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The production of prompt Î+c baryons has been measured at midrapidity in the transverse momentum interval 0<pT<1 GeV/c for the first time, in pp and p-Pb collisions at a centre-of-mass energy per nucleon-nucleon collision sNNââââ=5.02 TeV. The measurement was performed in the decay channel Î+câpK0S by applying new decay reconstruction techniques using a Kalman-Filter vertexing algorithm and adopting a machine-learning approach for the candidate selection. The pT-integrated Î+c production cross sections in both collision systems were determined and used along with the measured yields in Pb-Pb collisions to compute the pT-integrated nuclear modification factors RpPb and RAA of Î+c baryons, which are compared to model calculations that consider nuclear modification of the parton distribution functions. The Î+c/D0 baryon-to-meson yield ratio is reported for pp and p-Pb collisions. Comparisons with models that include modified hadronisation processes are presented, and the implications of the results on the understanding of charm hadronisation in hadronic collisions are discussed. A significant (3.7Ï) modification of the mean transverse momentum of Î+c baryons is seen in p-Pb collisions with respect to pp collisions, while the pT-integrated Î+c/D0 yield ratio was found to be consistent between the two collision systems within the uncertainties.
The production of ϱ, K±, and (pÂŻÂŻÂŻ)p is measured in pp collisions at sâ=13 TeV in different topological regions. Particle transverse momentum (pT) spectra are measured in the ``toward'', ``transverse'', and ``away'' angular regions defined with respect to the direction of the leading particle in the event. While the toward and away regions contain the fragmentation products of the near-side and away-side jets, respectively, the transverse region is dominated by particles from the Underlying Event (UE). The relative transverse activity classifier, RT=NT/âšNTâ©, is used to group events according to their UE activity, where NT is the measured charged-particle multiplicity per event in the transverse region and âšNTâ© is the mean value over all the analysed events. The first measurements of identified particle pT spectra as a function of RT in the three topological regions are reported. The yield of high transverse momentum particles relative to the RT-integrated measurement decreases with increasing RT in both the toward and away regions, indicating that the softer UE dominates particle production as RT increases and validating that RT can be used to control the magnitude of the UE. Conversely, the spectral shapes in the transverse region harden significantly with increasing RT. This hardening follows a mass ordering, being more significant for heavier particles. The pT-differential particle ratios (p+pÂŻÂŻÂŻ)/(Ï++Ïâ) and (K++Kâ)/(Ï++Ïâ) in the low UE limit (RTâ0) approach expectations from Monte Carlo generators such as PYTHIA 8 with Monash 2013 tune and EPOS LHC, where the jet-fragmentation models have been tuned to reproduce e+eâ results.
The production of ϱ, K±, and (pÂŻÂŻÂŻ)p is measured in pp collisions at sâ=13 TeV in different topological regions. Particle transverse momentum (pT) spectra are measured in the ``toward'', ``transverse'', and ``away'' angular regions defined with respect to the direction of the leading particle in the event. While the toward and away regions contain the fragmentation products of the near-side and away-side jets, respectively, the transverse region is dominated by particles from the Underlying Event (UE). The relative transverse activity classifier, RT=NT/âšNTâ©, is used to group events according to their UE activity, where NT is the measured charged-particle multiplicity per event in the transverse region and âšNTâ© is the mean value over all the analysed events. The first measurements of identified particle pT spectra as a function of RT in the three topological regions are reported. The yield of high transverse momentum particles relative to the RT-integrated measurement decreases with increasing RT in both the toward and away regions, indicating that the softer UE dominates particle production as RT increases and validating that RT can be used to control the magnitude of the UE. Conversely, the spectral shapes in the transverse region harden significantly with increasing RT. This hardening follows a mass ordering, being more significant for heavier particles. The pT-differential particle ratios (p+pÂŻÂŻÂŻ)/(Ï++Ïâ) and (K++Kâ)/(Ï++Ïâ) in the low UE limit (RTâ0) approach expectations from Monte Carlo generators such as PYTHIA 8 with Monash 2013 tune and EPOS LHC, where the jet-fragmentation models have been tuned to reproduce e+eâ results.
