Inverse design of core-shell particles with discrete material classes using neural networks

The design of scatterers on demand is a challenging task that requires the investigation and development of novel and flexible approaches. In this paper, we propose a machine learning-assisted optimization framework to design multi-layered core-shell particles that provide a scattering response on demand. Artificial neural networks can learn to predict the scattering spectrum of core-shell particles with high accuracy and can act as fully differentiable surrogate models for a gradient-based design approach. To enable the fabrication of the particles, we consider existing materials and introduce a novel two-step optimization to treat continuous geometric parameters and discrete feasible materials simultaneously. Moreover, we overcome the non-uniqueness of the problem and expand the design space to particles of varying numbers of shells, i.e., different number of optimization parameters, with a classification network. Our method is 1–2 orders of magnitudes faster than conventional approaches in both forward prediction and inverse design and is potentially scalable to even larger and more complex scatterers

Following Darwin: Biopolitics and the Grotesque in American and German Culture, 1890-1933

My dissertation investigates turn-of-the-20th-century fiction’s fascination with ‘other’ bodies—their forms, constitutions, and meanings—and the corresponding biopolitical enterprises meant to address them. Prompted by Charles Darwin’s evolutionary theories in the 19th century, and adopting his language of the “normal” and “abnormal,” a host of wide-ranging efforts to optimize human development emerged on either side of the Atlantic during this period. My project examines the contemporaneous literary and filmic responses to such efforts, specifically those aimed at identifying and correcting ‘abnormality’ in the fields of degeneration, psychology, criminal law, and genetic science. I reconceptualize the aesthetic grotesque, as traditionally defined by Wolfgang Kayser and Mikhail Bakhtin, to include a biological component that reveals how grotesque characters might simultaneously embody and destabilize the concept of abnormality. In attending to the grotesque as individualizing the impact of biopower’s mass, population-based interventions, I demonstrate how the violence of biopolitical classifications results, paradoxically, from their instability—i.e., from attempts to ‘fix’ what, in essence, eludes human comprehension and control. Each chapter studies a different biopolitical discipline and its target subjects, pairing a German and an American work to investigate the surprisingly under-examined parallels between the racist American after-effects of slavery and pre-Holocaust German anti-Semitism, especially in their common systematic attempts to classify and then neutralize perceived threats to their populations. I look at American and German fictional texts by authors Frank Norris, Thomas Mann, Charlotte Perkins Gilman, Georg Heym, Gertrude Barrows Bennett, Franz Kafka, H.P. Lovecraft, and director Fritz Lang. Reading across these texts, I uncover a surprising contrast between an American willingness to define difference as biological, while the German fiction remains more circumspect, refusing to either endorse or reject biological classifications of humanity. Ultimately, I show how literature and film, rather than providing solutions to the problem of biopolitics and its obsession with categorization, tease out the nuances of that problem; unfettered by real-world stakes, fictional characters have the freedom to test multiple modes of dealing with such issues of control.Doctor of Philosoph

Inverse Design of All-dielectric Metasurfaces with Bound States in the Continuum

Metasurfaces with bound states in the continuum (BICs) have proven to be a powerful platform for drastically enhancing light-matter interactions, improving biosensing, and precisely manipulating near- and far-fields. However, engineering metasurfaces to provide an on-demand spectral and angular position for a BIC remains a prime challenge. A conventional solution involves a fine adjustment of geometrical parameters, requiring multiple time-consuming calculations. In this work, to circumvent such tedious processes, we develop a physics-inspired, inverse design method on all-dielectric metasurfaces for an on-demand spectral and angular position of a BIC. Our suggested method predicts the core-shell particles that constitute the unit cell of the metasurface, while considering practical limitations on geometry and available materials. Our method is based on a smart combination of a semi-analytical solution, for predicting the required dipolar Mie coefficients of the meta-atom, and a machine learning algorithm, for finding a practical design of the meta-atom that provides these Mie coefficients. Although our approach is exemplified in designing a metasurface sustaining a BIC, it can, also, be applied to many more objective functions. With that, we pave the way toward a general framework for the inverse design of metasurfaces in specific and nanophotonic structures in general.Comment: 20 pages, 5 figures, Supplementary Materia

Inverse design of all-dielectric metasurfaces with accidental bound states in the continuum

