Global entrainment of transcriptional systems to periodic inputs

This paper addresses the problem of giving conditions for transcriptional systems to be globally entrained to external periodic inputs. By using contraction theory, a powerful tool from dynamical systems theory, it is shown that certain systems driven by external periodic signals have the property that all solutions converge to a fixed limit cycle. General results are proved, and the properties are verified in the specific case of some models of transcriptional systems. The basic mathematical results needed from contraction theory are proved in the paper, making it self-contained

Bounded Verification with On-the-Fly Discrepancy Computation

Simulation-based verification algorithms can provide formal safety guarantees for nonlinear and hybrid systems. The previous algorithms rely on user provided model annotations called discrepancy function, which are crucial for computing reachtubes from simulations. In this paper, we eliminate this requirement by presenting an algorithm for computing piece-wise exponential discrepancy functions. The algorithm relies on computing local convergence or divergence rates of trajectories along a simulation using a coarse over-approximation of the reach set and bounding the maximal eigenvalue of the Jacobian over this over-approximation. The resulting discrepancy function preserves the soundness and the relative completeness of the verification algorithm. We also provide a coordinate transformation method to improve the local estimates for the convergence or divergence rates in practical examples. We extend the method to get the input-to-state discrepancy of nonlinear dynamical systems which can be used for compositional analysis. Our experiments show that the approach is effective in terms of running time for several benchmark problems, scales reasonably to larger dimensional systems, and compares favorably with respect to available tools for nonlinear models.Comment: 24 page

Simulation-based reachability analysis for nonlinear systems using componentwise contraction properties

A shortcoming of existing reachability approaches for nonlinear systems is the poor scalability with the number of continuous state variables. To mitigate this problem we present a simulation-based approach where we first sample a number of trajectories of the system and next establish bounds on the convergence or divergence between the samples and neighboring trajectories. We compute these bounds using contraction theory and reduce the conservatism by partitioning the state vector into several components and analyzing contraction properties separately in each direction. Among other benefits this allows us to analyze the effect of constant but uncertain parameters by treating them as state variables and partitioning them into a separate direction. We next present a numerical procedure to search for weighted norms that yield a prescribed contraction rate, which can be incorporated in the reachability algorithm to adjust the weights to minimize the growth of the reachable set

Spectroscopic Properties of a Biologically Relevant [Fe2(μ-O)2] Diamond Core Motif with a Short Iron-Iron Distance

Diiron cofactors in enzymes perform diverse challenging transformations. The structures of high valent intermediates (Q in methane monooxygenase and X in ribonucleotide reductase) are debated since Fe−Fe distances of 2.5–3.4 Å were attributed to “open” or “closed” cores with bridging or terminal oxido groups. We report the crystallographic and spectroscopic characterization of a FeIII2(μ-O)2 complex (2) with tetrahedral (4C) centres and short Fe−Fe distance (2.52 Å), persisting in organic solutions. 2 shows a large Fe K-pre-edge intensity, which is caused by the pronounced asymmetry at the TD FeIII centres due to the short Fe−μ−O bonds. A ≈2.5 Å Fe−Fe distance is unlikely for six-coordinate sites in Q or X, but for a Fe2(μ-O)2 core containing four-coordinate (or by possible extension five-coordinate) iron centres there may be enough flexibility to accommodate a particularly short Fe−Fe separation with intense pre-edge transition. This finding may broaden the scope of models considered for the structure of high-valent diiron intermediates formed upon O2 activation in biology

Lagrangian Reachabililty

We introduce LRT, a new Lagrangian-based ReachTube computation algorithm that conservatively approximates the set of reachable states of a nonlinear dynamical system. LRT makes use of the Cauchy-Green stretching factor (SF), which is derived from an over-approximation of the gradient of the solution flows. The SF measures the discrepancy between two states propagated by the system solution from two initial states lying in a well-defined region, thereby allowing LRT to compute a reachtube with a ball-overestimate in a metric where the computed enclosure is as tight as possible. To evaluate its performance, we implemented a prototype of LRT in C++/Matlab, and ran it on a set of well-established benchmarks. Our results show that LRT compares very favorably with respect to the CAPD and Flow* tools.Comment: Accepted to CAV 201

