Tumor necrosis factor-alpha regulates the expression of inducible costimulator receptor ligand on CD34+ progenitor cells during differentiation into antigen presenting cells

The inducible costimulator receptor (ICOS) is a third member of the CD28 receptor family that regulates T cell activation and function. ICOS binds to a newly identified ligand on antigen presenting cells different from the CD152 ligands CD80 and CD86. We used soluble ICOSIg and a newly developed murine anti-human ICOS ligand (ICOSL) monoclonal antibody to further characterize the ICOSL during ontogeny of antigen presenting cells. In a previous study, we found that ICOSL is expressed on monocytes, dendritic cells, and B cells. To define when ICOSL is first expressed on myeloid antigen presenting cells, we examined ICOSL expression on CD34 cells in bone marrow. We found that CD34bright cells regardless of their myeloid commitment were ICOSL , whereas ICOSL was first expressed when CD34 expression diminished and the myeloid marker CD33 appeared

The effect of social exclusion on state paranoia and explicit and implicit self-esteem in a non-clinical sample

Background and objectives: The relationship between self-esteem and paranoia may be influenced by social stress. This study aimed to replicate previous research on the impact ofsocial exclusion on paranoia and self-esteem in a non-clinical sample and to extend this work by examining the effect of exclusion on self-esteem at the 'implicit' level. Methods: Non-clinical participants (N = 85) were randomly allocated to the Inclusion or Exclusion condition of a virtual ball-toss game ('Cyberball'). They completed self-reportmeasures of state paranoia and self-esteem, and two implicit measures of self-esteem - theImplicit Association Task (IAT) and Implicit Relational Assessment Procedure (IRAP) -prior to and after exposure to Cyberball. Results: Social exclusion increased state paranoia. This effect was moderated by distress associated with trait paranoia. Exclusion was also associated with decreased self-reported self-esteem, as well as reduced implicit self-esteem on the IAT. Changes in self-reported self-esteem were associated with state paranoia at post-Cyberball. The IRAP indicated that reductions in implicit self-esteem may be due to increases in 'Me-Negative' and 'Others-Positive' biases (rather than reductions in 'Me-Positive' bias). Limitations: The current study involved a non-clinical sample and so findings cannot be generalized to clinical paranoia. Conclusions: These findings are consistent with previous evidence that paranoia is associated with negative self-evaluations, whereas positive self-evaluations can persist in paranoia. They also provide support for the suggestion that investigations of self-esteem in paranoia should extend beyond global self-esteem and might benefit from a distinction between positive and negative components. (C) 2017 Elsevier Ltd. All rights reserved

Flow cytometric maturity score as a novel prognostic parameter in patients with acute myeloid leukemia

The European LeukemiaNet (ELN) classification is widely accepted for risk stratification of patients with acute myeloid leukemia (AML). In order to establish immunophenotypic features that predict prognosis, the expression of single AML blast cell antigens has been evaluated with partly conflicting results; however, the influence of immunophenotypic blast maturity is largely unknown. In our study, 300 AML patients diagnosed at our institution between January 2003 and April 2012 were analyzed. A flow cytometric maturity score was developed in order to distinguish "mature" AML (AML-ma) from "immature" AML (AML-im) by quantitative expression levels of early progenitor cell antigens (CD34, CD117, and TdT). AML-ma showed significantly longer relapse-free survival (RFS) and overall survival (OS) than AML-im (p < 0.001). Interestingly, statistically significant differences in RFS and OS were maintained within the "intermediate-risk" group according to ELN (RFS, 7.0 years (AML-ma) vs. 3.3 years (AML-im); p = 0.002; OS, 5.1 years (AML-ma) vs. 3.0 years (AML-im); p = 0.022). Our novel flow cytometric score easily determines AML blast maturity and can predict clinical outcome. It remains to be clarified whether these results simply reflect an accumulation of favorable molecular phenotypes in the AML-ma subgroup or whether they rely on biological differences such as a higher proportion of leukemia stem cells and/or a higher degree of genetic instability within the AML-im subgroup

Children's scale errors and object processing:Early evidence for cross-cultural differences

