Accelerated Bayesian Inference for Molecular Simulations using Local Gaussian Process Surrogate Models

While Bayesian inference is the gold standard for uncertainty quantification and propagation, its use within physical chemistry encounters formidable computational barriers. These bottlenecks are magnified for modeling data with many independent variables, such as X-ray/neutron scattering patterns and electromagnetic spectra. To address this challenge, we apply a Bayesian framework accelerated via local Gaussian process (LGP) surrogate models. We show that the time-complexity of LGPs scales linearly in the number of independent variables, in stark contrast to the computationally expensive cubic scaling of conventional Gaussian processes. To illustrate the method, we trained a LGP surrogate model on the experimental radial distribution function of liquid neon, and observed a remarkable 288,000-fold speed-up compared to molecular dynamics with insignificant loss in predictive accuracy. We conclude that LGPs are robust and efficient surrogate models, poised to expand the application of Bayesian inference in molecular simulations to a broad spectrum of ever-advancing experimental data

From the cell membrane to the nucleus: unearthing transport mechanisms for Dynein

Mutations in the motor protein cytoplasmic dynein have been found to cause Charcot-Marie-Tooth disease, spinal muscular atrophy, and severe intellectual disabilities in humans. In mouse models, neurodegeneration is observed. We sought to develop a novel model which could incorporate the effects of mutations on distance travelled and velocity. A mechanical model for the dynein mediated transport of endosomes is derived from first principles and solved numerically. The effects of variations in model parameter values are analysed to find those that have a significant impact on velocity and distance travelled. The model successfully describes the processivity of dynein and matches qualitatively the velocity profiles observed in experiments

Aging Studies for the Large Honeycomb Drift Tube System of the Outer Tracker of HERA-B

The HERA-B Outer Tracker consists of drift tubes folded from polycarbonate foil and is operated with Ar/CF4/CO2 as drift gas. The detector has to stand radiation levels which are similar to LHC conditions. The first prototypes exposed to radiation in HERA-B suffered severe radiation damage due to the development of self-sustaining currents (Malter effect). In a subsequent extended R&D program major changes to the original concept for the drift tubes (surface conductivity, drift gas, production materials) have been developed and validated for use in harsh radiation environments. In the test program various aging effects (like Malter currents, gain loss due to anode aging and etching of the anode gold surface) have been observed and cures by tuning of operation parameters have been developed.Comment: 14 pages, 6 figures, to be published in the Proceedings of the International Workshop On Aging Phenomena In Gaseous Detectors, 2-5 Oct 2001, Hamburg, German

Quality control and beam test of GEM detectors for future upgrades of the CMS muon high rate region at the LHC

Gas Electron Multipliers (GEM) are a proven position sensitive gas detector technology which nowadays is becoming more widely used in High Energy Physics. GEMs offer an excellent spatial resolution and a high particle rate capability, with a close to 100% detection efficiency. In view of the high luminosity phase of the CERN Large Hadron Collider, these aforementioned features make GEMs suitable candidates for the future upgrades of the Compact Muon Solenoid (CMS) detector. In particular, the CMS GEM Collaboration proposes to cover the high-eta region of the muon system with large-area triple-GEM detectors, which have the ability to provide robust and redundant tracking and triggering functions. In this contribution, after a general introduction and overview of the project, the construction of full-size trapezoidal triple-GEM prototypes will be described in more detail. The procedures for the quality control of the GEM foils, including gain uniformity measurements with an x-ray source will be presented. In the past few years, several CMS triple-GEM prototype detectors were operated with test beams at the CERN SPS. The results of these test beam campaigns will be summarised

Performance of a Large-Area GEM Detector Prototype for the Upgrade of the CMS Muon Endcap System

Gas Electron Multiplier (GEM) technology is being considered for the forward muon upgrade of the CMS experiment in Phase 2 of the CERN LHC. Its first implementation is planned for the GE1/1 system in the $1.5 < \mid\eta\mid < 2.2$ region of the muon endcap mainly to control muon level-1 trigger rates after the second long LHC shutdown. A GE1/1 triple-GEM detector is read out by 3,072 radial strips with 455 $\mu$rad pitch arranged in eight $\eta$-sectors. We assembled a full-size GE1/1 prototype of 1m length at Florida Tech and tested it in 20-120 GeV hadron beams at Fermilab using Ar/CO$_{2}$ 70:30 and the RD51 scalable readout system. Four small GEM detectors with 2-D readout and an average measured azimuthal resolution of 36 $\mu$rad provided precise reference tracks. Construction of this largest GEM detector built to-date is described. Strip cluster parameters, detection efficiency, and spatial resolution are studied with position and high voltage scans. The plateau detection efficiency is [97.1 $\pm$ 0.2 (stat)]\%. The azimuthal resolution is found to be [123.5 $\pm$ 1.6 (stat)] $\mu$rad when operating in the center of the efficiency plateau and using full pulse height information. The resolution can be slightly improved by $\sim$ 10 $\mu$rad when correcting for the bias due to discrete readout strips. The CMS upgrade design calls for readout electronics with binary hit output. When strip clusters are formed correspondingly without charge-weighting and with fixed hit thresholds, a position resolution of [136.8 $\pm$ 2.5 stat] $\mu$rad is measured, consistent with the expected resolution of strip-pitch/$\sqrt{12}$ = 131.3 $\mu$rad. Other $\eta$-sectors of the detector show similar response and performance.Comment: 8 pages, 32 figures, submitted to Proc. 2014 IEEE Nucl. Sci. Symposium, Seattle, WA, reference adde

