Machine learning for next-generation nanotechnology in healthcare

Funding: The authors acknowledge financial support from FCT Portugal in the framework of PhD grant 2020.06638.BD (to D.P.S.), and the European Research Council grant agreement 848325 (J. Conde for the ERC Starting Grant). T.R. is an Investigador Auxiliar supported by FCT Portugal (CEECIND/ 00684/2018).Nanotechnology for healthcare is coming of age, but automating the design of composite materials poses unique challenges. Although machine learning is supporting groundbreaking discoveries in materials science, new initiatives leveraging learned patterns are required to fully realize the promise of nanodelivery systems and accelerate development pipelines.publishersversionpublishe

A non-linear optimal estimation inverse method for radio occultation measurements of temperature, humidity and surface pressure

An optimal estimation inverse method is presented which can be used to retrieve simultaneously vertical profiles of temperature and specific humidity, in addition to surface pressure, from satellite-to-satellite radio occultation observations of the Earth's atmosphere. The method is a non-linear, maximum {\it a posteriori} technique which can accommodate most aspects of the real radio occultation problem and is found to be stable and to converge rapidly in most cases. The optimal estimation inverse method has two distinct advantages over the analytic inverse method in that it accounts for some of the effects of horizontal gradients and is able to retrieve optimally temperature and humidity simultaneously from the observations. It is also able to account for observation noise and other sources of error. Combined, these advantages ensure a realistic retrieval of atmospheric quantities. A complete error analysis emerges naturally from the optimal estimation theory, allowing a full characterisation of the solution. Using this analysis a quality control scheme is implemented which allows anomalous retrieval conditions to be recognised and removed, thus preventing gross retrieval errors. The inverse method presented in this paper has been implemented for bending angle measurements derived from GPS/MET radio occultation observations of the Earth. Preliminary results from simulated data suggest that these observations have the potential to improve NWP model analyses significantly throughout their vertical range.Comment: 18 (jgr journal) pages, 7 figure

Little groups of irreps of O(3), SO(3), and the infinite axial subgroups

Little groups are enumerated for the irreps and their components in any basis of O(3) and SO(3) up to rank 9, and for all irreps of C$_{\infty}$, C$_{\infty h}$, C$_{\infty v}$, D$_{\infty}$ and D$_{\infty h}$. The results are obtained by a new chain criterion, which distinguishes massive (rotationally inequivalent) irrep basis functions and allows for multiple branching paths, and are verified by inspection. These results are relevant to the determination of the symmetry of a material from its linear and nonlinear optical properties and to the choices of order parameters for symmetry breaking in liquid crystals.Comment: 28 pages and 3 figure

Ground states of a one-dimensional lattice-gas model with an infinite range nonconvex interaction. A numerical study

We consider a lattice-gas model with an infinite range pairwise noncovex interaction. It might be relevant, for example, for adsorption of alkaline elements on W(112) and Mo(112). We study a competition between the effective dipole-dipole and indirect interactions. The resulting ground state phase diagrams are analysed (numerically) in detail. We have found that for some model parameters the phase diagrams contain a region dominated by several phases only with periods up to nine lattice constants. The remaining phase diagrams reveal a complex structure of usually long periodic phases. We also discuss a possible role of surace states in phase transitions.Comment: 16 pages, 5 Postscript figures; Physical Review B15 (15 August 1996), in pres

A collagen IV-derived peptide disrupts α5β1 integrin and potentiates Ang2/Tie2 signaling

The angiopoietin (Ang)/Tie2 signaling pathway is essential for maintaining vascular homeostasis, and its dysregulation is associated with several diseases. Interactions between Tie2 and α5 β1 integrin have emerged as part of this control; however, the mechanism is incompletely understood. AXT107, a collagen IV–derived peptide, has strong antipermeability activity and has enabled the elucidation of this previously undetermined mechanism. Previously, AXT107 was shown to inhibit VEGFR2 and other growth factor signaling via receptor tyrosine kinase association with specific integrins. AXT107 disrupts α5 β1 and stimulates the relocation of Tie2 and α5 to cell junctions. In the presence of Ang2 and AXT107, junctional Tie2 is activated, downstream survival signals are upregulated, F-actin is rearranged to strengthen junctions, and, as a result, endothelial junctional permeability is reduced. These data suggest that α5 β1 sequesters Tie2 in nonjunctional locations in endothelial cell membranes and that AXT107-induced disruption of α5 β1 promotes clustering of Tie2 at junctions and converts Ang2 into a strong agonist, similar to responses observed when Ang1 levels greatly exceed those of Ang2. The potentiation of Tie2 activation by Ang2 even extended to mouse models in which AXT107 induced Tie2 phosphorylation in a model of hypoxia and inhibited vascular leakage in an Ang2-overexpression transgenic model and an LPS-induced inflammation model. Because Ang2 levels are very high in ischemic diseases, such as diabetic macular edema, neovascular age-related macular degeneration, uveitis, and cancer, targeting α5 β1 with AXT107 provides a potentially more effective approach to treat these diseases.Fil: Mirando, Adam C.. University Johns Hopkins; Estados UnidosFil: Shen, Jikui. University Johns Hopkins; Estados UnidosFil: Silva, Raquel Lima E.. University Johns Hopkins; Estados UnidosFil: Chu, Zenny. University Johns Hopkins; Estados UnidosFil: Sass, Nicholas C.. University Johns Hopkins; Estados UnidosFil: Lorenc, Valeria Erika. University Johns Hopkins; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Green, Jordan J.. University Johns Hopkins; Estados Unidos. AsclepiX Therapeutics; Estados UnidosFil: Campochiaro, Peter A.. University Johns Hopkins; Estados UnidosFil: Popel, Aleksander S.. University Johns Hopkins; Estados UnidosFil: Pandey, Niranjan B.. University Johns Hopkins; Estados Unidos. AsclepiX Therapeutics; Estados Unido

