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- Barucca, G., et al.
(author)
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The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
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In: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Journal article (peer-reviewed)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
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| 7. |
- Barucca, G., et al.
(author)
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Study of excited Ξ baryons with the P¯ ANDA detector
- 2021
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In: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Journal article (peer-reviewed)abstract
- The study of baryon excitation spectra provides insight into the inner structure of baryons. So far, most of the world-wide efforts have been directed towards N∗ and Δ spectroscopy. Nevertheless, the study of the double and triple strange baryon spectrum provides independent information to the N∗ and Δ spectra. The future antiproton experiment P¯ANDA will provide direct access to final states containing a Ξ¯ Ξ pair, for which production cross sections up to μb are expected in p¯p reactions. With a luminosity of L= 10 31 cm- 2 s- 1 in the first phase of the experiment, the expected cross sections correspond to a production rate of ∼106events/day. With a nearly 4 π detector acceptance, P¯ANDA will thus be a hyperon factory. In this study, reactions of the type p¯p → Ξ¯ +Ξ∗ - as well as p¯p → Ξ¯ ∗ +Ξ- with various decay modes are investigated. For the exclusive reconstruction of the signal events a full decay tree fit is used, resulting in reconstruction efficiencies between 3 and 5%. This allows high statistics data to be collected within a few weeks of data taking.
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- Wightman, D. P., et al.
(author)
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A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
- 2021
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
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Journal article (peer-reviewed)abstract
- Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
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| 10. |
- Eijsbouts, C., et al.
(author)
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Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
- 2021
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53:11, s. 1543-1552
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Journal article (peer-reviewed)abstract
- Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS. © 2021, The Author(s).
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| 11. |
- Tagliente, G., et al.
(author)
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The n_TOF facility at CERN
- 2024
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In: 16<sup>th</sup> Varenna Conference on Nuclear Reaction Mechanisms (NRM2023). - : EDP Sciences. - 9782759891245
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Conference paper (peer-reviewed)abstract
- The neutron Time-of-Flight facility (n_TOF) is an innovative facility operative since 2001 at CERN, with three experimental areas. In this paper the n_TOF facility will be described, together with the upgrade of the facility during the Long Shutdown 2 at CERN. The main features of the detectors used for capture fission cross section measurements will be presented with perspectives for the future measurements.
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| 12. |
- Echelmeier, A., et al.
(author)
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Segmented flow generator for serial crystallography at the European X-ray free electron laser
- 2020
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In: Nature Communications. - : Nature Research. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) allows structure determination of membrane proteins and time-resolved crystallography. Common liquid sample delivery continuously jets the protein crystal suspension into the path of the XFEL, wasting a vast amount of sample due to the pulsed nature of all current XFEL sources. The European XFEL (EuXFEL) delivers femtosecond (fs) X-ray pulses in trains spaced 100 ms apart whereas pulses within trains are currently separated by 889 ns. Therefore, continuous sample delivery via fast jets wastes >99% of sample. Here, we introduce a microfluidic device delivering crystal laden droplets segmented with an immiscible oil reducing sample waste and demonstrate droplet injection at the EuXFEL compatible with high pressure liquid delivery of an SFX experiment. While achieving ~60% reduction in sample waste, we determine the structure of the enzyme 3-deoxy-D-manno-octulosonate-8-phosphate synthase from microcrystals delivered in droplets revealing distinct structural features not previously reported.
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| 13. |
- Otegi, J. F., et al.
(author)
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TESS and HARPS reveal two sub-Neptunes around TOI 1062
- 2021
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 653
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Journal article (peer-reviewed)abstract
- The Transiting Exoplanet Survey Satellite (TESS) mission was designed to perform an all-sky search of planets around bright and nearby stars. Here we report the discovery of two sub-Neptunes orbiting around TOI 1062 (TIC 299799658), a V = 10.25 G9V star observed in the TESS Sectors 1, 13, 27, and 28. We use precise radial velocity observations from HARPS to confirm and characterize these two planets. TOI 1062b has a radius of 2.265 (+0.096)(-0.091) R-circle plus, a mass of 10.15 +/- 0.8 M-circle plus, and an orbital period of 4.1130 +/- 0.0015 days. The second planet is not transiting, has a minimum mass of 9.78 (+1.26)(-1.18) M-circle plus and is near the 2:1 mean motion resonance with the innermost planet with an orbital period of 7.972 (+0.018)(-0.024) days. We performed a dynamical analysis to explore the proximity of the system to this resonance, and to attempt further constraining the orbital parameters. The transiting planet has a mean density of 4.85(-0.74)(+0.84) g cm(-3) and an analysis of its internal structure reveals that it is expected to have a small volatile envelope accounting for 0.35% of the mass at most. The star's brightness and the proximity of the inner planet to what is know as the radius gap make it an interesting candidate for transmission spectroscopy, which could further constrain the composition and internal structure of TOI 1062b.
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| 14. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 16. |
- Lindahl, Johanna, et al.
