Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA

Abstract Streptococcus pneumoniae (S.pn.) is the most common bacterial pathogen causing community acquired pneumonia. The pore-forming toxin pneumolysin (PLY) is the major virulence factor of S.pn. and supposed to affect alveolar epithelial cells thereby activating the immune system by liberation of danger-associated molecular patterns (DAMP). To test this hypothesis, we established a novel live-cell imaging based assay to analyse mitochondrial function and associated release of mitochondrial DNA (mtDNA) as DAMP in real-time. We first revealed that bacterially released PLY caused significant changes of the cellular ATP homeostasis and led to morphologic alterations of mitochondria in human alveolar epithelial cells in vitro and, by use of spectral live-tissue imaging, in human alveoli. This was accompanied by strong mitochondrial calcium influx and loss of mitochondrial membrane potential resulting in opening of the mitochondrial permeability transition pore and mtDNA release without activation of intrinsic apoptosis. Moreover, our data indicate cellular mtDNA liberation via microvesicles, which may contribute to S.pn. related pro-inflammatory immune activation in the human alveolar compartment

Disziplinäre Sozialisation in die Wissenschaft: Fallstudien einer Lehrforschung

Dieses Diskussionspapier präsentiert und reflektiert die Ergebnisse aus der Lehrforschung "Sozialisation in die Wissenschaft. Ausbildung und Betreuung von Promovierenden", das im Winter- und Sommersemester 2013/2014 am Institut für Sozialwissenschaft der Humboldt Universität zu Berlin vom Herausgeber durchgeführt wurde. Die zentrale Forschungsfrage der Lehrforschung war, auf welche Weise Promovierende in unterschiedlichen Disziplinen in die Wissenschaft sozialisiert werden. Dabei gingen wir von einem engen Zusammenhang zwischen den spezifischen Sachfragen einer Disziplin, ihrer Alltagsorganisation und den tatsächlich praktizierten Formen der Promotionsbetreuung aus. Wir nahmen zudem an, dass die disziplinären Sozialisationsweisen zu den gegenwärtig neu entwickelten Organisationsweisen der Promotion (z.B. Graduiertenschulen) in Spannung geraten können, wenn sie nicht hinreichend berücksichtigt werden. Neben dem Erkenntnisgewinn zu dieser Thematik war ein weiteres Ziel der Lehrforschung die Sozialisation von Studierenden in die Wissenschaft. Studierende sollten die Praktiken der Sozialforschung nicht nur über Bücher kennenlernen, sondern sich über die eigene Erhebung und Auswertung von Daten im Team praktisch aneignen können. Vom Feldzugang, über die Teamkoordination, die fallspezifische Methodenverwendung bis zur materialnahen Hypothesenentwicklung konnten sie sich auf den verschiedensten Ebenen an den praktischen Unwägbarkeiten der Forschung austesten. Inwiefern das Zusammenbinden von Lehre und Forschung ein wichtiges Element in der Gestaltung sozialwissenschaftlicher Studiengänge sein kann, wird eingangs reflektiert. Anschließend werden vier Einzelstudien der Feldarbeit vorgestellt. Darin entwickeln die Studierenden ein Konzept zur Erhebung von Promotionsabbrüchen (Kapitel II), rekonstruieren Sozialisationsprozesse in der Mikrobiologie (Kapitel III), in der Ökonomie (Kapitel IV) sowie in den Professionen Medizin und Ingenieurwissenschaft (Kapitel V). In allen -sehr verschieden organisierten- Disziplinen ist die intellektuelle Selbständigkeit von Promovierenden ebenso wichtig wie ihre Ausrichtung auf das Forschungsprogramm der Betreuenden. Hieraus entsteht eine strukturelle Spannung zwischen Autonomie und Kontrolle in der Promotionsbetreuung. (Autorenreferat)This paper reflects the findings of the research seminar "Academic Socialization. Training and Supervision of PhD Students" in three dimensions (Institute for Social Sciences, Humoldt University Berlin, winter/summer term 2013/14): Firstly, the research seminar asks, in what way different disciplines shape the academic socialization processes of PhD students. The hypothesis was that content, social organization and socialization processes are tightly coupled in a discipline. In consequence, tensions between disciplinary and new organizational forms of doctoral education (i.e. graduate schools) emerge when central features of the discipline are not respected. Secondly, the paedagogical goal of the seminar was to introduce the students to the practice of social research. Students conducted empirical data in a team and had to cope with typical uncertainties of social research such as selecting and opening a field of inquiry, coordinating a team, using methods case sensitive or developing a hypothesis bottom up. The first chapter reflects on the possibilities and limitations of research rooted teaching processes in contemporary universities. In four studies the students, conceptionalize a survey on the drop off reasons of PhD students (Chapter II) and students analyze the socialization processes in microbiology (Chapter III), economics (Chapter IV) and the medical and engineering profession (Chapter V). We demonstrate that intellectual independence in persuing a PhD is as important as the link between the student and the reasearch program of the supervisor. This constitutes a structural tension between autonomy and control in all PhD supervisions. (author's abstract

