Portable Acceleration of CMS Computing Workflows with Coprocessors as a Service.

Computing demands for large scientific experiments, such as the CMS experiment at the CERN LHC, will increase dramatically in the next decades. To complement the future performance increases of software running on central processing units (CPUs), explorations of coprocessor usage in data processing hold great potential and interest. Coprocessors are a class of computer processors that supplement CPUs, often improving the execution of certain functions due to architectural design choices. We explore the approach of Services for Optimized Network Inference on Coprocessors (SONIC) and study the deployment of this as-a-service approach in large-scale data processing. In the studies, we take a data processing workflow of the CMS experiment and run the main workflow on CPUs, while offloading several machine learning (ML) inference tasks onto either remote or local coprocessors, specifically graphics processing units (GPUs). With experiments performed at Google Cloud, the Purdue Tier-2 computing center, and combinations of the two, we demonstrate the acceleration of these ML algorithms individually on coprocessors and the corresponding throughput improvement for the entire workflow. This approach can be easily generalized to different types of coprocessors and deployed on local CPUs without decreasing the throughput performance. We emphasize that the SONIC approach enables high coprocessor usage and enables the portability to run workflows on different types of coprocessors.

Corrigendum: Applying new approach methodologies to assess next-generation tobacco and nicotine products.

[This corrects the article DOI: 10.3389/ftox.2024.1376118.].

Electron cyclotron emission calibration with Thomson scattering using a wide scan of toroidal magnetic field of KSTAR.

The Korea Superconducting Tokamak Advanced Research (KSTAR) tokamak is capable of operating at a wide range of toroidal magnetic fields up to 3.5 T at the major radius. The electron cyclotron emission (ECE) diagnostic on KSTAR is required to cover a broad frequency range for electron temperature profile measurements in both the low and high field sides. To meet these broadband requirements, the ECE system consists of W-band (78-110 GHz) and D-band (110-162 GHz) heterodyne radiometers. The two radiometers are connected to 28 and 48 detection channels, respectively. However, since the absolute ECE calibration based on the hot-cold calibration has been very challenging, an alternative method of calibration was performed using Thomson scattering measurements and varying toroidal magnetic fields. As the toroidal magnetic field is scanned from 1.6 to 3.2 T in steps of 0.2 T, most of the 76 ECE channels are calibrated relatively by the electron temperature values of Thomson scattering in a narrow region (0.2 < r/a <0.6). In this article, the methodological details of the ECE calibration are described. In addition, to demonstrate the robustness of the ECE calibration factors, the calibrated electron temperature profiles from ECE measurements are compared with the ion temperature profiles in terms of the plasma position as the plasma positon shifts outward.

Pediatric mandibular malignancies: a comprehensive analysis of SEER data.

Mandibular malignancies are rare in the pediatric population and subsequently not well characterized. SEER 18 registry data was collected, applying age 0-18 years and ICD-O-3 code C41.1 ('mandible'). Univariate Cox regression analysis was conducted, and hazard ratios (HR) were calculated for overall survival (OS) and disease-specific survival (DSS) according to patient demographics, tumor characteristics, and treatment. Kaplan-Meier survival curves were generated for OS and DSS. Sixty-four patients met the inclusion criteria. The median age at diagnosis was 13.0 years, and median survival was 8.7 years. Osteosarcoma was the most common histological diagnosis (n = 22). Sex, race, age (<13 vs ≥13 years), histological type, odontogenic origin, and treatment modality were found not to be associated with OS or DSS. The SEER stage 'distant' was significantly associated with an elevated HR of 6.28 for DSS (P = 0.027) and 5.29 for OS (P = 0.025). Kaplan-Meier survival curves demonstrated significantly lower 5-year DSS (P<0.001) and OS (P<0.001) for SEER 'distant' stage. This study includes the analysis of a large number of pediatric mandibular malignancies when compared to previous studies. 'Distant' stage was associated with decreased survival. Early clinical suspicion and diagnosis are paramount for improved survival.

The GRB221009A gamma-ray burst as revealed by the gamma-ray spectrometer onboard the KPLO (Danuri).

The strongest gamma-ray burst (GRB) of the century, GRB20221009A, has been detected by the Korean Pathfinder Lunar Orbiter Gamma-ray Spectrometer (KGRS) instrument onboard the Korean Pathfinder Lunar Orbiter (KPLO). KGRS uses a LaBr3 detector to measure GRB counts with five energy bins in the energy range from 30 keV to 12 MeV. KGRS detected GRB221009A at a distance of 1.508 million kilometers from the Earth. The full duration of the main burst was recorded between 13:20 and 13:26 on October 9, 2022 with peak counts of over 1000 times background. The dead time of KGRS reached as high as 50%, and the intrinsic gamma-ray spectrum of LaBr3 was significantly altered.

