@article{11983, abstract = {A continuous process for the synthesis and inline separation of anhydrous trifluoromethyl diazomethane in a single continuous flow process is presented. The diazo building block is generated from the corresponding amine and NaNO2 under acidic, aqueous conditions and subsequently diffuses through a gas-permeable membrane into an organic stream. To avoid storage and transportation of the hazardous compound, a representative downstream process in a packed-bed reactor yielding highly functionalized building blocks was developed.}, author = {Pieber, Bartholomäus and Kappe, C. Oliver}, issn = {1523-7052}, journal = {Organic Letters}, number = {5}, pages = {1076--1079}, publisher = {American Chemical Society}, title = {{Generation and synthetic application of trifluoromethyl diazomethane utilizing continuous flow technologies}}, doi = {10.1021/acs.orglett.6b00194}, volume = {18}, year = {2016}, } @article{11985, abstract = {Hydrocodone, a high value active pharmaceutical ingredient (API), is usually produced in a semisynthetic pathway from morphine, codeine or thebaine. The latter alkaloid is an attractive precursor as it is not used as a remedy itself. The key step in this production route is a selective olefin reduction forming 8,14-dihydrothebaine which can be subsequently hydrolyzed to yield hydrocodone. Unfortunately, standard hydrogenation procedures cannot be applied due to severe selectivity problems. A transfer hydrogenation using in situ generated diimide is the only known alternative to achieve a selective transformation. The most (atom) economic generation of this highly unstable reducing agent is by oxidizing hydrazine hydrate (N2H4·H2O) with O2. In the past, this route was “forbidden” on an industrial scale due to its enormous explosion potential in batch. A continuous high-temperature/high-pressure methodology allows an efficient, safe, and scalable processing of the hazardous reaction mixture. The industrially relevant reduction was achieved by using four consecutive liquid feeds (of N2H4·H2O) and residence time units, resulting in a highly selective reduction within less than 1 h.}, author = {Pieber, Bartholomäus and Cox, D. Phillip and Kappe, C. Oliver}, issn = {1520-586X}, journal = {Organic Process Research and Development}, number = {2}, pages = {376--385}, publisher = {American Chemical Society}, title = {{Selective olefin reduction in thebaine using hydrazine hydrate and O₂ under intensified continuous flow conditions}}, doi = {10.1021/acs.oprd.5b00370}, volume = {20}, year = {2016}, } @article{11988, abstract = {A continuous Bucherer–Bergs hydantoin synthesis utilizing intensified conditions is reported. The methodology is characterized by a two-feed flow approach to independently feed the organic substrate and the aqueous reagent solution. The increased interfacial area of the biphasic reaction mixture and the lack of headspace enabled almost quantitative conversions within ca. 30 minutes at 120 °C and 20 bar even for unpolar starting materials. In addition, a selective N(3)-monoalkylation of the resulting heterocycles under batch microwave conditions is reported yielding potential acetylcholinesterase inhibitors.}, author = {Kappe, C. and Monteiro, Julia and Pieber, Bartholomäus and Corrêa, Arlene}, issn = {1437-2096}, journal = {Synlett}, number = {01}, pages = {83--87}, publisher = {Georg Thieme Verlag}, title = {{Continuous synthesis of hydantoins: Intensifying the Bucherer–Bergs reaction}}, doi = {10.1055/s-0035-1560317}, volume = {27}, year = {2016}, } @article{1200, author = {Hilbe, Christian and Traulsen, Arne}, journal = {Physics of Life Reviews}, pages = {29 -- 31}, publisher = {Elsevier}, title = {{Only the combination of mathematics and agent based simulations can leverage the full potential of evolutionary modeling: Comment on “Evolutionary game theory using agent-based methods” by C. Adami, J. Schossau and A. Hintze}}, doi = {10.1016/j.plrev.2016.10.004}, volume = {19}, year = {2016}, } @article{1201, abstract = {In this issue of Cell, Skau et al. show that the formin FMN2 organizes a perinuclear actin cytoskeleton that protects the nucleus and its genomic content of migrating cells squeezing through small spaces.