Running a Pre-Exascale, Geographically Distributed, Multi-Cloud Scientific Simulation

As we approach the Exascale era, it is important to verify that the existing frameworks and tools will still work at that scale. Moreover, public Cloud computing has been emerging as a viable solution for both prototyping and urgent computing. Using the elasticity of the Cloud, we have thus put in place a pre-exascale HTCondor setup for running a scientific simulation in the Cloud, with the chosen application being IceCube's photon propagation simulation. I.e. this was not a purely demonstration run, but it was also used to produce valuable and much needed scientific results for the IceCube collaboration. In order to reach the desired scale, we aggregated GPU resources across 8 GPU models from many geographic regions across Amazon Web Services, Microsoft Azure, and the Google Cloud Platform. Using this setup, we reached a peak of over 51k GPUs corresponding to almost 380 PFLOP32s, for a total integrated compute of about 100k GPU hours. In this paper we provide the description of the setup, the problems that were discovered and overcome, as well as a short description of the actual science output of the exercise.Comment: 18 pages, 5 figures, 4 tables, to be published in Proceedings of ISC High Performance 202

Programing stimuli-responsiveness of gelatin with electron beams: Basic effects and development of a hydration-controlled biocompatible demonstrator

Biomimetic materials with programmable stimuli responsiveness constitute a highly attractive material class for building bioactuators, sensors and active control elements in future biomedical applications. With this background, we demonstrate how energetic electron beams can be utilized to construct tailored stimuli responsive actuators for biomedical applications. Composed of collagen-derived gelatin, they reveal a mechanical response to hydration and changes in pH-value and ion concentration, while maintaining their excellent biocompatibility and biodegradability. While this is explicitly demonstrated by systematic characterizing an electron-beam synthesized gelatin-based actuator of cantilever geometry, the underlying materials processes are also discussed, based on the fundamental physical and chemical principles. When applied within classical electron beam lithography systems, these findings pave the way for a novel class of highly versatile integrated bioactuators from micro-to macroscales

An improved infrastructure for the IceCube realtime system

The IceCube realtime alert system has been operating since 2016. It provides prompt alerts on high-energy neutrino events to the astroparticle physics community. The localization regions for the incoming direction of neutrinos are published through NASA's Gamma-ray Coordinate Network (GCN). The IceCube realtime system consists of infrastructure dedicated to the selection of alert events, the reconstruction of their topology and arrival direction, the calculation of directional uncertainty contours and the distribution of the event information through public alert networks. Using a message-based workflow management system, a dedicated software (SkyDriver) provides a representational state transfer (REST) interface to parallelized reconstruction algorithms. In this contribution, we outline the improvements of the internal infrastructure of the IceCube realtime system that aims to streamline the internal handling of neutrino events, their distribution to the SkyDriver interface, the collection of the reconstruction results as well as their conversion into human- and machine-readable alerts to be publicly distributed through different alert networks. An approach for the long-term storage and cataloging of alert events according to findability, accessibility, interoperability and reusability (FAIR) principles is outlined.Comment: Presented at the 38th International Cosmic Ray Conference (ICRC2023). See arXiv:2307.13047 for all IceCube contributions. 8 pages, 3 figure

The XENON1T Data Distribution and Processing Scheme

The XENON experiment is looking for non-baryonic particle dark matter in the universe. The setup is a dual phase time projection chamber (TPC) filled with 3200 kg of ultra-pure liquid xenon. The setup is operated at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy. We present a full overview of the computing scheme for data distribution and job management in XENON1T. The software package Rucio, which is developed by the ATLAS collaboration, facilitates data handling on Open Science Grid (OSG) and European Grid Infrastructure (EGI) storage systems. A tape copy at the Center for High Performance Computing (PDC) is managed by the Tivoli Storage Manager (TSM). Data reduction and Monte Carlo production are handled by CI Connect which is integrated into the OSG network. The job submission system connects resources at the EGI, OSG, SDSC's Comet, and the campus HPC resources for distributed computing. The previous success in the XENON1T computing scheme is also the starting point for its successor experiment XENONnT, which starts to take data in autumn 2019.Comment: 8 pages, 2 figures, CHEP 2018 proceeding

