The Scope of the IBGP Routing Anomaly Problem

Correctness problems in the iBGP routing, the de-facto standard to spread global routing information in Autonomous Systems, are a well-known issue. Configurations may route cost-suboptimal, inconsistent, or even behave non-convergent and -deterministic. However, even if a lot of studies have shown many exemplary problematic configurations, the exact scope of the problem is largely unknown: Up to now, it is not clear which problems may appear under which iBGP architectures. The exact scope of the iBGP correctness problem is of high theoretical and practical interest. Knowledge on the resistance of specific architecture schemes against certain anomaly classes and the reasons may help to improve other iBGP schemes. Knowledge on the specific problems of the different schemes helps to identify the right scheme for an AS and develop workarounds

Light Stop Searches at the LHC in Events with two b-Jets and Missing Energy

We propose a new method to discover light top squarks (stops) in the co-annihilation region at the Large Hadron Collider (LHC). The bino-like neutralino is the lightest supersymmetric particle (LSP) and the lighter stop is the next-to-LSP. Such scenarios can be consistent with electroweak baryogenesis and also with dark matter constraints. We consider the production of two stops in association with two b-quarks, including pure QCD as well as mixed electroweak-QCD contributions. The stops decay into a charm quark and the LSP. For a higgsino-like light chargino the electroweak contributions can exceed the pure QCD prediction. We show the size of the electroweak contributions as a function of the stop mass and present the LHC discovery reach in the stop-neutralino mass plane.Comment: 12 pages, 10 figure

Scalability of iBGP Path Diversity Concepts

Abstract. Improving the path diversity seems to be the next fundamental step in the iBGP evolution. Focusing the advantages an improvement of the path diversity implies, network protocol designers have disregarded the most critical drawback so far: The effect on the scalability of the iBGP routing, a fundamental requirement for production usage. This aspect is examined by the analyses discussed in our paper. In this paper, we provide the theoretical groundwork for scalability analyses of four highly relevant path diversity schemes. Based on this groundwork, we exemplarily predict the information load the schemes induce in a system of a large ISP. Generalizing the system-specific results, we give an outlook on the load that can be expected in comparable ASs. We found that for two schemes currently in the standardization process, scalability problems in large ASs as they are operated by ISPs seem likely

Hadronic production of bottom-squark pairs with electroweak contributions

We present the complete computation of the tree-level and the next-to-leading order electroweak contributions to bottom-squark pair production at the LHC. The computation is performed within the minimal supersymmetric extension of the Standard Model. We discuss the numerical impact of these contributions in several supersymmetric scenarios.Comment: 33 pages, v2: preprint numbers correcte

Perturbations of mesenchymal stromal cells after allogeneic hematopoietic cell transplantation predispose for bone marrow graft- versus-host-disease

Functional impairment of the bone marrow (BM) niche has been suggested as a major reason for prolonged cytopenia and secondary graft failure after allogeneic hematopoietic cell transplantation (alloHCT). Because mesenchymal stromal cells (MSCs) serve as multipotent progenitors for several niche components in the BM, they might play a key role in this process. We used collagenase digested trephine biopsies to directly quantify MSCs in 73 patients before (n = 18) and/or after alloHCT (n = 65). For the first time, we demonstrate that acute graft-versus-host disease (aGvHD, n = 39) is associated with a significant decrease in MSC numbers. MSC reduction can be observed even before the clinical onset of aGvHD (n = 10). Assessing MSCs instantly after biopsy collection revealed phenotypic and functional differences depending on the occurrence of aGvHD. These differences vanished during ex vivo expansion. The MSC endotypes observed revealed an enhanced population of donor-derived classical dendritic cells type 1 and alloreactive T cells as the causing agent for compartmental inflammation and MSC damage before clinical onset of aGvHD was ascertained. In conclusion, MSCs endotypes may constitute a predisposing conductor of alloreactivity after alloHCT preceding the clinical diagnosis of aGvHD

Hadronic production of squark-squark pairs: The electroweak contributions

We compute the electroweak (EW) contributions to squark--squark pair production processes at the LHC within the framework of the Minimal Supersymmetric Standard Model (MSSM). Both tree-level EW contributions, of O(alpha_s alpha + alpha^2), and next-to-leading order (NLO) EW corrections, of O(alpha_s^2 alpha), are calculated. Depending on the flavor and chirality of the produced quarks, many interferences between EW-mediated and QCD-mediated diagrams give non-zero contributions at tree-level and NLO. We discuss the computational techniques and present an extensive numerical analysis for inclusive squark--squark production as well as for subsets and single processes. While the tree-level EW contributions to the integrated cross sections can reach the 20% level, the NLO EW corrections typically lower the LO prediction by a few percent.Comment: 36 pages, 18 figure

Venetoclax enhances the efficacy of therapeutic antibodies in B-cell malignancies by augmenting tumor cell phagocytosis

Immunotherapy has evolved as a powerful tool for the treatment of B-cell malignancies, and patient outcomes have improved by combining therapeutic antibodies with conventional chemotherapy. Overexpression of antiapoptotic B-cell lymphoma 2 (Bcl-2) is associated with a poor prognosis, and increased levels have been described in patients with "double-hit" diffuse large B-cell lymphoma, a subgroup of Burkitt's lymphoma, and patients with pediatric acute lymphoblastic leukemia harboring a t(17;19) translocation. Here, we show that the addition of venetoclax (VEN), a specific Bcl-2 inhibitor, potently enhanced the efficacy of the therapeutic anti-CD20 antibody rituximab, anti-CD38 daratumumab, and anti-CD19-DE, a proprietary version of tafasitamab. This was because of an increase in antibody-dependent cellular phagocytosis by macrophages as shown in vitro and in vivo in cell lines and patient-derived xenograft models. Mechanistically, double-hit lymphoma cells subjected to VEN triggered phagocytosis in an apoptosis-independent manner. Our study identifies the combination of VEN and therapeutic antibodies as a promising novel strategy for the treatment of B-cell malignancies

Threshold resummation for gaugino pair production at hadron colliders

We present a complete analysis of threshold resummation effects on direct light and heavy gaugino pair production at the Tevatron and the LHC. Based on a new perturbative calculation at next-to-leading order of SUSY-QCD, which includes also squark mixing effects, we resum soft gluon radiation in the threshold region at leading and next-to-leading logarithmic accuracy, retaining at the same time the full SUSY-QCD corrections in the finite coefficient function. This allows us to correctly match the resummed to the perturbative cross section. Universal subleading logarithms are resummed in full matrix form. We find that threshold resummation slightly increases and considerably stabilizes the invariant mass spectra and total cross sections with respect to the next-to-leading order calculation. For future reference, we present total cross sections and their theoretical errors in tabular form for several commonly used SUSY benchmark points, gaugino pairs, and hadron collider energies.Comment: 28 pages, 5 tables, 17 figure

Pediatric T-ALL type-1 and type-2 relapses develop along distinct pathways of clonal evolution

The mechanisms underlying T-ALL relapse remain essentially unknown. Multilevel-omics in 38 matched pairs of initial and relapsed T-ALL revealed 18 (47%) type-1 (defined by being derived from the major ancestral clone) and 20 (53%) type-2 relapses (derived from a minor ancestral clone). In both types of relapse, we observed known and novel drivers of multidrug resistance including MDR1 and MVP, NT5C2 and JAK-STAT activators. Patients with type-1 relapses were specifically characterized by IL7R upregulation. In remarkable contrast, type-2 relapses demonstrated (1) enrichment of constitutional cancer predisposition gene mutations, (2) divergent genetic and epigenetic remodeling, and (3) enrichment of somatic hypermutator phenotypes, related to BLM, BUB1B/PMS2 and TP53 mutations. T-ALLs that later progressed to type-2 relapses exhibited a complex subclonal architecture, unexpectedly, already at the time of initial diagnosis. Deconvolution analysis of ATAC-Seq profiles showed that T-ALLs later developing into type-1 relapses resembled a predominant immature thymic T-cell population, whereas T-ALLs developing into type-2 relapses resembled a mixture of normal T-cell precursors. In sum, our analyses revealed fundamentally different mechanisms driving either type-1 or type-2 T-ALL relapse and indicate that differential capacities of disease evolution are already inherent to the molecular setup of the initial leukemia