| 1. |
- Singh, B. P., et al.
(author)
-
Experimental access to Transition Distribution Amplitudes with the PANDA experiment at FAIR
- 2015
-
In: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 51:8
-
Journal article (peer-reviewed)abstract
- Baryon-to-meson Transition Distribution Amplitudes (TDAs) encoding valuable new information on hadron structure appear as building blocks in the collinear factorized description for several types of hard exclusive reactions. In this paper, we address the possibility of accessing nucleon-to-pion (pi N) TDAs from (p) over barp -> e(+)e(-)pi(0) reaction with the future PANDA detector at the FAIR facility. At high center-of-mass energy and high invariant mass squared of the lepton pair q(2), the amplitude of the signal channel (p) over barp -> e(+)e(-)pi(0) admits a QCD factorized description in terms of pi N TDAs and nucleon Distribution Amplitudes (DAs) in the forward aid backward kinematic regimes. Assuming the validity of this factorized description, we perform feasibility studies for measuring (p) over barp -> e(+)e(-)pi(0) with the PANDA detector. Detailed simulations on signal reconstruction efficiency as well as on rejection of the most severe background channel, i.e. (p) over barp -> pi(+)pi(-)pi(0) were performed for the center-of-mass energy squared s = 5 GeV2 and s = 10 GeV2, in the kinematic regions 3.0 < q(2) < 4.3 GeV2 and 5 < q(2) < 9 GeV2, respectively, with a neutral pion scattered in the forward or backward cone vertical bar cos theta(pi 0)vertical bar > 0.5 in the proton-antiproton center-of-mass frame. Results of the simulation show that the particle identification capabilities of the PANDA detector will allow to achieve a background rejection factor of 5 . 10(7) (1 . 10(7)) at low (high) q(2) for s = 5 GeV2, and of 1 . 10(8) (6 . 10(6)) at low (high) q(2) for s = 10 GeV2, while keeping the signal reconstruction efficiency at around 40%. At both energies, a clean lepton signal can be reconstructed with the expected statistics corresponding to 2 of integrated luminosity. The cross sections obtained from the simulations are used to show that a test of QCD collinear factorization can be done at the lowest order by measuring scaling laws and angular distributions. The future measurement of the signal channel cross section with PANDA will provide a new test of the perturbative QCD description of a novel class of hard exclusive reactions and will open the possibility of experimentally accessing pi N TDAs.
|
|
| 2. |
- Cossarizza, A., et al.
(author)
-
Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
- 2019
-
In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
-
Journal article (peer-reviewed)abstract
- These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
|
|
| 3. |
- Wendisch, M., et al.
(author)
-
Atmospheric and Surface Processes, and Feedback Mechanisms Determining Arctic Amplification: A Review of First Results and Prospects of the (AC)(3) Project
- 2023
-
In: Bulletin of the American Meteorological Society. - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 104:1
-
Journal article (peer-reviewed)abstract
- Mechanisms behind the phenomenon of Arctic amplification are widely discussed. To contribute to this debate, the (AC)(3) project was established in 2016 (www.ac3-tr.de/). It comprises modeling and data analysis efforts as well as observational elements. The project has assembled a wealth of ground-based, airborne, shipborne, and satellite data of physical, chemical, and meteorological properties of the Arctic atmosphere, cryosphere, and upper ocean that are available for the Arctic climate research community. Short-term changes and indications of long-term trends in Arctic climate parameters have been detected using existing and new data. For example, a distinct atmospheric moistening, an increase of regional storm activities, an amplified winter warming in the Svalbard and North Pole regions, and a decrease of sea ice thickness in the Fram Strait and of snow depth on sea ice have been identified. A positive trend of tropospheric bromine monoxide (BrO) column densities during polar spring was verified. Local marine/biogenic sources for cloud condensation nuclei and ice nucleating particles were found. Atmospheric-ocean and radiative transfer models were advanced by applying new parameterizations of surface albedo, cloud droplet activation, convective plumes and related processes over leads, and turbulent transfer coefficients for stable surface layers. Four modes of the surface radiative energy budget were explored and reproduced by simulations. To advance the future synthesis of the results, cross-cutting activities are being developed aiming to answer key questions in four focus areas: lapse rate feedback, surface processes, Arctic mixed-phase clouds, and airmass transport and transformation.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Payne, T., et al.