INPP4B promotes PDAC aggressiveness via PIKfyve and TRPML-1-mediated lysosomal exocytosis.

Aggressive solid malignancies, including pancreatic ductal adenocarcinoma (PDAC), can exploit lysosomal exocytosis to modify the tumor microenvironment, enhance motility, and promote invasiveness. However, the molecular pathways through which lysosomal functions are co-opted in malignant cells remain poorly understood. In this study, we demonstrate that inositol polyphosphate 4-phosphatase, Type II (INPP4B) overexpression in PDAC is associated with PDAC progression. We show that INPP4B overexpression promotes peripheral dispersion and exocytosis of lysosomes resulting in increased migratory and invasive potential of PDAC cells. Mechanistically, INPP4B overexpression drives the generation of PtdIns(3,5)P2 on lysosomes in a PIKfyve-dependent manner, which directs TRPML-1 to trigger the release of calcium ions (Ca2+). Our findings offer a molecular understanding of the prognostic significance of INPP4B overexpression in PDAC through the discovery of a novel oncogenic signaling axis that orchestrates migratory and invasive properties of PDAC via the regulation of lysosomal phosphoinositide homeostasis.

The transmembrane domain of the rice small protein OsS1Fa1 is responsible for subcellular localization and drought tolerance.

OsS1Fa1, a homologue of spinach S1Fa, is a small protein in rice that contains four distinct conserved motifs and participates in drought tolerance. However, the biological functions of these conserved motifs have not been characterized to date. Therefore, we investigated the roles of these conserved domains in the localization and cellular function of OsS1Fa1. We analysed the subcellular localization of OsS1Fa1 using confocal laser scanning microscopy (CLSM), following particle bombardment and bacterial infiltration. An E. coli in vivo reconstituted sumoylation assay was conducted to investigate sumoylation of OsS1Fa1. We characterized the function of the transmembrane domain of OsS1Fa1 in drought tolerance using transgenic Arabidopsis plants. Fluorescence analysis showed that OsS1Fa1 localized to the nuclear and cytoplasmic membranes. Mutation and cell fractionation analyses revealed that the membrane localization domain determined the subcellular localization of OsS1Fa1. The rice homologue OsS1Fa2 and Arabidopsis orthologs AtS1Fa1, AtS1Fa2, and AtS1Fa3 also exhibited similar localization patterns as OsS1Fa1. Sumoylation analysis demonstrated that OsS1Fa1 was conjugated with the small ubiquitin-related modifier (SUMO). Transgenic analysis showed that overexpression of OsS1Fa1(TMm1), a mutant form of the transmembrane domain of OsS1Fa1, in Arabidopsis did not enhance drought stress tolerance, whereas OsS1Fa1 overexpression improved the drought tolerance of transgenic Arabidopsis. Our data indicate that rice and Arabidopsis S1Fa1 proteins localize in the nuclear and cytoplasmic membranes, and that transmembrane domain determines subcellular localization and plays an important role in drought stress tolerance.

Measurement of Energy Correlators inside Jets and Determination of the Strong Coupling α_{S}(m_{Z}).

Energy correlators that describe energy-weighted distances between two or three particles in a hadronic jet are measured using an event sample of sqrt[s]=13 TeV proton-proton collisions collected by the CMS experiment and corresponding to an integrated luminosity of 36.3 fb^{-1}. The measured distributions are consistent with the trends in the simulation that reveal two key features of the strong interaction: confinement and asymptotic freedom. By comparing the ratio of the measured three- and two-particle energy correlator distributions with theoretical calculations that resum collinear emissions at approximate next-to-next-to-leading-logarithmic accuracy matched to a next-to-leading-order calculation, the strong coupling is determined at the Z boson mass: α_{S}(m_{Z})=0.1229_{-0.0050}^{+0.0040}, the most precise α_{S}(m_{Z}) value obtained using jet substructure observables.

A phase II study of tepotinib in patients with advanced solid cancers harboring MET exon 14 skipping mutations or amplification (KCSG AL19-17).

