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The Liguro-Provençal basin was formed as a back-arc basin of the retreating Calabrian–Apennines subduction zone during the Oligocene and Miocene. The resulting rotation of the Corsica–Sardinia block is associated with rifting, shaping the Ligurian Basin. It is still debated whether oceanic or atypical oceanic crust was formed or if the crust is continental and experienced extreme thinning during the opening of the basin. We perform ambient noise tomography, also taking into account teleseismic events, using an amphibious network of seismic stations, including 22 broadband ocean bottom seismometers (OBSs), to investigate the lithospheric structure of the Ligurian Basin. The instruments were installed in the Ligurian Basin for 8 months between June 2017 and February 2018 as part of the AlpArray seismic network. Because of additional noise sources in the ocean, OBS data are rarely used for ambient noise studies. However, we carefully pre-process the data, including corrections for instrument tilt and seafloor compliance and excluding higher modes of the ambient-noise Rayleigh waves. We calculate daily cross-correlation functions for the AlpArray OBS array and surrounding land stations. We also correlate short time windows that include teleseismic earthquakes, allowing us to derive surface wave group velocities for longer periods than using ambient noise only. We obtain group velocity maps by inverting Green's functions derived from the cross-correlation of ambient noise and teleseismic events, respectively. We then used the resulting 3D group velocity information to calculate 1D depth inversions for S-wave velocities. The group velocity and shear-wave velocity results compare well to existing large-scale studies that partly include the study area. In onshore France, we observe a high-velocity area beneath the Argentera Massif, roughly 10 km below sea level. We interpret this as the root of the Argentera Massif. Our results add spatial resolution to known seismic velocities in the Ligurian Basin, thereby augmenting existing seismic profiles. In agreement with existing seismic studies, our shear-wave velocity maps indicate a deepening of the Moho from 12 km at the south-western basin centre to 20–25 km at the Ligurian coast in the north-east and over 30 km at the Provençal coast. The maps also indicate that the south-western and north-eastern Ligurian Basin are structurally separate. The lack of high crustal vP/vS ratios beneath the south-western part of the Ligurian Basin preclude mantle serpentinisation there. [ABSTRACT FROM AUTHOR]

The Liguro-Provençal basin was formed as a back-arc basin of the retreating Calabrian-Apennines subduction zone during the Oligocene and Miocene. The resulting rotation of the Corsica-Sardinia block is associated with rifting, shaping the Ligurian Sea. It is still debated whether oceanic or atypical oceanic crust was formed or if the crust is continental and experienced extreme thinning during the opening of the basin. We invert velocity models using an amphibious network of seismic stations, including 22 broadband Ocean Bottom Seismometers (OBS) to investigate the lithospheric structure of the Ligurian sea. The instruments were installed in the Ligurian Sea for eight months between June 2017 and February 2018 as part of the AlpArray seismic network. Because of additional noise sources in the ocean, OBS data are rarely used for ambient noise studies. However, we attentively pre-process the data, including corrections for instrument tilt and seafloor compliance. We took extra care to exclude higher modes of the ambient-noise Rayleigh waves. We calculate daily cross-correlation functions for the LOBSTER array and surrounding land stations. Additionally, we correlate short time windows that include teleseismic earthquakes that allow us to derive surface wave group velocities for longer periods than using ambient noise only. Group velocity maps are obtained by inverting Green's functions derived from the cross-correlation of ambient noise and teleseismic events, respectively. We then used the resulting 3D group velocity information to calculate 1D depth inversions for S-wave velocities. The shear-wave velocity results show a deepening of the Moho from 12 km at the southwestern basin centre to 20-25 km at the Ligurian coast in the northeast and over 30 km at the Provençal coast. We find no hint on mantle serpentinisation and no evidence for an Alpine slab, at least down to depths of 25 km. However, we see a separation of the southwestern and northeastern Ligurian Basin that coincides with the promoted prolongation of the Alpine front. [ABSTRACT FROM AUTHOR]

We consider bisimulation-invariant monadic second-order logic over various classes of finite transition systems. We present several combinatorial characterisations of when the expressive power of this fragment coincides with that of the modal μ -calculus. Using these characterisations we prove for some simple classes of transition systems that this is indeed the case. In particular, we show that, over the class of all finite transition systems with Cantor–Bendixson rank at most k , bisimulation-invariant Image 1 coincides with L μ. [ABSTRACT FROM AUTHOR]

Cystargolides are natural products originally isolated from Kitasatospora cystarginea NRRL B16505 as inhibitors of the proteasome. They are composed of a dipeptide backbone linked to a β-lactone warhead. Recently, we identified the cystargolide biosynthetic gene cluster, but systematic genetic analyses had not been carried out because of the lack of a heterologous expression system. Here, we report the discovery of a homologous cystargolide biosynthetic pathway in Streptomyces durhamensis NRRL-B3309 by genome mining. The gene cluster was cloned via transformation-associated recombination and heterologously expressed in Streptomyces coelicolor M512. We demonstrate that it contains all genes necessary for the production of cystargolide A and B. Single gene deletion experiments reveal that only five of the eight genes from the initially proposed gene cluster are essential for cystargolide synthesis. Additional insights into the cystargolide pathway could be obtained from in vitro assays with CysG and chemical complementation of the respective gene knockout. This could be further supported by the in vitro investigation of the CysG homolog BelI from the belactosin biosynthetic gene cluster. Thereby, we confirm that CysG and BelI catalyze a cryptic SAM-dependent transfer of a methyl group that is critical for the construction of the cystargolide and belactosin β-lactone warheads. [ABSTRACT FROM AUTHOR]