IceCube experience using XRootD-based Origins with GPU workflows in PNRP

The IceCube Neutrino Observatory is a cubic kilometer neutrino telescope located at the geographic South Pole. Understanding detector systematic effects is a continuous process. This requires the Monte Carlo simulation to be updated periodically to quantify potential changes and improvements in science results with more detailed modeling of the systematic effects. IceCube's largest systematic effect comes from the optical properties of the ice the detector is embedded in. Over the last few years there have been considerable improvements in the understanding of the ice, which require a significant processing campaign to update the simulation. IceCube normally stores the results in a central storage system at the University of Wisconsin-Madison, but it ran out of disk space in 2022. The Prototype National Research Platform (PNRP) project thus offered to provide both GPU compute and storage capacity to IceCube in support of this activity. The storage access was provided via XRootD-based OSDF Origins, a first for IceCube computing. We report on the overall experience using PNRP resources, with both successes and pain points.Comment: 7 pages, 3 figures, 1 table, To be published in Proceedings of CHEP2

Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscopy 'Histolog® scanner' for breast margin assessment in comparison with conventional specimen radiography

Purpose: The Histolog® Scanner (SamanTree Medical SA, Lausanne, Switzerland) is a large field-of-view confocal laser scanning microscope designed to allow intraoperative margin assessment by the production of histological images ready for assessment in the operating room. We evaluated the feasibility and the performance of the Histolog® Scanner (HS) to correctly identify infiltrated margins in clinical practice of lumpectomy specimens. It was extrapolated if the utilization of the HS has the potential to reduce infiltrated margins and therefore reduce re-operation rates in patients undergoing breast conserving surgery (BCS) due to a primarily diagnosed breast cancer including ductal carcinoma in situ. Methods: This is a single-center, prospective, non-interventional, diagnostic pilot study including 50 consecutive patients receiving BCS. The complete surface of the specimen was scanned using the HS intraoperatively. The surgery and the intraoperative margin assessment of the specimen was performed according to the clinical routine consisting of conventional specimen radiography as well as the clinical impression of the surgeon. Three surgeons and an experienced pathologist assessed the scans produced by the HS for cancer cells on the surface. The potential of the HS to correctly identify involved margins was compared to the results of the conventional specimen radiography alone as well as the clinical routine. The histopathological report served as the gold standard. Results: 50 specimens corresponding to 300 surfaces were scanned by the HS. The mean sensitivity of the surgeons to identify involved margins with the HS was 37.5% ± 5.6%, the specificity was 75.2% ± 13.0%. The assessment of resection margins by the pathologist resulted in a sensitivity of 37.5% and a specificity of 81.0%, while the local clinical routine resulted in a sensitivity of 37.5% and a specificity of 78.2%. Conclusion: Acquisition of high-resolution histological images using the HS was feasible in clinical practice. Sensitivity and specificity were comparable to clinical routine. With more specific training and experience on image interpretation and acquisition, the HS may have the potential to enable more accuracy in the margin assessment of BCS specimens

Simultaneous Mass Spectrometry-Based Apolipoprotein Profiling and Apolipoprotein E Phenotyping in Patients with ASCVD and Mild Cognitive Impairment