(author)
-
Prospective analysis of plasma amyloid beta and postoperative delirium in the Interventions for Postoperative Delirium: Biomarker-3 study
- 2023
-
In: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912. ; 130:5, s. 546-556
-
Journal article (peer-reviewed)abstract
- Background: The effect of postoperative delirium on the amyloid cascade of Alzheimer's dementia is poorly understood. Using early postoperative plasma biomarkers, we explored whether surgery and delirium are associated with changes in amyloid pathways.Methods: We analysed data from 100 participants in the Interventions for Postoperative Delirium: Biomarker-3 (IPOD-B3) cohort study in the USA (NCT03124303 and NCT01980511), which recruited participants aged >65 yr undergoing non-intracranial surgery. We assessed the relationship between the change in plasma amyloid beta ratio (A(3R; A(342:A(340) and delirium incidence (defined by the 3-Minute Diagnostic Confusion Assessment Method) and severity (quantified by the Delirium Rating Scale-Revised-98, the study's primary outcome). We also tested the relationship between plasma amyloid beta and intraoperative variables.Results: Across all participants, the plasma A(3R increased from the preoperative period to postoperative Day 1 (Wilcoxon P<0.001). However, this increase was not associated with delirium incidence (Wilcoxon P=0.22) or peak severity after adjusting for confounders (log[incidence rate ratio]=0.43; P=0.14). Postoperative Day 1 change in plasma A(3R was not associated with postoperative Day 1 change in plasma tau, neurofilament light, or inflammatory markers (interleukin [IL]-1(3, IL-1Ra, IL-2, IL-4, IL-6, IL-8, IL-10, and IL-12), or with operative time or low intraoperative arterial pressure.Conclusions: Perioperative changes in plasma amyloid do not appear to be associated with postoperative delirium. Our findings do not support associations of dynamic changes in amyloid with postoperative delirium.Clinical trial registration: NCT03124303 and NCT01980511.
|
|
| 9. |
- Taylor, J., et al.
(author)
-
Postoperative delirium and changes in the blood–brain barrier, neuroinflammation, and cerebrospinal fluid lactate: a prospective cohort study
- 2022
-
In: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912. ; 129:2, s. 219-230
-
Journal article (peer-reviewed)abstract
- Background: Case-control studies have associated delirium with blood–brain barrier (BBB) permeability. However, this approach cannot determine whether delirium is attributable to high pre-existing permeability or to perioperative changes. We tested whether perioperative changes in cerebrospinal fluid/plasma albumin ratio (CPAR) and plasma S100B were associated with delirium severity. Methods: Participants were recruited to two prospective cohort studies of non-intracranial surgery (NCT01980511, NCT03124303, and NCT02926417). Delirium severity was assessed using the Delirium Rating Scale-98. Delirium incidence was diagnosed with the 3D-Confusion Assessment Method (3D-CAM) or CAM-ICU (CAM for the ICU). CSF samples from 25 patients and plasma from 78 patients were analysed for albumin and S100B. We tested associations between change in CPAR (n=11) and S100B (n=61) and delirium, blood loss, CSF interleukin-6 (IL-6), and CSF lactate. Results: The perioperative increase in CPAR and S100B correlated with delirium severity (CPAR ρ=0.78, P=0.01; S100B ρ=0.41, P<0.001), delirium incidence (CPAR P=0.012; S100B P<0.001) and CSF IL-6 (CPAR ρ=0.66 P=0.04; S100B ρ=0.75, P=0.025). Linear mixed-effect analysis also showed that decreased levels of S100B predicted recovery from delirium symptoms (P=0.001). Linear regression demonstrated that change in plasma S100B was independently associated with surgical risk, cardiovascular surgery, blood loss, and hypotension. Blood loss also correlated with CPAR (ρ=0.64, P=0.04), S100B (ρ=0.70, P<0.001), CSF lactate (R=0.81, P=0.01), and peak delirium severity (ρ=0.36, P=0.01). Conclusion: Postoperative delirium is associated with a breakdown in the BBB. This increased permeability is dynamic and associated with a neuroinflammatory and lactate response. Strategies to mitigate blood loss may protect the BBB. © 2022 British Journal of Anaesthesia
|
|
| 10. |
- Fellinger, Joris, et al.