A novel application of Fiber Bragg Grating (FBG) sensors in MPGD

We present a novel application of Fiber Bragg Grating (FBG) sensors in the construction and characterisation of Micro Pattern Gaseous Detector (MPGD), with particular attention to the realisation of the largest triple (Gas electron Multiplier) GEM chambers so far operated, the GE1/1 chambers of the CMS experiment at LHC. The GE1/1 CMS project consists of 144 GEM chambers of about 0.5 m2 active area each, employing three GEM foils per chamber, to be installed in the forward region of the CMS endcap during the long shutdown of LHC in 2108-2019. The large active area of each GE1/1 chamber consists of GEM foils that are mechanically stretched in order to secure their flatness and the consequent uniform performance of the GE1/1 chamber across its whole active surface. So far FBGs have been used in high energy physics mainly as high precision positioning and re-positioning sensors and as low cost, easy to mount, low space consuming temperature sensors. FBGs are also commonly used for very precise strain measurements in material studies. In this work we present a novel use of FBGs as flatness and mechanical tensioning sensors applied to the wide GEM foils of the GE1/1 chambers. A network of FBG sensors have been used to determine the optimal mechanical tension applied and to characterise the mechanical tension that should be applied to the foils. We discuss the results of the test done on a full-sized GE1/1 final prototype, the studies done to fully characterise the GEM material, how this information was used to define a standard assembly procedure and possible future developments.Comment: 4 pages, 4 figures, presented by Luigi Benussi at MPGD 2015 (Trieste, Italy). arXiv admin note: text overlap with arXiv:1512.0848

Development and performance of Triple-GEM detectors for the upgrade of the muon system of the CMS experiment

The CMS Collaboration is evaluating GEM detectors for the upgrade of the muon system. This contribution will focus on the R&D performed on chambers design features and will discuss the performance of the upgraded detector

Design of a constant fraction discriminator for the VFAT3 front-end ASIC of the CMS GEM detector

In this work the design of a constant fraction discriminator (CFD) to be used in the VFAT3 chip for the read-out of the triple-GEM detectors of the CMS experiment, is described. A prototype chip containing 8 CFDs was implemented using 130 nm CMOS technology and test results are shown. © CERN 2016

Decatransin, a novel natural product inhibiting protein translocation at the Sec61/SecY translocon

A new cyclic decadepsipeptide was isolated from Chaetosphaeria tulasneorum with potent bioactivity on mammalian and yeast cells. Chemogenomic profiling in S. cerevisiae indicated that the Sec61 translocon, the machinery for protein translocation and membrane insertion at the endoplasmic reticulum, is the target. The profiles were similar to those of cyclic heptadepsipeptides of a distinct chemotype (HUN-7293/cotransin) that had previously been shown to inhibit cotranslational translocation at the mammalian Sec61 translocon. Unbiased, genome-wide mutagenesis followed by full-genome sequencing in both fungal and mammalian cells identified dominant mutations in Sec61p/Sec61α1 to confer resistance. Most, but not all, of these mutations affected inhibition by both chemotypes, despite an absence of structural similarity. Biochemical analysis confirmed inhibition of protein translocation into the endoplasmic reticulum of both co- and posttranslationally translocated substrates by both chemotypes, demonstrating a mechanism independent of a translating ribosome. Most interestingly, both chemotypes were found to also inhibit SecYEG, the bacterial Sec61 homolog. We suggest "decatransin" as the name for this novel decadepsipeptide translocation inhibitor

Operational experience with the GEM detector assembly lines for the CMS forward muon upgrade

The CMS Collaboration has been developing large-area triple-gas electron multiplier (GEM) detectors to be installed in the muon Endcap regions of the CMS experiment in 2019 to maintain forward muon trigger and tracking performance at the High-Luminosity upgrade of the Large Hadron Collider (LHC); 10 preproduction detectors were built at CERN to commission the first assembly line and the quality controls (QCs). These were installed in the CMS detector in early 2017 and participated in the 2017 LHC run. The collaboration has prepared several additional assembly and QC lines for distributed mass production of 160 GEM detectors at various sites worldwide. In 2017, these additional production sites have optimized construction techniques and QC procedures and validated them against common specifications by constructing additional preproduction detectors. Using the specific experience from one production site as an example, we discuss how the QCs make use of independent hardware and trained personnel to ensure fast and reliable production. Preliminary results on the construction status of CMS GEM detectors are presented with details of the assembly sites involvement