Inthe design of superconducting acceleratormagnets, the shape of the coil cross section is mainly driven by the minimization of the conductor volume, constrained by requirements on the central magnetic field and its homogeneity. Such optimizations commonly assume either a Block or Cosine Theta coil type, which is then filledwith (predetermined) rectangular or key-stonedRutherford cables. By optimizing the positions, angles, and the number of turns, the field quality requirements and cost minimization are achieved. However, this leaves to wonder what the optimal coil geometry looks like, when such practical constraints are not present. Although such a coil cross section has always been presented as the intersection between two ellipses, this method results in a noncircular aperture and is thus not fully representative of a realistic coil. This paper introduces a method in which organically shaped (nongraded) dipole coil layouts are optimized without any assumptions on the conductor. The resulting layouts are presented as a function of overall current density, aperture size, and required magnetic field (inside the aperture). The layouts presented should be viewed as an ultimate limit of what can be achieved, for comparison with real coil layouts, and as an initial guide for finding an optimal cross section for a realistic magnet. [ABSTRACT FROM AUTHOR]

Coils of high-field Nb3Sn magnets are submitted to large loads during assembly at ambient temperature and during operation at cold. This paper addresses the characterization of the stress distribution on reacted and impregnated Nb3Sn Rutherford cables under transverse compression, at ambient temperature, and in a similar configuration as seen duringmagnet assembly. We performed an experimental campaign on impregnated Nb3Sn Rutherford cable stacks. Different test configurations have been compared in order to optimize the stress homogeneity applied on the contact surface. The cable surface reconstruction based on X-ray microtomography has been used to generate the cable geometry as input for finite-element simulations that allow to predict the effect of coil materials parameters on stress concentrations in the conductor. [ABSTRACT FROM AUTHOR]

Belactosins and cystargolides are natural product proteasome inhibitors from Actinobacteria. Both feature dipeptidic backbones and a unique β-lactone building block. Herein, we present a detailed investigation of their biosynthesis. Identification and analysis of the corresponding gene clusters indicated that both compounds are assembled by rare single-enzyme amino acid ligases. Feeding experiments with isotope-labeled precursors and in vitro biochemistry showed that the formation of the β-lactone warhead is unprecedented and reminiscent of leucine biosynthesis, and that it involves the action of isopropylmalate synthase homologues. [ABSTRACT FROM AUTHOR]

Belactosine und Cystargolide sind von Actinobakterien produzierte Naturstoffe mit proteasominhibitorischen Eigenschaften. Beide weisen ein Peptidrückgrat aus zwei Aminosäuren sowie einen einzigartigen β‐Lacton‐Baustein auf. Hier wird eine detaillierte Untersuchung der Biosynthese der beiden Naturstoffe beschrieben. Die Identifizierung und Analyse der entsprechenden Gencluster weist darauf hin, dass beide Stoffe über seltene Aminosäure‐Ligasen gebildet werden. Fütterungsversuche mit isotopenmarkierten Vorstufen und In‐vitro‐Biochemie zeigen einen bislang unbeschriebenen Mechanismus zur β‐Lacton‐Biosynthese, der sich aus der Leucin‐Bildung ableitet und die Beteiligung eines Isopropylmalat‐Synthase‐ähnlichen Enzyms vorsieht. Der Weg zum Lacton: Die Biosynthese der peptidischen β‐Lacton‐haltigen Proteasominhibitoren Belactosin und Cystargolid folgt einem NRPS‐ und PKS‐unabhängigen Syntheseweg. Ihr β‐Lacton‐Rest wird unter Mithilfe eines Isopropylmalat‐Synthase‐ähnlichen Enzyms in Analogie zur Leucin‐Biosynthese gebildet. Die Bildung des Peptidrückgrats erfolgt durch eigenständige Aminosäuren‐Ligasen. [ABSTRACT FROM AUTHOR]

The Pd-catalyzed Heck-type coupling (Matsuda-Heck reaction) of electron rich arene diazonium salts with electron deficient olefins has been exploited for the synthesis of phenylpropanoid natural products. Examples described herein are the naturally occurring benzofurans methyl wutaifuranate, wutaifuranol, wutaifuranal, their 7-methoxy derivatives, and the O-prenylated natural products boropinols A and C. [ABSTRACT FROM AUTHOR]

α-Methylene-γ-butyrolactone and α-methylene-δ-valerolactone undergo Pd-catalyzed Matsuda-Heck couplings with arene diazonium salts to α-benzyl butenolides or pentenolides, respectively, or to α-benzylidene lactones. The observed regioselectivity is strongly ring size dependent, with six-membered rings giving exclusively α-benzyl pentenolides, whereas the five-membered α-methylene lactone reacts to mixtures of regioisomers with a high proportion of (E)-α-benzylidene-γ-butyrolactones. DFT calculations suggest that the reasons for these differences are not thermodynamic but kinetic in nature. The relative energies of the conformers of the Pd σ-complexes resulting from insertion into the Pd-aryl bond were correlated with the dihedral angles between Pd and endo-β-H. This correlation revealed that in the case of the six-membered lactone an energetically favorable conformer adopts a nearly synperiplanar Pd/endo-β-H arrangement, whereas for the analogous Pd σ-complex of the five-membered lactone the smallest Pd/endo-β-H dihedral angle is observed for a conformer with a comparatively high potential energy. The optimized conditions for Matsuda-Heck arylations of exo-methylene lactones were eventually applied to the synthesis of the natural product anemarcoumarin A. [ABSTRACT FROM AUTHOR]