(author)
-
Tungsten based divertor development for Wendelstein 7-X
- 2023
-
In: Nuclear Materials and Energy. - 2352-1791. ; 37
-
Journal article (peer-reviewed)abstract
- Wendelstein 7-X, the world’s largest superconducting stellarator in Greifswald (Germany), started plasma experiments with a water-cooled plasma-facing wall in 2022, allowing for long pulse operation. In parallel, a project was launched in 2021 to develop a W based divertor, replacing the current CFC divertor, to demonstrate plasma performance of a stellarator with a reactor relevant plasma facing materials with low tritium retention. The project consists of two tasks: Based on experience from the previous experimental campaigns and improved physics modelling, the geometry of the plasma-facing surface of the divertor and baffles is optimized to prevent overloads and to improve exhaust. In parallel, the manufacturing technology for a W based target module is qualified. This paper gives a status update of project. It focusses on the conceptual design of a W based target module, the manufacturing technology and its qualification, which is conducted in the framework of the EUROfusion funded WPDIV program. A flat tile design in which a target module is made of a single target element is pursued. The technology must allow for moderate curvatures of the plasma-facing surface to follow the magnetic field lines. The target element is designed for steady state heat loads of 10 MW/m2 (as for the CFC divertor). Target modules of a similar size and weight as for the CFC divertor are assumed (approx. < 0.25 m2 and < 60 kg) using the existing water cooling infrastructure providing 5 l/s and roughly maximum 15 bar pressure drop per module. The main technology under qualification is based on a CuCrZr heat sink made either by additive manufacturing using laser powder bed fusion (LPBF) or by uniaxial diffusion welding of pre-machined forged CuCrZr plates. After heat treatment, the plasma-facing side of the heat sink is covered by W or if feasible by the more ductile WNiFe, preferably by coating or alternatively by hot isostatic pressing W based tiles with a soft OFE-Cu interlayer. Last step is a final machining of the plasma-exposed surface and the interfaces to the water supply lines and supports to correct manufacturing deformations.
|
|
| 11. |
- Olahova, M., et al.
(author)
-
POLRMT mutations impair mitochondrial transcription causing neurological disease
- 2021
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- While >300 disease-causing variants have been identified in the mitochondrial DNA (mtDNA) polymerase gamma, no mitochondrial phenotypes have been associated with POLRMT, the RNA polymerase responsible for transcription of the mitochondrial genome. Here, we characterise the clinical and molecular nature of POLRMT variants in eight individuals from seven unrelated families. Patients present with global developmental delay, hypotonia, short stature, and speech/intellectual disability in childhood; one subject displayed an indolent progressive external ophthalmoplegia phenotype. Massive parallel sequencing of all subjects identifies recessive and dominant variants in the POLRMT gene. Patient fibroblasts have a defect in mitochondrial mRNA synthesis, but no mtDNA deletions or copy number abnormalities. The in vitro characterisation of the recombinant POLRMT mutants reveals variable, but deleterious effects on mitochondrial transcription. Together, our in vivo and in vitro functional studies of POLRMT variants establish defective mitochondrial transcription as an important disease mechanism. POLRMT is key for transcription of the mitochondrial genome, yet has not been implicated in mitochondrial disease to date. Here, the authors identify mutations in POLRMT in individuals with mitochondrial disease-related phenotypes and characterise underlying defects in mitochondrial transcription.
|
|
| 12. |
- Orebaugh, Clinton D, et al.