}, author = {Renkawitz, Jörg and Sixt, Michael K}, journal = {Cell}, number = {6}, pages = {1448 -- 1449}, publisher = {Cell Press}, title = {{Formin’ a nuclear protection}}, doi = {10.1016/j.cell.2016.11.024}, volume = {167}, year = {2016}, } @article{1202, author = {Milutinovic, Barbara and Peuß, Robert and Ferro, Kevin and Kurtz, Joachim}, journal = {Zoology }, number = {4}, pages = {254 -- 261}, publisher = {Elsevier}, title = {{Immune priming in arthropods: an update focusing on the red flour beetle}}, doi = {10.1016/j.zool.2016.03.006}, volume = {119}, year = {2016}, } @article{1203, abstract = {Haemophilus haemolyticus has been recently discovered to have the potential to cause invasive disease. It is closely related to nontypeable Haemophilus influenzae (NT H. influenzae). NT H. influenzae and H. haemolyticus are often misidentified because none of the existing tests targeting the known phenotypes of H. haemolyticus are able to specifically identify H. haemolyticus. Through comparative genomic analysis of H. haemolyticus and NT H. influenzae, we identified genes unique to H. haemolyticus that can be used as targets for the identification of H. haemolyticus. A real-time PCR targeting purT (encoding phosphoribosylglycinamide formyltransferase 2 in the purine synthesis pathway) was developed and evaluated. The lower limit of detection was 40 genomes/PCR; the sensitivity and specificity in detecting H. haemolyticus were 98.9% and 97%, respectively. To improve the discrimination of H. haemolyticus and NT H. influenzae, a testing scheme combining two targets (H. haemolyticus purT and H. influenzae hpd, encoding protein D lipoprotein) was also evaluated and showed 96.7% sensitivity and 98.2% specificity for the identification of H. haemolyticus and 92.8% sensitivity and 100% specificity for the identification of H. influenzae, respectively. The dual-target testing scheme can be used for the diagnosis and surveillance of infection and disease caused by H. haemolyticus and NT H. influenzae.}, author = {Hu, Fang and Rishishwar, Lavanya and Sivadas, Ambily and Mitchell, Gabriel and King, Jordan and Murphy, Timothy and Gilsdorf, Janet and Mayer, Leonard and Wang, Xin}, journal = {Journal of Clinical Microbiology}, number = {12}, pages = {3010 -- 3017}, publisher = {American Society for Microbiology}, title = {{Comparative genomic analysis of Haemophilus haemolyticus and nontypeable Haemophilus influenzae and a new testing scheme for their discrimination}}, doi = {10.1128/JCM.01511-16}, volume = {54}, year = {2016}, } @article{1204, abstract = {In science, as in life, "surprises" can be adequately appreciated only in the presence of a null model, what we expect a priori. In physics, theories sometimes express the values of dimensionless physical constants as combinations of mathematical constants like π or e. The inverse problem also arises, whereby the measured value of a physical constant admits a "surprisingly" simple approximation in terms of well-known mathematical constants. Can we estimate the probability for this to be a mere coincidence, rather than an inkling of some theory? We answer the question in the most naive form.}, author = {Amir, Ariel and Lemeshko, Mikhail and Tokieda, Tadashi}, journal = {American Mathematical Monthly}, number = {6}, pages = {609 -- 612}, publisher = {Mathematical Association of America}, title = {{Surprises in numerical expressions of physical constants}}, doi = {10.4169/amer.math.monthly.123.6.609}, volume = {123}, year = {2016}, } @inproceedings{1205, abstract = {In this paper, we present a formal model-driven engineering approach to establishing a safety-assured implementation of Multifunction vehicle bus controller (MVBC) based on the generic reference models and requirements described in the International Electrotechnical Commission (IEC) standard IEC-61375. First, the generic models described in IEC-61375 are translated into a network of timed automata, and some safety requirements tested in IEC-61375 are formalized as timed computation tree logic (TCTL) formulas. With the help of Uppaal, we check and debug whether the timed automata satisfy the formulas or not. Within this step, several logic inconsistencies in the original standard are detected and corrected. Then, we apply the tool Times to generate C code from the verified model, which was later synthesized into a real MVBC chip. Finally, the runtime verification tool RMOR is applied to verify some safety requirements at the implementation level. We set up a real platform with worldwide mostly used MVBC D113, and verify the correctness and the scalability of the synthesized MVBC chip more comprehensively. The errors in the standard has been confirmed and the resulted MVBC has been deployed in real train communication network.