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2. p120 RasGAP and ZO-2 are essential for Hippo signaling and tumor-suppressor function mediated by p190A RhoGAP

Author

Hanyue Ouyang, Shuang Wu, Wangji Li, Michael J. Grey, Wenchao Wu, and Steen H. Hansen

Subjects
CP: Cancer, CP: Molecular biology, Biology (General), QH301-705.5
Abstract

Summary: ARHGAP35, which encodes p190A RhoGAP (p190A), is a major cancer gene. p190A is a tumor suppressor that activates the Hippo pathway. p190A was originally cloned via direct binding to p120 RasGAP (RasGAP). Here, we determine that interaction of p190A with the tight-junction-associated protein ZO-2 is dependent on RasGAP. We establish that both RasGAP and ZO-2 are necessary for p190A to activate large tumor-suppressor (LATS) kinases, elicit mesenchymal-to-epithelial transition, promote contact inhibition of cell proliferation, and suppress tumorigenesis. Moreover, RasGAP and ZO-2 are required for transcriptional modulation by p190A. Finally, we demonstrate that low ARHGAP35 expression is associated with shorter survival in patients with high, but not low, transcript levels of TJP2 encoding ZO-2. Hence, we define a tumor-suppressor interactome of p190A that includes ZO-2, an established constituent of the Hippo pathway, and RasGAP, which, despite strong association with Ras signaling, is essential for p190A to activate LATS kinases.

Published
2023
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3. Cosmological Test of an Ultraviolet Origin of Dark Energy

Author

Hans Christiansen, Bence Takács, and Steen H. Hansen

Subjects
dark energy, black hole physics, large-scale structure of the Universe, galaxies: kinematics and dynamics, Elementary particle physics, QC793-793.5
Abstract

The accelerated expansion of the Universe is impressively well described by a cosmological constant. However, the observed value of the cosmological constant is much smaller than expected based on quantum field theories. Recent efforts to achieve consistency in these theories have proposed a relationship between Dark Energy and the most compact objects, such as black holes (BHs). However, experimental tests are very challenging to devise and perform. In this article, we present a testable model with no cosmological constant in which the accelerated expansion can be driven by black holes. The model couples the expansion of the Universe (the Friedmann equation) with the mass function of cosmological halos (using the Press–Schechter formalism). Through the observed link between halo masses and BH masses, one thus gets a coupling between the expansion rate of the Universe and the BHs. We compare the predictions of this simple BH model with SN1a data and find poor agreement with observations. Our method is sufficiently general to allow us to also test a fundamentally different model, also without a cosmological constant, where the accelerated expansion is driven by a new force proportional to the internal velocity dispersion of galaxies. Surprisingly enough, this model cannot be excluded using the SN1a data.

Published
2024
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4. Mitochondrial transporter expression patterns distinguish tumor from normal tissue and identify cancer subtypes with different survival and metabolism

Author

Hartmut Wohlrab, Sabina Signoretti, Lucia E. Rameh, Derrick K. DeConti, and Steen H. Hansen

Subjects
Medicine, Science
Abstract

Abstract Transporters of the inner mitochondrial membrane are essential to metabolism. We demonstrate that metabolism as represented by expression of genes encoding SLC25 transporters differentiates human cancers. Tumor to normal tissue expression ratios for clear cell renal cell carcinoma, colon adenocarcinoma, lung adenocarcinoma and breast invasive carcinoma were found to be highly significant. Affinity propagation trained on SLC25 gene expression patterns from 19 human cancer types (6825 TCGA samples) and normal tissues (2322 GTEx samples) was used to generate clusters. They differentiate cancers from normal tissues. They also indicate cancer subtypes with survivals distinct from the total patient population of the cancer type. Probing the kidney, colon, lung, and breast cancer clusters, subtype pairs of cancers were identified with distinct prognoses and differing in expression of protein coding genes from among 2080 metabolic enzymes assayed. We demonstrate that SLC25 expression clusters facilitate the identification of the tissue-of-origin, essential to efficacy of most cancer therapies, of CUPs (cancer-unknown-primary) known to have poor prognoses. Different cancer types within a single cluster have similar metabolic patterns and this raises the possibility that such cancers may respond similarly to existing and new anti-cancer therapies.

Published
2022
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5. Preserved pharmacokinetics and pharmacodynamics of insulin degludec and liraglutide when administered as insulin degludec/liraglutide in a Chinese population

Author

Hongzhong Liu, Bin Luo, Xia Chen, Steen H. Ingwersen, Ting Jia, Lisbeth Vestergård Jacobsen, and Pei Hu

Subjects
IDegLira, Pharmacokinetics, Type 2 diabetes mellitus, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Abstract We report the findings of a single‐dose, randomized, three‐period cross‐over, clinical trial in healthy Chinese individuals (n = 24) comparing the pharmacokinetics of insulin degludec/liraglutide (IDegLira) with its individual components. Furthermore, we report a population pharmacokinetic analysis of a 26‐week, phase III, treat‐to‐target, randomized trial of 720 Chinese individuals with type 2 diabetes. Participants were randomized to IDegLira, degludec or liraglutide, all once daily with metformin. The pharmacokinetic profiles of IDegLira were similar to its individual components. Dose proportionality was indicated for both IDegLira components. Although there were no relevant covariate effects on degludec exposure, liraglutide exposure was inversely correlated with bodyweight. In conclusion, for the Chinese population, the pharmacokinetics of the fixed‐ratio combination IDegLira is similar to that of its individual components.

Published
2022
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6. Transthyretin Gene Variants and Associated Phenotypes in Danish Patients with Amyloid Cardiomyopathy

Author

Torsten B. Rasmussen, Bertil T. Ladefoged, Anne M. Dybro, Tor S. Clemmensen, Rikke H. Sørensen, Astrid J. Terkelsen, Henning Mølgaard, Henrik Vase, and Steen H. Poulsen

Subjects
transthyretin, amyloidosis, cardiomyopathy, genetics, TTR, ATTRv, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Genotyping divides transthyretin cardiac amyloidosis (ATTR-CA) in hereditary (ATTRv) and wild type (ATTRwt) forms. This study investigated the prevalence and clinical presentation of ATTRv in a contemporary cohort of consecutive ATTR-CA patients diagnosed at a tertiary Danish amyloidosis center. Age at diagnosis, clinical- and echocardiographic data, and transthyretin (TTR) genotype were recorded. Relatives of ATTRv patients underwent clinical phenotyping and predictive gene testing. Genetic testing in 102 patients identified four TTR variant carriers: p.Pro63Ser, p.Ala65Ser (n = 2) and p.Val142Ile. The mean age of ATTRv index patients was significantly lower compared to ATTRwt patients: 70.2 ± 1.2 versus 80.0 ± 6.2, p-value: 0.005. Evaluation of ATTRv families identified seven TTR variant carriers with a median age of 65 years (range 48–76) and three were diagnosed with ATTR-CA by DPD-scintigraphy. Family members with ATTR-CA were all asymptomatic and had normal levels of cardiac biomarkers. In conclusion, the prevalence of ATTRv in a contemporary Danish ATTR-CA cohort is 4%. ATTRv index patients were significantly younger age at diagnosis than ATTRwt patients. Non-p.Leu131Met TTR variants have reduced penetrance at the age of 65 years in which approximately half of variant carriers have asymptomatic ATTR-CA with normal LV systolic function and cardiac biomarker analyses.