(author)
-
Mapping Ribonucleotides Incorporated into DNA by Hydrolytic End-Sequencing.
- 2018
-
In: Methods in molecular biology (Clifton, N.J.). - New York, NY : Springer New York. - 1940-6029. ; 1672, s. 329-345
-
Journal article (peer-reviewed)abstract
- Ribonucleotides embedded within DNA render the DNA sensitive to the formation of single-stranded breaks under alkali conditions. Here, we describe a next-generation sequencing method called hydrolytic end sequencing (HydEn-seq) to map ribonucleotides inserted into the genome of Saccharomyce cerevisiae strains deficient in ribonucleotide excision repair. We use this method to map several genomic features in wild-type and replicase variant yeast strains.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Vollmer, Tino, et al.
(author)
-
The intratumoral CXCR3 chemokine system is predictive of chemotherapy response in human bladder cancer
- 2021
-
In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:576
-
Journal article (peer-reviewed)abstract
- Chemotherapy has direct toxic effects on cancer cells; however, long-term cancer control and complete remission are likely to involve CD8+ T cell immune responses. To study the role of CD8+ T cell infiltration in the success of chemotherapy, we examined patients with muscle invasive bladder cancer (MIBC) who were categorized on the basis of the response to neoadjuvant chemotherapy (NAC). We identified the intratumoral CXCR3 chemokine system (ligands and receptor splice variants) as a critical component for tumor eradication upon NAC in MIBC. Through characterization of CD8+ T cells, we found that stem-like T cell subpopulations with abundant CXCR3alt, a variant form of the CXCL11 receptor, responded to CXCL11 in culture as demonstrated by migration and enhanced effector function. In tumor biopsies of patients with MIBC accessed before treatment, CXCL11 abundance correlated with high numbers of tumor-infiltrating T cells and response to NAC. The presence of CXCR3alt and CXCL11 was associated with improved overall survival in MIBC. Evaluation of both CXCR3alt and CXCL11 enabled discrimination between responder and nonresponder patients with MIBC before treatment. We validated the prognostic role of the CXCR3-CXCL11 chemokine system in an independent cohort of chemotherapy-treated and chemotherapy-naïve patients with MIBC from data in TCGA. In summary, our data revealed stimulatory activity of the CXCR3alt-CXCL11 chemokine system on CD8+ T cells that is predictive of chemotherapy responsiveness in MIBC. This may offer immunotherapeutic options for targeted activation of intratumoral stem-like T cells in solid tumors.
|
|
| 16. |
- Wendland, F, et al.
(author)
-
Model system for the management of nitrogen leaching at the scale of river basins and regions
- 2001
-
In: Water Science and Technology. - 0273-1223 .- 1996-9732. ; 43:7, s. 215-222
-
Journal article (peer-reviewed)abstract
- In the framework of the EU-project RANR (Regional analysis of subsurface nitrogen retention and its impact on the nitrogen export from land to sea) a model system was developed to estimate groundwater-borne nitrogen inputs into river systems. The core of this model system is composed of a soil nitrogen leaching model (SOIL-N) and a groundwater residence time/denitrification model (WEKU). The application of the model system was carried out for the study catchment areas of the Uecker basin (ca. 2400 km(2), Germany) and the Gjern basin (ca. 200 km(2), Denmark). For both catchment areas, the modelled average nitrogen loads leached into the groundwater were about 40 kg N/ha a, while the remaining groundwater-borne nitrogen intake to rivers was quantified to an average of about 2 kg/ha a. The comparision with observed groundwater-borne riverine nitrogen loads showed a very good agreement, proofing the key role nitrogen retention in groundwater plays in the two catchment areas. With regard to the generalisation and transfer of the SOIL-N/WEKU model concept we assume that the model can be applicated in catchment areas in the European Pleistocene Lowland, which ranges from the Netherlands in the west to the Baltic States and the Ukraine in the east.
|
|
| 17. |
- Wendland, F, et al.