}, author = {Jiang, Yu and Liu, Han and Song, Houbing and Kong, Hui and Gu, Ming and Sun, Jiaguang and Sha, Lui}, location = {Limassol, Cyprus}, pages = {757 -- 763}, publisher = {Springer}, title = {{Safety assured formal model driven design of the multifunction vehicle bus controller}}, doi = {10.1007/978-3-319-48989-6_47}, volume = {9995}, year = {2016}, } @article{1206, abstract = {We study a polar molecule immersed in a superfluid environment, such as a helium nanodroplet or a Bose–Einstein condensate, in the presence of a strong electrostatic field. We show that coupling of the molecular pendular motion, induced by the field, to the fluctuating bath leads to formation of pendulons—spherical harmonic librators dressed by a field of many-particle excitations. We study the behavior of the pendulon in a broad range of molecule–bath and molecule–field interaction strengths, and reveal that its spectrum features a series of instabilities which are absent in the field-free case of the angulon quasiparticle. Furthermore, we show that an external field allows to fine-tune the positions of these instabilities in the molecular rotational spectrum. This opens the door to detailed experimental studies of redistribution of orbital angular momentum in many-particle systems. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim}, author = {Redchenko, Elena and Lemeshko, Mikhail}, journal = {ChemPhysChem}, number = {22}, pages = {3649 -- 3654}, publisher = {Wiley-Blackwell}, title = {{Libration of strongly oriented polar molecules inside a superfluid}}, doi = {10.1002/cphc.201601042}, volume = {17}, year = {2016}, } @article{1209, abstract = {NADH-ubiquinone oxidoreductase (complex I) is the largest (∼1 MDa) and the least characterized complex of the mitochondrial electron transport chain. Because of the ease of sample availability, previous work has focused almost exclusively on bovine complex I. However, only medium resolution structural analyses of this complex have been reported. Working with other mammalian complex I homologues is a potential approach for overcoming these limitations. Due to the inherent difficulty of expressing large membrane protein complexes, screening of complex I homologues is limited to large mammals reared for human consumption. The high sequence identity among these available sources may preclude the benefits of screening. Here, we report the characterization of complex I purified from Ovis aries (ovine) heart mitochondria. All 44 unique subunits of the intact complex were identified by mass spectrometry. We identified differences in the subunit composition of subcomplexes of ovine complex I as compared with bovine, suggesting differential stability of inter-subunit interactions within the complex. Furthermore, the 42-kDa subunit, which is easily lost from the bovine enzyme, remains tightly bound to ovine complex I. Additionally, we developed a novel purification protocol for highly active and stable mitochondrial complex I using the branched-chain detergent lauryl maltose neopentyl glycol. Our data demonstrate that, although closely related, significant differences exist between the biochemical properties of complex I prepared from ovine and bovine mitochondria and that ovine complex I represents a suitable alternative target for further structural studies. }, author = {Letts, James A and Degliesposti, Gianluca and Fiedorczuk, Karol and Skehel, Mark and Sazanov, Leonid A}, journal = {Journal of Biological Chemistry}, number = {47}, pages = {24657 -- 24675}, publisher = {American Society for Biochemistry and Molecular Biology}, title = {{Purification of ovine respiratory complex i results in a highly active and stable preparation}}, doi = {10.1074/jbc.M116.735142}, volume = {291}, year = {2016}, } @inbook{1210, abstract = {Mechanisms for cell protection are essential for survival of multicellular organisms. In plants, the apical hook, which is transiently formed in darkness when the germinating seedling penetrates towards the soil surface, plays such protective role and shields the vitally important shoot apical meristem and cotyledons from damage. The apical hook is formed by bending of the upper hypocotyl soon after germination, and it is maintained in a closed stage while the hypocotyl continues to penetrate through the soil and rapidly opens when exposed to light in proximity of the soil surface. To uncover the complex molecular network orchestrating this spatiotemporally tightly coordinated process, monitoring of the apical hook development in real time is indispensable. Here we describe an imaging platform that enables high-resolution kinetic analysis of this dynamic developmental process. © Springer Science+Business Media New York 2017.