Published
2022
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7. Clinical performance and exercise hemodynamics in patients with severe secondary tricuspid regurgitation and chronic atrial fibrillation

Author

Jesper K. Jensen, Tor S. Clemmensen, Christian A. Frederiksen, Joachim Schofer, Mads J. Andersen, and Steen H. Poulsen

Subjects
Atrial fibrillation, Secondary tricuspid regurgitation, Cardiac amyloid cardiomyopathy, Exercise hemodynamics, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Objective The study aimed to investigate the functional capacity and hemodynamics at rest and during exercise in patients with chronic atrial fibrillation and severe functional symptomatic tricuspid regurgitation (AF-FTR). Background Symptoms and clinical performance of severe AF-FTR mimic the population of patients with heart failure with preserved ejection fraction (HFpEF). Severe AF-FTR is known to be associated with an adverse prognosis whereas less is reported about the clinical performance including exercise capacity and hemodynamics in patients symptomatic AF-FTR. Methods Right heart catheterization (RHC) at rest and during exercise was conducted in a group of patients with stable chronic AF-TR and compared with a group of patients with HFpEF diagnosed with cardiac amyloid cardiomyopathy (CA). All patients had preserved ejection fraction and no significant left-sided disease. Results Patients with AF-FTR demonstrated a low exercise capacity that was comparable to CA patients (TR 4.9 ± 1.2 METS vs. CA 4. 7 ± 1.5 METS; P = 0.78) with an average peak maximal oxygen consumption of 15 mL/min/kg. Right atrium pressure increased significantly more in the AF-FTR patients as compared to CA patients at peak exercise (25 ± 8 vs 19 ± 9, p

Published
2021
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8. The Destiny of Dark Matter

Author

Fabiano Tracanna and Steen H. Hansen

Subjects
Dark matter, Cosmology, Gravitational waves, Black holes, Astrophysics, QB460-466
Abstract

The majority of baryons, which account for 15% of the matter in the Universe, will end their lives as carbon and oxygen inside cold black dwarfs. Dark matter (DM) makes up the remaining 85% of the matter in the Universe; however, the fate of DM is unknown. Here we show that the destiny of purely gravitationally interacting DM particles follows one of two possible routes. The first possible route, the “radiation-destiny” scenario, is that massive DM particles lose sufficient energy through gravitational radiation, causing them to spiral into a supermassive black hole that ultimately disappears through Hawking radiation. The second possible route, the “drifting-alone” destiny, applies to lighter DM particles, where only the central DM halo region spirals into the central BH, which is then Hawking radiated away. The rest of the DM halo is ripped apart by the accelerated expansion of the Universe.

Published
2023
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9. Levels of circulating semaglutide determine reductions in HbA1c and body weight in people with type 2 diabetes

Author

Rune V. Overgaard, Christin L. Hertz, Steen H. Ingwersen, Andrea Navarria, and Daniel J. Drucker

Subjects
diabetes, obesity, G protein coupled receptor, glucagon-like peptide, GLP-1, weight loss, Medicine (General), R5-920
Abstract

Summary: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used for the treatment of type 2 diabetes. Whether clinically important responses and adverse events (AEs) are dependent on the route of administration has not been determined. We demonstrate that nearly identical exposure-response pharmacodynamic relationships are determined by plasma semaglutide levels achieved through oral versus injectable administration for changes in HbA1c, body weight, biomarkers of cardiovascular risk, and AEs such as nausea and vomiting. At typical exposure levels for oral semaglutide, the estimated response is 1.58% (oral) versus −1.62% (subcutaneous) for HbA1c and 3.77% (oral) versus 3.48% (subcutaneous) reduction in body weight relative to baseline after 6 months. Increased body weight is the most important variable associated with reduced semaglutide exposure for both formulations. Hence, interindividual variation in GLP-1R responsivity or route of administration are not major determinants of GLP-1RA effectiveness in the clinic.

Published
2021
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10. Screening of novel HSP-inducing compounds to conserve cardiomyocyte function in experimental atrial fibrillation

Author

van Marion DMS, Hu X, Zhang D, Hoogstra-Berends F, Seerden JPG, Loen L, Heeres A, Steen H, Henning RH, and Brundel BJJM

Subjects
atrial fibrillation, heat shock protein, Drosophila, proteostasis, geranylgeranylacetone, Therapeutics. Pharmacology, RM1-950
Abstract

Denise MS van Marion,1,* Xu Hu,1,* Deli Zhang,1 Femke Hoogstra-Berends,2 Jean-Paul G Seerden,3 Lizette Loen,3 Andre Heeres,3,4 Herman Steen,5 Robert H Henning,2 Bianca JJM Brundel1 1Department of Physiology, Amsterdam Cardiovascular Sciences, VU University Medical Center, Amsterdam, The Netherlands; 2Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands; 3Syncom BV, Groningen, The Netherlands; 4Hanze University of Applied Sciences, Groningen, The Netherlands; 5Chaperone Pharma BV, Groningen, The Netherlands *These authors contributed equally to this work Background: The heat shock protein (HSP) inducer, geranylgeranylacetone (GGA), was previously found to protect against atrial fibrillation (AF) remodeling in experimental model systems. Clinical application of GGA in AF is limited, due to low systemic concentrations owing to the hydrophobic character of GGA.Objectives: To identify novel HSP-inducing compounds, with improved physicochemical properties, that prevent contractile dysfunction in experimental model systems for AF.Methods: Eighty-one GGA-derivatives were synthesized and explored for their HSP-inducing properties by assessment of HSP expression in HL-1 cardiomyocytes pretreated with or without a mild heat shock (HS), followed by incubation with 10 µM GGA or GGA-derivative. Subsequently, the most potent HSP-inducers were tested for preservation of calcium transient (CaT) amplitudes or heart wall contraction in pretreated tachypaced HL-1 cardiomyocytes (with or without HSPB1 siRNA) and Drosophilas, respectively. Finally, CaT recovery in tachypaced HL-1 cardiomyocytes posttreated with GGA or protective GGA-derivatives was determined.Results: Thirty GGA-derivatives significantly induced HSPA1A expression after HS, and seven showed exceeding HSPA1A expression compared to GGA. GGA and nine GGA-derivatives protected significantly from tachypacing (TP)-induced CaT loss, which was abrogated by HSPB1 suppression. GGA and four potent GGA-derivatives protected against heart wall dysfunction after TP compared to non-paced control Drosophilas. Of these compounds, GGA and three GGA-derivatives induced a significant restoration from CaT loss after TP of HL-1 cardiomyocytes.Conclusion: We identified novel GGA-derivatives with improved physicochemical properties compared to GGA. GGA-derivatives, particularly GGA*-59, boost HSP expression resulting in prevention and restoration from TP-induced remodeling, substantiating their role as novel therapeutics in clinical AF. Keywords: atrial fibrillation, heat shock protein, Drosophila, proteostasis, geranylger­anylacetone

Published
2019

11. Fractional laser-assisted topical delivery of bleomycin quantified by LC-MS and visualized by MALDI mass spectrometry imaging

Author

Kristoffer K. Hendel, Charlotte Bagger, Uffe H. Olesen, Christian Janfelt, Steen H. Hansen, Merete Haedersdal, and Catharina M. Lerche

Subjects
bleomycin, drug delivery, fractional laser, maldi-msi, skin cancer, Therapeutics. Pharmacology, RM1-950
Abstract

Bleomycin exhibits antiproliferative effects desirable for use in dermato-oncology but topical use is limited by its 1415 Da molar mass. Ablative fractional laser (AFL)-assisted drug delivery has been shown to enhance drug uptake in skin. The aim of this study was with AFL to deliver bleomycin into skin, quantify uptake, and visualize biodistribution with mass spectrometry. In a Franz diffusion cell study, pig skin samples (n = 66) were treated with AFL (λ = 10,600 nm), 5% density, and 0, 5, 20, or 80 mJ/microbeam (mb) pulse energies before exposure to bleomycin for 0.5, 4, or 24 h. Bleomycin was quantified in biopsy cryosections at depths of 100, 500, and 1500 µm using high-performance liquid chromatography-mass spectrometry (LC-MS), and drug biodistribution was visualized for 80 mJ/mb samples by matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). The pulse energies 5, 20, and 80 mJ/mb resulted in microscopic ablation zones (MAZs) reaching superficial, mid, and deep dermis respectively. Bleomycin was successfully delivered into the skin and deeper MAZs and longer exposure time resulted in higher skin concentrations. After 24 h, AFL exposure resulted in significant amounts of bleomycin throughout all skin layers (≥510 µg/cm3, p ≤ .002). In comparison, concentrations in intact skin exposed to bleomycin remained below limit of quantification. MALDI-MSI supported the quantitative LC-MS results by visualizing bleomycin biodistribution and revealing high uptake around MAZs with delivery into surrounding skin tissue. In conclusion, topical drug delivery of the large and hydrophilic molecule bleomycin is feasible, promising, and should be explored in an in vivo setting.