(author)
-
The SOIL-N/WEKU model system - a GIS-supported tool for the assessment and management of diffuse nitrogen leaching at the scale of river basins
- 2002
-
In: Water Science and Technology. - 0273-1223 .- 1996-9732. ; 45:9, s. 285-292
-
Journal article (peer-reviewed)abstract
- The SOIL-N/WEKU model system was developed to estimate groundwater-borne nitrogen inputs into river systems. The core of this model system is composed of a soil nitrogen leaching model (SOIL-N) and a groundwater residence time/denitrification model (WEKU). The application of the model system was carried out in the framework of the EU-project RANR (Regional analysis of subsurface nitrogen retention and its impact on the nitrogen export from land to sea) for a macroscale study river basin in Germany (the Uecker basin, ca. 2,400 km(2)) and a mesoscale study catchment area in Denmark (the Gjern basin, ca. 200 km2). For both catchment areas, the,modelled average nitrogen loads leached into the groundwater were about 40 kg N/ha a, while the remaining groundwater-borne nitrogen intake to rivers was quantified to an average of about 2 kg/ha a. The comparison with observed groundwater-borne riverine nitrogen loads showed a very good agreement, proving the key role nitrogen retention in groundwater plays in the two catchment areas.
|
|
| 18. |
- Williams, Jessica S, et al.
(author)
-
Evidence that processing of ribonucleotides in DNA by topoisomerase 1 is leading-strand specific
- 2015
-
In: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 22:4, s. 291-U35
-
Journal article (peer-reviewed)abstract
- Ribonucleotides incorporated during DNA replication are removed by RNase H2-dependent ribonucleotide excision repair (RER). In RER-defective yeast, topoisomerase 1 (Top1) incises DNA at unrepaired ribonucleotides, initiating their removal, but this is accompanied by RNA-DNA-damage phenotypes. Here we show that these phenotypes are incurred by a high level of ribonucleotides incorporated by a leading strand-replicase variant, DNA polymerase (Pol) ɛ, but not by orthologous variants of the lagging-strand replicases, Pols α or δ. Moreover, loss of both RNases H1 and H2 is lethal in combination with increased ribonucleotide incorporation by Pol ɛ but not by Pols α or δ. Several explanations for this asymmetry are considered, including the idea that Top1 incision at ribonucleotides relieves torsional stress in the nascent leading strand but not in the nascent lagging strand, in which preexisting nicks prevent the accumulation of superhelical tension.
|
|
| 19. |
- Williams, Jessica S, et al.
(author)
-
Proofreading of ribonucleotides inserted into DNA by yeast DNA polymerase ɛ.
- 2012
-
In: DNA Repair. - : Elsevier BV. - 1568-7864 .- 1568-7856. ; 11:8, s. 649-656
-
Journal article (peer-reviewed)abstract
- We have investigated the ability of the 3' exonuclease activity of Saccharomyces cerevisiae DNA polymerase ɛ (Pol ɛ) to proofread newly inserted ribonucleotides (rNMPs). During DNA synthesis in vitro, Pol ɛ proofreads ribonucleotides with apparent efficiencies that vary from none at some locations to more than 90% at others, with rA and rU being more efficiently proofread than rC and rG. Previous studies show that failure to repair ribonucleotides in the genome of rnh201Δ strains that lack RNase H2 activity elevates the rate of short deletions in tandem repeat sequences. Here we show that this rate is increased by 2-4-fold in pol2-4 rnh201Δ strains that are also defective in Pol ɛ proofreading. In comparison, defective proofreading in these same strains increases the rate of base substitutions by more than 100-fold. Collectively, the results indicate that although proofreading of an 'incorrect' sugar is less efficient than is proofreading of an incorrect base, Pol ɛ does proofread newly inserted rNMPs to enhance genome stability.
|
|