(author)
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Brucellosis in India : results of a collaborative workshop to define One Health priorities
- 2020
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In: Tropical Animal Health and Production. - : Springer Science and Business Media LLC. - 0049-4747 .- 1573-7438. ; 52, s. 387-396
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Journal article (peer-reviewed)abstract
- Brucellosis is an important zoonosis worldwide. In livestock, it frequently causes chronic disease with reproductive failures that contribute to production losses, and in humans, it causes an often-chronic febrile illness that is frequently underdiagnosed in many low- and middle-income countries, including India. India has one of the largest ruminant populations in the world, and brucellosis is endemic in the country in both humans and animals. In November 2017, the International Livestock Research Institute invited experts from government, national research institutes, universities, and different international organizations to a one-day meeting to set priorities towards a "One Health" control strategy for brucellosis in India. Using a risk prioritization exercise followed by discussions, the meeting agreed on the following priorities: collaboration (transboundary and transdisciplinary); collection of more epidemiological evidence in humans, cattle, and in small ruminants (which have been neglected in past research); Economic impact studies, including cost effectiveness of control programmes; livestock vaccination, including national facilities for securing vaccines for the cattle population; management of infected animals (with the ban on bovine slaughter, alternatives such as sanctuaries must be explored); laboratory capacities and diagnostics (quality must be assured and better rapid tests developed); and increased awareness, making farmers, health workers, and the general public more aware of risks of brucellosis and zoonoses in general. Overall, the meeting participants agreed that brucellosis control will be challenging in India, but with collaboration to address the priority areas listed here, it could be possible.
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| 17. |
- Rodrigues, M., et al.
(author)
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Structure-specific amyloid precipitation in biofluids
- 2022
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In: Nature Chemistry. - : Springer Science and Business Media LLC. - 1755-4330 .- 1755-4349. ; 14, s. 1045-1053
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Journal article (peer-reviewed)abstract
- The composition of soluble toxic protein aggregates formed in vivo is currently unknown in neurodegenerative diseases, due to their ultra-low concentration in human biofluids and their high degree of heterogeneity. Here we report a method to capture amyloid-containing aggregates in human biofluids in an unbiased way, a process we name amyloid precipitation. We use a structure-specific chemical dimer, a Y-shaped, bio-inspired small molecule with two capture groups, for amyloid precipitation to increase affinity. Our capture molecule for amyloid precipitation (CAP-1) consists of a derivative of Pittsburgh Compound B (dimer) to target the cross beta-sheets of amyloids and a biotin moiety for surface immobilization. By coupling CAP-1 to magnetic beads, we demonstrate that we can target the amyloid structure of all protein aggregates present in human cerebrospinal fluid, isolate them for analysis and then characterize them using single-molecule fluorescence imaging and mass spectrometry. Amyloid precipitation enables unbiased determination of the molecular composition and structural features of the in vivo aggregates formed in neurodegenerative diseases.
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| 21. |
- Guimond, S. E., et al.
(author)
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Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction
- 2022
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In: ACS Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 8:5, s. 527-545
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Journal article (peer-reviewed)abstract
- Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein receptor binding domain and directly inhibits its binding to ACE2, consistent with molecular modeling identification of multiple molecular contacts and overlapping pixatimod and ACE2 binding sites. Assays with multiple clinical isolates of SARS-CoV-2 virus show that pixatimod potently inhibits the infection of monkey Vero E6 cells and physiologically relevant human bronchial epithelial cells at safe therapeutic concentrations. Pixatimod also retained broad potency against variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, in a K18-hACE2 mouse model, pixatimod significantly reduced SARS-CoV-2 viral titers in the upper respiratory tract and virus-induced weight loss. This demonstration of potent anti-SARS-CoV-2 activity tolerant to emerging mutations establishes proof-of-concept for targeting the HS-Spike protein-ACE2 axis with synthetic HS mimetics and provides a strong rationale for clinical investigation of pixatimod as a potential multimodal therapeutic for COVID-19.
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| 24. |
- Gandhi, Hemi H., et al.
(author)
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Gold-Hyperdoped Germanium with Room-Temperature Sub-Band-Gap Optoelectronic Response
- 2020
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In: Physical Review Applied. - : AMER PHYSICAL SOC. - 2331-7019. ; 14:6
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Journal article (peer-reviewed)abstract
- Short-wavelength-infrared (SWIR; 1.4-3.0 mu m) photodetection is important for various applications. Inducing a low-cost silicon-compatible material, such as germanium, to detect SWIR light would be advantageous for SWIR applications compared with using conventional (III-V or II-VI) SWIR materials. Here, we present a scalable nonequilibrium method for hyperdoping germanium with gold for dopant-mediated SWIR photodetection. Using ion implantation followed by nanosecond pulsed laser melting, we obtain a single-crystal material with a peak gold concentration of 3 x 10(19) cm(-3) (10(3) times the solubility limit). This hyperdoped germanium has fundamentally different optoelectronic properties from those of intrinsic and conventionally doped germanium. This material exhibits sub-band-gap absorption of light up to wavelengths of at least 3 mu m, with a sub-band-gap optical absorption coefficient comparable to that of commercial SWIR photodetection materials. We show that germanium hyperdoped with gold exhibits sub-band-gap SWIR photodetection at room temperature, in contrast with previous doped-germanium photodetector studies, which only show a low-temperature response. This material is a potential pathway to low-cost room-temperature silicon-compatible SWIR photodetection.
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| 25. |
- Khullar, S., et al.
(author)
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Influence of axial water jet size on RVR mitigation in draft tube of Francis turbine
- 2022
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In: 31st IAHR Symposium on Hydraulic Machinery and Systems 26/06/2022 - 01/07/2022 Trondheim, Norway. - : Institute of Physics Publishing (IOPP).
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Conference paper (peer-reviewed)abstract
- The present work investigates the effect of the axial water jet nozzle size on the unsteady pressure fluctuations arising from RVR formation in the draft tube of a Francis turbine operating at part load. The results compare two different nozzle diameter jets for their effect on the pressure pulsations and pressure recovery in the draft tube. Simulations were carried out at four jet injections varying from 2% to 10% of the main discharge. The study also presents the changes in the net effective area and average swirl in the draft tube with the introduction of the water jet.
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