Arene diazonium salts undergo Matsuda-Heck reactions with vinylsulfonates and -sulfonamides to give styrylsulfonic acid derivatives in high to excellent yields and with high to excellent selectivities. By quantifying the evolution of nitrogen over time in a gas-meter apparatus, the reactivities of ethylvinylsulfonate and the benchmark olefin methyl acrylate were compared for an electron-rich and an -deficient arene diazonium salt. Tertiary sulfonamides react in Matsuda-Heck couplings with high conversions, but require long reaction times, which prevents the determination of kinetic data through the measurement of nitrogen evolution. Secondary sulfonamides were found to be unreactive. From these results, the following order of reactivity could be deduced: H2C=CHCO2Me > H2C=CHSO2OEt > H2C=CHSO2N(Me)Bn >> H2C=CHSO2NHBn. Through the Matsuda-Heck coupling of 5-indolyldiazonium salt and a tertiary vinylsulfonamide, the synthesis of the C-5-substituted indole part of the antimigraine drug naratriptan was accomplished in high yield. [ABSTRACT FROM AUTHOR]

A notorious class of concurrency bugs are race condition related to correlated variables, which make up about 30 % of all non-deadlock concurrency bugs. A solution to prevent this problem is the automatic generation of parallel unit tests. This paper presents an approach to generate parallel unit tests for variable correlations in multithreaded code. We introduce a hybrid approach for identifying correlated variables. Furthermore, we estimate the number of potentially violated correlations for methods executed in parallel. In this way, we are capable of creating unit tests that are suited for race detectors considering correlated variables. We were able to identify more than 85 % of all race conditions on correlated variables in eight applications after applying our parallel unit tests. At the same time, we reduced the number of unnecessary generated unit tests. In comparison to a test generator unaware of variable correlations, redundant unit tests are reduced by up to 50 %, while maintaining the same precision and accuracy in terms of the number of detected races. [ABSTRACT FROM AUTHOR]

Exposure simulations are fundamental to many xVA calculations and are a nested expectation problem where repeated portfolio valuations create a significant computational expense. Sensitivity calculations which require shocked and unshocked valuations in bump-and-revalue schemes exacerbate the computational load. A known reduction of the portfolio valuation cost is understood to be found in polynomial approximations, which we apply in this article to interest rate sensitivities of expected exposures. We consider a method based on the approximation of the shocked and unshocked valuation functions, as well as a novel approach in which the difference between these functions is approximated. Convergence results are shown, and we study the choice of interpolation nodes. Numerical experiments with interest rate derivatives are conducted to demonstrate the high accuracy and remarkable computational cost reduction. We further illustrate how the method can be extended to more general xVA models using the example of CVA with wrong-way risk. [ABSTRACT FROM AUTHOR]

This paper proposes a numerical discrete formulation for an inverted hysteresis model, which is based on the classic Preisach model, but applies an inverted switch operator. The inverted switch operator is modified from the switch operator of the classic Preisach model. By applying this inverted switch operator, the inverted model retains the wiping-out and congruency properties. The distribution of the weight function can be approximated with an analytical function. By means of a quasi-Newton method algorithm, the small number of parameters in this function can be directly determined from major loops. Iterative procedure is circumvented in the implementation of this model in finite-element analysis. The simulated hysteresis loops, such as minor loops and reversal curves, show good agreement to the measurement data. To realize efficient numerical calculation, the integral expression of the inverted model is rewritten in a discrete form. The double integration of the weight function is numerically approximated in the precalculation stage. In this way, it costs low memory usage and short calculation time during the calculation procedure. [ABSTRACT FROM AUTHOR]

Structural plasticity of the brain describes the creation of new and the deletion of old synapses over time. Rinke et al. (JPDC 2018) introduced a scalable algorithm that simulates structural plasticity for up to one billion neurons on current hardware using a variant of the Barnes–Hut algorithm. They demonstrate good scalability and prove a runtime complexity of O (n log 2 ⁡ n). In this comment paper, we show that with careful consideration of the algorithm and a rigorous proof, the theoretical runtime can even be classified as O (n log ⁡ n). • Improved serial runtime bound for the adapted Barnes–Hut algorithm to Θ(n*log(n)). • Improved the parallel runtime bound to Θ(n/p*log(n)+p). • Mathematical justification that the given runtime bound is sharp. [ABSTRACT FROM AUTHOR]

Abstract: For various piezoceramic actuator applications, the active materials are exposed to mechanical bias stresses. Such mechanical loading strongly modifies the hysteretic transfer characteristic of the actuators. An appropriate approach to model the hysteretic characteristic is based on the Preisach operator. However, the classical Preisach model is incapable of reflecting the influence of mechanical loading. The scope of the present study is, thus, the development of a generalized Preisach model incorporating the impact of compressive stress. To accomplish this goal, the effects of stress and mechanical creep on the polarization hysteresis are characterized by means of measurements. For our model, we take advantage of an analytic Preisach distribution function, introduced in our recent work. This function is extended to a formulation incorporating uniaxial compressive bias stress. As the results clearly demonstrate, the utilized distribution function is very promising to be further extended with respect to mechanical creep behavior. [Copyright &y& Elsevier]

