Showing papers by "Andreas Pfeiffer published in 2023"

Search for light Higgs bosons from supersymmetric cascade decays in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\t

Abstract: Abstract A search is reported for pairs of light Higgs bosons ( $${\textrm{H}} _1$$ H 1 ) produced in supersymmetric cascade decays in final states with small missing transverse momentum. A data set of LHC $$\hbox {pp}$$ pp collisions collected with the CMS detector at $$\sqrt{s}=13\,\text {TeV} $$ s = 13 TeV and corresponding to an integrated luminosity of 138 $$\,\text {fb}^{-1}$$ fb - 1 is used. The search targets events where both $${\textrm{H}} _1$$ H 1 bosons decay into "Equation missing" pairs that are reconstructed as large-radius jets using substructure techniques. No evidence is found for an excess of events beyond the background expectations of the standard model (SM). Results from the search are interpreted in the next-to-minimal supersymmetric extension of the SM, where a “singlino” of small mass leads to squark and gluino cascade decays that can predominantly end in a highly Lorentz-boosted singlet-like $${\textrm{H}} _1$$ H 1 and a singlino-like neutralino of small transverse momentum. Upper limits are set on the product of the squark or gluino pair production cross section and the square of the "Equation missing" branching fraction of the $${\textrm{H}} _1$$ H 1 in a benchmark model containing almost mass-degenerate gluinos and light-flavour squarks. Under the assumption of an SM-like "Equation missing" branching fraction, $${\textrm{H}} _1$$ H 1 bosons with masses in the range 40–120 $$\,\text {GeV}$$ GeV arising from the decays of squarks or gluinos with a mass of 1200–2500 $$\,\text {GeV}$$ GeV are excluded at 95% confidence level.

Search for heavy resonances and quantum black holes in eμ, eτ, and μτ final states in proton-proton collisions at $$ \sqrt{s} $$ = 13 TeV

Abstract: A bstract A search is reported for heavy resonances and quantum black holes decaying into eμ, eτ, and μτ final states in proton-proton collision data recorded by the CMS experiment at the CERN LHC during 2016–2018 at $$ \sqrt{s} $$ s = 13 TeV, corresponding to an integrated luminosity of 138 fb − 1 . The eμ, eτ, and μτ invariant mass spectra are reconstructed, and no evidence is found for physics beyond the standard model. Upper limits are set at 95% confidence level on the product of the cross section and branching fraction for lepton flavor violating signals. Three benchmark signals are studied: resonant τ sneutrino production in R parity violating supersymmetric models, heavy Z′ gauge bosons with lepton flavor violating decays, and nonresonant quantum black hole production in models with extra spatial dimensions. Resonant τ sneutrinos are excluded for masses up to 4.2TeV in the eμ channel, 3.7TeV in the eτ channel, and 3.6TeV in the μτ channel. A Z′ boson with lepton flavor violating couplings is excluded up to a mass of 5.0TeV in the eμ channel, up to 4.3Te V in the eτ channel, and up to 4.1TeV in the μτ channel. Quantum black holes in the benchmark model are excluded up to the threshold mass of 5.6TeV in the eμ channel, 5.2TeV in the eτ channel, and 5.0TeV in the μτ channel. In addition, model-independent limits are extracted to allow comparisons with other models for the same final states and similar event selection requirements. The results of these searches provide the most stringent limits available from collider experiments for heavy particles that undergo lepton flavor violating decays.

732-P: Biomarkers of Inflammation and Long-Term Microvasculature Integrity in Weight Loss–Induced Prediabetes Remission

