69 research outputs found
Reconstructing nonlinear plasma wakefields using a generalized temporally encoded spectral shifting analysis
We generalize the temporally encoded spectral shifting (TESS) analysis for measuring plasma wakefields using spectral interferometry to dissimilar probe pulses of arbitrary spectral profile and to measuring nonlinear wakefields. We demonstrate that the Gaussian approximation used up until now results in a substantial miscalculation of the wakefield amplitude, by a factor of up to two. A method to accurately measure higher amplitude quasilinear and nonlinear wakefields is suggested, using an extension to the TESS procedure, and we place some limits on its accuracy in these regimes. These extensions and improvements to the analysis demonstrate its potential for rapid and accurate on-shot diagnosis of plasma wakefields, even at low plasma densities
Risks Posed by Reston, the Forgotten Ebolavirus
Out of the five members of the Ebolavirus family, four cause lifethreatening disease, whereas the fifth, Reston virus (RESTV), is nonpathogenic in humans. The reasons for this discrepancy remain unclear. In this review, we analyze the currently available information to provide a state-of-the-art summary of the factors that determine the human pathogenicity of Ebolaviruses. RESTV causes sporadic infections in cynomolgus monkeys and is found in domestic pigs throughout the Philippines and China. Phylogenetic analyses revealed that RESTV is most closely related to the Sudan virus, which causes a high mortality rate in humans. Amino acid sequence differences between RESTV and the other Ebolaviruses are found in all nine Ebolavirus proteins, though no one residue appears sufficient to confer pathogenicity. Changes in the glycoprotein contribute to differences in Ebolavirus pathogenicity but are not sufficient to confer pathogenicity on their own. Similarly, differences in VP24 and VP35 affect viral immune evasion and are associated with changes in human pathogenicity. A recent in silico analysis systematically determined the functional consequences of sequence variations between RESTV and human-pathogenic Ebolaviruses. Multiple positions in VP24 were differently conserved between RESTV and the other Ebolaviruses and may alter human pathogenicity. In conclusion, the factors that determine the pathogenicity of Ebolaviruses in humans remain insufficiently understood. An improved understanding of these pathogenicity-determining factors is of crucial importance for disease prevention and for the early detection of emergent and potentially human-pathogenic RESTVs
Proton radiography in background magnetic fields
Proton radiography has proved increasingly successful as a diagnostic for electric and magnetic fields in high-energy-density physics experiments. Most experiments use target-normal sheath acceleration sources with a wide energy range in the proton beam, since the velocity spread can help differentiate between electric and magnetic fields and provide time histories in a single shot. However, in magnetized plasma experiments with strong background fields, the broadband proton spectrum leads to velocity-spread-dependent displacement of the beam and significant blurring of the radiograph. We describe the origins of this blurring and show how it can be removed from experimental measurements, and we outline the conditions under which such deconvolutions are successful. As an example, we apply this method to a magnetized plasma experiment that used a background magnetic field of 3 T and in which the strong displacement and energy spread of the proton beam reduced the spatial resolution from tens of micrometers to a few millimeters. Application of the deconvolution procedure accurately recovers radiographs with resolutions better than 100 µm, enabling the recovery of more accurate estimates of the path-integrated magnetic field. This work extends accurate proton radiography to a class of experiments with significant background magnetic fields, particularly those experiments with an applied external magnetic field
Metaphysical Foundations of Knowledge and Ethics in Chinese and European Philosophy
In the history of Chinese and European philosophy, metaphysics has played an outstanding role: it is a theoretical framework which provides the basis for a philosophical understanding of the world and the self. A theory of the self is well integrated in a metaphysical understanding of the totality of nature as a dynamic process of continuous changes. According to this view, the purpose of existence can be conceived of as the development and realization of the full potential given to the individual by its nature. In regard to human nature specifically, this idea of self-realization includes the development of all cognitive faculties as well as of the moral character.
Metaphysics has, however, suffered a loss of importance in current debates, especially in ethics. As a result, we observe the emergence of such philosophical views as moral skepticism and even nihilism. The consequence of this tendency has been the renunciation of a claim to understanding and to providing a solid ground for ethics.