Piezoceramic materials are widely utilized in actuator and sensor devices. In order to model the behavior of these devices and to reduce their development time, numerical simulation tools are frequently applied. However, the simulation results strongly rely on the material behavior assumed for piezoceramics. Here, we present approaches for reliable modeling of this material behavior which have been developed at the Chair of Sensor Technology (Friedrich-Alexander-University Erlangen-Nuremberg) in recent years. Both the small signal behavior and the large signal behavior of piezoceramic materials are discussed. For the identification of material parameters required within the small signal model, we apply a mathematical Inverse Method. The large signal behavior of piezoceramics is described by means of a phenomenological approach that is based on the so-called Preisach hysteresis operator. As the presented results for different piezoceramics clearly show, the utilized modeling approaches lead to reliable simulation results and can, therefore, be applied to predict the behavior of piezoceramic materials. [ABSTRACT FROM AUTHOR]

Abstract: We present a new model for the simulation of the hysteretic large-signal behavior in ferroelectric materials. The model is based on the Preisach operator and takes advantage of an analytic weight function for the underlying fundamental switching operators. The five independent parameters describing this weight function have been determined for a discoidal piezoceramic actuator by adapting the model output to measurements of the polarization. Since the classical Preisach model is only valid for creep- and rate-independent hysteresis loops, it is inappropriate to describe the entire ferroelectric material behavior. Therefore, we extended our model by an additional drift operator to consider creep phenomena. Furthermore, the rate-dependence of the hysteresis loops is described by a frequency-dependent parameter of the analytic weight function. For the identification and verification of the model, measurements have been performed using two different measurement principles: A modified Sawyer–Tower circuit as well as a method based on the integration of the electrical current. The agreement between measurements and simulations highlights the benefits of the enhanced hysteresis model. [Copyright &y& Elsevier]

Abstract: When scaling message-passing applications to thousands of processors, their performance is often affected by wait states that occur when processes fail to reach synchronization points simultaneously. As a first step in reducing the performance impact, we have shown in our earlier work that wait states can be diagnosed by searching event traces for characteristic patterns. However, our initial sequential search method did not scale beyond several hundred processes. Here, we present a scalable approach, based on a parallel replay of the target application’s communication behavior, that can efficiently identify wait states at the previously inaccessible scale of 65,536 processes and that has potential for even larger configurations. We explain how our new approach has been integrated into a comprehensive parallel tool architecture, which we use to demonstrate that wait states may consume a major fraction of the execution time at larger scales. [Copyright &y& Elsevier]

The EXPERT performance-analysis environment provides a complete tracing-based solution for automatic performance analysis of MPI, OpenMP, or hybrid applications running on parallel computers with SMP nodes. EXPERT describes performance problems using a high level of abstraction in terms of execution patterns that result from an inefficient use of the underlying programming model(s). The set of predefined problems can be extended to meet application-specific needs. The analysis is carried out along three interconnected dimensions: class of performance behavior, call tree, and thread of execution. Each dimension is arranged in a hierarchy so that the user can investigate the behavior on varying levels of detail. All three dimensions are interactively accessible using a single integrated view. [Copyright &y& Elsevier]

The caseinolytic protease is a highly conserved serine protease, crucial to prokaryotic and eukaryotic protein homeostasis, and a promising antibacterial and anticancer drug target. Herein, we describe the potent cystargolides as the first natural β‐lactone inhibitors of the proteolytic core ClpP. Based on the discovery of two clpP genes next to the cystargolide biosynthetic gene cluster in Kitasatospora cystarginea, we explored ClpP as a potential cystargolide target. We show the inhibition of Staphylococcus aureus ClpP by cystargolide A and B by different biochemical methods in vitro. Synthesis of semisynthetic derivatives and probes with improved cell penetration allowed us to confirm ClpP as a specific target in S. aureus cells and to demonstrate the anti‐virulence activity of this natural product class. Crystal structures show cystargolide A covalently bound to all 14 active sites of ClpP from S. aureus, Aquifex aeolicus, and Photorhabdus laumondii, and reveal the molecular mechanism of ClpP inhibition by β‐lactones, the predominant class of ClpP inhibitors. [ABSTRACT FROM AUTHOR]

The caseinolytic protease is a highly conserved serine protease, crucial to prokaryotic and eukaryotic protein homeostasis, and a promising antibacterial and anticancer drug target. Herein, we describe the potent cystargolides as the first natural β‐lactone inhibitors of the proteolytic core ClpP. Based on the discovery of two clpP genes next to the cystargolide biosynthetic gene cluster in Kitasatospora cystarginea, we explored ClpP as a potential cystargolide target. We show the inhibition of Staphylococcus aureus ClpP by cystargolide A and B by different biochemical methods in vitro. Synthesis of semisynthetic derivatives and probes with improved cell penetration allowed us to confirm ClpP as a specific target in S. aureus cells and to demonstrate the anti‐virulence activity of this natural product class. Crystal structures show cystargolide A covalently bound to all 14 active sites of ClpP from S. aureus, Aquifex aeolicus, and Photorhabdus laumondii, and reveal the molecular mechanism of ClpP inhibition by β‐lactones, the predominant class of ClpP inhibitors. [ABSTRACT FROM AUTHOR]

The main objective of this study is to analyze the effect of treated wastewater from the Salguero station (Valledupar, Colombia) on the yield and microbiological quality of hydroponic paprika (Capsicum annun L.). The design is completely randomized with two treatments: 1) ARCSN: Cesar River water with nutrient solution; 2) ARTSN: residual treated water with nutritive solution. Total coliforms and thermotolerant coliforms are assessed on paprika fruits. The results show that the germination percentages for ARCSN and ARTSN are 78% and 82% respectively. The physicochemical and microbiological properties of the Cesar River wastewater and water comply with Colombian regulations. The levels of coliforms (<2 NMP/g) reported on paprika fruits are within the limits (<1000 NMP/g) allowed by the European Union. It is concluded that using urban wastewater for irrigating paprika is not a public health risk. [ABSTRACT FROM AUTHOR]