Apolipoprotein E (apoE) occurs on the majority of plasma lipoproteins and plays a major role in the lipid metabolism in the periphery and in the central nervous system. ApoE is a polymorphic protein with three common isoforms, apoE2, apoE3 and apoE4, derived from respective alleles '2, '3 and '4. The aim of this study was to develop a sample pretreatment protocol combined with rapid mass spectrometry (MS)-based assay for simultaneous apolipoprotein profiling and apoE phenotype identification. This assay was validated in 481 samples from patients with stable atherosclerotic cardiovascular disease (ASCVD) and applied to study association with mild cognitive impairment (MCI) in the LIFE Adult study, including overall 690 study subjects. Simultaneous quantification of 8–12 major apolipoproteins including apoA-I, apoB-100 and apoE could be performed within 6.5 min. Phenotyping determined with the developed MS assay had good agreement with the genotyping by real-time fluorescence PCR (97.5%). ApoE2 isoform was associated with the highest total apoE concentration compared to apoE3 and apoE4 (p < 0.001). In the subgroup of diabetic atherosclerotic cardiovascular disease (ASCVD) patients, apoE2 isoform was related to higher apoC-I levels (apoE2 vs. apoE3, p < 0.05), while in the subgroup of ASCVD patients under statin therapy apoE2 was related to lower apoB-100 levels (apoE2 vs. apoE3/apoE4, p < 0.05). A significant difference in apoE concentration observed between mild cognitive impairment (MCI) subjects and controls was confirmed for each apoE phenotype. In conclusion, this study provides evidence for the successful implementation of an MS-based apoE phenotyping assay, which can be used to assess phenotype effects on plasma lipid and apolipoprotein levels

RESPONDER – diagnosis of pathological complete response by vacuum-assisted biopsy after neoadjuvant chemotherapy in breast Cancer - a multicenter, confirmative, one-armed, intra-individually-controlled, open, diagnostic trial

Background: Neoadjuvant chemotherapy (NACT) is a standard approach of the multidisciplinary treatment of breast cancer. Depending on the biological subtype a pathological complete response in the breast (bpCR) can be achieved in up to 60% of the patients. However, only limited accuracy can be reached when using imaging for prediction of bpCR prior to surgery. Due to this diagnostic uncertainty, surgery after NACT is considered to be obligatory for all patients in order to either completely remove residual disease or to diagnose a bpCR histologically. The purpose of this trial is to evaluate the accuracy of a vacuum-assisted biopsy (VAB) to diagnose a bpCR after NACT prior to surgery. Methods: This study is a multicenter, confirmative, one-armed, intra-individually-controlled, open, diagnostic trial. The study will take place at 21 trial sites in Germany. Six hundred female patients with breast cancer after completed NACT showing at least a partial response to NACT treatment will be enrolled. A vacuum-assisted biopsy (VAB) guided either by ultrasound or mammography will be performed followed by histopathological evaluation of the VAB specimen before standard, guideline-adherent breast surgery. The study is designed to prove that the false negative rate of the VAB is below 10%. Discussion: As a bpCR is becoming a more frequent result after NACT, the question arises whether breast surgery is therapeutically necessary in such cases. To study this subject further, it will be crucial to develop a reliable test to diagnose a bpCR without surgery. During the study we anticipate possible problems in patient recruitment as the VAB intervention does not provide participating patients with any personal benefit. Hence, a proficient informed consent discussion with the patient and a detailed explanation of the study aim will be crucial for patient recruitment. Another critical issue is the histopathological VAB evaluation of a non-tumorous specimen as this may have been taken either from the former tumor region (bpCR) or outside of the (former) tumor region (non-representative VAB, sampling error). Trial registration: The trial has been registered at clinicaltrials.gov with the identifier NCT02948764 on October 28, 2016 and at the German Clinical Trials Register ( DRKS00011761 ) on February 20, 2017. The date of enrolment of the first participant to the trial was on March 8, 2017

Reproducibility of `COST Reference Microplasma Jets'

Atmospheric pressure plasmas have been ground-breaking for plasma science and technologies, due to their significant application potential in many fields, including medicinal, biological, and environmental applications. This is predominantly due to their efficient production and delivery of chemically reactive species under ambient conditions. One of the challenges in progressing the field is comparing plasma sources and results across the community and the literature. To address this a reference plasma source was established during the `Biomedical Applications of Atmospheric Pressure Plasmas' EU COST Action MP1101. It is crucial that reference sources are reproducible. Here, we present the reproducibility and variance across multiple sources through examining various characteristics, including: absolute atomic oxygen densities, absolute ozone densities, electrical characteristics, optical emission spectroscopy, temperature measurements, and bactericidal activity. The measurements demonstrate that the tested COST jets are mainly reproducible within the intrinsic uncertainty of each measurement technique