Published
2019
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12. Cosmological test of an ultraviolet origin of Dark Energy

Author

Christiansen, Hans, Takács, Bence, and Hansen, Steen H.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics, High Energy Physics - Phenomenology
Abstract

The accelerated expansion of the Universe is impressively well described by a cosmological constant. However, the observed value of the cosmological constant is much smaller than expected based on quantum field theories. Recent efforts to achieve consistency in these theories have proposed a relationship between Dark Energy and the most compact objects, such as black holes (BH). However, experimental tests are very challenging to devise and perform. In this article, we present a testable model with no cosmological constant, in which the accelerated expansion can be driven by black holes. The model couples the expansion of the Universe (the Friedmann equation) with the mass-function of cosmological haloes (using the Press-Schechter formalism). Through the observed link between halo-masses and BH-masses one thus gets a coupling between the expansion rate of the Universe and the BHs. We compare the predictions of this simple BH model with SN1a data and find a poor agreement with observations. Our method is sufficiently general that it allows us to also test a fundamentally different model, also without a cosmological constant, where the accelerated expansion is driven by a new force proportional to the internal velocity dispersion of galaxies. Surprisingly enough this model cannot be excluded using the SN1a data., Comment: 11 pages, 2 figures, Accepted by Universe, special issue "The Nature of Dark Energy", https://www.mdpi.com/2218-1997/10/5/193

Published
2024

13. A phenomenological model for dark matter phase space distribution

Author

Li, Zhen and Hansen, Steen H.

Subjects
Astrophysics - Astrophysics of Galaxies, General Relativity and Quantum Cosmology
Abstract

Understanding the nature of dark matter is among the top priorities of modern physics. However, due to its inertness, detecting and studying it directly in terrestrial experiments is extremely challenging. Numerical N-body simulations currently represent the best approach for studying the particle properties and phase space distribution, assuming the collisionless nature of dark matter. These simulations also address the lack of a satisfactory theory for predicting the universal properties of dark matter halos, including the density profile and velocity distribution. In this work, we propose a new phenomenological model for the dark matter phase space distribution. This model aims to provide an NFW-like density profile, velocity magnitude distribution, and velocity component distributions that align closely with simulation data. Our model is relevant both for theoretical modeling of dark matter distributions, as well as for underground detector experiments that rely on the dark matter velocity distribution for experimental analysis., Comment: 9 pages, 13 figures, 2 tables

Published
2023

14. Green tea extract as a treatment for patients with wild-type transthyretin amyloidosis: an observational study

Author

aus dem Siepen F, Bauer R, Aurich M, Buss SJ, Steen H, Altl, K, Katus HA, and Kristen AV

Subjects
wildtype-ATTR, cardiomyopathy, polyphenol, EGCG, Therapeutics. Pharmacology, RM1-950
Abstract

Fabian aus dem Siepen,1 Ralf Bauer,1 Matthias Aurich,1 Sebastian J Buss,1 Henning Steen,1 Klaus Altland,2 Hugo A Katus,1 Arnt V Kristen1 1Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany; 2Institute of Human Genetics, Justus-Liebig-University, Giessen, Germany Background: Causative treatment of patients with wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is lacking. Recent reports indicate the potential use of epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, to inhibit amyloid fibril formation. We sought to investigate changes of cardiac function and morphology in patients with wtATTR-CM after consumption of green tea extract (GTE). Methods: Twenty-five male patients (71 [64; 80] years) with wtATTR-CM were submitted to clinical examination, echocardiography, cardiac magnetic resonance imaging (cMRI) (n=14), and laboratory testing before and after daily consumption of GTE capsules containing 600 mg epigallocatechin-3-gallate for at least 12 months. Results: A significant decrease of left ventricular (LV) myocardial mass by 6% (196 [100; 247] vs 180 [85; 237] g; P=0.03) by cMRI and total cholesterol by 8.4% (191 [118; 267] vs 173 [106; 287] mg/dL; P=0.006) was observed after a 1-year period of GTE consumption. LV ejection fraction by cMRI (53% [33%; 69%] vs 54% [28%; 71%]; P=0.75), LV wall thickness (17 [13; 21] vs 18 [14; 25] mm; P=0.1), and mitral annular plane systolic excursion (10 [5; 23] vs 8 [4; 13] mm; P=0.3) by echocardiography remained unchanged. Conclusion: This study supports LV mass stabilization in patients with wtATTR-CM consuming GTE potentially indicating amyloid fibril reduction. Keywords: wild-type ATTR, cardiomyopathy, polyphenol, EGCG

Published
2015

15. INAVA-ARNO complexes bridge mucosal barrier function with inflammatory signaling

Author

Phi Luong, Matija Hedl, Jie Yan, Tao Zuo, Tian-Min Fu, Xiaomo Jiang, Jay R Thiagarajah, Steen H Hansen, Cammie F Lesser, Hao Wu, Clara Abraham, and Wayne I Lencer

Subjects
ARNO, IL-1b, TRAF6, epithelial barrier, actin assembly, inflammatory bowel disease, Medicine, Science, Biology (General), QH301-705.5
Abstract

Homeostasis at mucosal surfaces requires cross-talk between the environment and barrier epithelial cells. Disruption of barrier function typifies mucosal disease. Here we elucidate a bifunctional role in coordinating this cross-talk for the inflammatory bowel disease risk-gene INAVA. Both activities require INAVA’s DUF3338 domain (renamed CUPID). CUPID stably binds the cytohesin ARF-GEF ARNO to effect lateral membrane F-actin assembly underlying cell-cell junctions and barrier function. Unexpectedly, when bound to CUPID, ARNO affects F-actin dynamics in the absence of its canonical activity as a guanine nucleotide-exchange factor. Upon exposure to IL-1β, INAVA relocates to form cytosolic puncta, where CUPID amplifies TRAF6-dependent polyubiquitination and inflammatory signaling. In this case, ARNO binding to CUPID negatively-regulates polyubiquitination and the inflammatory response. INAVA and ARNO act similarly in primary human macrophages responding to IL-1β and to NOD2 agonists. Thus, INAVA-CUPID exhibits dual functions, coordinated directly by ARNO, that bridge epithelial barrier function with extracellular signals and inflammation.

Published
2018
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16. Accuracy of the Aspartic Acid Racemization Technique in Age Estimation of Mammals and the Influence of Body Temperature

Author

Eva Garde, Mads F. Bertelsen, Susanne Ditlevsen, Mads Peter Heide-Jørgensen, Nynne H. Nielsen, Anne K. Frie, Droplaug Olafsdottir, Ursula Siebert, and Steen H. Hansen

Subjects
age estimation, aspartic acid racemization, pygmy goat, Ecology, QH540-549.5
Abstract

The aspartic acid racemization (AAR) technique has been applied for age estimation of humans and other mammals for more than four decades. In this study, eye lenses from 124 animals representing 25 mammalian species were collected and D/L ratios obtained using the AAR technique. The animals were either of known age or had the age estimated by other methods. The purpose of the study was to: a) estimate the accuracy of the AAR technique, and b) examine the effect of body temperature on racemization rates. Samples from four of the 25 species covered the range of ages that is needed to estimate species-specific racemization rates. The sample size from a single species of known age, the pygmy goat (Capra hircus, n = 35), was also large enough to investigate the accuracy of ages obtained using the AAR technique. The 35 goats were divided into three datasets: all goats (n = 35), goats >0.5 yrs old (n = 26) and goats >2 yrs old (n = 19). Leave-one-out analyses were performed on the three sets of data. Normalized root mean squared errors for the group of goats >0.5 yrs old were found to be the smallest. The higher variation in D/L measurements found for young goats 0.5 yrs old was for three age groups of the goats: 0.934 yrs for young goats 8 yrs (n = 4). Thus, the age of an adult or an old animal can be predicted with approximately 10% accuracy, whereas the age of a young animal is difficult to predict. A goat specific racemization rate, as a 2kAsp value, was estimated to 0.0107 ± 3.8 x 10-4 SE (n = 26). The 2kAsp values from 12 species, four estimated in this study and another eight published, were used to examine the effect of core body temperature on the rate of racemization. A positive relationship between AAR and temperature was found (r2 = 0.321) but results also suggest that other factors besides temperature are involved in the racemization process in living animals. Based on our results we emphasize that non-species-specific racemization rates should be used with care in AAR age estimation studies and that the period of postnatal growth of the eye lens be considered when estimating species-specific D/L0 values and ages of young individuals.