Quality assessment of the land administration system in Pakistan

Performance issues of land administration systems, specifically the quality aspects, have been getting more attention over the last few years. Different assessment attempts have been carried out at international level, across different land administration systems in the world, to evaluate the performance of land administration systems by comparing different aspects of these systems. In all these evaluations, prime attention is given to only those measuring parameters which are common to all these systems. In some cases, legal and technical parameters are considered while the institutional and organisational parameters receive more attention in others. There have been a few efforts to standardise the procedures for assessing the performance of land administration systems at international level but there is no internationally accepted or standardised method to assess the quality of a standalone land administration system (LAS) within a country's environment. To be able to assess the quality of a standalone LAS, this paper develops a conceptual and methodological framework for carrying out in-depth analysis of the system. This research identifies those elements, indicators and variables that are required for assessing the quality of a standalone LAS. In order to identify such elements, indicators and variables to be included in the framework, a theoretical background is first discussed. A quality assessment framework and the methodological approach for assessing the quality of LASs are then developed. The approach is finally applied to assess the quality situation of the LAS in Pakistan by using the quality assessment framework via an explanatory case-study approac

Measurement of the double-differential inclusive jet cross section in proton-proton collisions at s\sqrt{s} = 5.02 TeV

International audienceThe inclusive jet cross section is measured as a function of jet transverse momentum $p_\mathrm{T}$ and rapidity $y$. The measurement is performed using proton-proton collision data at $\sqrt{s}$ = 5.02 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 27.4 pb$^{-1}$. The jets are reconstructed with the anti-$k_\mathrm{T}$ algorithm using a distance parameter of $R$ = 0.4, within the rapidity interval $\lvert y\rvert$$\lt$ 2, and across the kinematic range 0.06 $\lt$$p_\mathrm{T}$$\lt$ 1 TeV. The jet cross section is unfolded from detector to particle level using the determined jet response and resolution. The results are compared to predictions of perturbative quantum chromodynamics, calculated at both next-to-leading order and next-to-next-to-leading order. The predictions are corrected for nonperturbative effects, and presented for a variety of parton distribution functions and choices of the renormalization/factorization scales and the strong coupling $\alpha_\mathrm{S}$

Measurement of the double-differential inclusive jet cross section in proton-proton collisions at s= \sqrt{s} = 5.02 TeV

The inclusive jet cross section is measured as a function of jet transverse momentum $p_{\mathrm{T}}$ and rapidity $y$. The measurement is performed using proton-proton collision data at $\sqrt{s} =$ 5.02 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 27.4$\,\text{pb}^{-1}$. The jets are reconstructed with the anti-$k_{\mathrm{T}}$ algorithm using a distance parameter of $R=$ 0.4, within the rapidity interval $|y| <$ 2, and across the kinematic range 0.06 $< p_{\mathrm{T}} <$ 1 TeV. The jet cross section is unfolded from detector to particle level using the determined jet response and resolution. The results are compared to predictions of perturbative quantum chromodynamics, calculated at both next-to-leading order and next-to-next-to-leading order. The predictions are corrected for nonperturbative effects, and presented for a variety of parton distribution functions and choices of the renormalization/factorization scales and the strong coupling $\alpha_\mathrm{S}$.The inclusive jet cross section is measured as a function of jet transverse momentum $p_\mathrm{T}$ and rapidity $y$. The measurement is performed using proton-proton collision data at $\sqrt{s}$ = 5.02 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 27.4 pb$^{-1}$. The jets are reconstructed with the anti-$k_\mathrm{T}$ algorithm using a distance parameter of $R$ = 0.4, within the rapidity interval $\lvert y\rvert$$\lt$ 2, and across the kinematic range 0.06 $\lt$$p_\mathrm{T}$$\lt$ 1 TeV. The jet cross section is unfolded from detector to particle level using the determined jet response and resolution. The results are compared to predictions of perturbative quantum chromodynamics, calculated at both next-to-leading order and next-to-next-to-leading order. The predictions are corrected for nonperturbative effects, and presented for a variety of parton distribution functions and choices of the renormalization/factorization scales and the strong coupling $\alpha_\mathrm{S}$

Two-particle Bose-Einstein correlations and their Lévy parameters in PbPb collisions at sNN\sqrt{s_\mathrm{NN}} = 5.02 TeV

Two-particle Bose-Einstein momentum correlation functions are studied for charged-hadron pairs in lead-lead collisions at a center-of-mass energy per nucleon pair of $\sqrt{s_\mathrm{NN}}$ = 5.02 TeV. The data sample, containing 4.27$\times10^{9}$ minimum bias events corresponding to an integrated luminosity of 0.607 nb$^{-1}$, was collected by the CMS experiment in 2018. The experimental results are discussed in terms of a L\'evy-type source distribution. The parameters of this distribution are extracted as functions of particle pair average transverse mass and collision centrality. These parameters include the L\'evy index or shape parameter ($\alpha$), the L\'evy scale parameter ($R$), and the correlation strength parameter ($\lambda$). The source shape, characterized by $\alpha$, is found to be neither Cauchy nor Gaussian, implying the need for a full L\'evy analysis. Similarly to what was previously found for systems characterized by Gaussian source radii, a hydrodynamical scaling is observed for the L\'evy $R$ parameter. The $\lambda$ parameter is studied in terms of the core-halo model.Comment: Submitted to Physical Review C. All figures and tables can be found at http://cms-results.web.cern.ch/cms-results/public-results/publications/HIN-21-011 (CMS Public Pages

Measurement of the double-differential inclusive jet cross section in proton-proton collisions at s\sqrt{s} = 5.02 TeV

International audienceThe inclusive jet cross section is measured as a function of jet transverse momentum $p_\mathrm{T}$ and rapidity $y$. The measurement is performed using proton-proton collision data at $\sqrt{s}$ = 5.02 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 27.4 pb$^{-1}$. The jets are reconstructed with the anti-$k_\mathrm{T}$ algorithm using a distance parameter of $R$ = 0.4, within the rapidity interval $\lvert y\rvert$$\lt$ 2, and across the kinematic range 0.06 $\lt$$p_\mathrm{T}$$\lt$ 1 TeV. The jet cross section is unfolded from detector to particle level using the determined jet response and resolution. The results are compared to predictions of perturbative quantum chromodynamics, calculated at both next-to-leading order and next-to-next-to-leading order. The predictions are corrected for nonperturbative effects, and presented for a variety of parton distribution functions and choices of the renormalization/factorization scales and the strong coupling $\alpha_\mathrm{S}$

Measurement of the double-differential inclusive jet cross section in proton-proton collisions at s\sqrt{s} = 5.02 TeV

International audienceThe inclusive jet cross section is measured as a function of jet transverse momentum $p_\mathrm{T}$ and rapidity $y$. The measurement is performed using proton-proton collision data at $\sqrt{s}$ = 5.02 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 27.4 pb$^{-1}$. The jets are reconstructed with the anti-$k_\mathrm{T}$ algorithm using a distance parameter of $R$ = 0.4, within the rapidity interval $\lvert y\rvert$$\lt$ 2, and across the kinematic range 0.06 $\lt$$p_\mathrm{T}$$\lt$ 1 TeV. The jet cross section is unfolded from detector to particle level using the determined jet response and resolution. The results are compared to predictions of perturbative quantum chromodynamics, calculated at both next-to-leading order and next-to-next-to-leading order. The predictions are corrected for nonperturbative effects, and presented for a variety of parton distribution functions and choices of the renormalization/factorization scales and the strong coupling $\alpha_\mathrm{S}$