Yet an intercultural dialogue can provide us with some hope as the consolidation of debates on crucial topics of our traditions might indeed serve as the basis for a more powerful philosophy in the future
Stepping Beyond the Newtonian Paradigm in Biology. Towards an Integrable Model of Life: Accelerating Discovery in the Biological Foundations of Science
The INBIOSA project brings together a group of experts across many disciplines
who believe that science requires a revolutionary transformative
step in order to address many of the vexing challenges presented by the
world. It is INBIOSA’s purpose to enable the focused collaboration of an
interdisciplinary community of original thinkers.
This paper sets out the case for support for this effort. The focus of the
transformative research program proposal is biology-centric. We admit
that biology to date has been more fact-oriented and less theoretical than
physics. However, the key leverageable idea is that careful extension of the
science of living systems can be more effectively applied to some of our
most vexing modern problems than the prevailing scheme, derived from
abstractions in physics. While these have some universal application and
demonstrate computational advantages, they are not theoretically mandated
for the living. A new set of mathematical abstractions derived from biology
can now be similarly extended. This is made possible by leveraging
new formal tools to understand abstraction and enable computability. [The
latter has a much expanded meaning in our context from the one known
and used in computer science and biology today, that is "by rote algorithmic
means", since it is not known if a living system is computable in this
sense (Mossio et al., 2009).] Two major challenges constitute the effort.
The first challenge is to design an original general system of abstractions
within the biological domain. The initial issue is descriptive leading to the
explanatory. There has not yet been a serious formal examination of the
abstractions of the biological domain. What is used today is an amalgam;
much is inherited from physics (via the bridging abstractions of chemistry)
and there are many new abstractions from advances in mathematics (incentivized
by the need for more capable computational analyses). Interspersed
are abstractions, concepts and underlying assumptions “native” to biology
and distinct from the mechanical language of physics and computation as
we know them. A pressing agenda should be to single out the most concrete
and at the same time the most fundamental process-units in biology
and to recruit them into the descriptive domain. Therefore, the first challenge
is to build a coherent formal system of abstractions and operations
that is truly native to living systems.
Nothing will be thrown away, but many common methods will be philosophically
recast, just as in physics relativity subsumed and reinterpreted
Newtonian mechanics.
This step is required because we need a comprehensible, formal system to
apply in many domains. Emphasis should be placed on the distinction between
multi-perspective analysis and synthesis and on what could be the
basic terms or tools needed.
The second challenge is relatively simple: the actual application of this set
of biology-centric ways and means to cross-disciplinary problems. In its
early stages, this will seem to be a “new science”.
This White Paper sets out the case of continuing support of Information
and Communication Technology (ICT) for transformative research in biology
and information processing centered on paradigm changes in the epistemological,
ontological, mathematical and computational bases of the science
of living systems. Today, curiously, living systems cannot be said to
be anything more than dissipative structures organized internally by genetic
information. There is not anything substantially different from abiotic
systems other than the empirical nature of their robustness. We believe that
there are other new and unique properties and patterns comprehensible at
this bio-logical level. The report lays out a fundamental set of approaches
to articulate these properties and patterns, and is composed as follows.
Sections 1 through 4 (preamble, introduction, motivation and major biomathematical
problems) are incipient. Section 5 describes the issues affecting
Integral Biomathics and Section 6 -- the aspects of the Grand Challenge
we face with this project. Section 7 contemplates the effort to
formalize a General Theory of Living Systems (GTLS) from what we have
today. The goal is to have a formal system, equivalent to that which exists
in the physics community. Here we define how to perceive the role of time
in biology. Section 8 describes the initial efforts to apply this general theory
of living systems in many domains, with special emphasis on crossdisciplinary
problems and multiple domains spanning both “hard” and
“soft” sciences. The expected result is a coherent collection of integrated
mathematical techniques. Section 9 discusses the first two test cases, project
proposals, of our approach. They are designed to demonstrate the ability
of our approach to address “wicked problems” which span across physics,
chemistry, biology, societies and societal dynamics. The solutions
require integrated measurable results at multiple levels known as “grand
challenges” to existing methods. Finally, Section 10 adheres to an appeal
for action, advocating the necessity for further long-term support of the
INBIOSA program.
