A model-based approach to associate complexity and robustness in engineering systems
Göhler, Simon Moritz; Howard, Thomas J.; Frey, Daniel
Ever increasing functionality and complexity of products and systems challenge development companies in achieving high and consistent quality. A model-based approach is used to investigate the relationship between system complexity and system robustness. The measure for complexity is based on the degree of functional coupling and the level of contradiction in the couplings. Whilst Suh’s independence axiom states that functional independence (uncoupled designs) produces more robust designs, this study proves this not to be the case for max-/min-is-best requirements, and only to be true in the general sense for nominal-is-best requirements. In specific cases, the independence axiom has exceptions as illustrated with a machining example, showing how a coupled solution is more robust than its uncoupled counterpart. This study also shows with statistical significance, that for max- and min-is-best requirements, the robustness is most affected by the level of contradiction between coupled functional requirements (p = 1.4e−36). In practice, the results imply that if the main influencing factors for each function in a system are known in the concept phase, an evaluation of the contradiction level can be used to evaluate concept robustness.
A model-based approach to associate complexity and robustness in engineering systems
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Structural default model with mutual obligations
Structural default model with mutual obligations
Itkin, Andrey; Lipton, Alexander
In this paper we consider mutual obligations in an interconnected bank system and analyze their impact on the joint and marginal survival probabilities for individual banks. We also calculate prices of the corresponding credit default swaps and first-to-default swaps. To make the role of mutual obligations more transparent, we develop a simple structural default model with banks’ assets driven by correlated multidimensional Brownian motion with drift. We calculate closed form expressions for many quantities of interest and use them for the efficient model calibration. We demonstrate that mutual obligations have noticeable impact on the system behavior.
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Improving dopant incorporation during femtosecond-laser doping of Si with a Se thin-film dopant precursor
Improving dopant incorporation during femtosecond-laser doping of Si with a Se thin-film dopant precursor
Sher, Meng-Ju; Franta, Benjamin; Lin, Yu-Ting; Mazur, Eric; Smith, Matthew J; Gradecak, Silvija
We study the dopant incorporation processes during thin-film fs-laser doping of Si and tailor the dopant distribution through optimization of the fs-laser irradiation conditions. Scanning electron microscopy, transmission electron microscopy, and profilometry are used to study the interrelated dopant incorporation and surface texturing mechanisms during fs-laser irradiation of Si coated with a Se thin-film dopant precursor. We show that the crystallization of Se-doped Si and micrometer-scale surface texturing are closely coupled and produce a doped surface that is not conducive to device fabrication. Next, we use this understanding of the dopant incorporation process to decouple dopant crystallization from surface texturing by tailoring the irradiation conditions. A low-fluence regime is identified in which a continuous surface layer of doped crystalline material forms in parallel with laser-induced periodic surface structures over many laser pulses. This investigation demonstrates the ability to tailor the dopant distribution through a systematic investigation of the relationship between fs-laser irradiation conditions, microstructure, and dopant distribution.
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Circadian Rhythms in Rho1 Activity Regulate Neuronal Plasticity and Network Hierarchy
Circadian Rhythms in Rho1 Activity Regulate Neuronal Plasticity and Network Hierarchy
Petsakou, Afroditi; Blau, Justin; Sapsis, Themistoklis P.
Neuronal plasticity helps animals learn from their environment. However, it is challenging to link specific changes in defined neurons to altered behavior. Here, we focus on circadian rhythms in the structure of the principal s-LNv clock neurons in Drosophila. By quantifying neuronal architecture, we observed that s-LNv structural plasticity changes the amount of axonal material in addition to cycles of fasciculation and defasciculation. We found that this is controlled by rhythmic Rho1 activity that retracts s-LNv axonal termini by increasing myosin phosphorylation and simultaneously changes the balance of pre-synaptic and dendritic markers. This plasticity is required to change clock network hierarchy and allow seasonal adaptation. Rhythms in Rho1 activity are controlled by clock-regulated transcription of Puratrophin-1-like (Pura), a Rho1 GEF. Since spinocerebellar ataxia is associated with mutations in human Puratrophin-1, our data support the idea that defective actin-related plasticity underlies this ataxia.
