CMS Pixel Data Quality Monitoring

We present the CMS Pixel Data Quality Monitoring (DQM) system. The concept and architecture are discussed. The monitored quantities are introduced, and the methods on how to ensure that the detector takes high quality data with large efficiency are explained. Finally we describe the automated data certification scheme, which is used to certify and classify the data from the Pixel detector for physics analyses

Solid-phase-assisted synthesis of targeting peptide-PEG-oligo(ethane amino)amides for receptor-mediated gene delivery.

In the forthcoming era of cancer gene therapy, efforts will be devoted to the development of new efficient and non-toxic gene delivery vectors. In this regard, the use of Fmoc/Boc-protected oligo(ethane amino)acids as building blocks for solid-phase-supported assembly represents a novel promising approach towards fully controlled syntheses of effective gene vectors. Here we report on the synthesis of defined polymers containing the following: (i) a plasmid DNA (pDNA) binding domain of eight succinoyl-tetraethylenpentamine (Stp) units and two terminal cysteine residues; (ii) a central polyethylene glycol (PEG) chain (with twenty-four oxyethylene units) for shielding; and (iii) specific peptides for targeting towards cancer cells. Peptides B6 and c(RGDfK), which bind transferrin receptor and αvβ3 integrin, respectively, were chosen because of the high expression of these receptors in many tumoral cells. This study shows the feasibility of designing these kinds of fully controlled vectors and their success for targeted pDNA-based gene transfer

Upregulation of CD20 Positive B-Cells and B-Cell Aggregates in the Tumor Infiltration Zone is Associated with Better Survival of Patients with Pancreatic Ductal Adenocarcinoma

Patients with pancreatic ductal adenocarcinoma (PDAC) normally have a poor long-term prognosis. However, some rare cases of long-term survivors have been reported. The tumor microenvironment, consisting of cellular and stromal components, possibly plays an important role and might influence prognosis. In this context, the role of tumor-infiltrating B-cells and its impact on the survival in patients with PDAC remains controversial. We therefore aimed to assess the prognostic value of CD20-positive B-cells and CD20-positive B-cell aggregates as well as CD138, IgM, Pax5, and Ki67 on the survival of patients with PDAC using immunohistochemistry of FFPE pancreatectomy tissue sections from patients that underwent primary surgery for pT3- and R0-pancreatic adenocarcinoma between 1995 and 2016. Patients with PDAC were matched and grouped in 16 long-term-survivors (LTS, median overall survival (OS): 96 months [range: 61–177 months]) and 16 short-term-survivors (STS, median OS: 16 months [range: 7–32 months]). CD20-positive B-cells and B-cell aggregates in the tumor infiltration zone were significantly upregulated in the LTS-group compared to the STS-group (p = 0.0499 respectively p = 0.0432). Regarding the entire patient cohort (n = 32) CD20 positive B-cell aggregates in the tumor infiltration zone were an independent prognostic marker for overall survival in multivariate analysis (HR 9.2, CI 1.6–51.4, p = 0.012). These results underline the importance of tumor-associated B-cells for prognosis of patients with PDAC. The detailed role of B cells in the pathomechanism of PDAC should be further investigated for predicting outcome, identifying appropriate treatment regimens, and developing novel therapeutic option

Report of the 2021 U.S. Community Study on the Future of Particle Physics (Snowmass 2021) Summary Chapter

The 2021-22 High-Energy Physics Community Planning Exercise (a.k.a. ``Snowmass 2021'') was organized by the Division of Particles and Fields of the American Physical Society. Snowmass 2021 was a scientific study that provided an opportunity for the entire U.S. particle physics community, along with its international partners, to identify the most important scientific questions in High Energy Physics for the following decade, with an eye to the decade after that, and the experiments, facilities, infrastructure, and R&D needed to pursue them. This Snowmass summary report synthesizes the lessons learned and the main conclusions of the Community Planning Exercise as a whole and presents a community-informed synopsis of U.S. particle physics at the beginning of 2023. This document, along with the Snowmass reports from the various subfields, will provide input to the 2023 Particle Physics Project Prioritization Panel (P5) subpanel of the U.S. High-Energy Physics Advisory Panel (HEPAP), and will help to guide and inform the activity of the U.S. particle physics community during the next decade and beyond.Comment: 75 pages, 3 figures, 2 tables. This is the first chapter and summary of the full report of the Snowmass 2021 Workshop. This version fixes an important omission from Table 2, adds two references that were not available at the time of the original version, fixes a minor few typos, and adds a small amount of material to section 1.1.