}, author = {Zhu, Qiang and Žádníková, Petra and Smet, Dajo and Van Der Straeten, Dominique and Benková, Eva}, booktitle = {Plant Hormones}, pages = {1 -- 8}, publisher = {Humana Press}, title = {{Real time analysis of the apical hook development}}, doi = {10.1007/978-1-4939-6469-7_1}, volume = {1497}, year = {2016}, } @article{1212, abstract = {Plants adjust their growth according to gravity. Gravitropism involves gravity perception, signal transduction, and asymmetric growth response, with organ bending as a consequence [1]. Asymmetric growth results from the asymmetric distribution of the plant-specific signaling molecule auxin [2] that is generated by lateral transport, mediated in the hypocotyl predominantly by the auxin transporter PIN-FORMED3 (PIN3) [3–5]. Gravity stimulation polarizes PIN3 to the bottom sides of endodermal cells, correlating with increased auxin accumulation in adjacent tissues at the lower side of the stimulated organ, where auxin induces cell elongation and, hence, organ bending. A curvature response allows the hypocotyl to resume straight growth at a defined angle [6], implying that at some point auxin symmetry is restored to prevent overbending. Here, we present initial insights into cellular and molecular mechanisms that lead to the termination of the tropic response. We identified an auxin feedback on PIN3 polarization as underlying mechanism that restores symmetry of the PIN3-dependent auxin flow. Thus, two mechanistically distinct PIN3 polarization events redirect auxin fluxes at different time points of the gravity response: first, gravity-mediated redirection of PIN3-mediated auxin flow toward the lower hypocotyl side, where auxin gradually accumulates and promotes growth, and later PIN3 polarization to the opposite cell side, depleting this auxin maximum to end the bending. Accordingly, genetic or pharmacological interference with the late PIN3 polarization prevents termination of the response and leads to hypocotyl overbending. This observation reveals a role of auxin feedback on PIN polarity in the termination of the tropic response. © 2016 Elsevier Ltd}, author = {Rakusová, Hana and Abbas, Mohamad and Han, Huibin and Song, Siyuan and Robert, Hélène and Friml, Jirí}, journal = {Current Biology}, number = {22}, pages = {3026 -- 3032}, publisher = {Cell Press}, title = {{Termination of shoot gravitropic responses by auxin feedback on PIN3 polarity}}, doi = {10.1016/j.cub.2016.08.067}, volume = {26}, year = {2016}, } @inproceedings{1214, abstract = {With the accelerated development of robot technologies, optimal control becomes one of the central themes of research. In traditional approaches, the controller, by its internal functionality, finds appropriate actions on the basis of the history of sensor values, guided by the goals, intentions, objectives, learning schemes, and so forth. While very successful with classical robots, these methods run into severe difficulties when applied to soft robots, a new field of robotics with large interest for human-robot interaction. We claim that a novel controller paradigm opens new perspective for this field. This paper applies a recently developed neuro controller with differential extrinsic synaptic plasticity to a muscle-tendon driven arm-shoulder system from the Myorobotics toolkit. In the experiments, we observe a vast variety of self-organized behavior patterns: when left alone, the arm realizes pseudo-random sequences of different poses. By applying physical forces, the system can be entrained into definite motion patterns like wiping a table. Most interestingly, after attaching an object, the controller gets in a functional resonance with the object's internal dynamics, starting to shake spontaneously bottles half-filled with water or sensitively driving an attached pendulum into a circular mode. When attached to the crank of a wheel the neural system independently develops to rotate it. In this way, the robot discovers affordances of objects its body is interacting with.