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Pathway-based network modeling finds hidden genes in shRNA screen for regulators of acute lymphoblastic leukemia
Pathway-based network modeling finds hidden genes in shRNA screen for regulators of acute lymphoblastic leukemia
Wilson, Jennifer Lynn; Dalin, Simona; Gosline, Sara Calafell; Hemann, Michael; Fraenkel, Ernest; Lauffenburger, Douglas A
Data integration stands to improve interpretation of RNAi screens which, as a result of off-target effects, typically yield numerous gene hits of which only a few validate. These off-target effects can result from seed matches to unintended gene targets (reagent-based) or cellular pathways, which can compensate for gene perturbations (biology-based). We focus on the biology-based effects and use network modeling tools to discover pathways de novo around RNAi hits. By looking at hits in a functional context, we can uncover novel biology not identified from any individual ‘omics measurement. We leverage multiple ‘omic measurements using the Simultaneous Analysis of Multiple Networks (SAMNet) computational framework to model a genome scale shRNA screen investigating Acute Lymphoblastic Leukemia (ALL) progression in vivo. Our network model is enriched for cellular processes associated with hematopoietic differentiation and homeostasis even though none of the individual ‘omic sets showed this enrichment. The model identifies genes associated with the TGF-beta pathway and predicts a role in ALL progression for many genes without this functional annotation. We further experimentally validate the hidden genes – Wwp1, a ubiquitin ligase, and Hgs, a multi-vesicular body associated protein – for their role in ALL progression. Our ALL pathway model includes genes with roles in multiple types of leukemia and roles in hematological development. We identify a tumor suppressor role for Wwp1 in ALL progression. This work demonstrates that network integration approaches can compensate for off-target effects, and that these methods can uncover novel biology retroactively on existing screening data. We anticipate that this framework will be valuable to multiple functional genomic technologies – siRNA, shRNA, and CRISPR – generally, and will improve the utility of functional genomic studies.
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Probability distributions for directed polymers in random media with correlated noise
Probability distributions for directed polymers in random media with correlated noise
Chu, Sherry; Kardar, Mehran
The probability distribution for the free energy of directed polymers in random media (DPRM) with uncorrelated noise in d=1+1 dimensions satisfies the Tracy-Widom distribution. We inquire if and how this universal distribution is modified in the presence of spatially correlated noise. The width of the distribution scales as the DPRM length to an exponent β, in good (but not full) agreement with previous renormalization group and numerical results. The scaled probability is well described by the Tracy-Widom form for uncorrelated noise, but becomes symmetric with increasing correlation exponent. We thus find a class of distributions that continuously interpolates between Tracy-Widom and Gaussian forms.
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Drag suppression in anomalous chiral media
Drag suppression in anomalous chiral media
Yin, Yi; Sadofyev, Andrey
We study a heavy impurity moving longitudinal with the direction of an external magnetic field in an anomalous chiral medium. Such system would carry a nondissipative current of chiral magnetic effect associated with the anomaly. We show, by generalizing Landau’s criterion for superfluidity, that the “anomalous component” which gives rise to the anomalous transport will not contribute to the drag experienced by an impurity. We argue on a very general basis that those systems with a strong magnetic field would exhibit an interesting transport phenomenon—the motion of the heavy impurity is frictionless, in analogy to the case of a superfluid. We demonstrate and confirm our general results with two complementary examples: weakly coupled chiral fermion gases and strongly interacting chiral liquids.
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Transgenic Mice for Intersectional Targeting of Neural Sensors and Effectors with High Specificity and Performance
Transgenic Mice for Intersectional Targeting of Neural Sensors and Effectors with High Specificity and Performance
Madisen, Linda; Garner, Aleena R.; Shimaoka, Daisuke; Li, Lu; van der Bourg, Alexander; Niino, Yusuke; Egolf, Ladan; Monetti, Claudio; Gu, Hong; Mills, Maya; Cheng, Adrian; Tasic, Bosiljka; Nguyen, Thuc Nghi; Sunkin, Susan M.; Benucci, Andrea; Nagy, Andras; Miyawaki, Atsushi; Helmchen, Fritjof; Empson, Ruth M.; Knöpfel, Thomas; Reid, R. Clay; Carandini, Matteo; Zeng, Hongkui; Chuong, Amy S; Klapoetke, Nathan Cao; Boyden, Edward
An increasingly powerful approach for studying brain circuits relies on targeting genetically encoded sensors and effectors to specific cell types. However, current approaches for this are still limited in functionality and specificity. Here we utilize several intersectional strategies to generate multiple transgenic mouse lines expressing high levels of novel genetic tools with high specificity. We developed driver and double reporter mouse lines and viral vectors using the Cre/Flp and Cre/Dre double recombinase systems and established a new, retargetable genomic locus, TIGRE, which allowed the generation of a large set of Cre/tTA-dependent reporter lines expressing fluorescent proteins, genetically encoded calcium, voltage, or glutamate indicators, and optogenetic effectors, all at substantially higher levels than before. High functionality was shown in example mouse lines for GCaMP6, YCX2.60, VSFP Butterfly 1.2, and Jaws. These novel transgenic lines greatly expand the ability to monitor and manipulate neuronal activities with increased specificity.