This article reports measurements of the angle between differently defined jet axes in pp collisions at sâ=5.02 TeV carried out by the ALICE Collaboration. Charged particles at midrapidity are clustered into jets with resolution parameters R=0.2 and 0.4. The jet axis, before and after Soft Drop grooming, is compared to the jet axis from the Winner-Takes-All (WTA) recombination scheme. The angle between these axes, ÎRaxis, probes a wide phase space of the jet formation and evolution, ranging from the initial high-momentum-transfer scattering to the hadronization process. The ÎRaxis observable is presented for 20<pchjetT<100 GeV/c, and compared to predictions from the PYTHIA 8 and Herwig 7 event generators. The distributions can also be calculated analytically with a leading hadronization correction related to the non-perturbative component of the CollinsâSoperâSterman (CSS) evolution kernel. Comparisons to analytical predictions at next-to-leading-logarithmic accuracy with leading hadronization correction implemented from experimental extractions of the CSS kernel in DrellâYan measurements are presented. The analytical predictions describe the measured data within 20% in the perturbative regime, with surprising agreement in the non-perturbative regime as well. These results are compatible with the universality of the CSS kernel in the context of jet substructure.
This letter reports the first measurement of spin alignment, with respect to the helicity axis, for Dâ+ vector mesons and their charge conjugates from charm-quark hadronisation (prompt) and from beauty-meson decays (non-prompt) in hadron collisions. The measurements were performed at midrapidity (|y|<0.8) as a function of transverse momentum (pT) in proton-proton (pp) collisions collected by ALICE at the centre-of-mass energy sâ=13 TeV. The diagonal spin density matrix element Ï00 of Dâ+ mesons was measured from the angular distribution of the Dâ+âD0(âKâÏ+)Ï+ decay products, in the Dâ+ rest frame, with respect to the Dâ+ momentum direction in the pp centre of mass frame. The Ï00 value for prompt Dâ+ mesons is consistent with 1/3, which implies no spin alignment. However, for non-prompt Dâ+ mesons an evidence of Ï00 larger than 1/3 is found. The measured value of the spin density element is Ï00=0.455±0.022(stat.)±0.035(syst.) in the 5<pT<20 GeV/c interval, which is consistent with a PYTHIA 8 Monte Carlo simulation coupled with the EVTGEN package, which implements the helicity conservation in the decay of Dâ+ meson from beauty mesons. In non-central heavy-ion collisions, the spin of the Dâ+ mesons may be globally aligned with the direction of the initial angular momentum and magnetic field. Based on the results for pp collisions reported in this letter it is shown that alignment of non-prompt Dâ+ mesons due to the helicity conservation coupled to the collective anisotropic expansion may mimic the signal of global spin alignment in heavy-ion collisions.
A new, more precise measurement of the Î hyperon lifetime is performed using a large data sample of PbâPb collisions at âsNN p ÂŒ 5.02 TeV with ALICE. The Î and ÎÂŻ hyperons are reconstructed at midrapidity using their two-body weak decay channel Î â p ĂŸ Ïâ and ÎÂŻ â pÂŻ ĂŸ ÏĂŸ. The measured value of the Î lifetime is ÏÎ ÂŒ Âœ261.07 0.37Ă°stat:Ă 0.72Ă°syst:Ă ps. The relative difference between the lifetime of Î and ÎÂŻ , which represents an important test of CPT invariance in the strangeness sector, is also measured. The obtained value Ă°ÏÎ â ÏÎÂŻĂ=ÏÎ ÂŒ 0.0013 0.0028Ă°stat:Ă 0.0021Ă°syst:Ă is consistent with zero within the uncertainties. Both measurements of the Î hyperon lifetime and of the relative difference between ÏÎ and ÏÎÂŻ are in agreement with the corresponding world averages of the Particle Data Group and about a factor of three more precise.