}, author = {Martius, Georg S and Hostettler, Raphael and Knoll, Alois and Der, Ralf}, location = {Daejeon, Korea}, publisher = {IEEE}, title = {{Compliant control for soft robots: Emergent behavior of a tendon driven anthropomorphic arm}}, doi = {10.1109/IROS.2016.7759138}, volume = {2016-November}, year = {2016}, } @article{1216, abstract = {A framework fo r extracting features in 2D transient flows, based on the acceleration field to ensure Galilean invariance is proposed in this paper. The minima of the acceleration magnitude (a superset of acceleration zeros) are extracted and discriminated into vortices and saddle points, based on the spectral properties of the velocity Jacobian. The extraction of topological features is performed with purely combinatorial algorithms from discrete computational topology. The feature points are prioritized with persistence, as a physically meaningful importance measure. These feature points are tracked in time with a robust algorithm for tracking features. Thus, a space-time hierarchy of the minima is built and vortex merging events are detected. We apply the acceleration feature extraction strategy to three two-dimensional shear flows: (1) an incompressible periodic cylinder wake, (2) an incompressible planar mixing layer and (3) a weakly compressible planar jet. The vortex-like acceleration feature points are shown to be well aligned with acceleration zeros, maxima of the vorticity magnitude, minima of the pressure field and minima of λ2.}, author = {Kasten, Jens and Reininghaus, Jan and Hotz, Ingrid and Hege, Hans and Noack, Bernd and Daviller, Guillaume and Morzyński, Marek}, journal = {Archives of Mechanics}, number = {1}, pages = {55 -- 80}, publisher = {Polish Academy of Sciences Publishing House}, title = {{Acceleration feature points of unsteady shear flows}}, volume = {68}, year = {2016}, } @article{1217, abstract = {Understanding the regulation of T-cell responses during inflammation and auto-immunity is fundamental for designing efficient therapeutic strategies against immune diseases. In this regard, prostaglandin E 2 (PGE 2) is mostly considered a myeloid-derived immunosuppressive molecule. We describe for the first time that T cells secrete PGE 2 during T-cell receptor stimulation. In addition, we show that autocrine PGE 2 signaling through EP receptors is essential for optimal CD4 + T-cell activation in vitro and in vivo, and for T helper 1 (Th1) and regulatory T cell differentiation. PGE 2 was found to provide additive co-stimulatory signaling through AKT activation. Intravital multiphoton microscopy showed that triggering EP receptors in T cells is also essential for the stability of T cell-dendritic cell (DC) interactions and Th-cell accumulation in draining lymph nodes (LNs) during inflammation. We further demonstrated that blocking EP receptors in T cells during the initial phase of collagen-induced arthritis in mice resulted in a reduction of clinical arthritis. This could be attributable to defective T-cell activation, accompanied by a decline in activated and interferon-γ-producing CD4 + Th1 cells in draining LNs. In conclusion, we prove that T lymphocytes secret picomolar concentrations of PGE 2, which in turn provide additive co-stimulatory signaling, enabling T cells to attain a favorable activation threshold. PGE 2 signaling in T cells is also required for maintaining long and stable interactions with DCs within LNs. Blockade of EP receptors in vivo impairs T-cell activation and development of T cell-mediated inflammatory responses. This may have implications in various pathophysiological settings.}, author = {Sreeramkumar, Vinatha and Hons, Miroslav and Punzón, Carmen and Stein, Jens and Sancho, David and Fresno Forcelledo, Manuel and Cuesta, Natalia}, journal = {Immunology and Cell Biology}, number = {1}, pages = {39 -- 51}, publisher = {Nature Publishing Group}, title = {{Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors}}, doi = {10.1038/icb.2015.62}, volume = {94}, year = {2016}, } @article{1218, abstract = {Investigating the physiology of cyanobacteria cultured under a diel light regime is relevant for a better understanding of the resulting growth characteristics and for specific biotechnological applications that are foreseen for these photosynthetic organisms. Here, we present the results of a multiomics study of the model cyanobacterium Synechocystis sp. strain PCC 6803, cultured in a lab-scale photobioreactor in physiological conditions relevant for large-scale culturing. The culture was sparged withN2 andCO2, leading to an anoxic environment during the dark period. Growth followed the availability of light. Metabolite analysis performed with 1Hnuclear magnetic resonance analysis showed that amino acids involved in nitrogen and sulfur assimilation showed elevated levels in the light. Most protein levels, analyzed through mass spectrometry, remained rather stable. However, several high-light-response proteins and stress-response proteins showed distinct changes at the onset of the light period. Microarray-based transcript analysis found common patterns of~56% of the transcriptome following the diel regime. These oscillating transcripts could be grouped coarsely into genes that were upregulated and downregulated in the dark period. The accumulated glycogen was degraded in the anaerobic environment in the dark. A small part was degraded gradually, reflecting basic maintenance requirements of the cells in darkness. Surprisingly, the largest part was degraded rapidly in a short time span at the end of the dark period. This degradation could allow rapid formation of metabolic intermediates at the end of the dark period, preparing the cells for the resumption of growth at the start of the light period.