Abstract: The Diabetes Prevention Program Outcomes Study demonstrated that even temporary resolution of prediabetes (remission) to normal glucose regulation (NGR) prevents development of T2D and vascular complications. However, cellular mechanisms are unknown. We have previously shown in the Prediabetes Lifestyle Intervention Study, a German Center for Diabetes Research multicenter study (n = 1105), that lifestyle intervention (LI)-mediated weight loss-induced remission of prediabetes to NGR vs. non-remission is largely driven by improved insulin sensitivity. We hypothesized that these two groups differ by markers of chronic low-grade inflammation. Therefore, we analyzed 31 cytokines implicated in energy metabolism and T2D complications before and after LI in subjects losing ≥5% body weight (n = 113) to compare responders achieving NGR (R, n = 40) to non-responders not achieving NGR (NR, n = 73). Cytokines linked to insulin resistance and T2D such as TNF-α (p = 0.73), IFNγ (p = 0.45) and IL-6 (p = 0.34) did not differ between groups. However, responders showed a significantly stronger reduction of lymphotoxin α (LTα, -0.15 ± 0.29-fold in NR vs. -0.23 ± 0.32 in R, p = 0.02). VCAM (-0.04 ± 0.14 NR vs. -0.08 ±10.9 R, p = 0.02) and ICAM (-0.11 ±0.15 NR vs. -0.16 ± 0.14 R, p = 0.02), which are induced by LTα and have been implied in mediating cardiovascular complications, were also more strongly reduced in responders. To assess if this is linked with long-term microvasculature integrity, we applied optoacoustic mesoscopy up to 5 years after LI (n = 22). Total vessel and junction density and number of junction to endpoint branches (NJEB) were higher in responders at follow-up (NJEB: 154.9 ± 25.3 vs. 186.9 ± 16.1, p < 0.01). These data describe a distinct pattern of reduced low-grade inflammation characterizing remission of prediabetes to NGR. Although limited by low n, this pattern may help explain the positive effects of prediabetes remission on vascular complications. A.Sandforth: None. J.Szendroedi: None. S.M.Meyhöfer: Speaker's Bureau; Novo Nordisk, AstraZeneca, Lilly, Amgen Inc., Boehringer-Ingelheim, Novartis. M.Roden: Advisory Panel; Eli Lilly and Company, Consultant; TARGET PharmaSolutions, Inc., Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis, Sanofi. L.Fritsche: None. N.Stefan: Advisory Panel; Pfizer Inc., Research Support; Sanofi, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Lilly Diabetes, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. R.Wagner: Advisory Panel; Daiichi Sankyo, Speaker's Bureau; Novo Nordisk, Sanofi. A.Fritsche: Advisory Panel; Novo Nordisk, Lilly, Sanofi, Boehringer-Ingelheim, Speaker's Bureau; AstraZeneca, SYNLAB Holding Deutschland GmbH. R.Jumpertz von schwartzenberg: Other Relationship; Sanofi, Amgen Inc., Lilly, Novo Nordisk. A.L.Birkenfeld: None. S.Katzenstein: None. J.Seissler: None. S.R.Bornstein: None. N.Perakakis: Advisory Panel; Bayer Inc., Other Relationship; Novo Nordisk, Novo Nordisk. S.Kabisch: Other Relationship; Berlin-Chemie AG, Sanofi, Lilly, Boehringer Ingelheim Inc., JuZo Akademie, Research Support; J. Rettenmaier / Söhne, Wilhelm-Doerenkamp Foundation, German Center of Diabetes Research. A.F.Pfeiffer: Advisory Panel; Abbott Diabetes, Speaker's Bureau; Novo Nordisk, Sanofi-Aventis Deutschland GmbH. H.Häring: None. M.Blüher: Advisory Panel; Boehringer Ingelheim Inc., Lilly, Novo Nordisk, Consultant; Novo Nordisk Foundation, Speaker's Bureau; Amgen Inc., AstraZeneca, Bayer Inc., Daiichi Sankyo, Novartis, Sanofi-Aventis Deutschland GmbH.

Probing Heavy Majorana Neutrinos and the Weinberg Operator through Vector Boson Fusion Processes in Proton-Proton Collisions at sqrt[s]=13 TeV.