The production of prompt +c baryons has been measured at midrapidity in the transverse momentum interval 0 < pT < 1 GeV/c for the first time, in pp and pâPb collisions at a center-of-mass energy per nucleon-nucleon collision âsNN = 5.02 TeV. The measurement was performed in the decay channel +c â pK0S by applying new decay reconstruction techniques using a Kalman-Filter vertexing algorithm and adopting a machine-learning approach for the candidate selection. The pT -integrated +c production cross sections in both collision systems were determined and used along with the measured yields in PbâPb collisions to compute the pT -integrated nuclear modification factors RpPb and RAA of +c baryons, which are compared to model calculations that consider nuclear modification of the parton distribution functions. The +c /D0 baryon-to-meson yield ratio is reported for pp and pâPb collisions. Comparisons with models that include modified hadronization processes are presented, and the implications of the results on the understanding of charm hadronization in hadronic collisions are discussed. A significant (3.7Ï) modification of the mean transverse momentum of + c baryons is seen in pâPb collisions with respect to pp collisions, while the pT -integrated +c /D0 yield ratio was found to be consistent between the two collision systems within the uncertainties.
Hintergrund: Ab FrĂŒhjahr 2020 kam es zur weltweiten Verbreitung von SARS-CoVâ2 mit der heute als erste Welle der Pandemie bezeichneten Phase ab MĂ€rz 2020. Diese resultierte an vielen Kliniken in Umstrukturierungen und Ressourcenverschiebungen. Ziel unserer Arbeit war die Erfassung der Auswirkungen der Pandemie auf die universitĂ€re Hals-Nasen-Ohren(HNO)-Heilkunde fĂŒr die Forschung, Lehre und Weiterbildung. Material und Methoden: Die Direktorinnen und Direktoren der 39 UniversitĂ€ts-HNO-Kliniken in Deutschland wurden mithilfe einer strukturierten Online-Befragung zu den Auswirkungen der Pandemie im Zeitraum von MĂ€rz bis April 2020 auf die Forschung, Lehre und die Weiterbildung befragt. Ergebnisse: Alle 39 Direktorinnen und Direktoren beteiligten sich an der Umfrage. Hiervon gaben 74,4âŻ% (29/39) an, dass es zu einer Verschlechterung ihrer ForschungstĂ€tigkeit infolge der Pandemie gekommen sei. Von 61,5âŻ% (24/39) wurde berichtet, dass pandemiebezogene Forschungsaspekte aufgegriffen wurden. Von allen Kliniken wurde eine EinschrĂ€nkung der PrĂ€senzlehre berichtet und 97,5âŻ% (38/39) fĂŒhrten neue digitale Lehrformate ein. Im Beobachtungszeitraum sahen 74,4âŻ% der Klinikdirektoren die Weiterbildung der Assistenten nicht gefĂ€hrdet. Schlussfolgerung: Die Ergebnisse geben einen Einblick in die heterogenen Auswirkungen der Pandemie. Die kurzfristige Bearbeitung pandemiebezogener Forschungsthemen und die EinfĂŒhrung innovativer digitaler Konzepte fĂŒr die studentische Lehre belegt eindrĂŒcklich das groĂe innovative Potenzial und die schnelle ReaktionsfĂ€higkeit der HNO-UniversitĂ€tskliniken, um auch wĂ€hrend der Pandemie ihre Aufgaben in der Forschung, Lehre und Weiterbildung bestmöglich zu erfĂŒllen.
Aims: We investigated N471D WASH complex subunit strumpellin (Washc5) knock-in and Washc5 knock-out mice as models for hereditary spastic paraplegia type 8 (SPG8). Methods: We generated heterozygous and homozygous N471D Washc5 knock-in mice and subjected them to a comprehensive clinical, morphological and laboratory parameter screen, and gait analyses. Brain tissue was used for proteomic analysis. Furthermore, we generated heterozygous Washc5 knock-out mice. WASH complex subunit strumpellin expression was determined by qPCR and immunoblotting. Results: Homozygous N471D Washc5 knock-in mice showed mild dilated cardiomyopathy, decreased acoustic startle reactivity, thinner eye lenses, increased alkaline phosphatase and potassium levels and increased white blood cell counts. Gait analyses revealed multiple aberrations indicative of locomotor instability. Similarly, the clinical chemistry, haematology and gait parameters of heterozygous mice also deviated from the values expected for healthy animals, albeit to a lesser extent. Proteomic analysis of brain tissue depicted consistent upregulation of BPTF and downregulation of KLHL11 in heterozygous and homozygous knock-in mice. WASHC5-related protein interaction partners and complexes showed no change in abundancies. Heterozygous Washc5 knock-out mice showing normal WASHC5 levels could not be bred to homozygosity. Conclusions: While biallelic ablation of Washc5 was prenatally lethal, expression of N471D mutated WASHC5 led to several mild clinical and laboratory parameter abnormalities, but not to a typical SPG8 phenotype. The consistent upregulation of BPTF and downregulation of KLHL11 suggest mechanistic links between the expression of N471D mutated WASHC5 and the roles of both proteins in neurodegeneration and protein quality control, respectively.