available in PMC 2016 March 04
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A mechanistic model for drug release in PLGA biodegradable stent coatings coupled with polymer degradation and erosion
A mechanistic model for drug release in PLGA biodegradable stent coatings coupled with polymer degradation and erosion
Zhu, Xiaoxiang; Braatz, Richard D
Biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) coating for applications in drug-eluting stents has been receiving increasing interest as a result of its unique properties compared with biodurable polymers in delivering drug for reducing stents-related side effects. In this work, a mathematical model for describing the PLGA degradation and erosion and coupled drug release from PLGA stent coating is developed and validated. An analytical expression is derived for PLGA mass loss that predicts multiple experimental studies in the literature. An analytical model for the change of the number-average degree of polymerization [or molecular weight (MW)] is also derived. The drug transport model incorporates simultaneous drug diffusion through both the polymer solid and the liquid-filled pores in the coating, where an effective drug diffusivity model is derived taking into account factors including polymer MW change, stent coating porosity change, and drug partitioning between solid and aqueous phases. The model is used to describe in vitro sirolimus release from PLGA stent coating, and demonstrates the significance of simultaneous sirolimus release via diffusion through both polymer solid and pore space. The proposed model is compared to existing drug transport models, and the impact of model parameters, limitations and possible extensions of the model are also discussed.
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The Work of the 2014 Fields Medalists
The Work of the 2014 Fields Medalists
de Melo, Welington; Quastel, Jeremy; Zorich, Anton; Poonen, Bjorn
The Work of the 2014 Fields Medalists Welington de Melo, Bjorn Poonen, Jeremy Quastel, and Anton Zorich The Notices solicited the following articles about the works of the four individuals to whom Fields Medals were awarded at the International Congress of Mathematicians in Seoul, South Korea, in August 2014. This was a historic occasion, as it marked the first time since the medal was established in 1936 that a woman was among the recipients. The International Mathematical Union also issued news releases describing the medalists' work, and these appeared in the October 2014 issue of the Notices.
--Allyn Jackson
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Comparing P and S wave heterogeneity in the mantle
Comparing P and S wave heterogeneity in the mantle
Saltzer, Rebecca L.; van der Hilst, Robert D; Karason, Hrafnkell
From the reprocessed data set of Engdahl and co-workers we have carefully selected matching P and S data for tomographic imaging. We assess data and model error and conclude that our S model uncertainty is twice that of the P model. We account for this in our comparison of the perturbations in P and S-wavespeed. In accord with previous studies we find that P and S perturbations are positively correlated at all depths. However, in the deep mantle systematic differences occur between regions that have undergone subduction in the last 120 million years and those that have not. In particular, below 1500 km depth ∂ln V[subscript s]/∂ln V[subscript p] is significantly larger in mantle regions away from subduction than in mantle beneath convergent margins. This inference is substantiated by wavespeed analyses with random realizations of the slab/non-slab distribution. Through much of the mantle there is no significant correlation between bulk sound and S-wave perturbations, but they appear to be negatively correlated between 1700 and 2100 km depth, which is also where the largest differences in ∂ln V[subscript s]/∂ln V[subscript p] occur. This finding supports convection models with compositional heterogeneity in the lowermost mantle.
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Investigating Effects of Proteasome Inhibitor on Multiple Myeloma Cells Using Confocal Raman Microscopy
Investigating Effects of Proteasome Inhibitor on Multiple Myeloma Cells Using Confocal Raman Microscopy
Kang, Jeon Woong; Singh, Surya Pratap; Nguyen, Freddy T.; Lue, Niyom; Sung, Yongjin; So, Peter T. C.; Dasari, Ramachandra Rao
Due to its label-free and non-destructive nature, applications of Raman spectroscopic imaging in monitoring therapeutic responses at the cellular level are growing. We have recently developed a high-speed confocal Raman microscopy system to image living biological specimens with high spatial resolution and sensitivity. In the present study, we have applied this system to monitor the effects of Bortezomib, a proteasome inhibitor drug, on multiple myeloma cells. Cluster imaging followed by spectral profiling suggest major differences in the nuclear and cytoplasmic contents of cells due to drug treatment that can be monitored with Raman spectroscopy. Spectra were also acquired from group of cells and feasibility of discrimination among treated and untreated cells using principal component analysis (PCA) was accessed. Findings support the feasibility of Raman technologies as an alternate, novel method for monitoring live cell dynamics with minimal external perturbation.