BACKGROUND: We evaluated the efficacy and safety of tepotinib in patients with various solid cancers harboring MET exon 14 skipping mutation (METex14) or MET gene amplification. PATIENTS AND METHODS: A phase II, multicenter study was conducted in patients with advanced or metastatic solid cancers who progressed after standard treatment, harboring either METex14 or MET amplification detected in tissue-based next-generation sequencing (NGS). The primary endpoint was objective response rate (ORR). For exploratory analyses, we analyzed the gene profiles using plasma NGS test. RESULTS: Thirty-five patients were enrolled. The ORR was 57.6% for all patients, 52.2% for those with METex14, and 70% for those with MET amplification. Median progression-free survival (PFS) was 8 months [95% confidence interval (CI) 4.5-11.5 months] and median overall survival (OS) was 14 months (95% CI 7.8-20.2 months) in all patients. For patients with non-small-cell lung cancer with METex14, the median PFS was 9 months (95% CI 4.7-13.4 months) and the median OS was 17 months [95% CI not applicable (NA)-NA]. For patients with MET amplification, the median PFS was 7 months (95% CI 1.5-12.5 months) and the median OS was 10 months (95% CI 5.8-14.2 months). The ORR of patients with MET dysregulation detected by plasma NGS was 72.2%, whereas the ORR was 30% in those without detection. The most common adverse events were peripheral edema, asthenia, transaminase elevation, and anorexia, mostly grade 1 or 2. CONCLUSIONS: Tepotinib demonstrated consistent antitumor activity in patients with METex14, and promising antitumor activity in various cancers with MET amplification. Detection of MET dysregulation by plasma NGS may predict the response to tepotinib.

Search for Narrow Trijet Resonances in Proton-Proton Collisions at sqrt[s]=13 TeV.

The first search for singly produced narrow resonances decaying to three well-separated hadronic jets is presented. The search uses proton-proton collision data corresponding to an integrated luminosity of 138 fb^{-1} at sqrt[s]=13 TeV, collected at the CERN LHC. No significant deviations from the background predictions are observed between 1.75 and 9.00 TeV. The results provide the first mass limits on a right-handed boson Z_{R} decaying to three gluons and on an excited quark decaying via a vector boson to three quarks, as well as updated limits on a Kaluza-Klein gluon decaying via a radion to three gluons.

Magnetic Resonance Imaging-Negative Cerebral Amyloid Angiopathy: Cerebrospinal Fluid Amyloid-ß42 over Amyloid Positron Emission Tomography.

BACKGROUND: Cerebral amyloid angiopathy (CAA) pathology is becoming increasingly important in Alzheimer's disease (AD) because of its potential link to amyloid-related imaging abnormalities, a critical side effect observed during AD immunotherapy. Identification of CAA without typical magnetic resonance imaging (MRI) markers (MRI-negative CAA) is challenging, and novel detection biomarkers are needed. METHODS: We included 69 participants with high neuritic plaques (NP) burden, with and without CAA pathology (NP with CAA vs. NP without CAA) based on autopsy data from the Alzheimer's Disease Neuroimaging Initiative. Two participants with hemorrhagic CAA markers based on MRI were excluded and the final analysis involved 36 NP without CAA and 31 NP with CAA. A logistic regression model was used to compare the cerebrospinal fluid (CSF) amyloid-ß42 (Aß42), phosphorylated tau181, and total tau levels, the amyloid positron emission tomography (PET) standardized uptake ratio (SUVR), and cognitive profiles between NP with and without CAA. Regression models for CSF and PET were adjusted for age at death, sex, and the last assessed clinical dementia rating sum of boxes score. Models for cognitive performances was adjusted for age at death, sex, and education level. RESULTS: NP with CAA had significantly lower CSF Aß42 levels when compared with those without CAA (110.5 pg/mL vs. 134.5 pg/mL, p-value = 0.002). Logistic regression analysis revealed that low CSF Aß42 levels were significantly associated with NP with CAA (odds ratio [OR]: 0.957, 95% confidence interval [CI]: 0.928, 0.987, p-value = 0.005). However, amyloid PET SUVR did not differ between NP with CAA and those without CAA (1.39 vs. 1.48, p-value = 0.666). Logistic regression model analysis did not reveal an association between amyloid PET SUVR and NP with CAA (OR: 0.360, 95% CI: 0.007, 1.741, p-value = 0.606). CONCLUSIONS: CSF Aß42 is more sensitive to predict MRI-negative CAA in high NP burden than amyloid PET.

Meteorological gaps in audits of pedestrian environments: a scoping review.