The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status

Abstract: Resistance to anaplastic lymphoma kinase (ALK)-targeted therapy in ALK-positive non-small cell lung cancer has been reported, with the majority of acquired resistance mechanisms relying on bypass signaling. To proactively identify resistance mechanisms in ALK-positive neuroblastoma (NB), we herein employ genome-wide CRISPR activation screens of NB cell lines treated with brigatinib or ceritinib, identifying PIM1 as a putative resistance gene, whose high expression is associated with high-risk disease and poor survival. Knockdown of PIM1 sensitizes cells of differing MYCN status to ALK inhibitors, and in patient-derived xenografts of high-risk NB harboring ALK mutations, the combination of the ALK inhibitor ceritinib and PIM1 inhibitor AZD1208 shows significantly enhanced anti-tumor efficacy relative to single agents. These data confirm that PIM1 overexpression decreases sensitivity to ALK inhibitors in NB, and suggests that combined front-line inhibition of ALK and PIM1 is a viable strategy for the treatment of ALK-positive NB independent of MYCN status

Lessons to Be Learned: Political Party Research and Political Party Assistance

Generally speaking, the effects of international political party assistance are viewed nega-tively, or at least controversially. This study attributes some of the shortcomings of political party aid to the poor relationship between assistance providers and political science party research. They simply operate in different worlds. Party assistance lacks clear-cut concepts and strategies in practice, which makes it difficult to adequately evaluate it. At issue is its 'standard method,' with its 'transformative' intention to change the party organization of the assistance receivers. At the same time, the scholarship on political parties can provide only limited help to assistance providers due to its own conceptual and methodological re-strictions, such as the Western European bias underlying its major concepts, the predominance of a functionalist approach, and the scant empirical research on political parties outside of Europe and the US. Taking a cue from recent political party research, we could begin to question the overarching role of political parties in the transition and consolidation proc-ess of new democracies. Other research findings emphasize the coexistence of different types of party organizations, and the possibility of different organizational developments, which might all be consistent with consolidating democracy. All this suggests the necessity of abandoning the controversial aim of the 'transformative impact' of political party aid.Die Wirksamkeit der internationalen Parteienförderung wird als wenig effektiv beurteilt - auch wenn dieses Urteil umstritten ist. Ein Grund für die Schwierigkeiten der Parteienförderung wird hier in den kaum vorhandenen Beziehungen zwischen Parteienförderern und der Parteienforschung gesehen, die weitgehend isoliert voneinander arbeiten. Der Parteienförderung fehlen klare Konzepte und Strategien, die eine angemessene Evaluierung ihrer Aktivitäten erlauben würden. Ein Grundproblem ist ihre so genannte 'Standardmethode' mit ihrem 'Transformationsziel', dem zufolge die Organisation der Empfängerpartei verändert werden soll. Zugleich kann die Parteienforschung aufgrund ihrer eigenen Wissensgrenzen bisher nur beschränkt Hilfe anbieten. Dazu zählen der westeuropäische Bias ihrer zentralen Konzepte, die Dominanz des funktionalistischen Ansatzes und die noch immer geringen empirischen Forschungsergebnisse zu Parteien außerhalb Europas und der USA. Jüngste Forschungsergebnisse lassen vermuten, dass die Rolle der Parteien im Transitions- und Konsolidierungsprozess überschätzt wurde, andere betonen die gleichzeitige Koexistenz ganz unterschiedlicher Parteitypen und die Möglichkeit unterschiedlicher Organisationsentwicklung, was letztlich zur Konsolidierung von Demokratie führen kann. All dies legt schließlich nahe, das grundlegende Transformationsziel der Parteienförderung aufzugeben