Transverse-momentum spectra of electroweak bosons near threshold at NNLO

We obtain the next-to-next-to-leading order corrections to transverse-momentum spectra of W, Z and Higgs bosons near the partonic threshold. In the threshold limit, the electroweak boson recoils against a low-mass jet and all radiation is either soft, or collinear to the jet or the beam directions. We extract the virtual corrections from known results for the relevant two-loop four-point amplitudes and combine them with the soft and collinear two-loop functions as defined in Soft-Collinear Effective Theory. We have implemented these results in a public code PeTeR and present numerical results for the threshold resummed cross section of W and Z bosons at next-to-next-to-next-to-leading logarithmic accuracy, matched to next-to-leading fixed-order perturbation theory. The two-loop corrections lead to a moderate increase in the cross section and reduce the scale uncertainty by about a factor of two. The corrections are significantly larger for Higgs production.Comment: 33 pages, 3 figures; v2: journal version, correction in (73); v3: corrected qg-channel in (73

The transverse-momentum spectrum of Higgs bosons near threshold at NNLO

We give next-to-next-to-leading order (NNLO) predictions for the Higgs production cross section at large transverse momentum in the threshold limit. Near the partonic threshold, all radiation is either soft or collinear to the final state jet which recoils against the Higgs boson. We find that the real emission corrections are of moderate size, but that the virtual corrections are large. We discuss the origin of these corrections and give numerical predictions for the transverse-momentum spectrum. The threshold result is matched to the known NLO result and implemented in the public code PeTeR.Comment: 17 pages, 9 Figures; v2: journal version, correction in the qg channe

NNLO soft function for electroweak boson production at large transverse momentum

The soft function relevant for the production of an electroweak boson (photon, W, Z or H) with large transverse momentum at a hadron collider is computed at next-to-next-to-leading order. This is the first two-loop computation of a soft function involving three light-cone directions. With the result, the threshold resummation for these processes can now be performed at next-to-next-to-next-to-leading logarithmic accuracy.Comment: 16 pages, 3 figure

Blocking the CD47-SIRPα interaction reverses the disease phenotype in a polycythemia vera mouse model

Polycythemia vera (PV) is a hematopoietic stem cell neoplasm driven by somatic mutations in JAK2, leading to increased red blood cell (RBC) production uncoupled from mechanisms that regulate physiological erythropoiesis. At steady-state, bone marrow macrophages promote erythroid maturation, whereas splenic macrophages phagocytose aged or damaged RBCs. The binding of the anti-phagocytic ("don't eat me") CD47 ligand expressed on RBCs to the SIRPα receptor on macrophages inhibits phagocytic activity protecting RBCs from phagocytosis. In this study, we explore the role of the CD47-SIRPα interaction on the PV RBC life cycle. Our results show that blocking CD47-SIRPα in a PV mouse model due to either anti-CD47 treatment or loss of the inhibitory SIRPα-signal corrects the polycythemia phenotype. Anti-CD47 treatment marginally impacted PV RBC production while not influencing erythroid maturation. However, upon anti-CD47 treatment, high-parametric single-cell cytometry identified an increase of MerTK+ splenic monocyte-derived effector cells, which differentiate from Ly6C$^{hi}$ monocytes during inflammatory conditions, acquire an inflammatory phagocytic state. Furthermore, in vitro, functional assays showed that splenic JAK2 mutant macrophages were more "pro-phagocytic," suggesting that PV RBCs exploit the CD47-SIRPα interaction to escape innate immune attacks by clonal JAK2 mutant macrophages

Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates

BACKGROUND AND OBJECTIVES Myasthenia gravis (MG) can in rare cases be an autoimmune phenomenon associated with hematologic malignancies such as chronic lymphocytic leukemia (CLL). It is unclear whether in patients with MG and CLL, the leukemic B cells are the ones directly driving the autoimmune response against neuromuscular endplates. METHODS We identified patients with acetylcholine receptor antibody-positive (AChR$^{+}$) MG and CLL or monoclonal B-cell lymphocytosis (MBL), a precursor to CLL, and described their clinical features, including treatment responses. We generated recombinant monoclonal antibodies (mAbs) corresponding to the B-cell receptors of the CLL phenotype B cells and screened them for autoantigen binding. RESULTS A computational immune cell screen revealed a subgroup of 5/38 patients with MG and 0/21 healthy controls who displayed a CLL-like B-cell phenotype. In follow-up hematologic flow cytometry, 2 of these 5 patients were diagnosed with an MBL. An additional patient with AChR$^{+}$ MG as a complication of manifest CLL presented at our neuromuscular clinic and was successfully treated with the anti-CD20 therapy obinutuzumab plus chlorambucil. We investigated the specificities of expanding CLL-like B-cell clones to assess a direct causal link between the 2 diseases. However, we observed no reactivity of the clones against the AChR, antigens at the neuromuscular junction, or other common autoantigens. DISCUSSION Our study suggests that AChR autoantibodies are produced by nonmalignant, polyclonal B cells The new anti-CD20 treatment obinutuzumab might be considered in effectively treating AChR$^{+}$ MG. CLASSIFICATION OF EVIDENCE This is a single case study and provides Class IV evidence that obinutuzumab is safe to use in patients with MG