The Ligurian Basin is situated at the transition from the western Alpine orogeny to the Apennine system, an area where a change in subduction polarity ('Ligurian Knot') is observed. The Back-arc basin was generated by the southeast trench retreat of the Apennines-Calabrian subduction zone. The opening took place from late Oligocene to Miocene. While the extension led to continental thinning and subsidence, oceanic spreading with unroofing of mantle material was proposed for the late period of opening 21-16 Ma.To shed light on the present day crustal and lithospheric architecture of the Ligurian Basin, active and passive seismic data have been recorded on ocean bottom seismometers. A seismic long-term network comprising of 29 broad band stations was installed from June 2017 to February 2018 in the framework of SPP2017 4D-MB, the German component of AlpArray. Refraction seismic profiles were shot to serve two aspects: (1) Determine the orientation of the horizontal components of the long-term ocean bottom seismometers and (2) estimate the velocity distribution of the upper lithosphere, to provide a better earth velocity model for the analysis of the passive seismic data. The ambient noise technique is applied to compute surface wave phase velocity maps of Rayleigh waves for the Ligurian Basin.Good quality data have been recorded, regional and teleseismic events could be detected by stations of the network. Active shots have been recorded by all stations on the seafloor during shooting. The majority of the refraction seismic data show mantle phases at offsets up to 70 km. The crust mantle boundary in the central basin is observed at ~9 km depth below seafloor. The mantle shows rather high velocities > 7.8 km/s. [ABSTRACT FROM AUTHOR]

The article presents the synthesis of styrylsulfonates and -sulfonamides via Palladium-catalyzed Matsuda-Heck reactions resulting in vinylsulfonic acid derivatives and arenediazonium salts.

We present first numerical examples of how the framework of isogeometric boundary element methods, in the context of electromagnetism also known as method of moments, can be used to achieve higher accuracies by elevation of the degree of basis functions. Our numerical examples demonstrate the computation of the electric field in the exterior domain. [ABSTRACT FROM AUTHOR]

Manors are an important component of the cultural-economic history of Northern Germany and Southern Scandinavia. We present the results of a geophysical prospection that led to the identification of a previously unknown manor near the village of Noer, Schleswig-Holstein, Northern Germany. Although magnetic gradiometry provides a fast way to cover large areas, it does not provide accurate depth estimates, is affected by magnetic blanking and is unable to detect differences in water content. Therefore, we applied a combination of different geophysical methods to optimize the non-invasive reconstruction of the target and its surroundings not only with respect to building structures but also in relation to the surrounding landscape. In particular, a combination of magnetics, ground-penetrating radar (GPR), electromagnetic induction (EMI), electrical resistivity tomography (ERT), and soil samples were carried out to determine: (1) the object's exact location; (2) the building structure and state of preservation; and (3) any additional structures in the surrounding area. We detected a tripartite building of 22 by 27 m, with several inner walls, which was located underneath a topographic high on the surveyed field. The bulk structure is identifiable most clearly in the magnetic and EMI inphase component maps. GPR profiles and soil samples indicate flooring or foundations in part of the building. Their shallow depths of less than 2 m below the surface and debris clusters close to the surface indicate at least partial demolition. A surrounding wall was found about 5 m outside the building. The area in between shows no magnetic anomalies, lower resistivities in EMI and ERT, and low GPR reflection amplitudes. Soil samples suggest a moat or other water feature. Archaeological artifacts found at the location characterize the building as a 16th to 17th century brick manor. Other objects, like a suspected farmyard and access path could not be found. A comparison with historical sources suggest that the mansion is in relation to the manor Grönwohld. After a change of the owner it was degraded to a Meierhof, and subsequently the building decayed and was forgotten. [ABSTRACT FROM AUTHOR]

Data-dependence profiling is a program-analysis technique for detecting parallelism opportunities in sequential programs. It captures data dependences that actually occur during program execution, filtering parallelism-preventing dependences that purely static methods assume only because they lack critical runtime information, such as the values of pointers and array indices. Profiling, however, suffers from high runtime overhead. In our earlier work, we accelerated data-dependence profiling by excluding polyhedral loops that can be handled statically using certain compilers and eliminating scalar variables that create statically-identifiable data dependences. In this paper, we combine the two methods and integrate them into DiscoPoP, a data-dependence profiler and parallelism discovery tool. Additionally, we detect reduction patterns statically and unify the three static analyses with the DiscoPoP framework to significantly diminish the profiling overhead and for a wider range of programs. We have evaluated our unified approaches with 49 benchmarks from three benchmark suites and two computer simulation applications. The evaluation results show that our approach reports fewer false positive and negative data dependences than the original data-dependence profiler and reduces the profiling time by at least 43%, with a median reduction of 76% across all programs. Also, we identify 40% of reduction cases statically and eliminate the associated profiling overhead for these cases. • Presenting a unified framework for hybrid data-dependence analysis. • Implementing the approach as an extension to DiscoPoP's data-dependence profiler. • Introducing a method for detecting parallel reduction patterns statically. • Evaluating the approach with two larger-scale applications and 49 benchmarks. [ABSTRACT FROM AUTHOR]