Evidence of Sulfur Non-Innocence in [CoII(dithiacyclam)]2+-Mediated Catalytic Oxygen Reduction Reactions

In many metalloenzymes, sulfur-containing ligands participate in catalytic processes, mainly via the involvement in electron transfer reactions. In a biomimetic approach, we now demonstrate the implication of S-ligation in cobalt mediated oxygen reduction reactions (ORR). A comparative study between the catalytic ORR capabilities of the four-nitrogen bound [Co(cyclam)]2+ (1; cyclam=1,5,8,11-tetraaza-cyclotetradecane) and the S-containing analog [Co(S2N2-cyclam)]2+ (2; S2N2-cyclam=1,8-dithia-5,11-diaza-cyclotetradecane) reveals improved catalytic performance once the chalcogen is introduced in the Co coordination sphere. Trapping and characterization of the intermediates formed upon dioxygen activation at the CoII centers in 1 and 2 point to the involvement of sulfur in the O2 reduction process as the key for the improved catalytic ORR capabilities of 2

Magnetic Anisotropy and Relaxation of Pseudotetrahedral [N2O2] Bis Chelate Cobalt II Single Ion Magnets Controlled by Dihedral Twist Through Solvomorphism

The methanol solvomorph 1 amp; 8201; amp; 8901; amp; 8201;2MeOH of the cobalt II complex [Co LSal,2 amp; 8722;Ph 2] 1 with the sterically demanding Schiff base ligand 2 [1,1 amp; 8242; biphenyl] 2 ylimino methyl phenol HLSal,2 amp; 8722;Ph shows the thus far largest dihedral twist distortion between the two chelate planes compared to an ideal pseudotetrahedral arrangement. The cobalt II ion in 1 amp; 8201; amp; 8901; amp; 8201;2MeOH exhibits an easy axis anisotropy leading to a spin reversal barrier of 55.3 amp; 8197;cm amp; 8722;1, which corresponds to an increase of about 17 amp; 8201; induced by the larger dihedral twist compared to the solvent free complex 1. The magnetic relaxation for 1 amp; 8201; amp; 8901; amp; 8201;2MeOH is significantly slower compared to 1. An in depth frequency domain Fourier transform FD FT THz EPR study not only allowed the direct measurement of the magnetic transition between the two lowest Kramers doublets for the cobalt II complexes, but also revealed the presence of spin phonon coupling. Interestingly, a similar dihedral twist correlation is also observed for a second pair of cobalt II based solvomorphs, which could be benchmarked by FD FT THz EP

Todellista asiakasarvoa luomassa – myynnistä arvomyyntiin : case Mediamaisteri Oy