BACKGROUND: Weather and season are determinants of physical activity. Therefore, it is important to ensure built environments are designed to mitigate negative impacts of weather and season on pedestrians to prevent these losses. This scoping review aims to identify built environment audits of pedestrian environments developed for use during a specific weather condition or season. Secondly, this review aims to investigate gaps in the inclusion of relevant weather mitigating built environment features in pedestrian environment audit tools. METHODS: Following a standard protocol, a systematic search was executed in CINAHL, Medline and Web of Science to identify built environment audit tools of pedestrian spaces. These databases were chosen since they are well-known to comprehensively cover health as well as multi-disciplinary research publications relevant to health. Studies were screened, and data were extracted from selected documents by two independent reviewers (e.g., psychometric properties and audit items included). Audit items were screened for the inclusion of weather mitigating built environment features, and the tool's capacity to measure temperature, precipitation, seasonal and sustainability impacts on pedestrians was calculated. RESULTS: The search returned 2823 documents. After screening and full text review, 27 articles were included. No tool was found that was developed specifically for use during a specific weather condition or season. Additionally, gaps in the inclusion of weather mitigating items were found for all review dimensions (thermal comfort, precipitation, seasonal, and sustainability items). Poorly covered items were: (1) thermal comfort related (arctic entry presence, materials, textures, and colours of buildings, roads, sidewalk and furniture, and green design features); (2) precipitation related (drain presence, ditch presence, hazards, and snow removal features); (3) seasonal features (amenities, pedestrian scale lighting, and winter destinations and aesthetics); and (4) sustainability features (electric vehicle charging stations, renewable energy, car share, and bike share facilities). CONCLUSIONS: Current built environment audit tools do not adequately include weather / season mitigating items. This is a limitation as it is important to investigate if the inclusion of these items in pedestrian spaces can promote physical activity during adverse weather conditions. Because climate change is causing increased extreme weather events, a need exists for the development of a new built environment audit tool that includes relevant weather mitigating features.

Observation of the ϒ(3S) Meson and Suppression of ϒ States in Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

The production of ϒ(2S) and ϒ(3S) mesons in lead-lead (Pb-Pb) and proton-proton (pp) collisions is studied in their dimuon decay channel using the CMS detector at the LHC. The ϒ(3S) meson is observed for the first time in Pb-Pb collisions, with a significance above 5 standard deviations. The ratios of yields measured in Pb-Pb and pp collisions are reported for both the ϒ(2S) and ϒ(3S) mesons, as functions of transverse momentum and Pb-Pb collision centrality. These ratios, when appropriately scaled, are significantly less than unity, indicating a suppression of ϒ yields in Pb-Pb collisions. This suppression increases from peripheral to central Pb-Pb collisions. Furthermore, the suppression is stronger for ϒ(3S) mesons compared to ϒ(2S) mesons, extending the pattern of sequential suppression of quarkonium states in nuclear collisions previously seen for the J/ψ, ψ(2S), ϒ(1S), and ϒ(2S) mesons.

Filling the gaps in peptide maps with a platform assay for top-down characterization of purified protein samples.

Liquid chromatography-mass spectrometry (LC-MS) intact mass analysis and LC-MS/MS peptide mapping are decisional assays for developing biological drugs and other commercial protein products. Certain PTM types, such as truncation and oxidation, increase the difficulty of precise proteoform characterization owing to inherent limitations in peptide and intact protein analyses. Top-down MS (TDMS) can resolve this ambiguity via fragmentation of specific proteoforms. We leveraged the strengths of flow-programmed (fp) denaturing online buffer exchange (dOBE) chromatography, including robust automation, relatively high ESI sensitivity, and long MS/MS window time, to support a TDMS platform for industrial protein characterization. We tested data-dependent (DDA) and targeted strategies using 14 different MS/MS scan types featuring combinations of collisional- and electron-based fragmentation as well as proton transfer charge reduction. This large, focused dataset was processed using a new software platform, named TDAcquireX, that improves proteoform characterization through TDMS data aggregation. A DDA-based workflow provided objective identification of αLac truncation proteoforms with a two-termini clipping search. A targeted TDMS workflow facilitated the characterization of αLac oxidation positional isomers. This strategy relied on using sliding window-based fragment ion deconvolution to generate composite proteoform spectral match (cPrSM) results amenable to fragment noise filtering, which is a fundamental enhancement relevant to TDMS applications generally.

Right atrial and right ventricular strain: prognostic value depends on the severity of tricuspid regurgitation.

