Monte Carlo event generator validation and tuning for the LHC

We summarise the motivation for, and the status of, the tools developed by CEDAR/MCnet for validating and tuning Monte Carlo event generators for the LHC against data from previous colliders. We then present selected preliminary results from studies of event shapes and hadronisation observables from e+e- colliders, and of minimum bias and underlying event observables from the Tevatron, and comment on the approach needed with early LHC data to best exploit the potential for new physics discoveries at the LHC in the next few years.Comment: Prepared for Proceedings of XII Advanced Computing and Analysis Techniques in Physics Research, November 3-7 2008, Erice, Ital

New developments in event generator tuning techniques

Data analyses in hadron collider physics depend on background simulations performed by Monte Carlo (MC) event generators. However, calculational limitations and non-perturbative effects require approximate models with adjustable parameters. In fact, we need to simultaneously tune many phenomenological parameters in a high-dimensional parameter-space in order to make the MC generator predictions fit the data. It is desirable to achieve this goal without spending too much time or computing resources iterating parameter settings and comparing the same set of plots over and over again. We present extensions and improvements to the MC tuning system, Professor, which addresses the aforementioned problems by constructing a fast analytic model of a MC generator which can then be easily fitted to data. Using this procedure it is for the first time possible to get a robust estimate of the uncertainty of generator tunings. Furthermore, we can use these uncertainty estimates to study the effect of new (pseudo-) data on the quality of tunings and therefore decide if a measurement is worthwhile in the prospect of generator tuning. The potential of the Professor method outside the MC tuning area is presented as well.Comment: To appear in the proceedings of the 13th International Workshop on Advanced Computing and Analysis Techniques in Physics Research, ACAT2010, Jaipur, India, February 22-27, 201

Crystal Structure Analysis of the Polysialic Acid Specific O-Acetyltransferase NeuO

The major virulence factor of the neuroinvasive pathogen Escherichia coli K1 is the K1 capsule composed of α2,8-linked polysialic acid (polySia). K1 strains harboring the CUS-3 prophage modify their capsular polysaccharide by phase-variable O-acetlyation, a step that is associated with increased virulence. Here we present the crystal structure of the prophage-encoded polysialate O-acetyltransferase NeuO. The homotrimeric enzyme belongs to the left-handed β-helix (LβH) family of acyltransferases and is characterized by an unusual funnel-shaped outline. Comparison with other members of the LβH family allowed the identification of active site residues and proposal of a catalytic mechanism and highlighted structural characteristics of polySia specific O-acetyltransferases. As a unique feature of NeuO, the enzymatic activity linearly increases with the length of the N-terminal poly-ψ-domain which is composed of a variable number of tandem copies of an RLKTQDS heptad. Since the poly-ψ-domain was not resolved in the crystal structure it is assumed to be unfolded in the apo-enyzme

DAS PROJEKT LOSTART.DE: EINE INTERNET-DATENBANK FÜR KULTURGUTVERLUSTE

Die Suche nach Kulturgütern, die infolge des Zweiten Weltkrieges und des Nationalsozialismus geraubt wurden oder verloren gingen, ist auch heute noch eine aktuelle Aufgabe – nicht nur für Kunsthistoriker, sondern auch für betroffene Privatpersonen, Institutionen und natürlich die Politik. In diesem Beitrag wird das „Lost Art“-Projekt vorgestellt, in dessen Rahmen eine Web-Datenbank zur Unterstützung dieser Suche entwickelt wurde. Die Datenbank umfasst eine Vielzahl von Informationen zu den registrierten Kulturgütern und erlaubt unterschiedliche Such- und Navigationsmodi in verschiedenen Sprachen. Ausgehend von der Architektur dieses Systems werden Aspekte der Implementierung, der Recherchemöglichkeiten sowie des Datenaustausches zwischen der öffentlichen Web-Datenbank und der eigentlichen internen Datenbank beschrieben

A Finely Segmented Semi-Monolithic Detector tailored for High Resolution PET

Preclinical research and organ-dedicated applications require high-resolution positron emission tomography (PET) detectors to visualize small structures and understand biological processes at a finer level of detail. Current commercial systems often employ finely pixelated or monolithic scintillators, each with its limitations. We present a semi-monolithic detector, tailored for high-resolution PET applications, and merging concepts of monolithic and pixelated crystals. The detector features slabs measuring (24 x 10 x 1) sq. mm, coupled to a 12 x 12 readout channel photosensor with 4 mm pitch. The slabs are grouped in two arrays of 44 slabs each to achieve a higher optical photon density. We employ a fan beam collimator for fast calibration to train machine-learning-based positioning models for all three dimensions, including slab identification and depth-of-interaction (DOI), utilizing gradient tree boosting (GTB). Energy calculation was based on a position-dependent energy calibration. Using an analytical timing calibration, time skews were corrected for coincidence timing resolution (CTR) estimation. Leveraging machine-learning-based calibration in all three dimensions, we achieved high detector spatial resolution: down to 1.18 mm full width at half maximum (FWHM) detector spatial resolution and 0.75 mm mean absolute error (MAE) in the planar-monolithic direction along the slabs, and 2.14 mm FWHM and 1.03 mm MAE for depth-of-interaction (DOI) at an energy window of (435-585) keV. Correct slab interaction identification exceeded 80%, alongside an energy resolution of 13.8% and a CTR of 450 ps FWHM. Therewith, the introduced finely segmented, high-resolution slab detector demonstrates an appealing performance suitable for high-resolution PET applications. The current benchtop-based detector calibration routine allows these detectors to be used in PET systems.Comment: 14 pages, 11 figures, IEEE NSS MIC RTSD 202