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A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing
A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing
Madisen, Linda; Mao, Tianyi; Koch, Henner; Zhuo, Jia-min; Berenyi, Antal; Fujisawa, Shigeyoshi; Hsu, Yun-Wei A; Garcia, Alfredo J; Gu, Xuan; Zanella, Sebastien; Kidney, Jolene; Gu, Hong; Mao, Yimei; Hooks, Bryan M; Buzsáki, György; Ramirez, Jan Marino; Jones, Allan R; Svoboda, Karel; Han, Xue; Turner, Eric E; Zeng, Hongkui; Boyden, Edward
We report on wide-field optically detected magnetic resonance imaging of nitrogen-vacancy centers (NVs) in type IIa polycrystalline diamond. These studies reveal a heterogeneous crystalline environment that produces a varied density of NV centers, including preferential orientation within
some individual crystal grains, but preserves long spin coherence times. Using the native NVs as nanoscale sensors, we introduce a three-dimensional strain imaging technique with high sensitivity (
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Topological crystalline magnets: Symmetry-protected topological phases of fermions
Topological crystalline magnets: Symmetry-protected topological phases of fermions
Watanabe, Haruki; Fu, Liang
We introduce a novel class of interaction-enabled topological crystalline insulators in two- and three-dimensional electronic systems, which we call “topological crystalline magnet.” It is protected by the product of the time-reversal symmetry T and a mirror symmetry or a rotation symmetry R. A topological crystalline magnet exhibits two intriguing features: (i) it cannot be adiabatically connected to any Slater insulator and (ii) the edge state is robust against coupling electrons to the edge. These features are protected by the anomalous symmetry transformation property (RT)[superscript 2]=−1 of the edge state. An anisotropic response to the external magnetic field can be an experimental signature.
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Antipolar ordering of topological defects in active liquid crystals
Antipolar ordering of topological defects in active liquid crystals
Oza, Anand U; Dunkel, Joern
ATP-driven microtubule-kinesin bundles can self-assemble into two-dimensional active liquid crystals (ALCs) that exhibit a rich creation and annihilation dynamics of topological defects, reminiscent of particle-pair production processes in quantum systems. This recent discovery has sparked considerable interest but a quantitative theoretical description is still lacking. We present and validate a minimal continuum theory for this new class of active matter systems by generalizing the classical Landau–de Gennes free-energy to account for the experimentally observed spontaneous buckling of motor-driven extensile microtubule bundles. The resulting model agrees with recently published data and predicts a regime of antipolar order. Our analysis implies that ALCs are governed by the same generic ordering principles that determine the non-equilibrium dynamics of dense bacterial suspensions and elastic bilayer materials. Moreover, the theory manifests an energetic analogy with strongly interacting quantum gases. Generally, our results suggest that complex nonequilibrium pattern-formation phenomena might be predictable from a few fundamental symmetry-breaking and scale-selection principles.
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Using electrodermal activity to recognize ease of engagement in children during social interactions
Using electrodermal activity to recognize ease of engagement in children during social interactions
Riobo, Ivan; Rozga, Agata; Abowd, Gregory D.; Picard, Rosalind W.; Hernandez Rivera, Javier
The recent emergence of comfortable wearable sensors has focused almost entirely on monitoring physical activity, ignoring opportunities to monitor more subtle phenomena, such as the quality of social interactions. We argue that it is compelling to address whether physiological sensors can shed light on quality of social interactive behavior. This work leverages the use of a wearable electrodermal activity (EDA) sensor to recognize ease of engagement of children during a social interaction with an adult. In particular, we monitored 51 child-adult dyads in a semi-structured play interaction and used Support Vector Machines to automatically identify children who had been rated by the adult as more or less difficult to engage. We report on the classification value of several features extracted from the child's EDA responses, as well as several other features capturing the physiological synchrony between the child and the adult.