AIMS: Assessing right heart function is challenging, particularly when significant tricuspid regurgitation (TR) is present. Among available echocardiographic techniques for assessment, literatures suggests that strain imaging may be more reliable and less susceptible to loading conditions. Thus, we aimed to assess the validity of RA and RV strain relative to conventional metrics as well as their utility in predicting patient outcomes in TR. METHODS: We studied 262 consecutive patients (mean age 74 ± 11.2 years, 53% male) who underwent same-day echocardiography and right heart catheterization between 2018 and 2023. We compared right heart strain to traditional metrics of RV function and subsequently correlated RA and RV strain to heart failure (HF)-related death or hospitalization, whichever came first. RESULTS: Over a mean follow-up of 34 ± 15 months, there were 103 deaths and HF hospitalizations. Both RA and RV strain were correlated with echocardiographic and invasive measures of right heart function. Across all patients, preserved RA strain was associated with lower risk of adverse outcomes (HR 0.763, 95% CI 0.618-0.943). Similarly, preserved RV strain was correlated with better outcomes, though this was only statistically significant in patients without severe TR or pulmonary hypertension (HR 2.450, 95% CI 1.244-4.825). Moreover, abnormal ratios of RV strain to pulmonary pressures and RV size were significantly correlated with adverse outcomes (p < 0.05 each). CONCLUSION: RA and RV strain are independently correlated with echocardiographic and invasive measures of cardiac function. Moreover, preserved RA and RV strain are likely associated with better clinical outcomes.

No improvement in AUDIT-C screening and brief intervention rates among wait-list controls following support of Aboriginal Community Controlled Health Services: evidence from a cluster randomised trial.

BACKGROUND: While Aboriginal and Torres Strait Islander Australians are less likely to drink any alcohol than other Australians, those who drink are more likely to experience adverse alcohol-related health consequences. In a previous study, providing Aboriginal Community Controlled Health Services (ACCHSs) with training and support increased the odds of clients receiving AUDIT-C alcohol screening. A follow-up study found that these results were maintained for at least two years, but there was large variability in the effectiveness of the intervention between services. In this study, we use services that previously received support as a comparison group to test whether training and support can improve alcohol screening and brief intervention rates among wait-list control ACCHSs. METHODS: Design: Cluster randomised trial using routinely collected health data. SETTING: Australia. CASES: Twenty-two ACCHSs that see at least 1000 clients a year and use Communicare as their practice management software. Intervention and comparator: After initiating support, we compare changes in screening and brief intervention between wait-list control services and services that had previously received support. MEASUREMENT: Records of AUDIT-C screening and brief intervention activity in routinely collected data. RESULTS: During the reference period we observed 357,257 instances where one of 74,568 clients attended services at least once during a two-monthly data extraction period. Following the start of support, the odds of screening (OR = 0.94 [95% CI 0.67, 1.32], p = 0.74, [Formula: see text]≈ 0.002) and brief intervention (OR = 1.43 [95% CI 0.69, 2.95], p = 0.34, [Formula: see text]≈ 0.002) did not improve for the wait-list control group, relative to comparison services. CONCLUSIONS: We did not replicate the finding that support and training improves AUDIT-C screening rates with wait-list control data. The benefits of support are likely context dependent. Coincidental policy changes may have sensitised services to the effects of support in the earlier phase of the study. Then the COVID-19 pandemic may have made services less open to change in this latest phase. Future efforts could include practice software prompts to alcohol screening and brief intervention, which are less reliant on individual staff time or resources. TRIAL REGISTRATION: Retrospectively registered on 2018-11-21: ACTRN12618001892202.

Search for Baryon Number Violation in Top Quark Production and Decay Using Proton-Proton Collisions at sqrt[s]=13 TeV.

A search is presented for baryon number violating interactions in top quark production and decay. The analysis uses data from proton-proton collisions at a center-of-mass energy of 13 TeV, collected with the CMS detector at the LHC with an integrated luminosity of 138 fb^{-1}. Candidate events are selected by requiring two oppositely charged leptons (electrons or muons) and exactly one jet identified as originating from a bottom quark. Multivariate discriminants are used to separate the signal from the background. No significant deviation from the standard model prediction is observed. Upper limits are placed on the strength of baryon number violating couplings. For the first time the production of single top quarks via baryon number violating interactions is studied. This allows the search to set the most stringent constraints to date on the branching fraction of the top quark decay to a lepton, an up-type quark (u or c), and a down-type quark (d, s, or b). The results improve the previous bounds by 3 to 6 orders of magnitude based on the fermion flavor combination of the baryon number violating interactions.