Prevalence and patterns of higher-order drug interactions in Escherichia coli.

Interactions and emergent processes are essential for research on complex systems involving many components. Most studies focus solely on pairwise interactions and ignore higher-order interactions among three or more components. To gain deeper insights into higher-order interactions and complex environments, we study antibiotic combinations applied to pathogenic Escherichia coli and obtain unprecedented amounts of detailed data (251 two-drug combinations, 1512 three-drug combinations, 5670 four-drug combinations, and 13608 five-drug combinations). Directly opposite to previous assumptions and reports, we find higher-order interactions increase in frequency with the number of drugs in the bacteria's environment. Specifically, as more drugs are added, we observe an elevated frequency of net synergy (effect greater than expected based on independent individual effects) and also increased instances of emergent antagonism (effect less than expected based on lower-order interaction effects). These findings have implications for the potential efficacy of drug combinations and are crucial for better navigating problems associated with the combinatorial complexity of multi-component systems

Nonlinear finite element analysis of functionally graded circular plates with modified couple stress theory

Finite element models of microstructure-dependent geometrically nonlinear theories for axisymmetric bending of circular plates, which accounts for through-thickness power-law variation of a two constituent material, the von Karman nonlinearity, and the strain gradient effects are developed for the classical and first-order plate theories. The strain gradient effects are included through the modified couple stress theory that contains a single material length scale parameter which can capture the size effect in a functionally graded material plate. The developed finite element models are used to determine the effect of the geometric nonlinearity, power-law index, and microstructure-dependent constitutive relations on the bending response of functionally graded circular plates with different boundary conditions. (C) 2015 Elsevier Masson SAS. All rights reserved.AcknowledgmentsThefirst author gratefully acknowledges the support of thiswork by the FidiPro Professorship from Aalto University (Finland)and Chair of Excellence from University Carlos III of Madrid (Spain).The second author acknowledges the“Finland Distinguished Pro-fessor (FiDiPro) -program: Non-linear response of large, complexthin-walled structures”supported by Tekes and industrial partnersNapa, SSAB, Deltamarin, Koneteknologiakeskus Turku and MeyerTurku to Aalto University, while the third author gratefully ac-knowledges the support of the Chair of Excellence granted to thefirst author at University Carlos III of Madrid

Fits & Starts: The Difficult Path for Working Single Parents

With dramatic shifts in the economy in recent years, it has become increasingly difficult for families to move into or stay in the middle class without access to higher education and skills training. Government-sponsored work supports help by providing direct assistance to working families to meet basic needs, such as child care, food, and housing. Yet, many supports do not reach low-wage working families in Massachusetts because of low eligibility thresholds, inadequate funding, limited availability, limited awareness, and numerous barriers to accessing such supports. Even for low-wage workers who do receive key work supports, such as subsidized child care and housing, reductions and elimination of these supports at low wages can impede vulnerable families’ progress toward the middle class. This report highlights the difficult choices Massachusetts low-wage workers must make between moving up the wage ladder and losing critical work supports before they are economically stable. It identifies specific points along the income ladder at which workers are faced with difficult trade-offs between higher earnings and career advancement on the one hand and the resulting loss of important supports on the other. Those receiving work supports find that their net monthly resources—their after-tax income from earnings plus the value of work supports, minus the cost of all basic needs—do not rise in step with wage increases for full-time workers earning between $11 and$29 per hour. Instead, these workers discover that at higher wage levels they can be left with fewer resources at the end of the month than they had at lower wages. This report also highlights opportunities for state programs to adjust eligibility criteria and for service providers to offer new kinds of guidance in order to more effectively support those who are trying to work their way into the middle class. Most importantly, this report calls for greater investments in work supports for low-wage earners seeking to combine work with education or skills development. Such education and training can provide crucial leverage to help families leap over some of the pitfalls on the path toward middle-class membership. In fact, wages are closely linked to educational attainment, with post-secondary education contributing to significantly higher earnings than those attained by high school graduates and non-completers. In 2005, having an associate’s degree added $8,154 to a Massachusetts high school graduate’s annual median income, while earning a bachelor’s degree added$18,346. In view of the critical role of education and training in facilitating workers’ access to family-supportive wages, we recommend transforming the current work support system to sustain work, school, and family

Resonator-based detection in nanorods

In this paper the axial vibrational behaviour of nanorods with an attached point-mass is studied, using the modified strain energy theory. The natural frequencies of the nanorod with the concentrated mass are obtained for different boundary conditions. The effects of the concentrated mass intensity, mass location, as well as the value of scale parameters have been analysed. For the case of small intensity of the concentrated mass, the natural frequencies of the nanorod can be estimated using a first order perturbative solution. These approximate results are compared with those corresponding to the exact solution. For this case, from the properties of the eigenvalue perturbative theory, the identification of single point mass in uniform nanorods (mass intensity and position) is addressed. The results obtained encourage the use of axial vibrations of nanorods as a very precise sensing technique

Theories and analyses of functionally graded circular plates

This paper presents the governing equations and analytical solutions of the classical and shear deformation theories of functionally graded axisymmetric circular plates. The classical, first-order, and third-order shear deformation theories are presented, accounting for through-thickness variation of two-constituent functionally graded material, modified couple stress effect, and the von Kármán nonlinearity. Analytical solutions for bending of the linear theories, some of which are not readily available in the literature, are included to show the influence of the material variation, boundary conditions, and loads