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Phylogenetic Diversity in the Macromolecular Composition of Microalgae
Phylogenetic Diversity in the Macromolecular Composition of Microalgae
Finkel, Zoe V.; Liefer, Justin D.; Brown, Chris M.; Benner, Ina; Irwin, Andrew J.; Follows, Michael J
The elemental stoichiometry of microalgae reflects their underlying macromolecular composition and influences competitive interactions among species and their role in the food web and biogeochemistry. Here we provide a new estimate of the macromolecular composition of microalgae using a hierarchical Bayesian analysis of data compiled from the literature. The median macromolecular composition of nutrient-sufficient exponentially growing microalgae is 32.2% protein, 17.3% lipid, 15.0% carbohydrate, 17.3% ash, 5.7% RNA, 1.1% chlorophyll-a and 1.0% DNA as percent dry weight. Our analysis identifies significant phylogenetic differences in macromolecular composition undetected by previous studies due to small sample sizes and the large inherent variability in macromolecular pools. The phylogenetic differences in macromolecular composition lead to variations in carbon-to-nitrogen ratios that are consistent with independent observations. These phylogenetic differences in macromolecular and elemental composition reflect adaptations in cellular architecture and biochemistry; specifically in the cell wall, the light harvesting apparatus, and storage pools.
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The impact of historical land use change from 1850 to 2000 on secondary particulate matter and ozone
The impact of historical land use change from 1850 to 2000 on secondary particulate matter and ozone
Geddes, Jeffrey A.; Heald, Colette L.
Anthropogenic land use change (LUC) since preindustrial (1850) has altered the vegetation distribution and density around the world. We use a global model (GEOS-Chem) to assess the attendant changes in surface air quality and the direct radiative forcing (DRF). We focus our analysis on secondary particulate matter and tropospheric ozone formation. The general trend of expansion of managed ecosystems (croplands and pasturelands) at the expense of natural ecosystems has led to an 11 % decline in global mean biogenic volatile organic compound emissions. Concomitant growth in agricultural activity has more than doubled ammonia emissions and increased emissions of nitrogen oxides from soils by more than 50 %. Conversion to croplands has also led to a widespread increase in ozone dry deposition velocity. Together these changes in biosphere–atmosphere exchange have led to a 14 % global mean increase in biogenic secondary organic aerosol (BSOA) surface concentrations, a doubling of surface aerosol nitrate concentrations, and local changes in surface ozone of up to 8.5 ppb. We assess a global mean LUC-DRF of +0.017, −0.071, and −0.01 W m−2 for BSOA, nitrate, and tropospheric ozone, respectively. We conclude that the DRF and the perturbations in surface air quality associated with LUC (and the associated changes in agricultural emissions) are substantial and should be considered alongside changes in anthropogenic emissions and climate feedbacks in chemistry–climate studies.
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Moral status of accidents
Moral status of accidents
Saxe, Rebecca R
No one is naive enough to expect that all moral beliefs are universal. Today, some countries legally beat and imprison homosexuals, and others recognize gay marriage; in some places, killing a bull is a sport, and, in others, it is an abomination; in some places, corporal punishment is the obligation of a responsible parent and, in others, grounds for forced removal. Indeed, the burden of proof seems to be on the other side: Is there anything universal about human moral cognition? In PNAS, Barrett et al. (1) test one candidate for a universal principle of human morality: that an action’s moral value depends not only on the action’s consequences but on the person’s intentions.
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Parent-of-Origin DNA Methylation Dynamics during Mouse Development
Parent-of-Origin DNA Methylation Dynamics during Mouse Development
Stelzer, Yonatan; Wu, Hao; Shivalila, Chikdu S.; Markoulaki, Styliani; Song, Yuelin; Jaenisch, Rudolf
Parent-specific differentially methylated regions (DMRs) are established during gametogenesis and regulate parent-specific expression of imprinted genes. Monoallelic expression of imprinted genes is essential for development, suggesting that imprints are faithfully maintained in embryos and adults. To test this hypothesis, we targeted a reporter for genomic methylation to the imprinted Dlk1-Dio3 intergenic DMR (IG-DMR) to assess the methylation of both parental alleles at single-cell resolution. Biallelic gain or loss of IG-DMR methylation occurred in a small fraction of mouse embryonic stem cells, significantly affecting developmental potency. Mice carrying the reporter in either parental allele showed striking parent-specific changes in IG-DMR methylation, causing substantial and consistent tissue- and cell-type-dependent signatures in embryos and postnatal animals. Furthermore, dynamics in DNA methylation persisted during adult neurogenesis, resulting in inter-individual diversity. This substantial cell-cell DNA methylation heterogeneity implies that dynamic DNA methylation variations in the adult may be of functional importance.
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