Published
2018
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17. The destiny of Dark Matter

Author

Tracanna, Fabiano and Hansen, Steen H.

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

The majority of baryons, which account for $15\%$ of the matter in the Universe, will end their lives as carbon and oxygen inside cold black dwarfs. Dark matter (DM) makes up the remaining $85\%$ of the matter in the universe, however, the fate of DM is unknown. Here we show that the destiny of purely gravitationally interacting DM particles follows one of two possible routes. The first possible route, the "radiation-destiny" scenario, is that massive DM particles lose sufficient energy through gravitational radiation causing them to spiral into a supermassive black hole that ultimately disappears through Hawking radiation. The second possible route, the "drifting-alone" destiny, applies to lighter DM particles, where only the central DM halo region spirals into the central BH which is then Hawking radiated away. The rest of the DM halo is ripped apart by the accelerated expansion of the Universe., Comment: 15 pages, 5 figures, accepted by ApJ

Published
2023

18. Two techniques of age estimation in cetaceans: GLGs in teeth and earplugs, and measuring the AAR rate in eye lens nucleus

Author

Nynne H Nielsen, Gísli A. Víkingsson, Steen H. Hansen, Susanne Ditlevsen, and Mads Peter Heide-Jørgensen

Subjects
Fin whale, Balaenoptera physalus, minke whale, Balaenoptera acutorostrata, harbour porpoise, Phocoena phocoena, aspartic acid racemization, AAR, age estimation, growth layer groups, GLGs, Ecology, QH540-549.5
Abstract

The ages of three species of cetaceans were estimated by counting the growth layer groups (GLG) and measuring the aspartic acid racemization rate (kAsp) by what is referred to as the Aspartic Acid Racemization (AAR) technique. Data on kAsp and the D/L ratio of aspartic acid at birth [(D/L)0] in North Atlantic common minke whales (Balaenoptera acutorostrata) are presented along with data on fin whales (B. physalus) and harbour porpoises (Phocoena phocoena) already published by Nielsen et al. (2012). The kAsp specific for minke whales was 1.40 x 10-3 yr-1 (SE ± 0.00005) and the (D/L)0 was 0.0194 (SE ± 0.0012). The correlation of GLG age and D/L ratio for all three species was highly significant; however, the correlation coefficient varied greatly (fin whales: R2 = 0.59, p

Published
2017
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19. Aspartic acid racemization rate in narwhal (Monodon monoceros) eye lens nuclei estimated by counting of growth layers in tusks

Author

Eva Garde, Susanne Ditlevsen, Steen H. Hansen, and Mads Peter Heide-Jørgensen

Subjects
Age estimation, Greenland, species-specific racemization rate, growth layers groups, Environmental sciences, GE1-350, Oceanography, GC1-1581
Abstract

Ages of marine mammals have traditionally been estimated by counting dentinal growth layers in teeth. However, this method is difficult to use on narwhals (Monodon monoceros) because of their special tooth structures. Alternative methods are therefore needed. The aspartic acid racemization (AAR) technique has been used in age estimation studies of cetaceans, including narwhals. The purpose of this study was to estimate a species-specific racemization rate for narwhals by regressing aspartic acid d/l ratios in eye lens nuclei against growth layer groups in tusks (n=9). Two racemization rates were estimated: one by linear regression (r2=0.98) based on the assumption that age was known without error, and one based on a bootstrap study, taking into account the uncertainty in the age estimation (r2 between 0.88 and 0.98). The two estimated 2kAsp values were identical up to two significant figures. The 2k Asp value from the bootstrap study was found to be 0.00229±0.000089 SE, which corresponds to a racemization rate of 0.00114−yr±0.000044 SE. The intercept of 0.0580±0.00185 SE corresponds to twice the (d/l)0 value, which is then 0.0290±0.00093 SE. We propose that this species-specific racemization rate and (d/l)0 value be used in future AAR age estimation studies of narwhals, but also recommend the collection of tusks and eyes of narwhals for further improving the (d/l)0 and 2kAsp estimates obtained in this study.

Published
2012
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20. Benefits of a ball and chain: simple environmental enrichments improve welfare and reproductive success in farmed American mink (Neovison vison).

Author

Rebecca K Meagher, Jamie Ahloy Dallaire, Dana L M Campbell, Misha Ross, Steen H Møller, Steffen W Hansen, María Díez-León, Rupert Palme, and Georgia J Mason

Subjects
Medicine, Science
Abstract

Can simple enrichments enhance caged mink welfare? Pilot data from 756 sub-adults spanning three colour-types (strains) identified potentially practical enrichments, and suggested beneficial effects on temperament and fur-chewing. Our main experiment started with 2032 Black mink on three farms: from each of 508 families, one juvenile male-female pair was enriched (E) with two balls and a hanging plastic chain or length of hose, while a second pair was left as a non-enriched (NE) control. At 8 months, more than half the subjects were killed for pelts, and 302 new females were recruited (half enriched: 'late E'). Several signs of improved welfare or productivity emerged. Access to enrichment increased play in juveniles. E mink were calmer (less aggressive in temperament tests; quieter when handled; less fearful, if male), and less likely to fur-chew, although other stereotypic behaviours were not reduced. On one farm, E females had lower cortisol (inferred from faecal metabolites). E males tended to copulate for longer. E females also weaned more offspring: about 10% more juveniles per E female, primarily caused by reduced rates of barrenness ('late E' females also giving birth to bigger litters on one farm), effects that our data cautiously suggest were partly mediated by reduced inactivity and changes in temperament. Pelt quality seemed unaffected, but E animals had cleaner cages. In a subsidiary side-study using 368 mink of a second colour-type ('Demis'), similar temperament effects emerged, and while E did not reduce fur-chewing or improve reproductive success in this colour-type, E animals were judged to have better pelts. Overall, simple enrichments were thus beneficial. These findings should encourage welfare improvements on fur farms (which house 60-70 million mink p.a.) and in breeding centres where endangered mustelids (e.g. black-footed ferrets) often reproduce poorly. They should also stimulate future research into more effective practical enrichments.

Published
2014
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23. Fast and non-toxic in situ hybridization without blocking of repetitive sequences.

Author

Steen H Matthiesen and Charles M Hansen

Subjects
Medicine, Science
Abstract

Formamide is the preferred solvent to lower the melting point and annealing temperature of nucleic acid strands in in situ hybridization (ISH). A key benefit of formamide is better preservation of morphology due to a lower incubation temperature. However, in fluorescence in situ hybridization (FISH), against unique DNA targets in tissue sections, an overnight hybridization is required to obtain sufficient signal intensity. Here, we identified alternative solvents and developed a new hybridization buffer that reduces the required hybridization time to one hour (IQFISH method). Remarkably, denaturation and blocking against repetitive DNA sequences to prevent non-specific binding is not required. Furthermore, the new hybridization buffer is less hazardous than formamide containing buffers. The results demonstrate a significant increased hybridization rate at a lowered denaturation and hybridization temperature for both DNA and PNA (peptide nucleic acid) probes. We anticipate that these formamide substituting solvents will become the foundation for changes in the understanding and performance of denaturation and hybridization of nucleic acids. For example, the process time for tissue-based ISH for gene aberration tests in cancer diagnostics can be reduced from days to a few hours. Furthermore, the understanding of the interactions and duplex formation of nucleic acid strands may benefit from the properties of these solvents.