Abstract: The first search exploiting the vector boson fusion process to probe heavy Majorana neutrinos and the Weinberg operator at the LHC is presented. The search is performed in the same-sign dimuon final state using a proton-proton collision dataset recorded at sqrt[s]=13 TeV, collected with the CMS detector and corresponding to a total integrated luminosity of 138 fb^{-1}. The results are found to agree with the predictions of the standard model. For heavy Majorana neutrinos, constraints on the squared mixing element between the muon and the heavy neutrino are derived in the heavy neutrino mass range 50 GeV-25 TeV; for masses above 650 GeV these are the most stringent constraints from searches at the LHC to date. A first test of the Weinberg operator at colliders provides an observed upper limit at 95% confidence level on the effective μμ Majorana neutrino mass of 10.8 GeV.

Liver Fat Scores for Noninvasive Diagnosis and Monitoring of Nonalcoholic Fatty Liver Disease in Epidemiological and Clinical Studies

Abstract: Nonalcoholic fatty liver disease (NAFLD) is strongly associ- ated with the metabolic syndrome and type 2 diabetes and independently contributes to long-term complications. Being often asymptomatic but reversible, it would require population-wide screening

1452-P: Type 1 Diabetes Subphenotypes—A Cluster Analysis

Abstract: Adult-onset type 1 diabetes (T1D) is a chronic disease with progressive beta-cell destruction. However, individuals with adult-onset T1D are metabolically dissimilar. We aimed to identify metabolically distinct groups in a comprehensively phenotyped cohort of individuals with recent-onset T1D. Participants with T1D (n=550) were split by presence of glutamic-acid decarboxylase antibody (GADA) into a GADA- (n=95) and GADA+ groups (n=455). GADA+ was clustered using partitioning around medoids based on fasting C-peptide, glucose, triglycerides and HDL resulting in 2 distinguished GADA+ clusters. All 3 clusters were compared at baseline (first year of diabetes diagnosis) and after five years of follow-up using ANOVA, chi-squared test and logistic regression adjusted for age and sex. The larger GADA+ cluster (n=285) with younger age, lower BMI and lower C-peptide was termed “classic T1D”. The other GADA+ cluster (n=170) combined features of type 1 and type 2 diabetes and was named “mixed T1D”. Patients of the “mixed T1D” cluster did not gain weight over 5 years (p=0.29), which was not the case for “classic T1D” cluster (p<0.001, increased BMI with an effect size 0.07) and GADA-cluster (p=0.01, effect size 0.04) participants. The “classic T1D” cluster had the highest insulin sensitivity at baseline (p<0.001) that sharply decreased during five years of follow-up. At five years, there was no difference in insulin sensitivity across the 3 clusters (p=0.78). There were no differences in HbA1c levels across clusters neither at baseline (p=0.48) nor after 5 years (p=0.64). Classic T1D participants reported a higher incidence of hypoglycemia (OR 4.92, 95% CI 1.9-13.5, p=0.001). The incidence of both distal peripheral sensory (OR 2.89, 95%CI1.05-8.29, p= 0.041) and cardiac autonomic neuropathy (OR 9.61, 95%CI 2.35-49.8, p= 0.003), was higher in “mixed T1D”. Based on rapidly available laboratory variables, individuals with recent-onset adult type 1 diabetes can be stratified into clusters with different clinical course and complication risk K.Prystupa: Other Relationship; Berlin-Chemie AG. S.M.Meyhöfer: Speaker's Bureau; Novo Nordisk, AstraZeneca, Lilly, Amgen Inc., Boehringer-Ingelheim, Novartis. O.P.Zaharia: None. N.Saatmann: None. M.Huttasch: None. K.Strassburger: None. V.Burkart: None. M.Roden: Advisory Panel; Eli Lilly and Company, Consultant; TARGET PharmaSolutions, Inc., Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis, Sanofi. R.Wagner: Advisory Panel; Daiichi Sankyo, Speaker's Bureau; Novo Nordisk, Sanofi. A.Fritsche: Advisory Panel; Novo Nordisk, Lilly, Sanofi, Boehringer-Ingelheim, Speaker's Bureau; AstraZeneca, SYNLAB Holding Deutschland GmbH. G.J.Bönhof: None. A.Strom: None. M.Heni: Advisory Panel; Boehringer-Ingelheim, Sanofi, Research Support; Boehringer Ingelheim Inc., Speaker's Bureau; Lilly, Bayer Inc., Sanofi, Boehringer-Ingelheim, Novo Nordisk, Amryt Pharma Plc. J.Seissler: None. J.Szendroedi: None. A.F.Pfeiffer: Advisory Panel; Abbott Diabetes, Speaker's Bureau; Novo Nordisk, Sanofi-Aventis Deutschland GmbH. M.W.Stumvoll: None.