Tämän opinnäytetyön tavoite oli case-yritys Mediamaisteri Oy:n B2B-myyntiprosessin kehittäminen. Tarkoitus oli hyödyntää palvelumuotoilua lisäämään asiakasymmärrystä ja tukemaan asiakkaiden kokeman arvon muodostumista sekä positiivisten asiakaskokemusten syntymistä myyntiprosessin alkuvaiheen asiakaskohtaamisissa. Lisäksi tarkoitus oli kiteyttää empiirisen aineiston pohjalta saatu tieto asiakasprofiileiksi, joita voidaan hyödyntää asiakaslähtöisten ratkaisujen suunnittelussa heti asiakkuuden alusta ja ensimmäisestä myyntitapaamisesta lähtien. Opinnäytetyön tutkimuksellisen osuuden toteuttamisen pohjana on kvalitatiivinen tutkimusote ja palvelumuotoilun prosessi. Tutkimuskohde tarkennettiin kuvaamalla Mediamaisteri Oy:n asiakkuuden alkuvaiheen palvelupolku, josta rajattiin tutkimuksen kohteeksi ensimmäinen asiakastapaaminen ja sitä edeltävä aika, jolloin asiakas kiinnostuu yrityksen palveluista ja ensikontakti yritykseen tapahtuu. Tutkimusaineisto muodostuu kuudesta Mediamaisteri Oy:n yritysasiakkaan haastattelusta, jotka toteutettiin virtuaalisesti teemahaastattelun muodossa. Aineiston analysoinnissa hyödynnettiin induktiivista sisällönanalyysiä. Opinnäytetyön teoreettinen viitekehys rakentuu B2B-myynnin, asiakasarvon muodostumisen ja positiivisen asiakaskokemuksen teorioista. Opinnäytetyön empiirisessä osassa kuvataan yksityiskohtaisesti työn toteuttaminen ja toteutuksen vaiheittainen eteneminen. Opinnäytetyön tuloksien mukaan Mediamaisteri Oy:n yritysasiakkaan positiivinen asiakaskokemus palvelujen hankintavaiheessa ja ensimmäisen asiakastapaamisen aikana koostuu myyjäyrityksen koetusta osaamisesta ja ammattitaidosta, palveluasenteesta, asiakaslähtöisyydestä, vuorovaikutustaidoista, yhteistyötaidoista, avoimuuden ja luottamuksen tunteen herättämisestä ja projektinhallinnasta. Opinnäytetyön tutkimusaineiston pohjalta kerätty asiakastieto kiteytettiin Mediamaisteri Oy:n yritysasiakkaan asiakasprofiileiksi, joita voidaan tulevaisuudessa hyödyntää yrityksen asiakaslähtöisen myyntiprosessin kehittämisessä suuntaamaan toimintaa kohti todellista asiakasarvoa asiakkuuden alkuvaiheesta alkaen. Voidaan todeta, että opinnäytetyön tuloksilla on yhteyttä opinnäytetyön viitekehyksessä esitettyyn aikaisempaan teoreettiseen tietoon B2B-myynnistä, asiakasarvon muodostumisesta ja positiivisesta asiakaskokemuksesta. Opinnäytetyön tuloksissa ilmeni, että asiakasymmärryksen tavoittelu jää palvelujen hankintavaiheessa ja ensimmäisessä asiakastapaamisessa usein pinnalliselle tasolle. Jatkotutkimus etenkin vuorovaikutustaitojen merkityksestä B2B-myyntiprosessin alussa ja ensimmäisessä B2B-myyntitapaamisessa arvonluonnin ja arvomyynnin edellyttämän asiakasymmärryksen saavuttamiseksi on suositeltavaa.The aim of this thesis was to develop the B2B sales process of the case company Mediamaisteri Oy. The purpose was to utilize service design to promote the customer insight and to support the formation of the customer value and positive customer experiences in customer touchpoints during the early stages of the sales process. In addition, the purpose was to crystallize the information obtained from the empirical data into customer profiles that can be used to design customer-oriented solutions right from the beginning of a customer relationship and the initial B2B sales meeting. The basis for carrying out the empirical part of the thesis was the qualitative research and the process of service design. The research subject was defined by describing the business client’s customer journey in the beginning of the customer relationship with Mediamaisteri Oy, and by focusing to the initial B2B sales meeting and the time when the client became interested in the company's services and made the first contact. The research material consisted of six interviews of Mediamaisteri Oy's business clients, made as online theme interviews. The material was analyzed by utilizing inductive content analysis. The theoretical framework of the thesis was based on the theories of B2B sales, customer value creation and positive customer experience. In the empirical part of the thesis, the implementation of the work and the steps of the process are described in detail. The findings of the thesis indicate that the positive customer experience of a Mediamaisteri business client during the procurement phase and the initial B2B sales meeting consists of proven expertise and professionalism, service attitude, customer orientation, interaction skills, co-operation skills, openness and trust, and the project management. The research data collected was crystallized into the business client profiles of Mediamaisteri Oy, which can be used in the future to develop the customer-oriented sales process of the company in order to direct the business towards the real customer value starting right from the beginning of the customer relationship. It can be concluded that the results of the thesis are related to the previous theoretical knowledge of B2B sales, customer value creation and a positive customer experience presented in the theoretical framework of the thesis. The results of the thesis showed that the pursuit of customer understanding during the procurement phase and the initial B2B sales meeting often remains superficial. Further research on the significance of interaction skills in the beginning of the sales process and at the initial B2B sales meeting is desirable to achieve value creation and value-based customer insight