Published
2012
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24. Accelerated expansion induced by Dark Matter with two charges

Author

Hansen, Steen H.

Subjects
Physics - General Physics
Abstract

The accelerated expansion of the universe has been established through observations of supernovae, the growth of structure, and the cosmic microwave background. The most popular explanation is Einsteins cosmological constant, or dynamic variations hereof. A recent paper demonstrated that if dark matter particles are endowed with a repulsive force proportional to the internal velocity dispersion of galaxies, then the corresponding acceleration of the universe may follow that of a cosmological constant fairly closely. However, no such long-range force is known to exist. A concrete example of such a force is derived here, by equipping the dark matter particles with two new dark charges. This result lends support to the possibility that the current acceleration of the universe may be explained without the need for a cosmological constant., Comment: 5 pages, no figure, accepted by MNRAS

Published
2021
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25. A force proportional to velocity squared derived from spacetime algebra

Author

Hansen, Steen H.

Subjects
General Relativity and Quantum Cosmology, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

The underlying geometri of spacetime algebra allows one to derive a force by contracting the relativistic generalization of angular momentum, M, with the mass-current, mw, where w is a proper 4-vector velocity. By applying this force to a cosmological object, a repulsive inverse distance-square law is found, which is proportional to the velocity dispersion squared of that structure. It is speculated if this finding may be relevant to the recent suggestion, that such a force may accelerate the expanding universe with no need for a cosmological constant., Comment: 4 pages, no figure, submitted to MNRAS

Published
2021
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27. Consistency analysis of a Dark Matter velocity dependent force as an alternative to the Cosmological Constant

Author

Loeve, Karoline, Nielsen, Kristine Simone, and Hansen, Steen H.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

A range of cosmological observations demonstrate an accelerated expansion of the Universe, and the most likely explanation of this phenomenon is a cosmological constant. Given the importance of understanding the underlying physics, it is relevant to investigate alternative models. This article uses numerical simulations to test the consistency of one such alternative model. Specifically, this model has no cosmological constant, instead the dark matter particles have an extra force proportional to velocity squared, somewhat reminiscent of the magnetic force in electrodynamics. The constant strength of the force is the only free parameter. Since bottom-up structure formation creates cosmological structures whose internal velocity dispersions increase in time, this model may mimic the temporal evolution of the effect from a cosmological constant. It is shown that models with force linearly proportional to internal velocites, or models proportional to velocity to power three or more cannot mimic the accelerated expansion induced by a cosmological constant. However, models proportional to velocity squared are still consistent with the temporal evolution of a Universe with a cosmological model., Comment: 5 pages, 3 figures, ApJ format

Published
2021
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29. Baryons in the CosmicWeb of IllustrisTNG -- II: the Connection among Galaxies, Halos, their Formation Time and their Location in the Cosmic Web

Author

Martizzi, Davide, Vogelsberger, Mark, Torrey, Paul, Pillepich, Annalisa, Hansen, Steen H., Marinacci, Federico, and Hernquist, Lars

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

The connections among galaxies, the dark matter halos where they form and the properties of the large-scale Cosmic Web still need to be completely disentangled. We use the cosmological hydrodynamical simulation TNG100 of the IllustrisTNG suite to quantify the effects played by the large-scale density field and the Cosmic Web morphology on the relation between halo mass and galaxy stellar mass. We select objects with total dynamical mass in the range $\geq 6.3\times 10^{10} h ^{-1}\, M_{\odot}$ up to a few $10^{14} h^{-1} \, M_{\odot}$ between redshift $z=4$ and redshift $z=0$. A Cosmic Web class (knot, filament, sheet, void) is assigned to each region of the volume using a density field deformation tensor-based method. We find that galaxy stellar mass strongly correlates with total dynamical mass and formation time, and more weakly with large-scale overdensity and Cosmic Web class. The latter two quantities correlate with each other, but are not entirely degenerate. Furthermore, we find that at fixed halo mass, galaxies with stellar mass lower than the median value are more likely to be found in voids and sheets, whereas galaxies with stellar mass higher than the median are more likely to be found in filaments and knots. Finally, we find that the dependence on environment is stronger for satellites than for centrals, and discuss the physical implications of these results., Comment: Accepted by MNRAS. 12 pages, 6 figures, 3 tables

Published
2019
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30. Distinguishing cosmologies using the turn-around radius near galaxy clusters

Author

Hansen, Steen H., Hassani, Farbod, Lombriser, Lucas, and Kunz, Martin

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

Outside galaxy clusters the competition between the inwards gravitational attraction and the outwards expansion of the Universe leads to a special radius of velocity cancellation, which is called the turn-around radius. Measurements of the turn-around radius hold promises of constraining cosmological parameters, and possibly even properties of gravity. Such a measurement is, however, complicated by the fact that the surroundings of galaxy clusters are not spherical, but instead are a complicated collection of filaments, sheets and voids. In this paper we use the results of numerically simulated universes to quantify realistic error-bars of the measurement of the turn-around radius. We find that for a $\Lambda$CDM cosmology these error-bars are typically of the order of $20\%$. We numerically simulate three different implementations of dark energy models and of a scalar dark sector interaction to address whether the turn-around radius can be used to constrain non-trivial cosmologies, and we find that only rather extreme models can be distinguished from a $\Lambda$CDM universe due to the large error-bars arising from the non-trivial cluster environments., Comment: 15 pages, 8 figures. Updated to match version published in JCAP

Published
2019
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31. Estimating the dark matter velocity anisotropy to the cluster edge

Author

Svensmark, Jacob, Hansen, Steen H., Martizzi, Davide, Moore, Ben, and Teyssier, Romain

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics, 85A04
Abstract

Dark matter dominates the properties of large cosmological structures such as galaxy clusters, and the mass profiles of the dark matter have been measured for these equilibrated structures for years using X-rays, lensing or galaxy velocities. A new method has been proposed, which should allow us to estimate a dynamical property of the dark matter, namely the velocity anisotropy. For the gas a similar velocity anisotropy is zero due to frequent collisions, however, the collisionless nature of dark matter allows it to be non-trivial. Numerical simulations have for years found non-zero and radially varying dark matter velocity anisotropies. Here we employ the method proposed by Hansen and Pifaretti (2007), and developed by Host et al. (2009) to estimate the dark matter velocity anisotropy in the bright galaxy cluster Perseus, to near 5 times the radii previously obtained. We find the dark matter velocity anisotropy to be consistent with the results of numerical simulations, however, still with large error-bars. At half the virial radius we find the velocity anisotropy to be non-zero at 1.7 standard deviations, lending support to the collisionless nature of dark matter., Comment: 20 pages, 10 figures

Published
2019
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32. Prognostic Value of Preprocedural LV Global Longitudinal Strain for Post-TAVR-Related Morbidity and Mortality: A Meta-Analysis

Author

Stens, Niels A., van Iersel, Odette, Rooijakkers, Max J.P., van Wely, Marleen H., Nijveldt, Robin, Bakker, Esmée A., Rodwell, Laura, Pedersen, Anders L.D., Poulsen, Steen H., Kjønås, Didrik, Stassen, Jan, Bax, Jeroen J., Tanner, Felix C., Lerakis, Stamatios, Shimoni, Sara, Poulin, Frédéric, Ferreira, Vera, Reskovic Luksic, Vlatka, van Royen, Niels, and Thijssen, Dick H.J.