619-P: An Isocaloric High Saturated Fat Diet Increases Endogenous Cholesterol Production Which Is Reversed by a Protein-Enriched Diet in Normal-Weight Humans

Abstract: Lathosterol is a marker of endogenous cholesterol synthesis whereas plant sterols (e. g. campesterol) reflect cholesterol absorption. Obesity and type 2 diabetes mellitus are associated with increased endogenous cholesterol production and decreased cholesterol absorption. Only few studies evaluated cholesterol homeostasis under isocaloric nutritional conditions. This study investigated endogenous cholesterol production in healthy humans after consumption of isocaloric diets enriched with carbohydrates (KH) or saturated fat (HF) or protein (HP). 24 normal weight participants (women and men, age 18 - 70) were investigated for 18 weeks. An isocaloric diet rich in carbohydrates (55% carbohydrates, 30% fat, 15% protein, KH) was applied followed by an isocaloric diet rich in saturated fat (40% carbohydrates, 45% fat, 15% protein, HF) and finally followed by an isocaloric diet enriched with proteins (45% carbohydrates, 30% fat, 25% protein, HP); each for 6 weeks. Body weight (BW), serum total and LDL cholesterol and serum lathosterol and campesterol levels were analyzed after the KH period, after one week (HF1) and 6 weeks (HF6) of the HF and after the HP period. BW did not change during the study. Serum total and LDL cholesterol increased from 4.38±0.2 and 2.74±0.2 mmol/L, respectively at KH to 4.82±0.2 and 2.97±0.2 mmol/L, respectively at HF6 (both P<0.01) and were decreased back to KH levels at HP. Serum lathosterol levels increased 1.26-fold and 1.16-fold, respectively at HF1 and HF6 (P<0.05 compared to LF), however decreased by 10.1% at HP (compared to KH levels, P<0.05). Serum campesterol levels moderately decreased at HF1 and HF6 and were restored to KH levels at HP (P<0.01 compared to HF6). These data show that composition of macronutrients are responsible for diet induced elevation of serum cholesterol levels due to an increased endogenous cholesterol production in normal weight humans regardless of the energy content of the diet. M.Kruse: None. S.Matysik: None. D.Hoffmann: None. T.Frahnow: None. A.F.Pfeiffer: Advisory Panel; Abbott Diabetes, Speaker's Bureau; Novo Nordisk, Sanofi-Aventis Deutschland GmbH. German Federal Ministry of Education and Research (0315424)

An Isocaloric High-Fat Diet Regulates Partially Genetically Determined Fatty Acid and Carbohydrate Uptake and Metabolism in Subcutaneous Adipose Tissue of Lean Adult Twins

Abstract: Background: The dysfunction of energy metabolism in white adipose tissue (WAT) induces adiposity. Obesogenic diets that are high in saturated fat disturb nutrient metabolism in adipocytes. This study investigated the effect of an isocaloric high-fat diet without the confounding effects of weight gain on the gene expression of fatty acid and carbohydrate transport and metabolism and its genetic inheritance in subcutaneous (s.c.) WAT of healthy human twins. Methods: Forty-six healthy pairs of twins (34 monozygotic, 12 dizygotic) received an isocaloric carbohydrate-rich diet (55% carbohydrates, 30% fat, 15% protein; LF) for 6 weeks followed by an isocaloric diet rich in saturated fat (40% carbohydrates, 45% fat, 15% protein; HF) for another 6 weeks. Results: Gene expression analysis of s.c. WAT revealed that fatty acid transport was reduced after one week of the HF diet, which persisted throughout the study and was not inherited, whereas intracellular metabolism was decreased after six weeks and inherited. An increased inherited gene expression of fructose transport was observed after one and six weeks, potentially leading to increased de novo lipogenesis. Conclusion: An isocaloric dietary increase of fat induced a tightly orchestrated, partially inherited network of genes responsible for fatty acid and carbohydrate transport and metabolism in human s.c. WAT.