WESSBAS: extraction of probabilistic workload specifications for load testing and performance prediction—a model-driven approach for session-based application systems

The specification of workloads is required in order to evaluate performance characteristics of application systems using load testing and model-based performance prediction. Defining workload specifications that represent the real workload as accurately as possible is one of the biggest challenges in both areas. To overcome this challenge, this paper presents an approach that aims to automate the extraction and transformation of workload specifications for load testing and model-based performance prediction of session-based application systems. The approach (WESSBAS) comprises three main components. First, a system- and tool-agnostic domain-specific language (DSL) allows the layered modeling of workload specifications of session-based systems. Second, instances of this DSL are automatically extracted from recorded session logs of production systems. Third, these instances are transformed into executable workload specifications of load generation tools and model-based performance evaluation tools. We present transformations to the common load testing tool Apache JMeter and to the Palladio Component Model. Our approach is evaluated using the industry-standard benchmark SPECjEnterprise2010 and the World Cup 1998 access logs. Workload-specific characteristics (e.g., session lengths and arrival rates) and performance characteristics (e.g., response times and CPU utilizations) show that the extracted workloads match the measured workloads with high accuracy

Antiferromagnetic gap in the Hubbard model

We compute the temperature dependence of the antiferromagnetic order parameter and the gap in the two dimensional Hubbard model at and close to half filling. Our approach is based on truncations of an exact functional renormalization group equation. The explicit use of composite bosonic degrees of freedom permits a direct investigation of the ordered low temperature phase. We show that the Mermin--Wagner theorem is not practically applicable for the spontaneous breaking of the continuous spin symmetry in the antiferromagnetic state. The critical behavior is dominated by the fluctuations of composite Goldstone bosons.Comment: new discussion of critical behavior 4 pages,2 figures, LaTe

Systematic event generator tuning for the LHC

In this article we describe Professor, a new program for tuning model parameters of Monte Carlo event generators to experimental data by parameterising the per-bin generator response to parameter variations and numerically optimising the parameterised behaviour. Simulated experimental analysis data is obtained using the Rivet analysis toolkit. This paper presents the Professor procedure and implementation, illustrated with the application of the method to tunes of the Pythia 6 event generator to data from the LEP/SLD and Tevatron experiments. These tunes are substantial improvements on existing standard choices, and are recommended as base tunes for LHC experiments, to be themselves systematically improved upon when early LHC data is available.Comment: 28 pages. Submitted to European Physical Journal C. Program sources and extra information are available from http://projects.hepforge.org/professor

Study of an unusually high level of N-glycolylneuraminic acid (NGNA) sialylation on a monoclonal antibody expressed in Chinese hamster ovary cells

Sialic or neuraminic acids of recombinant therapeutic glycoproteins produced in mammalian cells, including monoclonal antibodies, have significant impact on the half-life, stability, and biological activity of these proteins (Hossler et al., 2009; Ghaderi et al., 2012). The predominant sialic acid N-acetylneuraminic acid (NANA or Neu5Ac) is added from precursor CMP-NANA to galactose residues of N-linked glycoproteins by sialytransferases. In most mammals CMP-NANA can also be modified to its hydroxylated derivative CMP-NGNA by CMP-N-acetylneuraminic acid hydroxylase (CMAH). NGNA can then be added from CMP-NGNA to galactose residues of the N-linked glycoproteins, also by sialytransferases. However, humans cannot make functional CMAH due to an inactivating exon deletion mutation in CMAH gene (Okerblom and Varki, 2017), and therefore cannot convert CMP-NANA to CMP-NGNA. Consequently, when injected into human patients, NGNA sialic acid containing mAbs or other recombinant glycoproteins may induce immune responses, which could negatively impact pharmacokinetics or efficacy. Therefore high levels of NGNA on therapeutic mAbs or other recombinant glycoproteins are an undesirable product quality attribute. The level of total sialic acids of recombinant glycoproteins produced in Chinese hamster ovary (CHO) cells is dictated largely by the selected cell lines, upstream process, and to a lesser degree, downstream process. NGNA sialylation is generally rare in CHO cells (Könitzer et al., 2015). Hence, therapeutic glycoproteins manufactured in these cells are considered safe for human use. However, during a first-in-human (FIH) upstream process development for a novel mAb, an initially selected desirable cell line (A) was found to produce the mAb with an unexpectedly high level of the NGNA sialic acid (\u3e30%). To the best of our knowledge such high level of NGNA sialylation on a mAb produced by CHO cells has not been reported. To mitigate potential risks associated with high NGNA in human patients, a new cell line (B) that produces the mAb with very low NGNA was selected as the manufacturing cell line for this project. In order to understand the molecular mechanism causing the high NGNA content in cell line A, we initiated comprehensive genetic gap analyses using next-generation sequencing technologies and determined the differences in genomic, transcriptomic, and miRnomic profiles of the two cell lines. The results indicate spontaneous upregulation of CMAH mRNA expression, at least 10 fold higher in cell line A compared to cell line B. In this talk we will summarize the results of our studies of this unusual sialylation behavior in CHO cells