Published
2023
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33. Subclinical leaflet thrombosis after transcatheter aortic valve implantation: no association with left ventricular reverse remodeling at 1-year follow-up

Author

Kuneman, Jurrien H., Singh, Gurpreet K., Hansson, Nicolaj C., Fusini, Laura, Poulsen, Steen H., Fortuni, Federico, Vollema, E. Mara, Pedersen, Anders L. D., Annoni, Andrea D., Nørgaard, Bjarne L., Pontone, Gianluca, Ajmone Marsan, Nina, Delgado, Victoria, Bax, Jeroen J., and Knuuti, Juhani

Published
2022
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36. The structure and assembly history of cluster-size haloes in Self-Interacting Dark Matter

Author

Brinckmann, Thejs, Zavala, Jesús, Rapetti, David, Hansen, Steen H., and Vogelsberger, Mark

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We perform dark-matter-only simulations of 28 relaxed massive cluster-sized haloes for Cold Dark Matter (CDM) and Self-Interacting Dark Matter (SIDM) models, to study structural differences between the models at large radii, where the impact of baryonic physics is expected to be very limited. We find that the distributions for the radial profiles of the density, ellipsoidal axis ratios, and velocity anisotropies ($\beta$) of the haloes differ considerably between the models (at the $\sim1\sigma$ level), even at $\gtrsim10\%$ of the virial radius, if the self-scattering cross section is $\sigma/m_\chi=1$ cm$^2$ gr$^{-1}$. Direct comparison with observationally inferred density profiles disfavours SIDM for $\sigma/m_\chi=1$ cm$^2$ gr$^{-1}$, but in an intermediate radial range ($\sim3\%$ of the virial radius), where the impact of baryonic physics is uncertain. At this level of the cross section, we find a narrower $\beta$ distribution in SIDM, clearly skewed towards isotropic orbits, with no SIDM (90\% of CDM) haloes having $\beta>0.12$ at $7\%$ of the virial radius. We estimate that with an observational sample of $\sim30$ ($\sim10^{15}$ M$_\odot$) relaxed clusters, $\beta$ can potentially be used to put competitive constraints on SIDM, once observational uncertainties improve by a factor of a few. We study the suppression of the memory of halo assembly history in SIDM clusters. For $\sigma/m_\chi=1$ cm$^2$ gr$^{-1}$, we find that this happens only in the central halo regions ($\sim1/4$ of the scale radius of the halo), and only for haloes that assembled their mass within this region earlier than a formation redshift $z_f\sim2$. Otherwise, the memory of assembly remains and is reflected in ways similar to CDM, albeit with weaker trends., Comment: 15 pages, 15 figures. Submitted to MNRAS. Revisions: added new figure with an observational comparison of density profiles, improvements and corrections to the section on velocity anisotropies

Published
2017
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37. Analytical derivation of the radial distribution function in spherical dark matter halos

Author

Eilersen, Andreas, Hansen, Steen H., and Zhang, Xingyu

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

The velocity distribution of dark matter near the Earth is important for an accurate analysis of the signals in terrestrial detectors. This distribution is typically extracted from numerical simulations. Here we address the possibility of deriving the velocity distribution function analytically. We derive a differential equation which is a function of radius and the radial component of the velocity. Under various assumptions this can be solved, and we compare the solution with the results from controlled numerical simulations. Our findings complement the previously derived tangential velocity distribution. We hereby demonstrate that the entire distribution function, below 0.7 v_esc, can be derived analytically for spherical and equilibrated dark matter structures., Comment: 6 pages, 5 figures, submitted to MNRAS

Published
2017
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46. Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Author

