving performance for those with lower extremity impairments with the assessments used for able-bodied persons. Very few articles were found concerning “Lower Extremity Disabilities,” thus confirming the need for further studies that can provide evidence and guidance for such assessments in the future. Little is known about the motor component of driving and its association with the other driving domains, such as vision and cognition. The available research demonstrates the need for a more evidenced-based understanding of how to best evaluate persons with lower extremity impairment