The report is concluded with preliminary non-exclusive list of challenging
research themes to address, as well as required administrative actions. The
efforts described in the ten sections of this White Paper will proceed concurrently.
Collectively, they describe a program that can be managed and
measured as it progresses
Assessing the impact of preventive mass vaccination campaigns on yellow fever outbreaks in Africa: A population-level self-controlled case series study.
The Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, to what extent PMVCs are associated with a decreased risk of outbreak has not yet been quantified. We used the self-controlled case series (SCCS) method to assess the association between the occurrence of yellow fever outbreaks and the implementation of PMVCs at the province level in the African endemic region. As all time-invariant confounders are implicitly controlled for in the SCCS method, this method is an alternative to classical cohort or case-control study designs when the risk of residual confounding is high, in particular confounding by indication. The locations and dates of outbreaks were identified from international epidemiological records, and information on PMVCs was provided by coordinators of vaccination activities and international funders. The study sample consisted of provinces that were both affected by an outbreak and targeted for a PMVC between 2005 and 2018. We compared the incidence of outbreaks before and after the implementation of a PMVC. The sensitivity of our estimates to a range of assumptions was explored, and the results of the SCCS method were compared to those obtained through a retrospective cohort study design. We further derived the number of yellow fever outbreaks that have been prevented by PMVCs. The study sample consisted of 33 provinces from 11 African countries. Among these, the first outbreak occurred during the pre-PMVC period in 26 (79%) provinces, and during the post-PMVC period in 7 (21%) provinces. At the province level, the post-PMVC period was associated with an 86% reduction (95% CI 66% to 94%, p < 0.001) in the risk of outbreak as compared to the pre-PMVC period. This negative association between exposure to PMVCs and outbreak was robustly observed across a range of sensitivity analyses, especially when using quantitative estimates of vaccination coverage as an alternative exposure measure, or when varying the observation period. In contrast, the results of the cohort-style analyses were highly sensitive to the choice of covariates included in the model. Based on the SCCS results, we estimated that PMVCs were associated with a 34% (95% CI 22% to 45%) reduction in the number of outbreaks in Africa from 2005 to 2018. A limitation of our study is the fact that it does not account for potential time-varying confounders, such as changing environmental drivers of yellow fever and possibly improved disease surveillance. In this study, we provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. This study illustrates that the SCCS method can be advantageously applied at the population level in order to evaluate a public health intervention
Laser Wakefield accelerator modelling with variational neural networks
A machine learning model was created to predict the electron spectrum generated by a GeVclass laser wakefield accelerator. The model was constructed from variational convolutional neural networks which mapped the results of secondary laser and plasma diagnostics to the generated electron spectrum. An ensemble of trained networks was used to predict the electron spectrum and to provide an estimation of the uncertainty on that prediction. It is anticipated that this approach will be useful for inferring the electron spectrum prior undergoing any process which can alter or destroy the beam. In addition, the model provides insight into the scaling of electron beam properties due to stochastic fluctuations in the laser energy and plasma electron density
Computational Approaches and Analysis for a Spatio-Structural-Temporal Invasive Carcinoma Model
Spatio-temporal models have long been used to describe biological systems of cancer, but it has not been until very recently that increased attention has been paid to structural dynamics of the interaction between cancer populations and the molecular mechanisms associated with local invasion. One system that is of particular interest is that of the urokinase plasminogen activator (uPA) wherein uPA binds uPA receptors on the cancer cell surface, allowing plasminogen to be cleaved into plasmin, which degrades the extracellular matrix and this way leads to enhanced cancer cell migration. In this paper, we develop a novel numerical approach and associated analysis for spatio-structuro-temporal modelling of the uPA system for up to two-spatial and two-structural dimensions. This is accompanied by analytical exploration of the numerical techniques used in simulating this system, with special consideration being given to the proof of stability within numerical regimes encapsulating a central differences approach to approximating numerical gradients. The stability analysis performed here reveals instabilities induced by the coupling of the structural binding and proliferative processes. The numerical results expound how the uPA system aids the tumour in invading the local stroma, whilst the inhibitor to this system may impede this behaviour and encourage a more sporadic pattern of invasion.PostprintPeer reviewe
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