Schwartz, Gregory G., Gabriel Steg, P.h., Bhatt, Deepak L., Bittner, Vera A., Diaz, Rafael, Goodman, Shaun G., Harrington, Robert A., Jukema, J. Wouter, Szarek, Michael, White, Harvey D., Zeiher, Andreas M., Tricoci, Pierluigi, Roe, Matthew T., Mahaffey, Kenneth W., Edelberg, Jay M., Hanotin, Corinne, Lecorps, Guillaume, Moryusef, Angèle, Pordy, Robert, Sasiela, William J., Tamby, Jean-François, Aylward, Philip E., Drexel, Heinz, Sinnaeve, Peter, Dilic, Mirza, Lopes, Renato D., Gotcheva, Nina N., Prieto, Juan-Carlos, Yong, Huo, López-Jaramillo, Patricio, Pećin, Ivan, Reiner, Zeljko, Ostadal, Petr, Poulsen, Steen Hvitfeldt, Viigimaa, Margus, Nieminen, Markku S., Danchin, Nicolas, Chumburidze, Vakhtang, Marx, Nikolaus, Liberopoulos, Evangelos, Montenegro Valdovinos, Pablo Carlos, Tse, Hung-Fat, Kiss, Robert Gabor, Xavier, Denis, Zahger, Doron, Valgimigli, Marco, Kimura, Takeshi, Kim, Hyo Soo, Kim, Sang-Hyun, Erglis, Andrejs, Laucevicius, Aleksandras, Kedev, Sasko, Yusoff, Khalid, Ramos López, Gabriel Arturo, Alings, Marco, Halvorsen, Sigrun, Correa Flores, Roger M., Sy, Rody G., Budaj, Andrzej, Morais, Joao, Dorobantu, Maria, Karpov, Yuri, Ristic, Arsen D., Chua, Terrance, Murin, Jan, Fras, Zlatko, Dalby, Anthony J., Tuñón, José, Asita de Silva, H., Hagström, Emil, Landmesser, Ulf, Müller, Christian, Chiang, Chern-En, Sritara, Piyamitr, Guneri, Sema, Parkhomenko, Alexander, Ray, Kausik K., Moriarty, Patrick M., Vogel, Robert, Chaitman, Bernard, Kelsey, Sheryl F., Olsson, Anders G., Rouleau, Jean-Lucien, Simoons, Maarten L., Alexander, Karen, Meloni, Chiara, Rosenson, Robert, Sijbrands, Eric J.G., Alexander, John H., Armaganijan, Luciana, Bagai, Akshay, Bahit, Maria Cecilia, Brennan, J. Matthew, Clifton, Shaun, DeVore, Adam D., Deloatch, Shalonda, Dickey, Sheila, Dombrowski, Keith, Ducrocq, Grégory, Eapen, Zubin, Endsley, Patricia, Eppinger, Arleen, Harrison, Robert W., Hess, Connie Ng, Hlatky, Mark A., Jordan, Joseph Dedrick, Knowles, Joshua W., Kolls, Bradley J., Kong, David F., Leonardi, Sergio, Lillis, Linda, Maron, David J., Marcus, Jill, Mathews, Robin, Mehta, Rajendra H., Mentz, Robert J., Moreira, Humberto Graner, Patel, Chetan B., Pereira, Sabrina Bernardez, Perkins, Lynn, Povsic, Thomas J., Puymirat, Etienne, Jones, William Schuyler, Shah, Bimal R., Sherwood, Matthew W., Stringfellow, Kenya, Sujjavanich, Darin, Toma, Mustafa, Trotter, Charlene, van Diepen, Sean F.P., Wilson, Matthew D., Tze-Kay Yan, Andrew, Schiavi, Lilia B., Garrido, Marcelo, Alvarisqueta, Andrés F., Sassone, Sonia A., Bordonava, Anselmo P., Alves De Lima, Alberto E., Schmidberg, Jorge M., Duronto, Ernesto A., Caruso, Orlando C., Novaretto, Leonardo P., Hominal, Miguel Angel, Montaña, Oscar R., Caccavo, Alberto, Gomez Vilamajo, Oscar A., Lorenzatti, Alberto J., Cartasegna, Luis R., Paterlini, Gustavo A., Mackinnon, Ignacio J., Caime, Guillermo D., Amuchastegui, Marcos, Salomone, Oscar, Codutti, Oscar R., Jure, Horacio O., Bono, Julio O.E., Hrabar, Adrian D., Vallejos, Julio A., Ahuad Guerrero, Rodolfo A., Novoa, Federico, Patocchi, Cristian A., Zaidman, Cesar J., Giuliano, Maria E., Dran, Ricardo D., Vico, Marisa L., Carnero, Gabriela S., Guzman, Pablo N., Medrano Allende, Juan C., Garcia Brasca, Daniela F., Bustamante Labarta, Miguel H., Nani, Sebastian, Blumberg, Eduardo D.S., Colombo, Hugo R., Liberman, Alberto, Fuentealba, Victorino, Luciardi, Hector L., Waisman, Gabriel D., Berli, Mario A., Garcia Duran, Ruben O., Cestari, Horacio G., Luquez, Hugo A., Giordano, Jorge A., Saavedra, Silvia S., Zapata, Gerardo, Costamagna, Osvaldo, Llois, Susana, Waites, Jonathon H., Collins, Nicholas, Soward, Allan, Hii, Chris L.S., Shaw, James, Arstall, Margaret A., Horowitz, John, Ninio, Daniel, Rogers, James F., Colquhoun, David, Oqueli Flores, Romulo E., Roberts-Thomson, Philip, Raffel, Owen, Lehman, Sam J., Aroney, Constantine, Coverdale, Steven G.M., Garrahy, Paul J., Starmer, Gregory, Sader, Mark, Carroll, Patrick A., Dick, Ronald, Zweiker, Robert, Hoppe, Uta, Huber, Kurt, Berger, Rudolf, Delle-Karth, Georg, Frey, Bernhard, Faes, Dirk, Hermans, Kurt, Pirenne, Bruno, Leone, Attilio, Hoffer, Etienne, Vrolix, Mathias C.M., De Wolf, Luc, Wollaert, Bart, Castadot, Marc, Dujardin, Karl, Beauloye, Christophe, Vervoort, Geert, Striekwold, Harry, Convens, Carl, Roosen, John, Barbato, Emanuele, Claeys, Marc, Cools, Frank, Terzic, Ibrahim, Barakovic, Fahir, Midzic, Zlatko, Pojskic, Belma, Fazlibegovic, Emir, Durak-Nalbantic, Azra, Kulić, Mehmed, Vulic, Dusko, Muslibegovic, Adis, Goronja, Boris, Reis, Gilmar, Sousa, Luciano, Nicolau, Jose C., Giorgeto, Flavio E., Silva, Ricardo P., Maia, Lilia Nigro, Rech, Rafael, Rossi, Paulo R.F., Cerqueira, Maria José A.G., Duda, Norberto, Kalil, Renato, Kormann, Adrian, Abrantes, José Antonio M., Filho, Pedro Pimentel, Soggia, Ana Priscila, de Santos, Mayler O.N., Neuenschwander, Fernando, Bodanese, Luiz C., Michalaros, Yorghos L., Eliaschewitz, Freddy G., Vidotti, Maria H., Leaes, Paulo E., Botelho, Roberto V., Kaiser, Sergio, Fernandes Manenti, Euler Roberto F., Precoma, Dalton B., Moura Jorge, Jose C., Silva, Pedro, Silveira, Jose A., Saporito, Wladmir, Marin Neto, Jose A., Feitosa, Gilson S., Ritt, Luiz Eduardo F., de Souza, Juliana A., Costa, Fernando, Souza, Weimar K.S.B., Reis, Helder J.L., Machado, Leandro, Aidar Ayoub, José Carlos, Todorov, Georgi V., Nikolov, Fedya P., Velcheva, Elena S., Tzekova, Maria L., Benov, Haralambi O., Petranov, Stanislav L., Tumbev, Haralin S., Shehova-Yankova, Nina S., Markov, Dimitar T., Raev, Dimitar H., Mollov, Mihail N., Kichukov, Kostadin N., Ilieva-Pandeva, Katya A., Ivanova, Raya, Gospodinov, Maryana, Mincheva, Valentina M., Lazov, Petar V., Dimov, Bojidar I., Senaratne, Manohara, Stone, James, Kornder, Jan, Pearce, Stephen, Dion, Danielle, Savard, Daniel, Pesant, Yves, Pandey, Amritanshu, Robinson, Simon, Gosselin, Gilbert, Vizel, Saul, Hoag, Gordon, Bourgeois, Ronald, Morisset, Anne, Sabbah, Eric, Sussex, Bruce, Kouz, Simon, MacDonald, Paul, Diaz, Ariel, Michaud, Nicolas, Fell, David, Leung, Raymond, Vuurmans, Tycho, Lai, Christopher, Nigro, Frank, Davies, Richard, Nogareda, Gustavo, Vijayaraghavan, Ram, Ducas, John, Lepage, Serge, Mehta, Shamir, Cha, James, Dupuis, Robert, Fong, Peter, Lutchmedial, Sohrab, Rodes-Cabau, Josep, Fadlallah, Hussein, Cleveland, David, Huynh, Thao, Bata, Iqbal, Hameed, Adnan, Pincetti, Cristian, Potthoff, Sergio, Prieto, Juan C., Acevedo, Monica, Aguirre, Arnoldo, Vejar, Margarita, Yañez, Mario, Araneda, Guillermo, Fernandez, Mauricio, Perez, Luis, Varleta, Paola, Florenzano, Fernando, Huidobro, Laura, Raffo, Carlos A., Olivares, Claudia, Nahuelpan, Leonardo, Montecinos, Humberto, Chen, Jiyan, Dong, Yugang, Huang, Weijian, Wang, Jianzhong, Huang, Shi'An, Yao, Zhuhua, Li, Xiang, Cui, Lan, Lin, Wenhua, Sun, Yuemin, Wang, Jingfeng, Li, Jianping, Zhang, Xuelian, Zhu, Hong, Chen, Dandan, Huang, Lan, Dong, Shaohong, Su, Guohai, Xu, Biao, Su, Xi, Cheng, Xiaoshu, Lin, Jinxiu, Zong, Wenxia, Li, Huanming, Feng, Yi, Xu, Dingli, Yang, Xinchun, Ke, Yuannan, Lin, Xuefeng, Zhang, Zheng, Zheng, Zeqi, Luo, Zhurong, Chen, Yundai, Ding, Chunhua, Zhong, Yi, Zheng, Yang, Li, Xiaodong, Peng, Daoquan, Zhao, Shuiping, Li, Ying, Liu, Xuebo, Wei, Meng, Liu, Shaowen, Yu, Yihua, Qu, Baiming, Jiang, Weihong, Zhou, Yujie, Zhao, Xingsheng, Yuan, Zuyi, Guo, Ying, Xu, Xiping, Shi, Xubo, Ge, Junbo, Fu, Guosheng, Bai, Feng, Fang, Weiyi, Shou, Xiling, Yang, Xiangjun, Wang, Jian'An, Xiang, Meixiang, Sun, Yingxian, Lu, Qinghua, Zhang, Ruiyan, Zhu, Jianhua, Xu, Yizhou, Fan, Zhongcai, Li, Tianchang, Wu, Chun, Jaramillo, Nicolas, Vallejo, Gregorio Sanchez, Luna Botia, Diana C., Lopez, Rodrigo Botero, Molina De Salazar, Dora I., Cadena Bonfanti, Alberto J., Aroca, Carlos Cotes, Higuera, Juan Diego, Blanquicett, Marco, Barrera Silva, Sandra I., Garcia Lozada, Henry J., Coronel Arroyo, Julian A., Accini Mendoza, Jose L., Fernandez Ruiz, Ricardo L., Quintero Ossa, Alvaro M., Manzur Jatin, Fernando G., Herazo, Aristides Sotomayor, Parada, Jeffrey Castellanos, Arambula, Rafael Suarez, Urina Triana, Miguel A., Fernandez Trujillo, Angela M., Strozzi, Maja, Car, Siniša, Jerić, Melita, Miličić, Davor, Benčić, Martina Lovrić, Pintarić, Hrvoje, Prvulović, Đeiti, Šikić, Jozica, Peršić, Viktor, Mileta, Dean, Štambuk, Kresimir, Babić, Zdravko, Tomulic, Vjekoslav, Lukenda, Josip, Mejic-Krstulovic, Stanka, Starcevic, Boris, Spinar, Jindrich, Horak, David, Velicka, Zdenek, Stasek, Josef, Alan, David, Machova, Vilma, Linhart, Ales, Novotny, Vojtech, Kaucak, Vladimir, Rokyta, Richard, Naplava, Robert, Coufal, Zdenek, Adamkova, Vera, Podpera, Ivo, Zizka, Jiri, Motovska, Zuzana, Marusincova, Ivana, Svab, Premysl, Heinc, Petr, Kuchar, Jiri, Povolny, Petr, Matuska, Jiri, Poulsen, Steen H., Raungaard, Bent, Clemmensen, Peter, Bang, Lia E., May, Ole, Bøttcher, Morten, Hove, Jens D., Frost, Lars, Gislason, Gunnar, Larsen, John, Johansen, Peter Betton, Hald, Flemming, Johansen, Peter, Jeppesen, Jørgen, Nielsen, Tonny, Kristensen, Kjeld S., Walichiewicz, Piotr Maria, Lomholdt, Jens D., Klausen, Ib C., Nielsen, Peter Kaiser, Davidsen, Flemming, Videbaek, Lars, Soots, Mai, Vahula, Veiko, Hedman, Anu, Soopõld, Üllar, Märtsin, Kaja, Jurgenson, Tiina, Kristjan, Arved, Huikuri, Heikki, Pierre Coste, Juhani Airaksinen, Ferrari, Emile, Morel, Olivier, Montalescot, Gilles, Machecourt, Jacques, Barone-Rochette, Gilles, Mansourati, Jacques, Cottin, Yves, Leclercq, Florence, Belhassane, Abdelkader, Delarche, Nicolas, Boccara, Franck, Paganelli, Franck, Clerc, Jérôme, Schiele, Francois, Aboyans, Victor, Probst, Vincent, Berland, Jacques, Lefèvre, Thierry, Citron, Bernard, Khintibidze, Irakli, Shaburishvili, Tamaz, Pagava, Zurab, Ghlonti, Ramaz, Lominadze, Zaza, Khabeishvili, George, Hemetsberger, Rayyan, Edward, Kemala, Rauch-Kröhnert, Ursula, Stratmann, Matthias, Appel, Karl-Friedrich, Schmidt, Ekkehard, Omran, Heyder, Stellbrink, Christoph, Dorsel, Thomas, Lianopoulos, Emmanouil, Vöhringer, Hans Friedrich, Marx, Roger, Zirlik, Andreas, Schellenberg, Detlev, Heitzer, Thomas, Laufs, Ulrich, Werner, Christian, Gielen, Stephan, Nuding, Sebastian, Winkelmann, Bernhard, Behrens, Steffen, Sydow, Karsten, Karakas, Mahir, Simonis, Gregor, Muenzel, Thomas, Werner, Nikos, Leggewie, Stefan, Böcker, Dirk, Braun-Dullaeus, Rüdiger, Toursarkissian, Nicole, Jeserich, Michael, Weißbrodt, Matthias, Schaeufele, Tim, Weil, Joachim, Völler, Heinz, Waltenberger, Johannes, Natour, Mohammed, Schmitt, Susanne, Müller-Wieland, Dirk, Steiner, Stephan, Heidenreich, Lothar, Offers, Elmar, Gremmler, Uwe, Killat, Holger, Rieker, Werner, Patsilinakos, Sotiris, Kartalis, Athanasios, Manolis, Athanassios, Sionis, Dimitrios, Chachalis, Geargios, Skoumas, Ioannis, Athyros, Vasilios, Vardas, Panagiotis, Parthenakis, Frangkiskos, Lekakis, John, Hatzitolios, Apostolos, Fausto Ovando, Sergio R., Arango Benecke, Juan L., Rodriguez De Leon, Edgar R., Yan, Bryan P.Y., Siu, David C.W., Turi, Tibor, Merkely, Bela, Ungi, Imre, Lupkovics, Geza, Nagy, Lajos, Katona, András, Édes, István, Müller, Gábor, Horvath, Iván, Kapin, Tibor, Szigeti, Zsolt, Faluközy, József, Kumbla, Mukund, Sandhu, Manjinder, Annam, Sharath, Proddutur, Naveen Reddy, Regella, Reddy, Premchand, Rajendra K., Mahajan, Ajaykumar, Pawar, Sudhir, Abhyanakar, Atul D., Kerkar, Prafulla, Govinda, Ravishankar A., Oomman, Abraham, Sinha, Dhurjati, Patil, Sachin N., Kahali, Dhiman, Sawhney, Jitendra, Joshi, Abhijeet B., Chaudhary, Sanjeev, Harkut, Pankaj, Guha, Santanu, Porwal, Sanjay, Jujjuru, Srimannarayana, Pothineni, Ramesh B., Monteiro, Minguel R., Khan, Aziz, Iyengar, Shamanna S., Grewal, Jasprakash Singh, Chopda, Manoj, Fulwani, Mahesh C., Patange, Aparna, 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2021
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50. A facility to Search for Hidden Particles at the CERN SPS: the SHiP physics case