Evaluation and Implementation of Various Persistent Storage Options for CMSWEB Services in Kubernetes Infrastructure at CERN

Abstract: This paper summarizes the various storage options that we implemented for the CMSWEB cluster in Kubernetes infrastructure. All CMSWEB services require storage for logs, while some services also require storage for data. We also provide a feasibility analysis of various storage options and describe the pros/cons of each technique from the perspective of the CMSWEB cluster and its users. In the end, we also propose recommendations according to the service needs. The first option is the CephFS which can be mounted multiple times across various clusters and VMs and works very well with k8s. We use it both for data and the logs. The second option is the Cinder volume. It is the block storage that runs the filesystem on top of it. It can only be attached to one instance at a time. We use this option only for the data. The third option is S3 storage. It is object storage that offers a scalable storage service that can be used by applications compatible with the Amazon S3 protocol. It is used for the logs. For S3, we explored two mechanisms. For the first scenario, we consider fluentd that runs as a sidecar container in the service pods and sends logs to S3 bucket. For the second scenario, we considered filebeat that runs as a sidecar container in the service pod and scaps those logs to fluentd which runs as a daemonset in each node and sends those logs to S3 in the end. The fourth option is EOS. We configured EOS inside the pods of the CMSWEB services. The fifth option that we explored is to use dedicated VMs that have Ceph volume attached to them. In EOS and VM, the logs from the service pods are sent to EOS/VM using the rsync approach. The last option is to send service logs to Elasticsearch. It has been implemented using fluentd that runs as a daemonset in each node. In parallel to the sending logs to S3 fluentd also sends those logs to the Elasticsearch infrastructure at CERN.

Measurement of the differential tt¯ production cross section as a function of the jet mass and extraction of the top quark mass in hadronic decays of boosted top quarks.

Abstract: Abstract A measurement of the jet mass distribution in hadronic decays of Lorentz-boosted top quarks is presented. The measurement is performed in the lepton + jets channel of top quark pair production ( $$\hbox {t}\overline{\hbox {t}}$$ t t ¯ ) events, where the lepton is an electron or muon. The products of the hadronic top quark decay are reconstructed using a single large-radius jet with transverse momentum greater than 400 $$\,\text {Ge}\hspace{-.08em}\text {V}$$ Ge V . The data were collected with the CMS detector at the LHC in proton-proton collisions and correspond to an integrated luminosity of 138 $$\,\text {fb}^{-1}$$ fb - 1 . The differential $$\hbox {t}\overline{\hbox {t}}$$ t t ¯ production cross section as a function of the jet mass is unfolded to the particle level and is used to extract the top quark mass. The jet mass scale is calibrated using the hadronic W boson decay within the large-radius jet. The uncertainties in the modelling of the final state radiation are reduced by studying angular correlations in the jet substructure. These developments lead to a significant increase in precision, and a top quark mass of $$173.06 \pm 0.84\,\text {Ge}\hspace{-.08em}\text {V} $$ 173.06 ± 0.84 Ge V .

Search for light Higgs bosons from supersymmetric cascade decays in pp collisions at s=13TeV.