Abstract: Partitioned global address space (PGAS) languages combine the convenient abstraction of shared memory with the notion of affinity, extending multi-threaded programming to large-scale systems with physically distributed memory. However, in spite of their obvious advantages, PGAS languages still lack appropriate tool support for performance analysis, one of the reasons why their adoption is still in its infancy. Some of the performance problems for which tool support is needed occur at the level of the underlying one-sided communication substrate, such as the Aggregate Remote Memory Copy Interface (ARMCI). One such example is the waiting time in situations where asynchronous data transfers cannot be completed without software intervention at the target side. This is not uncommon on systems with reduced operating-system kernels such as IBM Blue Gene/P where the use of progress threads would double the number of cores necessary to run an application. In this paper, we present an extension of the Scalasca trace-analysis infrastructure aimed at the identification and quantification of progress-related waiting times at larger scales. We demonstrate its utility and scalability using a benchmark running with up to 32,768 processes. [Copyright &y& Elsevier]

Abstract: Event traces are helpful in understanding the performance behavior of message-passing applications since they allow the in-depth analysis of communication and synchronization patterns. However, the absence of synchronized clocks may render the analysis ineffective because inaccurate relative event timings may misrepresent the logical event order and lead to errors when quantifying the impact of certain behaviors. Although linear offset interpolation can restore consistency to some degree, time-dependent drifts and other inaccuracies may still disarrange the original succession of events – especially during longer runs. The controlled logical clock algorithm accounts for such violations in point-to-point communication by shifting message events in time as much as needed while trying to preserve the length of local intervals. In this article, we describe how the controlled logical clock is extended to collective communication to enable the correction of realistic message-passing traces. We present a parallel version of the algorithm scaling to more than thousand processes and evaluate its accuracy by showing that it eliminates inconsistent inter-process timings while preserving the length of local intervals. [Copyright &y& Elsevier]

Developers of applications with large-scale computing requirements are currently presented with a variety of high-performance systems optimised for message-passing, however, effectively exploiting the available computing resources remains a major challenge. In addition to fundamental application scalability characteristics, application and system peculiarities often only manifest at extreme scales, requiring highly scalable performance measurement and analysis tools that are convenient to incorporate in application development and tuning activities. We present our experiences with a multigrid solver benchmark and state-of-the-art real-world applications for numerical weather prediction and computational fluid dynamics, on three quite different multi-thousand-processor supercomputer systems – Cray XT3/4, MareNostrum & Blue Gene/L – using the newly-developed SCALASCA toolset to quantify and isolate a range of significant performance issues. [ABSTRACT FROM AUTHOR]

We solve Maxwell's eigenvalue problem via isogeometric boundary elements and a contour integral method. We discuss the analytic properties of the discretization, outline the implementation, and showcase numerical examples. [ABSTRACT FROM AUTHOR]

We discuss numerical experiments to compare an isogeometric discretization of the electric field integral equation and a parametric Raviart–Thomas approach. Therein, we focus on accuracy with respect to degrees of freedom, briefly commenting on the conditioning of the system as well. Due to the utilization of parametric mappings even in the Raviart–Thomas approach, our investigation disregards any errors induced by meshing, which commonly favors the isogeometric approach when compared to curvilinear higher order Raviart–Thomas elements. [ABSTRACT FROM AUTHOR]

We analyze a new approach to three-dimensional electromagnetic scattering problems via fast isogeometric boundary element methods. Starting with an investigation of the theoretical setting around the electric field integral equation within the isogeometric framework, we show existence, uniqueness, and quasi optimality of the isogeometric approach. For a fast and efficient computation, we then introduce and analyze an interpolation-based fast multipole method tailored to the isogeometric setting, which admits competitive algorithmic and complexity properties. This is followed by a series of numerical examples of industrial scope, together with a detailed presentation and interpretation of the results. [ABSTRACT FROM AUTHOR]

Many libraries in the HPC field use sophisticated algorithms with clear theoretical scalability expectations. However, hardware constraints or programming bugs may sometimes render these expectations inaccurate or even plainly wrong. While algorithm and performance engineers have already been advocating the systematic combination of analytical performance models with practical measurements for a very long time, we go one step further and show how this comparison can become part of automated testing procedures. The most important applications of our method include initial validation, regression testing, and benchmarking to compare implementation and platform alternatives. Advancing the concept of performance assertions, we verify asymptotic scaling trends rather than precise analytical expressions, relieving the developer from the burden of having to specify and maintain very fine-grained and potentially non-portable expectations. In this way, scalability validation can be continuously applied throughout the whole development cycle with very little effort. Using MPI and parallel sorting algorithms as examples, we show how our method can help uncover non-obvious limitations of both libraries and underlying platforms. [ABSTRACT FROM AUTHOR]

We introduce the concept of isogeometric boundary element methods, by first reviewing the required trace spaces and then constructing a conforming spline discretisation. We highlight how to use this approach to solve Dirichlet problems induced by the Helmholtz‐ and electric wave equation, and conclude by presenting numerical examples. [ABSTRACT FROM AUTHOR]

The neural network in the brain is not hard-wired. Even in the mature brain, new connections between neurons are formed and existing ones are deleted, which is called structural plasticity. The dynamics of the connectome is key to understanding how learning, memory, and healing after lesions such as stroke work. However, with current experimental techniques even the creation of an exact static connectivity map, which is required for various brain simulations, is very difficult. One alternative is to use network models to simulate the evolution of synapses between neurons based on their specified activity targets. This is particularly useful as experimental measurements of the spiking frequency of neurons are more easily accessible and reliable than biological connectivity data. The Model of Structural Plasticity (MSP) by Butz and van Ooyen is an example of this approach. However, to predict which neurons connect to each other, the current MSP model computes probabilities for all pairs of neurons, resulting in a complexity O ( n 2 ) . To enable large-scale simulations with millions of neurons and beyond, this quadratic term is prohibitive. Inspired by hierarchical methods for solving n -body problems in particle physics, we propose a scalable approximation algorithm for MSP that reduces the complexity to O ( n log 2 n ) without any notable impact on the quality of the results. We show that an MPI-based parallel implementation of our scalable algorithm can simulate the structural plasticity of up to 1 0 9 neurons—four orders of magnitude more than the naïve O ( n 2 ) version. [ABSTRACT FROM AUTHOR]