Author

Alekhin, Sergey, Altmannshofer, Wolfgang, Asaka, Takehiko, Batell, Brian, Bezrukov, Fedor, Bondarenko, Kyrylo, Boyarsky, Alexey, Craig, Nathaniel, Choi, Ki-Young, Corral, Cristóbal, Curtin, David, Davidson, Sacha, de Gouvêa, André, Dell'Oro, Stefano, deNiverville, Patrick, Dev, P. S. Bhupal, Dreiner, Herbi, Drewes, Marco, Eijima, Shintaro, Essig, Rouven, Fradette, Anthony, Garbrecht, Björn, Gavela, Belen, Giudice, Gian F., Gorbunov, Dmitry, Gori, Stefania, Grojean, Christophe, Goodsell, Mark D., Guffanti, Alberto, Hambye, Thomas, Hansen, Steen H., Helo, Juan Carlos, Hernandez, Pilar, Ibarra, Alejandro, Ivashko, Artem, Izaguirre, Eder, Jaeckel, Joerg, Jeong, Yu Seon, Kahlhoefer, Felix, Kahn, Yonatan, Katz, Andrey, Kim, Choong Sun, Kovalenko, Sergey, Krnjaic, Gordan, Lyubovitskij, Valery E., Marcocci, Simone, Mccullough, Matthew, McKeen, David, Mitselmakher, Guenakh, Moch, Sven-Olaf, Mohapatra, Rabindra N., Morrissey, David E., Ovchynnikov, Maksym, Paschos, Emmanuel, Pilaftsis, Apostolos, Pospelov, Maxim, Reno, Mary Hall, Ringwald, Andreas, Ritz, Adam, Roszkowski, Leszek, Rubakov, Valery, Ruchayskiy, Oleg, Shelton, Jessie, Schienbein, Ingo, Schmeier, Daniel, Schmidt-Hoberg, Kai, Schwaller, Pedro, Senjanovic, Goran, Seto, Osamu, Shaposhnikov, Mikhail, Shuve, Brian, Shrock, Robert, Shchutska, Lesya, Spannowsky, Michael, Spray, Andy, Staub, Florian, Stolarski, Daniel, Strassler, Matt, Tello, Vladimir, Tramontano, Francesco, Tripathi, Anurag, Tulin, Sean, Vissani, Francesco, Winkler, Martin W., and Zurek, Kathryn M.

Subjects
High Energy Physics - Phenomenology, High Energy Physics - Experiment
Abstract

This paper describes the physics case for a new fixed target facility at CERN SPS. The SHiP (Search for Hidden Particles) experiment is intended to hunt for new physics in the largely unexplored domain of very weakly interacting particles with masses below the Fermi scale, inaccessible to the LHC experiments, and to study tau neutrino physics. The same proton beam setup can be used later to look for decays of tau-leptons with lepton flavour number non-conservation, $\tau\to 3\mu$ and to search for weakly-interacting sub-GeV dark matter candidates. We discuss the evidence for physics beyond the Standard Model and describe interactions between new particles and four different portals - scalars, vectors, fermions or axion-like particles. We discuss motivations for different models, manifesting themselves via these interactions, and how they can be probed with the SHiP experiment and present several case studies. The prospects to search for relatively light SUSY and composite particles at SHiP are also discussed. We demonstrate that the SHiP experiment has a unique potential to discover new physics and can directly probe a number of solutions of beyond the Standard Model puzzles, such as neutrino masses, baryon asymmetry of the Universe, dark matter, and inflation, Comment: 200 pages + appendices/references

Published
2015
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