Considering methodological options for reviews of theory: illustrated by a review of theories linking income and health

Background: Review of theory is an area of growing methodological advancement. Theoretical reviews are particularly useful where the literature is complex, multi-discipline, or contested. It has been suggested that adopting methods from systematic reviews may help address these challenges. However, the methodological approaches to reviews of theory, including the degree to which systematic review methods can be incorporated, have received little discussion in the literature. We recently employed systematic review methods in a review of theories about the causal relationship between income and health. Methods: This article discusses some of the methodological issues we considered in developing the review and offers lessons learnt from our experiences. It examines the stages of a systematic review in relation to how they could be adapted for a review of theory. The issues arising and the approaches taken in the review of theories in income and health are considered, drawing on the approaches of other reviews of theory. Results: Different approaches to searching were required, including electronic and manual searches, and electronic citation tracking to follow the development of theories. Determining inclusion criteria was an iterative process to ensure that inclusion criteria were specific enough to make the review practical and focused, but not so narrow that key literature was excluded. Involving subject specialists was valuable in the literature searches to ensure principal papers were identified and during the inductive approaches used in synthesis of theories to provide detailed understanding of how theories related to another. Reviews of theory are likely to involve iterations and inductive processes throughout, and some of the concepts and techniques that have been developed for qualitative evidence synthesis can be usefully translated to theoretical reviews of this kind. Conclusions: It may be useful at the outset of a review of theory to consider whether the key aim of the review is to scope out theories relating to a particular issue; to conduct in-depth analysis of key theoretical works with the aim of developing new, overarching theories and interpretations; or to combine both these processes in the review. This can help decide the most appropriate methodological approach to take at particular stages of the review

Hadronic Structure in the Decay τ−→π−π0ντ\tau^{-}\to \pi^{-}\pi^{0}\nu_{\tau}

We report on a study of the invariant mass spectrum of the hadronic system in the decay tau- -> pi- pi0 nu_tau. This study was performed with data obtained with the CLEO II detector operating at the CESR e+ e- collider. We present fits to phenomenological models in which resonance parameters associated with the rho(770) and rho(1450) mesons are determined. The pi- pi0 spectral function inferred from the invariant mass spectrum is compared with data on e+ e- -> pi+ pi- as a test of the Conserved Vector Current theorem. We also discuss the implications of our data with regard to estimates of the hadronic contribution to the muon anomalous magnetic moment.Comment: 39 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes

This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version is available in Diabetes in print and online at http://diabetes.diabetesjournals.orgThe erratum to this article is available in ORE at http://hdl.handle.net/10871/40335Studies in type 1 diabetes indicate potential disease heterogeneity, notably in the rate of β-cell loss, responsiveness to immunotherapies, and, in limited studies, islet pathology. We sought evidence for different immunological phenotypes using two approaches. First, we defined blood autoimmune response phenotypes by combinatorial, multiparameter analysis of autoantibodies and autoreactive T-cell responses in 33 children/adolescents with newly diagnosed diabetes. Multidimensional cluster analysis showed two equal-sized patient agglomerations characterized by proinflammatory (interferon-γ-positive, multiautoantibody-positive) and partially regulated (interleukin-10-positive, pauci-autoantibody-positive) responses. Multiautoantibody-positive nondiabetic siblings at high risk of disease progression showed similar clustering. Additionally, pancreas samples obtained post mortem from a separate cohort of 21 children/adolescents with recently diagnosed type 1 diabetes were examined immunohistologically. This revealed two distinct types of insulitic lesions distinguishable by the degree of cellular infiltrate and presence of B cells that we termed "hyper-immune CD20Hi" and "pauci-immune CD20Lo." Of note, subjects had only one infiltration phenotype and were partitioned by this into two equal-sized groups that differed significantly by age at diagnosis, with hyper-immune CD20Hi subjects being 5 years younger. These data indicate potentially related islet and blood autoimmune response phenotypes that coincide with and precede disease. We conclude that different immunopathological processes (endotypes) may underlie type 1 diabetes, carrying important implications for treatment and prevention strategies.JDRFNational Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College LondonEuropean Union (EU FP7) award - Persistent Virus Infection in Diabetes Network Study Group (PEVNET)EU FP7 Large-Scale Focused Collaborative Research Project on Natural Immunomodulators as Novel Immunotherapies for Type 1 Diabetes (NAIMIT)EU FP7 Large-Scale Focused Collaborative Research Project on β-cell preservation through antigen-specific immunotherapy in Type 1 Diabetes: Enhanced Epidermal Antigen Delivery Systems (EE-ASI)National Institutes of Health (NIH)National Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Allergy and Infectious DiseasesEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Center for Research ResourcesGeneral Clinical Research CenterAmerican Diabetes Association (ADA

Rare Decays of the η′\eta^{'}

We have searched for the rare decays of the eta prime meson to e+ e- eta, e+ e- pizero, e+ e- gamma, and e mu in hadronic events at the CLEO II detector. The search is conducted on 4.80 fb^-1 of e+ e- collisions at the Cornell Electron Storage Ring. We find no signal in any of these modes, and set 90% confidence level upper limits on their branching fractions of 2.4 X 10^-3, 1.4 X 10^-3, 0.9 X 10^-3, and 4.7 X 10^-4, respectively. We also investigate the Dalitz plot of the common decay of the eta prime to pi+ pi- eta. We fit the matrix element with the Particle Data Group parameterization and find Re(alpha) = -0.021 +- 0.025, where alpha is a linear function of the kinetic energy of the eta.Comment: 12 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN