Resummation and Matching of bb-quark Mass Effects in bbˉHb\bar{b}H Production

We use a systematic effective field theory setup to derive the $b\bar{b}H$ production cross section. Our result combines the merits of both fixed 4-flavor and 5-flavor schemes. It contains the full 4-flavor result, including the exact dependence on the $b$-quark mass, and improves it with a resummation of collinear logarithms of $m_b/m_H$. In the massless limit, it corresponds to a reorganized 5-flavor result. While we focus on $b\bar{b}H$ production, our method applies to generic heavy-quark initiated processes at hadron colliders. Our setup resembles the variable flavor number schemes known from heavy-flavor production in deep-inelastic scattering, but also differs in some key aspects. Most importantly, the effective $b$-quark PDF appears as part of the perturbative expansion of the final result where it effectively counts as an $O(\alpha_s)$ object. The transition between the fixed-order (4-flavor) and resummation (5-flavor) regimes is governed by the low matching scale at which the $b$-quark is integrated out. Varying this scale provides a systematic way to assess the perturbative uncertainties associated with the resummation and matching procedure and reduces by going to higher orders. We discuss the practical implementation and present numerical results for the $b\bar{b}H$ production cross section at NLO+NLL. We also provide a comparison to the corresponding predictions in the fixed 4-flavor and 5-flavor results and the Santander matching prescription. Compared to the latter, we find a slightly reduced uncertainty and a larger central value, with its central value lying at the lower edge of our uncertainty band.Comment: 54 pages, 16 figures. Final version to be published in JHEP (one ref added

Resummation prescriptions and ambiguities in SCET vs. direct QCD: Higgs production as a case study

We perform a comparison of soft-gluon resummation in SCET vs. direct QCD (dQCD), using Higgs boson production in gluon fusion as a case study, with the goal of tracing the quantitative impact of each source of difference between the two approaches. We show that saddle-point methods enable a direct quantitative comparison despite the fact that the scale which is resummed in the two approaches is not the same. As a byproduct, we put in one-to-one analytic correspondence various features of either approach: specifically, we show how the SCET method for treating the Landau pole can be implemented in dQCD, and how the resummation of the optimal partonic scale of dQCD can be implemented in SCET. We conclude that the main quantitative difference comes from power-suppressed subleading contributions, which could in fact be freely tuned in either approach, and not really characteristic of either. This conclusion holds for Higgs production in gluon fusion, but it is in fact generic for processes with similar kinematics. For Higgs production, everything else being equal, SCET resummation at NNLL in the Becher-Neubert implementation leads to essentially no enhancement of the NNLO cross-section, unlike dQCD in the standard implementation of Catani et al

Tailoring CD19xCD3-DART exposure enhances T-cells to eradication of B-cell neoplasms.

Many patients with B-cell malignancies can be successfully treated, although tumor eradication is rarely achieved. T-cell-directed killing of tumor cells using engineered T-cells or bispecific antibodies is a promising approach for the treatment of hematologic malignancies. We investigated the efficacy of CD19xCD3 DART bispecific antibody in a broad panel of human primary B-cell malignancies. The CD19xCD3 DART identified 2 distinct subsets of patients, in which the neoplastic lymphocytes were eliminated with rapid or slow kinetics. Delayed responses were always overcome by a prolonged or repeated DART exposure. Both CD4 and CD8 effector cytotoxic cells were generated, and DART-mediated killing of CD4+ cells into cytotoxic effectors required the presence of CD8+ cells. Serial exposures to DART led to the exponential expansion of CD4 + and CD8 + cells and to the sequential ablation of neoplastic cells in absence of a PD-L1-mediated exhaustion. Lastly, patient-derived neoplastic B-cells (B-Acute Lymphoblast Leukemia and Diffuse Large B Cell Lymphoma) could be proficiently eradicated in a xenograft mouse model by DART-armed cytokine induced killer (CIK) cells. Collectively, patient tailored DART exposures can result in the effective elimination of CD19 positive leukemia and B-cell lymphoma and the association of bispecific antibodies with unmatched CIK cells represents an effective modality for the treatment of CD19 positive leukemia/lymphoma

Tiotropium modulates transient receptor potential V1 (TRPV1) in airway sensory nerves: A beneficial off-target effect?⋆

BackgroundRecent studies have suggested that the long-acting muscarinic receptor antagonist tiotropium, a drug widely prescribed for its bronchodilator activity in patients with chronic obstructive pulmonary disease and asthma, improves symptoms and attenuates cough in preclinical and clinical tussive agent challenge studies. The mechanism by which tiotropium modifies tussive responses is not clear, but an inhibition of vagal tone and a consequent reduction in mucus production from submucosal glands and bronchodilation have been proposed.ObjectiveThe aim of this study was to investigate whether tiotropium can directly modulate airway sensory nerve activity and thereby the cough reflex.MethodsWe used a conscious cough model in guinea pigs, isolated vagal sensory nerve and isolated airway neuron tissue– and cell-based assays, and in vivo single-fiber recording electrophysiologic techniques.ResultsInhaled tiotropium blocked cough and single C-fiber firing in the guinea pig to the transient receptor potential (TRP) V1 agonist capsaicin, a clinically relevant tussive stimulant. Tiotropium and ipratropium, a structurally similar muscarinic antagonist, inhibited capsaicin responses in isolated guinea pig vagal tissue, but glycopyrrolate and atropine did not. Tiotropium failed to modulate other TRP channel–mediated responses. Complementary data were generated in airway-specific primary ganglion neurons, demonstrating that tiotropium inhibited capsaicin-induced, but not TRPA1-induced, calcium movement and voltage changes.ConclusionFor the first time, we have shown that tiotropium inhibits neuronal TRPV1-mediated effects through a mechanism unrelated to its anticholinergic activity. We speculate that some of the clinical benefit associated with taking tiotropium (eg, in symptom control) could be explained through this proposed mechanism of action

NLL soft and Coulomb resummation for squark and gluino production at the LHC

We present predictions of the total cross sections for pair production of squarks and gluinos at the LHC, including the stop-antistop production process. Our calculation supplements full fixed-order NLO predictions with resummation of threshold logarithms and Coulomb singularities at next-to-leading logarithmic (NLL) accuracy, including bound-state effects. The numerical effect of higher-order Coulomb terms can be as big or larger than that of soft-gluon corrections. For a selection of benchmark points accessible with data from the 2010-2012 LHC runs, resummation leads to an enhancement of the total inclusive squark and gluino production cross section in the 15-30 % range. For individual production processes of gluinos, the corrections can be much larger. The theoretical uncertainty in the prediction of the hard-scattering cross sections is typically reduced to the 10 % level.Comment: 45 pages, 16 Figures, LaTex. v2: published version. Grids with numerical results for the NLL cross sections for squark and gluino production at the 7/8 TeV LHC are included in the submission and are also available at http://omnibus.uni-freiburg.de/~cs1010/susy.htm

Transient receptor potential cation channel, subfamily V, member 4 and airway sensory afferent activation: Role of adenosine triphosphate

BackgroundSensory nerves innervating the airways play an important role in regulating various cardiopulmonary functions, maintaining homeostasis under healthy conditions and contributing to pathophysiology in disease states. Hypo-osmotic solutions elicit sensory reflexes, including cough, and are a potent stimulus for airway narrowing in asthmatic patients, but the mechanisms involved are not known. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is widely expressed in the respiratory tract, but its role as a peripheral nociceptor has not been explored.ObjectiveWe hypothesized that TRPV4 is expressed on airway afferents and is a key osmosensor initiating reflex events in the lung.MethodsWe used guinea pig primary cells, tissue bioassay, in vivo electrophysiology, and a guinea pig conscious cough model to investigate a role for TRPV4 in mediating sensory nerve activation in vagal afferents and the possible downstream signaling mechanisms. Human vagus nerve was used to confirm key observations in animal tissues.ResultsHere we show TRPV4-induced activation of guinea pig airway–specific primary nodose ganglion cells. TRPV4 ligands and hypo-osmotic solutions caused depolarization of murine, guinea pig, and human vagus and firing of Aδ-fibers (not C-fibers), which was inhibited by TRPV4 and P2X3 receptor antagonists. Both antagonists blocked TRPV4-induced cough.ConclusionThis study identifies the TRPV4-ATP-P2X3 interaction as a key osmosensing pathway involved in airway sensory nerve reflexes. The absence of TRPV4-ATP–mediated effects on C-fibers indicates a distinct neurobiology for this ion channel and implicates TRPV4 as a novel therapeutic target for neuronal hyperresponsiveness in the airways and symptoms, such as cough

Charm in Deep-Inelastic Scattering

We show how to extend systematically the FONLL scheme for inclusion of heavy quark mass effects in DIS to account for the possible effects of an intrinsic charm component in the nucleon. We show that when there is no intrinsic charm, FONLL is equivalent to S-ACOT to any order in perturbation theory, while when an intrinsic charm component is included FONLL is identical to ACOT, again to all orders in perturbation theory. We discuss in detail the inclusion of top and bottom quarks to construct a variable flavour number scheme, and give explicit expressions for the construction of the structure functions $F^c_2$, $F^c_L$ and $F^c_3$ to NNLO

Les bulles « robustes »:Pourquoi il faut construire des logements en région parisienne

« Bulle » ou « pas bulle » ? La question taraude les observateurs et les acteurs du marché immobilier français. Nous examinons dans cet article les éléments empiriques et théoriques qui expliquent la hausse des prix récente et sa résistance aux retournements conjoncturels. En combinant la notion de bulle économique, les arguments de l’économie spatiale et une analyse d’économie politique, nous suggérons que la valorisation importante de l’immobilier en France est le résultat d’une logique rationnelle et conforte les intérêts des acteurs locaux. Dès lors, la forte valorisation peut être considérée comme une « bulle robuste », à même de résister à des chocs importants. Cette bulle organise un transfert intergénérationnel et peut avoir des effets positifs. Elle peut également renforcer la ségrégation spatiale, alimenter les inégalités territoriales et empêcher d’exploiter les économies d’agglomération possibles. L’analyse est détaillée sur la région Ile-de-France où ces phénomènes sont particulièrement marqués