A Two Coordinate Iron II Imido Complex with NHC Ligation Synthesis, Characterization, and Its Diversified Reactivity of Nitrene Transfer and C H Bond Activation

Iron terminal imido species are typically implicated as reaction intermediates in iron catalyzed transformations. While a large body of work has been devoted to mid and high valent iron imidos, to date the chemistry of iron II imidos has remained largely unexplored due to the difficulty in accessing them. Herein, we present a study on the two coordinate iron II imido complex [ IPr Fe NArTrip ] 3; IPr 1,3 bis 2 amp; 8242;,6 amp; 8242; diisopropylphenyl imidazol 2 ylidene; ArTrip 2,6 bis 2 amp; 8242;,4 amp; 8242;,6 amp; 8242; triisopropylphenyl phenyl prepared from the reaction of an iron 0 complex with the bulky azide ArTripN3. Spectroscopic investigations in combination with DFT calculations established a high spin S 2 ground spin state for 3, consistent with its long Fe N multiple bond of 1.715 2 revealed by X ray diffraction analysis. Complex 3 exhibits unusual activity of nitrene transfer and C H bond activation in comparison to the reported iron imido complexes. Specifically, the reactions of 3 with CH2 amp; 9552;CHArCF3, an electron deficient alkene, and CO, a strong amp; 960; acid, readily afford nitrene transfer products, ArCF3CH amp; 9552;CHNHArTrip and ArTripNCO, respectively, yet no similar reaction occurs when 3 is treated with electron rich alkenes and PMe3. Moreover, 3 is inert toward the weak C sp3 H bonds in 1,4 cyclohexadiene, THF, and toluene, whereas it can cleave the stronger C sp H bond in p trifluoromethylphenylacetylene to form an iron II amido alkynyl complex. Interestingly, intramolecular C sp3 H bond functionalization was observed by adding p Tol 2CN2 to 3. The unique reactivity of 3 is attributed to its low coordinate nature and the high negative charge population on the imido N atom, which render its iron imido unit nucleophilic in natur

Experimental assignment of long range magnetic communication through Pd amp; Pt metallophilic contacts

Record breaking magnetic exchange interactions have previously been reported for 3d metal dimers of the form [M Pt SAc 4 pyNO2 ]2 M Ni or Co that are linked in the solid state via metallophilic Pt amp; 8943;Pt bridges. This contrasts the terminally capped monomers [M Pt SAc 4 py 2], for which neither metallophilic bridges nor magnetic exchange interactions are found. Computational modeling has shown that the magnetic exchange interaction is facilitated by the pseudo closed shell d8 amp; 8943;d8 metallophilic interaction between the filled Pt2 5dz2 orbitals. We present here inelastic neutron scattering experiments on these complexes, wherein the dimers present an oscillatory momentum transfer dependence of the magnetic transitions. This allows for the unequivocal experimental assignment of the distance between the coupled ions, which matches exactly the coupling pathway via the metallophilic bridges. Furthermore, we have synthesized and magnetically characterized the isostructural palladium analogues. The magnetic coupling across the Pd amp; 8943;Pd bridge is found through SQUID magnetometry and FD FT THz EPR spectroscopy to be much weaker than via the Pt amp; 8943;Pt bridge. The weaker coupling is traced to the larger radial extent of the 5dz2 orbitals compared to that of the 4dz2 orbitals. The existence of a palladium metallophilic interaction is evaluated computationally from potential surface cuts along the metal stretching direction. Similar behavior is found for the Pd amp; 8943;Pd and Pt amp; 8943;Pt systems with clear minima along this coordinate and provide estimates for the force constant for this distortion. The estimated M amp; 8943;M stretching frequencies are found to match experimental observed, polarized bands in single crystal Raman spectra close to 45 cm amp; 8722;1. This substantiates the existence of energetically relevant Pd amp; 8943;Pd metallophilic interactions. The unique properties of both Pt2 and Pd2 constitutes an orthogonal reactivity, which can be utilized for steering both the direction and strength of magnetic interaction