}, author = {Angermayr, Andreas and Van Alphen, Pascal and Hasdemir, Dicle and Kramer, Gertjan and Iqbal, Muzamal and Van Grondelle, Wilmar and Hoefsloot, Huub and Choi, Younghae and Hellingwerf, Klaas}, journal = {Applied and Environmental Microbiology}, number = {14}, pages = {4180 -- 4189}, publisher = {American Society for Microbiology}, title = {{Culturing synechocystis sp. Strain pcc 6803 with N2 and CO2 in a diel regime reveals multiphase glycogen dynamics with low maintenance costs}}, doi = {10.1128/AEM.00256-16}, volume = {82}, year = {2016}, } @article{1219, abstract = {We consider N×N random matrices of the form H = W + V where W is a real symmetric or complex Hermitian Wigner matrix and V is a random or deterministic, real, diagonal matrix whose entries are independent of W. We assume subexponential decay for the matrix entries of W, and we choose V so that the eigenvalues ofW and V are typically of the same order. For a large class of diagonal matrices V , we show that the local statistics in the bulk of the spectrum are universal in the limit of large N.}, author = {Lee, Jioon and Schnelli, Kevin and Stetler, Ben and Yau, Horngtzer}, journal = {Annals of Probability}, number = {3}, pages = {2349 -- 2425}, publisher = {Institute of Mathematical Statistics}, title = {{Bulk universality for deformed wigner matrices}}, doi = {10.1214/15-AOP1023}, volume = {44}, year = {2016}, } @article{122, abstract = {Four rigid panels connected by hinges that meet at a point form a four-vertex, the fundamental building block of origami metamaterials. Most materials designed so far are based on the same four-vertex geometry, and little is known regarding how different geometries affect folding behavior. Here we systematically categorize and analyze the geometries and resulting folding motions of Euclidean four-vertices. Comparing the relative sizes of sector angles, we identify three types of generic vertices and two accompanying subtypes. We determine which folds can fully close and the possible mountain-valley assignments. Next, we consider what occurs when sector angles or sums thereof are set equal, which results in 16 special vertex types. One of these, flat-foldable vertices, has been studied extensively, but we show that a wide variety of qualitatively different folding motions exist for the other 15 special and 3 generic types. Our work establishes a straightforward set of rules for understanding the folding motion of both generic and special four-vertices and serves as a roadmap for designing origami metamaterials.}, author = {Waitukaitis, Scott R and Van Hecke, Martin}, journal = {Physical Review E - Statistical, Nonlinear, and Soft Matter Physics}, number = {2}, publisher = {American Physiological Society}, title = {{Origami building blocks: Generic and special four-vertices}}, doi = {10.1103/PhysRevE.93.023003}, volume = {93}, year = {2016}, } @inproceedings{1220, abstract = {Theoretical and numerical aspects of aerodynamic efficiency of propulsion systems coupled to the boundary layer of a fuselage are studied. We discuss the effects of local flow fields, which are affected both by conservative flow acceleration as well as total pressure losses, on the efficiency of boundary layer immersed propulsion devices. We introduce the concept of a boundary layer retardation turbine that helps reduce skin friction over the fuselage. We numerically investigate efficiency gains offered by boundary layer and wake interacting devices. We discuss the results in terms of a total energy consumption framework and show that efficiency gains of any device depend on all the other elements of the propulsion system.}, author = {Mikić, Gregor and Stoll, Alex and Bevirt, Joe and Grah, Rok and Moore, Mark}, location = {Washington, D.C., USA}, pages = {1 -- 19}, publisher = {AIAA}, title = {{Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency}}, doi = {10.2514/6.2016-3764}, year = {2016}, }