Staphylococcal PknB as the First Prokaryotic Representative of the Proline-Directed Kinases

In eukaryotic cell types, virtually all cellular processes are under control of proline-directed kinases and especially MAP kinases. Serine/threonine kinases in general were originally considered as a eukaryote-specific enzyme family. However, recent studies have revealed that orthologues of eukaryotic serine/threonine kinases exist in bacteria. Moreover, various pathogenic species, such as Yersinia and Mycobacterium, require serine/threonine kinases for successful invasion of human host cells. The substrates targeted by bacterial serine/threonine kinases have remained largely unknown. Here we report that the serine/threonine kinase PknB from the important pathogen Staphylococcus aureus is released into the external milieu, which opens up the possibility that PknB does not only phosphorylate bacterial proteins but also proteins of the human host. To identify possible human targets of purified PknB, we studied in vitro phosphorylation of peptide microarrays and detected 68 possible human targets for phosphorylation. These results show that PknB is a proline-directed kinase with MAP kinase-like enzymatic activity. As the potential cellular targets for PknB are involved in apoptosis, immune responses, transport, and metabolism, PknB secretion may help the bacterium to evade intracellular killing and facilitate its growth. In apparent agreement with this notion, phosphorylation of the host-cell response coordinating transcription factor ATF-2 by PknB was confirmed by mass spectrometry. Taken together, our results identify PknB as the first prokaryotic representative of the proline-directed kinase/MAP kinase family of enzymes

Pocket depth and bleeding on probing and their associations with dental, lifestyle, socioeconomic and blood variables: a cross-sectional, multicenter feasibility study of the German National Cohort

Background: To investigate the periodontal disease status in a multi-center cross-sectional study in Germany. Associations of dental, socio-economic, blood and biomedical variables with periodontal outcome parameters were evaluated. Methods: From 4 different centers N = 311 persons were included, drawn randomly from the registration offices. Maximal pocket depth (PD) was used as primary indicator for periodontitis. It was classified as: no/mild ≤3 mm, moderate 4-5 mm, severe ≥6 mm. Associations between socioeconomic (household income, education), lifestyle, and biomedical factors and PD or bleeding on probing (BOP) per site (“Yes”/”No”) was analyzed with logistic regression analysis. Results: Mean age of subjects was 46.4 (range 20–77) years. A significantly higher risk of deeper pockets for smokers (OR = 2.4, current vs. never smoker) or persons with higher BMI (OR = 1.6, BMI increase by 5) was found. Severity of periodontitis was significantly associated with caries lesions (p = 0.01), bridges (p < .0001), crowns (p < .0001), leukocytes (p = 0.04), HbA1c (p &lt; .0001) and MCV (p = 0.04). PD was positively correlated with BOP. No significant associations with BOP were found in regression analysis. Conclusions: Earlier findings for BMI and smoking with severity of PD were confirmed. Dental variables might be influenced by potential confounding factors e.g. dental hygiene. For blood parameters interactions with unknown systemic diseases may exist

a cross-sectional, multicenter feasibility study of the German National Cohort

Background To investigate the periodontal disease status in a multi-center cross-sectional study in Germany. Associations of dental, socio-economic, blood and biomedical variables with periodontal outcome parameters were evaluated. Methods From 4 different centers N = 311 persons were included, drawn randomly from the registration offices. Maximal pocket depth (PD) was used as primary indicator for periodontitis. It was classified as: no/mild ≤3 mm, moderate 4-5 mm, severe ≥6 mm. Associations between socioeconomic (household income, education), lifestyle, and biomedical factors and PD or bleeding on probing (BOP) per site (“Yes”/”No”) was analyzed with logistic regression analysis. Results Mean age of subjects was 46.4 (range 20–77) years. A significantly higher risk of deeper pockets for smokers (OR = 2.4, current vs. never smoker) or persons with higher BMI (OR = 1.6, BMI increase by 5) was found. Severity of periodontitis was significantly associated with caries lesions (p = 0.01), bridges (p < .0001), crowns (p < .0001), leukocytes (p = 0.04), HbA1c (p < .0001) and MCV (p = 0.04). PD was positively correlated with BOP. No significant associations with BOP were found in regression analysis. Conclusions Earlier findings for BMI and smoking with severity of PD were confirmed. Dental variables might be influenced by potential confounding factors e.g. dental hygiene. For blood parameters interactions with unknown systemic diseases may exist