Non-standard errors
(2021)
In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants.
Introduction: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development.
Methods: To identify mutational de novo events in EA/TEF patients, we surveyed the exome of 30 case-parent trios. Identified and confirmed de novo variants were prioritized using in silico prediction tools. To investigate the embryonic role of genes harboring prioritized de novo variants we performed targeted analysis of mouse transcriptome data of esophageal tissue obtained at the embryonic day (E) E8.5, E12.5, and postnatal.
Results: In total we prioritized 14 novel de novo variants in 14 different genes (APOL2, EEF1D, CHD7, FANCB, GGT6, KIAA0556, NFX1, NPR2, PIGC, SLC5A2, TANC2, TRPS1, UBA3, and ZFHX3) and eight rare de novo variants in eight additional genes (CELSR1, CLP1, GPR133, HPS3, MTA3, PLEC, STAB1, and PPIP5K2). Through personal communication during the project, we identified an additional EA/TEF case-parent trio with a rare de novo variant in ZFHX3. In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes. Re-sequencing of ZFHX3 in additional 192 EA/TEF patients did not identify further putative EA/TEF-associated variants.
Conclusion: Our study suggests that rare mutational de novo events in genes involved in foregut development contribute to the development of EA/TEF.
In this paper, the concepts of microscopic transport theory are introduced and the features and shortcomings of the most commonly used ansatzes are discussed. In particular, the Ultrarelativistic Quantum Molecular Dynamics (UrQMD) transport model is described in great detail. Based on the same principles as QMD and RQMD, it incorporates a vastly extended collision term with full baryon-antibaryon symmetry, 55 baryon and 32 meson species. Isospin is explicitly treated for all hadrons. The range of applicability stretches from E lab < 100$ MeV/nucleon up to E lab> 200$ GeV/nucleon, allowing for a consistent calculation of excitation functions from the intermediate energy domain up to ultrarelativistic energies. The main physics topics under discussion are stopping, particle production and collective flow.
Neutron total cross sections are an important source of experimental data in the evaluation of neutron-induced cross sections. The sum of all neutron-induced reaction cross sections can be determined with a precision of a few per cent in a relative measurement. The neutron spectrum of the photoneutron source nELBE extends in the fast region from about 100 keV to 10 MeV and has favourable conditions for transmission measurements due to the low instantaneous flux of neutrons and low gamma-flash background. Several materials of interest (in part included in the CIELO evaluation or on the HPRL of OECD/NEA) have been investigated: 197Au [1, 2], natFe [2], natW [2], 238U, natPt, 4He, natO, natNe, natXe. For gaseous targets high pressure gas cells with flat end-caps have been built that hold up to 200 bar pressure. The experimental setup will be presented including results from several transmission experiments and the data analysis leading to the total cross sections will be discussed.
The HITRAP linear decelerator currently being set up at GSI will provide slow, few keV/u highly charged ions for atomic physics experiments. The expected beam intensity is up to 105 ions per shot. To optimize phase and amplitude of the RF systems intensity, bunch length and kinetic energy of the particles need to be monitored. The bunch length that we need to fit is about 2 ns, which is typically measured by capacitive pickups. However, they do not work for the low beam intensities that we face. We investigated the bunch length with a fast CVD diamond detector working in single particle counting mode. Averaging over 8 shots yields a clear, regular picture of the bunched beam. Energy measurements by capacitive pickups are limited by the presence of intense primary and partially decelerated beam and hence make tuning of the IH-structure impossible. The energy of the decelerated fraction of the beam behind the first deceleration cavity was determined to about 10 % accuracy with a permanent dipole magnet combined with a MCP. Better detector calibration should help reaching the required 1%. Design of the detectors as well as the results of the measurements will be presented.
Background: The importance of the Notch signaling in the development of glomerular diseases has been recently described. Therefore we analyzed in podocytes the expression and activity of ADAM10, one important component of the Notch signaling complex. Methods: By Western blot, immunofluorescence and immunohistochemistry analysis we characterized the expression of ADAM10 in human podocytes, human urine and human renal tissue. Results: We present evidence, that differentiated human podocytes possessed increased amounts of mature ADAM10 and released elevated levels of L1 adhesion molecule, one well known substrate of ADAM10. By using specific siRNA and metalloproteinase inhibitors we demonstrate that ADAM10 is involved in the cleavage of L1 in human podocytes. Injury of podocytes enhanced the ADAM10 mediated cleavage of L1. In addition, we detected ADAM10 in urinary podocytes from patients with kidney diseases and in tissue sections of normal human kidney. Finally, we found elevated levels of ADAM10 in urinary vesicles of patients with glomerular kidney diseases. Conclusions: The activity of ADAM10 in human podocytes may play an important role in the development of glomerular kidney diseases.
As a surrogate of live cells, proteo-lipobeads are presented, encapsulating functional membrane proteins in a strict orientation into a lipid bilayer. Assays can be performed just as on live cells, for example using fluorescence measurements. As a proof of concept, we have demonstrated proton transport through cytochrome c oxidase.
The adult human body contains about 4 g of iron. About 1â2 mg of iron is absorbed every day, and in healthy individuals, the same amount is excreted. We describe a patient who presents with severe iron deficiency anemia with hemoglobin levels below 6 g/dL and ferritin levels below 30 ng/mL. Although red blood cell concentrates and intravenous iron have been substituted every month for years, body iron stores remain depleted. Diagnostics have included several esophago-gastro-duodenoscopies, colonoscopies, MRI of the liver, repetitive bone marrow biopsies, psychological analysis, application of radioactive iron to determine intact erythropoiesis, and measurement of iron excretion in urine and feces. Typically, gastrointestinal bleeding is a major cause of iron loss. Surprisingly, intestinal iron excretion in stool in the patient was repetitively increased, without gastrointestinal bleeding. Furthermore, whole exome sequencing was performed in the patient and additional family members to identify potential causative genetic variants that may cause intestinal iron loss. Under different inheritance models, several rare mutations were identified, two of which (in CISD1 and KRI1) are likely to be functionally relevant. Intestinal iron loss in the current form has not yet been described and is, with high probability, the cause of the severe iron deficiency anemia in this patient.
Bipolar disorder (BD) is a major psychiatric illness affecting around 1% of the global population. BD is characterized by recurrent manic and depressive episodes, and has an estimated heritability of around 70%. Research has identified the first BD susceptibility genes. However, the underlying pathways and regulatory networks remain largely unknown. Research suggests that the cumulative impact of common alleles with small effects explains only around 25â38% of the phenotypic variance for BD. A plausible hypothesis therefore is that rare, high penetrance variants may contribute to BD risk. The present study investigated the role of rare, nonsynonymous, and potentially functional variants via whole exome sequencing in 15 BD cases from two large, multiply affected families from Cuba. The high prevalence of BD in these pedigrees renders them promising in terms of the identification of genetic risk variants with large effect sizes. In addition, SNP array data were used to calculate polygenic risk scores for affected and unaffected family members. After correction for multiple testing, no significant increase in polygenic risk scores for common, BD-associated genetic variants was found in BD cases compared to healthy relatives. Exome sequencing identified a total of 17 rare and potentially damaging variants in 17 genes. The identified variants were shared by all investigated BD cases in the respective pedigree. The most promising variant was located in the gene SERPING1 (p.L349F), which has been reported previously as a genome-wide significant risk gene for schizophrenia. The present data suggest novel candidate genes for BD susceptibility, and may facilitate the discovery of disease-relevant pathways and regulatory networks.
Protein turnover and quality control by the proteasome is of paramount importance for cell homeostasis. Dysfunction of the proteasome is associated with aging processes and human diseases such as neurodegeneration, cardiomyopathy, and cancer. The regulation, i.e. activation and inhibition of this fundamentally important protein degradation system, is still widely unexplored. We demonstrate here that the evolutionarily highly conserved type II triple-A ATPase VCP and the proteasome inhibitor PSMF1/PI31 interact directly, and antagonistically regulate proteasomal activity. Our data provide novel insights into the regulation of proteasomal activity.