During Rutherford cable production, the wires are plastically deformed and their initially round shape is distorted. Using X-ray absorption tomography, we have determined the threedimensional shape of an unreacted Nb3Sn 11-T dipole Rutherford cable and of a reacted and impregnated Nb3 Sn cable double stack. State-of-the-art image processing was applied to correct for tomographic artifacts caused by the large cable aspect ratio, for the segmentation of the individual wires and subelement bundles inside the wires, and for the calculation of the wire cross-sectional area and shape variations. The 11-T dipole cable cross section oscillates by 2%with a frequency of 1.24 mm (1/80 of the transposition pitch length of the 40 wire cable). A comparatively stronger crosssectional area variation is observed in the individual wires at the thin edge of the keystoned cable where the wire aspect ratio is largest. [ABSTRACT FROM AUTHOR]

Future high temperature superconductor (HTS) high field magnets using multitape HTS cables need 10-kA lowresistance connections. The connections are needed between the poles of the magnets and at the terminals in a wide-operating temperature range, from 1.9-85 K. The EuCARD-WP10 Future Magnets collaboration aims at testing HTS-based Roebel cables in an accelerator magnet. Usually, low temperature superconductor (LTS) cables are jointed inside a relatively short soldered block. Powering tests at CERN have highlighted excess heating of a joint following classical LTS joint design. The HTS Roebel cables are assembled from REBCO-coated conductor tapes in a transposed configuration. Due to this, the tapes surface the cable at an angle with the cable axis. A low-resistance joint requires a sufficiently large interface area for each tape. Within one twist pitch length, each tape is located at the surface of the cable over a relatively small non-constant area. This geometry prevents making a wellcontrolled joint in a compact length along the cable. This paper presents a compact joint configuration for the Roebel cable overcoming these practical challenges. A new joint called fin-block is designed. The joint resistance is estimated computationally. Finally, the test results as a function of current and temperature are presented. [ABSTRACT FROM AUTHOR]

We present an indirect higher order boundary element method utilising NURBS mappings for exact geometry representation and an interpolation-based fast multipole method for compression and reduction of computational complexity, to counteract the problems arising due to the dense matrices produced by boundary element methods. By solving Laplace and Helmholtz problems via a single layer approach we show, through a series of numerical examples suitable for easy comparison with other numerical schemes, that one can indeed achieve extremely high rates of convergence of the pointwise potential through the utilisation of higher order B-spline-based ansatz functions. [ABSTRACT FROM AUTHOR]

Background & objectives: The implementation of ICT-supported, integrated health and social care services is effort-intensive. There is a number of reasons for that, all of which are well understood on a conceptual level (see Goodwin and Alonso (2014) and Leutz (1999)). Hard data underpinning these challenges and pointing to possible solutions are rare, impacting negatively on attempts to scale up ICT-supported services in the field (Billings et al., 2013). One key topic in this regard addressed in literature concerns the necessity to duly consider efforts required for the development of both the IT- and the human infrastructure of a service (see Kubitschke et al. (2014), Kubitschke et al. (2010)). But practical experiences suggest that this necessity is not yet fully shared among those involved in the development and implementation of integrated services, who seem to underestimate the role of staff efforts compared to costs for hard- and software. Based on the results of several cost-benefit analyses, this presentation intends to show that staff costs actually make up a majority of of the implementation cost in integrated care and therefore deserve to receive more attention. Approach & methods: From 2008 to 2014, two EU-funded projects (CommonWell (2012), INDEPENDENT (2013)) developed and piloted ten integrated services in nine European regions. Service models ranged from call forwarding and data exchange between call centres to earlysupported discharge of COPD patients and support services for patients with Alzheimer and their informal carers. Socio-economic impact assessments based on cost-benefit analysis and following an approach described in Hammerschmidt and Meyer (2014) were carried out for all ten services. A re-analysis of these assessments was carried out to determine the share of staff cost compared to hard- and software cost for all services. Results: A comparative analysis of the findings across all services determined that, on average, the total cost of service implementation and operation are made up of 25.3% costs related to hard- and software and 74.7% related to staff efforts, i.e. working time invested in the setting up and operation of a service. Discussion & conclusion: Experiences from the application of the cost-benefit analysis approach at the pilot sites suggest that one reason for this underestimation of staff efforts is to be seen in commonly used approaches for economic assessments as well as accounting systems that do not capture actual staff cost, ideally on a per-case basis. Another reason seems to lie in the consideration of personnel as a readily available asset. This point of view is especially pronounced among (public) providers working on the basis of annual budgets, even if it can also be met in pay-per-service systems. The problem arises whenever additional staff time is considered only in those cases where the total number of staff needs to be increased but not where new tasks are added to the workload of staff already in place. Compared to this, costs for hard- and software usually need to be budgeted specifically for the implementation of the new service. Potentially, this requires effort-intensive negotiations and achieving buy-in from higher tiers in the hierarchy, for which reasons people seem to be much more aware of those costs. As long as the full role of staff efforts in the overall cost structure of a service stays under the radar of those responsible for its implementation, there are serious risks to the sustained operation of the service. Prolonged and unnoticed overburdening of staff can counter any positive effects on service efficiency as well as lead to decreased outcome quality and dissatisfaction among patients or clients. The situation can be aggravated by reductions in personnel budgets made on the basis of assumed (but not realized) efficiency improvements. The present findings suggest that awareness raising for the role of staff efforts among those involved in the implementation of integrated e-care services (service providers, payers, policy makers) should receive increased attention. Furthermore, the more widespread use of analytical methods for economic assessments measuring actual staff efforts per case would allow an early detection of the associated risks, ideally already at the service design stage. [ABSTRACT FROM AUTHOR]