Metasurfaces with bound states in the continuum (BICs) have proven to be a powerful platform for drastically enhancing light–matter interactions, improving biosensing, and precisely manipulating near- and far-fields. However, engineering metasurfaces to provide an on-demand spectral and angular position for a BIC remains a prime challenge. A conventional solution involves a fine adjustment of geometrical parameters, requiring multiple time-consuming calculations. In this work, to circumvent such tedious processes, we develop a physics-inspired, inverse design method on all-dielectric metasurfaces for an on-demand spectral and angular position of a BIC. Our suggested method predicts the core–shell particles that constitute the unit cell of the metasurface, while considering practical limitations on geometry and available materials. Our method is based on a smart combination of a semi-analytical solution, for predicting the required dipolar Mie coefficients of the meta-atom, and a machine learning algorithm, for finding a practical design of the meta-atom that provides these Mie coefficients. Although our approach is exemplified in designing a metasurface sustaining a BIC, it can, also, be applied to many more objective functions. With that, we pave the way toward a general framework for the inverse design of metasurfaces in specific and nanophotonic structures in general

Drug specificity and affinity are encoded in the probability of cryptic pocket opening in myosin motor domains

The design of compounds that can discriminate between closely related target proteins remains a central challenge in drug discovery. Specific therapeutics targeting the highly conserved myosin motor family are urgently needed as mutations in at least six of its members cause numerous diseases. Allosteric modulators, like the myosin-II inhibitor blebbistatin, are a promising means to achieve specificity. However, it remains unclear why blebbistatin inhibits myosin-II motors with different potencies given that it binds at a highly conserved pocket that is always closed in blebbistatin-free experimental structures. We hypothesized that the probability of pocket opening is an important determinant of the potency of compounds like blebbistatin. To test this hypothesis, we used Markov state models (MSMs) built from over 2 ms of aggregate molecular dynamics simulations with explicit solvent. We find that blebbistatin\u27s binding pocket readily opens in simulations of blebbistatin-sensitive myosin isoforms. Comparing these conformational ensembles reveals that the probability of pocket opening correctly identifies which isoforms are most sensitive to blebbistatin inhibition and that docking against MSMs quantitatively predicts blebbistatin binding affinities (

Bamberg in the Early Modern Period. New Essays on the History of Town and Bishopric

Die Beiträge dieses Bandes behandeln Aspekte der Verwaltungs-, Herrschafts-, Wirtschafts-, Sozial- und Kulturgeschichte Bambergs zwischen 1500 und 1800 und schließen damit einige der weißen Flecken auf der Landkarte der frühneuzeitlichen Stadt- und Regionalforschung. Zugleich werden aktuelle geschichtswissenschaftliche Fragestellungen und Konzepte empirisch erprobt. Damit sollen die Möglichkeiten, die Bamberg als Forschungsfeld bietet, und das Potential, das sich mit der Anwendung von Konzepten und Methoden der modernen Geschichtswissenschaft auf das reichhaltige Bamberger Material verbindet, aufgezeigt und Anregungen für künftige Forschungen gegeben werden.The essays in this volume cover aspects of Bamberg’s political, administrative, economic, social and cultural history from 1500 to 1800 and thus close some of the gaps in the city’s and region’s historiography. At the same time the essays provide empirical explorations of current scholarly concepts and approaches. They intend to point out the possibilities which Bamberg offers as a field of research and the potentials inherent in the application of modern historical concepts and methods on the rich source materials available for Bamberg

Basal Immunoglobulin Signaling Actively Maintains Developmental Stage in Immature B Cells

In developing B lymphocytes, a successful V(D)J heavy chain (HC) immunoglobulin (Ig) rearrangement establishes HC allelic exclusion and signals pro-B cells to advance in development to the pre-B stage. A subsequent functional light chain (LC) rearrangement then results in the surface expression of IgM at the immature B cell stage. Here we show that interruption of basal IgM signaling in immature B cells, either by the inducible deletion of surface Ig via Cre-mediated excision or by incubating cells with the tyrosine kinase inhibitor herbimycin A or the phosphatidylinositol 3-kinase inhibitor wortmannin, led to a striking “back-differentiation” of cells to an earlier stage in B cell development, characterized by the expression of pro-B cell genes. Cells undergoing this reversal in development also showed evidence of new LC gene rearrangements, suggesting an important role for basal Ig signaling in the maintenance of LC allelic exclusion. These studies identify a previously unappreciated level of plasticity in the B cell developmental program, and have important implications for our understanding of central tolerance mechanisms

Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014

In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: “Makona”, Middle Africa: “Lomela”) and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures

Ebola virus epidemiology, transmission, and evolution during seven months in Sierra Leone

The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics