Poles, the only true resonant-state signals, are extracted from a worldwide collection of partial wave amplitudes using only one, well controlled pole-extraction method

Each and every energy dependent partial-wave analysis is parameterizing the pole positions in a procedure defined by the way how the continuous energy dependence is implemented. These pole positions are, henceforth, inherently model dependent. To reduce this model dependence, we use only one, coupled-channel, unitary, fully analytic method based on the isobar approximation to extract the pole positions from the each available member of the worldwide collection of partial wave amplitudes which are understood as nothing more but a good energy dependent representation of genuine experimental numbers assembled in a form of partial-wave data. In that way, the model dependence related to the different assumptions on the analytic form of the partial-wave amplitudes is avoided, and the true confidence limit for the existence of a particular resonant state, at least in one model, is established. The way how the method works, and first results are demonstrated for the S11 partial wave.Comment: 22 pages, 8 figures, 2 table

Singularity structure of the pi N scattering amplitude in a meson-exchange model up to energies W < 2.0 GeV

Within the previously developed Dubna-Mainz-Taipei meson-exchange model, the singularity structure of the pi N scattering amplitudes has been investigated. For all partial waves up to F waves and c.m. energies up to W = 2 GeV, the T-matrix poles have been calculated by three different techniques: analytic continuation into the complex energy plane, speed-plot and the regularization method. For all 4-star resonances, we find a perfect agreement between the analytic continuation and the regularization method. We also find resonance poles for resonances that are not so well established, but in these cases the pole positions and residues obtained by analytic continuation can substantially differ from the results predicted by the speed-plot and regularization methods.Comment: 21 pages, 4 figures, 4 table

Multichannel Anomaly of the Resonance Pole Parameters Resolved

Inspired by anomalies which the standard scattering matrix pole-extraction procedures have produced in a mathematically well defined coupled-channel model, we have developed a new method based solely on the assumption of partial-wave analyticity. The new method is simple and applicable not only to theoretical predictions but to the empirical partial-wave data as well. Since the standard pole-extraction procedures turn out to be the lowest-order term of the proposed method the anomalies are understood and resolved.Comment: 5 page

Targeting tumor-associated macrophages to increase the efficacy of immune checkpoint inhibitors: a glimpse into novel therapeutic approaches for metastatic melanoma

Immune checkpoint inhibitors (ICIs) represent a promising therapeutic intervention for a variety of advanced/metastatic solid tumors, including melanoma, but in a large number of cases, patients fail to establish a sustained anti-tumor immunity and to achieve a long-lasting clinical benefit. Cells of the tumor micro-environment such as tumor-associated M2 macrophages (M2-TAMs) have been reported to limit the efficacy of immunotherapy, promoting tumor immune evasion and progression. Thus, strategies targeting M2-TAMs have been suggested to synergize with immune checkpoint blockade. This review recapitulates the molecular mechanisms by which M2-TAMs promote cancer immune evasion, with focus on the potential cross-talk between pharmacological interventions targeting M2-TAMs and ICIs for melanoma treatment

BROCCOLI: overlapping and outlier-robust biclustering through proximal stochastic gradient descent

Matrix tri-factorization subject to binary constraints is a versatile and powerful framework for the simultaneous clustering of observations and features, also known as biclustering. Applications for biclustering encompass the clustering of high-dimensional data and explorative data mining, where the selection of the most important features is relevant. Unfortunately, due to the lack of suitable methods for the optimization subject to binary constraints, the powerful framework of biclustering is typically constrained to clusterings which partition the set of observations or features. As a result, overlap between clusters cannot be modelled and every item, even outliers in the data, have to be assigned to exactly one cluster. In this paper we propose Broccoli, an optimization scheme for matrix factorization subject to binary constraints, which is based on the theoretically well-founded optimization scheme of proximal stochastic gradient descent. Thereby, we do not impose any restrictions on the obtained clusters. Our experimental evaluation, performed on both synthetic and real-world data, and against 6 competitor algorithms, show reliable and competitive performance, even in presence of a high amount of noise in the data. Moreover, a qualitative analysis of the identified clusters shows that Broccoli may provide meaningful and interpretable clustering structures

Stability of the Zagreb Carnegie-Mellon-Berkeley model

In ref. [1] we have used the Zagreb realization of Carnegie-Melon-Berkeley coupled-channel, unitary model as a tool for extracting pole positions from the world collection of partial wave data, with the aim of eliminating model dependence in pole-search procedures. In order that the method is sensible, we in this paper discuss the stability of the method with respect to the strong variation of different model ingredients. We show that the Zagreb CMB procedure is very stable with strong variation of the model assumptions, and that it can reliably predict the pole positions of the fitted partial wave amplitudes.Comment: 25 pages, 12 figures, 19 table

Singularity structure of the pi N scattering amplitude in a meson-exchange model up to energies W < 2.0 GeV

Within the previously developed Dubna-Mainz-Taipei meson-exchange model, the singularity structure of the pi N scattering amplitudes has been investigated. For all partial waves up to F waves and c.m. energies up to W = 2 GeV, the T-matrix poles have been calculated by three different techniques: analytic continuation into the complex energy plane, speed-plot and the regularization method. For all 4-star resonances, we find a perfect agreement between the analytic continuation and the regularization method. We also find resonance poles for resonances that are not so well established, but in these cases the pole positions and residues obtained by analytic continuation can substantially differ from the results predicted by the speed-plot and regularization methods.Comment: 21 pages, 4 figures, 4 table

Interval training normalizes cCardiomyocyte function, diastolic Ca²⁺ control, and SR Ca²⁺ release synchronicity in a mouse model of diabetic cardiomyopathy

In the present study we explored the mechanisms behind excitation-contraction (EC)-coupling defects in cardiomyocytes from mice with type-2 diabetes (db/db), and determined whether 13-weeks of aerobic interval training could restore cardiomyocyte Ca2+ cycling and EC-coupling. Reduced contractility in cardiomyocytes isolated from sedentary db/db was associated with increased diastolic sarcoplasmic reticulum (SR)-Ca2+ leak, reduced synchrony of Ca2+ release, reduced transverse (T)-tubule density, and lower peak systolic and diastolic Ca2+ and caffeine-induced Ca2+ release. Additionally, the rate of SR Ca2+ ATPase (SERCA2a)-mediated Ca2+ uptake during diastole was reduced, whereas a faster recovery from caffeine-induced Ca2+ release indicated increased Na+/Ca2+- exchanger (NCX) activity. The increased SR-Ca2+ leak was attributed to increased Ca2+-calmodulindependent protein kinase (CaMKII&#948;) phosphorylation, supported by the normalization of SR-Ca2+ leak upon inhibition of CaMKII&#948; (AIP). Exercise training restored contractile function associated with restored SR Ca2+ release synchronicity, T-tubule density, twitch Ca2+ amplitude, SERCA2a and NCX activities, and SR-Ca2+ leak. The latter was associated with reduced phosphorylation of cytosolic CaMKII&#948;. Despite normal contractile function and Ca2+ handling after the training period, phospholamban was hyperphosphorylated at Serine-16. Protein kinase A (PKA) inhibition (H-89) in cardiomyocytes from the exercised db/db group abolished the differences in SR-Ca2+ load when compared with the sedentary db/db mice. EC-coupling changes were observed without changes in serum insulin or glucose levels, suggesting that the exercise training-induced effects are not via normalization of the diabetic condition. These data demonstrate that aerobic interval training almost completely restored the contractile function of the diabetic cardiomyocyte to levels close to sedentary wild type (WT)