Abstract: Abstract A search is reported for pairs of light Higgs bosons ( $${\textrm{H}} _1$$ H 1 ) produced in supersymmetric cascade decays in final states with small missing transverse momentum. A data set of LHC $$\hbox {pp}$$ pp collisions collected with the CMS detector at $$\sqrt{s}=13\,\text {TeV} $$ s = 13 TeV and corresponding to an integrated luminosity of 138 $$\,\text {fb}^{-1}$$ fb - 1 is used. The search targets events where both $${\textrm{H}} _1$$ H 1 bosons decay into "Equation missing" pairs that are reconstructed as large-radius jets using substructure techniques. No evidence is found for an excess of events beyond the background expectations of the standard model (SM). Results from the search are interpreted in the next-to-minimal supersymmetric extension of the SM, where a “singlino” of small mass leads to squark and gluino cascade decays that can predominantly end in a highly Lorentz-boosted singlet-like $${\textrm{H}} _1$$ H 1 and a singlino-like neutralino of small transverse momentum. Upper limits are set on the product of the squark or gluino pair production cross section and the square of the "Equation missing" branching fraction of the $${\textrm{H}} _1$$ H 1 in a benchmark model containing almost mass-degenerate gluinos and light-flavour squarks. Under the assumption of an SM-like "Equation missing" branching fraction, $${\textrm{H}} _1$$ H 1 bosons with masses in the range 40–120 $$\,\text {GeV}$$ GeV arising from the decays of squarks or gluinos with a mass of 1200–2500 $$\,\text {GeV}$$ GeV are excluded at 95% confidence level.

Metabolic-Associated Fatty Liver Disease and Insulin Resistance: A Review of Complex Interlinks

Abstract: Metabolic-associated fatty liver disease (MAFLD) has now surpassed alcohol excess as the most common cause of chronic liver disease globally, affecting one in four people. Given its prevalence, MAFLD is an important cause of cirrhosis, even though only a small proportion of patients with MAFLD ultimately progress to cirrhosis. MAFLD suffers as a clinical entity due to its insidious and often asymptomatic onset, lack of an accurate and reliable non-invasive diagnostic test, and lack of a bespoke therapy that has been designed and approved for use specifically in MAFLD. MAFLD sits at a crossroads between the gut and the periphery. The development of MAFLD (including activation of the inflammatory cascade) is influenced by gut-related factors that include the gut microbiota and intactness of the gut mucosal wall. The gut microbiota may interact directly with the liver parenchyma (through translocation via the portal vein), or indirectly through the release of metabolic metabolites that include secondary bile acids, trimethylamine, and short-chain fatty acids (such as propionate and acetate). In turn, the liver mediates the metabolic status of peripheral tissues (including insulin sensitivity) through a complex interplay of hepatokines, liver-secreted metabolites, and liver-derived micro RNAs. As such, the liver plays a key central role in influencing overall metabolic status. In this concise review, we provide an overview of the complex mechanisms whereby MAFLD influences the development of insulin resistance within the periphery, and gut-related factors impact on the development of MAFLD. We also discuss lifestyle strategies for optimising metabolic liver health.

Search for top squarks in the four-body decay mode with single lepton final states in proton-proton collisions at $$ \sqrt{s} $$ = 13 TeV

Abstract: A search for the pair production of the lightest supersymmetric partner of the top quark, the top squark ($\tilde{\mathrm{t}}_1$), is presented. The search targets the four-body decay of the $\tilde{\mathrm{t}}_1$, which is preferred when the mass difference between the top squark and the lightest supersymmetric particle is smaller than the mass of the W boson. This decay mode consists of a bottom quark, two other fermions, and the lightest neutralino ($\tilde{\chi}^0_1$), which is assumed to be the lightest supersymmetric particle. The data correspond to an integrated luminosity of 138 fb$^{-1}$ of proton-proton collisions at a center-of-mass energy of 13 TeV collected by the CMS experiment at the CERN LHC. Events are selected using the presence of a high-momentum jet, an electron or muon with low transverse momentum, and a significant missing transverse momentum. The signal is selected based on a multivariate approach that is optimized for the difference between $m(\tilde{\mathrm{t}}_1)$ and $m(\tilde{\chi}^0_1)$. The contribution from leading background processes is estimated from data. No significant excess is observed above the expectation from standard model processes. The results of this search exclude top squarks at 95% confidence level for masses up to 480 and 700 GeV for $m(\tilde{\mathrm{t}}_1) - m(\tilde{\chi}^0_1$) = 10 and 80 GeV, respectively.