Frañol radio : un métissage textuel reproductif dans les borderlands sociolinguistiques et culturels hispano-francophones

Ce mémoire de maitrise est une réflexion sur Frañol radio, une émission migrante qui se concentre sur la diffusion de musique d’origine latino. L’émission est conçue par Hugo, qui fait office d’animateur, de « DJ » et de responsable de la programmation. Le matériel le plus emblématique de l’émission vient d’artistes qui traversent la langue et la culture : les artistes francophones qui chantent en espagnol, les artistes hispaniques qui chantent en français et ceux qui chantent en frañol, une nouvelle expression artistique, linguistique et culturelle de la population d’origine latino à l’extérieur de l’Amérique latine. Dans cette ère de globalisation et de capitalisme, les structures de pouvoir politique et économique forcent une nouvelle vague de migration de l’Amérique latine vers le Canada francophone. Il s’agit d’un phénomène de colonisation renversée où les immigrants d’origine latino décident d’être acculturés et colonisés par choix pour vivre la liberté qu’ils n’ont pas en Amérique latine. Ce phénomène est opposé à la colonisation violente des Amériques par les Européens à l’époque de la conquête. Maintenant, il y a un groupe de gens, les nouveaux métis capitalisés, qui veulent être transformés linguistiquement et culturellement pour obtenir des papiers, rester dans le pays et conquérir une vie meilleure. Frañol radio touche la réalité de cette communauté migrante qui, dans le nouveau territoire, vise les interstices culturels et linguistiques particuliers des communautés de frontières. L’émission de radio contribue à l’existence du frañol comme code sociolinguistique et culturel qui aide la population d’origine latino dans le processus d’acculturation au sein de la nouvelle société. Le frañol comme code sociolinguistique et culturel alimente la programmation musicale et cette programmation revitalise l’existence de ce phénomène. Le frañol est un échelon linguistique qui rappelle aux personnes d’origine latino l’importance de parler français et de comprendre la culture d’accueil. Cependant, le frañol est aussi une esthétique et un style pratiqués par ceux qui habitent les frontières linguistiques et culturelles hispano-francophones. La musique en frañol exemplifie cette esthétique et nous invite à réfléchir aux manières dont la population d’origine latino s’imagine

Biological intratumoral therapy for the high-grade glioma part I: intratumoral delivery and immunotoxins.

Management of high-grade gliomas remains a complex challenge. Standard of care consists of microsurgical resection, chemotherapy and radiation, but despite these aggressive multimodality therapies the overall prognosis remains poor. A major focus of ongoing translational research studies is to develop novel therapeutic strategies that can maximize tumor cell eradication while minimizing collateral side effects. Particularly, biological intratumoral therapies have been the focus of new translational research efforts due to their inherent potential to be both dynamically adaptive and target specific. This two-part review will provide an overview of biological intratumoral therapies and summarize key advances and remaining challenges in intratumoral biological therapies for high-grade glioma. Part I focuses on discussion of the concepts of intratumoral delivery and immunotoxin therapies

Biological intratumoral therapy for the high-grade glioma part II: vector- and cell-based therapies and radioimmunotherapy.

Management of high-grade gliomas (HGGs) remains a complex challenge with an overall poor prognosis despite aggressive multimodal treatment. New translational research has focused on maximizing tumor cell eradication through improved tumor cell targeting while minimizing collateral systemic side effects. In particular, biological intratumoral therapies have been the focus of novel translational research efforts due to their inherent potential to be both dynamically adaptive and target specific. This two part review will provide an overview of biological intratumoral therapies that have been evaluated in human clinical trials in HGGs, and summarize key advances and remaining challenges in the development of these therapies as a potential new paradigm in the management of HGGs. Part II discusses vector-based therapies, cell-based therapies and radioimmunotherapy

Solar neutrino detection sensitivity in DARWIN via electron scattering

We detail the sensitivity of the proposed liquid xenon DARWIN observatory to solar neutrinos via elastic electron scattering. We find that DARWIN will have the potential to measure the fluxes of five solar neutrino components: pp, 7Be, 13N, 15O and pep. The precision of the13N, 15O and pep components is hindered by the doublebeta decay of 136Xe and, thus, would benefit from a depleted target. A high-statistics observation of pp neutrinos would allow us to infer the values of the electroweak mixing angle,sin2 θw, and the electron-type neutrino survival probability, Pee, in the electron recoil energy region from a few keV up to 200keV for the first time, with relative precision of 5% and 4%, respectively, with 10 live years of data and a 30 tonne fiducial volume. An observation of pp and 7Be neutrinos would constrain the neutrino-inferred solar luminosity down to 0.2%. A combination of all flux measurements would distinguish between the high- (GS98) and low-metallicity (AGS09) solar models with 2.1–2.5σ significance, independent of external measurements from other experiments or a measurement of8B neutrinos through coherent elastic neutrino-nucleus scattering in DARWIN. Finally, we demonstrate that with a depleted target DARWIN may be sensitive to the neutrino capture process of 131Xe