Performance models are powerful instruments for understanding the performance of parallel systems and uncovering their bottlenecks. Already during system design, performance models can help ponder alternative development options. However, creating a performance model – whether theoretically or empirically – for an entire application that does not exist yet is challenging. In this paper, we propose to generate performance models of full programs from performance models of their components using formal composition operators derived from parallel design patterns. As long as the design of the overall system follows such a pattern, its performance model can be predicted with reasonable accuracy without an actual implementation. We demonstrate our approach with design patterns of varying complexity, including pipeline, task pool, and eventually MapReduce, which is representative of a broad class of data-analytics applications. • Parallel design patterns are used to generate composable performance models. • Thorough benchmarking of parallel design patterns on multiple compute nodes. • Real-application use case of MapReduce with Hadoop. • Uniform theoretical treatment of parallel design patterns and their performance. [ABSTRACT FROM AUTHOR]

Event traces are helpful in understanding the performance behavior of parallel applications since they allow the in-depth analysis of communication and synchronization patterns. However, the absence of synchronized clocks on most cluster systems may render the analysis ineffective because inaccurate relative event timings may misrepresent the logical event order and lead to errors when quantifying the impact of certain behaviors or confuse the users of time-line visualization tools by showing messages flowing backward in time. In our earlier work, we have developed a scalable algorithm called the controlled logical clock that eliminates inconsistent inter-process timings postmortem in traces of pure MPI applications, potentially running on large processor configurations. In this paper, we first demonstrate that our algorithm also proves beneficial in computational grids, where a single application is executed using the combined computational power of several geographically dispersed clusters. Second, we present an extended version of the algorithm that-in addition to message-passing event semantics-also preserves and restores shared-memory event semantics, enabling the correction of traces from hybrid applications. [ABSTRACT FROM AUTHOR]

Wait states in parallel applications can be identified by scanning event traces for characteristic patterns. In our earlier work we defined such inefficiency patterns for MPI-2 one-sided communication, although still based on a serial trace-analysis scheme with limited scalability. In this article we show how wait states in one-sided communications can be detected in a more scalable fashion by taking advantage of a new scalable trace-analysis approach based on a parallel replay, which was originally developed for MPI-1 point-to-point and collective communication. Moreover, we demonstrate the scalability of our method and its usefulness for the optimization cycle with applications running on up to 32,768 cores. [ABSTRACT FROM AUTHOR]

Cray XT and IBM Blue Gene systems present current alternative approaches to constructing leadership computer systems relying on applications being able to exploit very large configurations of processor cores, and associated analysis tools must also scale commensurately to isolate and quantify performance issues that manifest at the largest scales. In studying the scalability of the Scalasca performance analysis toolset to several hundred thousand MPI processes on XT5 and BG/P systems, we investigated a progressive execution performance deterioration of the well-known ASCI Sweep3D compact application. Scalasca runtime summarization analysis quantified MPI communication time that correlated with computational imbalance, and automated trace analysis confirmed growing amounts of MPI waiting times. Further instrumentation, measurement and analyses pinpointed a conditional section of highly imbalanced computation which amplified waiting times inherent in the associated wavefront communication that seriously degraded overall execution efficiency at very large scales. By employing effective data collation, management and graphical presentation, in a portable and straightforward to use toolset, Scalasca was thereby able to demonstrate performance measurements and analyses with 294,912 processes. [ABSTRACT FROM AUTHOR]

The article presents a study which discusses the use of performance profiling in the measurement overhead of parallel message passing program execution. It offers four important outcomes including message passing interface (MPI) profiling support, schemes to local delays, tuning and analysis utilities (TAU) overhead compensation prototype and the transmission of delay information with messages. It was observed that the most parallel performance measurement tools ignore the overhead incurred by their use. It is concluded that the performance uncertainty principle implies accuracy of performance data and is inversely correlated with the degree of performance instrumentation.

The serine/threonine protein kinase AKT1 is a downstream target of the chemokine receptor 4 (CXCR4), and both proteins play a central role in the modulation of diverse cellular processes, including proliferation and cell survival. While in chronic myeloid leukemia (CML) the CXCR4 is downregulated, thereby promoting the mobilization of progenitor cells into blood, the receptor is highly expressed in breast cancer cells, favoring the migratory capacity of these cells. Recently, the LIM and SH3 domain protein 1 (LASP1) has been described as a novel CXCR4 binding partner and as a promoter of the PI3K/AKT pathway. In this study, we uncovered a direct binding of LASP1, phosphorylated at S146, to both CXCR4 and AKT1, as shown by immunoprecipitation assays, pull-down experiments, and immunohistochemistry data. In contrast, phosphorylation of LASP1 at Y171 abrogated these interactions, suggesting that both LASP1 phospho-forms interact. Finally, findings demonstrating different phosphorylation patterns of LASP1 in breast cancer and chronic myeloid leukemia may have implications for CXCR4 function and tyrosine kinase inhibitor treatment. [ABSTRACT FROM AUTHOR]