Scale errors are observed when young children make mistakes by attempting to put their bodies into miniature versions of everyday objects. Such errors have been argued to arise from children's insufficient integration of size into their object representations. The current study investigated whether Japanese and UK children's (18–24 months old, N = 80) visual exploration in a categorization task related to their scale error production. UK children who showed greater local processing made more scale errors, whereas Japanese children, who overall showed greater global processing, showed no such relationship. These results raise the possibility that children's suppression of scale errors emerges not from attention to size per se, but from a critical integration of global (i.e., size) and local (i.e., object features) information during object processing, and provide evidence that this mechanism differs cross-culturally

Production and Initial Characterization of Dad1p, a Component of the Dam1-DASH Kinetochore Complex

In all dividing eukaryotic cells, the mitotic spindle (composed primarily of microtubules) must interact with chromosomes through a complex protein assembly called the kinetochore. In Saccharomyces cerevisiae, the Dam1-DASH complex plays an important role in promoting attachment between the kinetochore and the mitotic spindle. It also actively participates in the physical separation of sister chromatids in anaphase. Understanding the biochemical mechanisms used by Dam1-DASH has been facilitated by bacterial co-expression of the ten Dam1-DASH genes, which results in the production of a heterodecameric protein complex that can be studied in vitro. However, individual protein subunits are not soluble when expressed in E. coli, thus precluding analysis of the nature of the interaction between subunits and an examination of the assembly of the functional complex. In this paper, we describe the expression, solubilization, purification and refolding of Dad1p, one of the Dam1-DASH complex subunits. In addition, we show that Dad1p, when isolated in this manner forms dimers and/or tetramers, dependent upon protein concentration. This work provides an important tool for studying the Dam1-DASH complex that was previously unavailable, and provides an avenue of investigation for understanding how the individual heterodecamers associate with each other to facilitate chromosome segregation

Investigation of cold Rb Rydberg atoms in a magneto-optical trap

We present our results on the experiments with cold Rb Rydberg atoms in a magneto-optical trap (MOT). Characteristic features of our experiment were the excitation of Rydberg atoms in a small volume within the cold atom cloud and sorting of the measured signals and spectra over the number of registered Rydberg atoms. We have measured the effective lifetime of the Rydberg state 37P, as well as its polarizability in a weak electric field. The results are in good agreement with the theoretical calculations. We have shown that localization of the small excitation volume around the zero-magnetic-field point makes possible to increase the spectral resolution and to obtain narrow microwave resonances in Rydberg atoms without switching off the MOT quadrupole magnetic field. We have measured the dependence of the amplitude of the dipole-dipole interaction resonances on the number of Rydberg atoms, which has a linear character and agrees with the theory for weak dipole-dipole interaction.Comment: 9 pages, 6 figures. To appear in JETP, 2009. Typo in eq.(7) corrected in v

Paying the Guard: An Entry-Guard-Based Payment System for Tor

When choosing the three relays that compose a circuit, Tor selects the first hop among a restricted number of relays called entry guards, pre-selected by the user himself. The reduced number of entry guards, that until recently was fixed to three, helps in mitigating the effects of several traffic analysis attacks. However, recent literature indicates that the number should be further reduced, and the time during which the user keeps the relays as guards increased. Therefore, developers of Tor recently proposed selecting only one entry guard, which is to be used by the user for all circuits and for a prolonged period of time (nine months). While this design choice was made to increase the security of the protocol, it also opens an unprecedented opportunity for a market mechanism where relays get paid for traffic by the users. In this paper, we propose to use the entry guard as the point-of-sale: users subscribe to their entry guard of choice, and deposit an amount that will be used for paying for the circuits. From the entry guard, income is then distributed to the other relays included in circuits through an inter-relay accounting system. While the user may pay the entry guard using BitCoins, or any other anonymous payment system, the relays exchange I Owe You (IOU) certificates during communication, and settle their balances only at synchronized, later points in time. This novel deferred payment approach overcomes the weaknesses of the previously proposed Tor payment mechanisms: we separate the user’s payment from the inter-relay payments, and we effectively unlink both from the chosen path, thus preserving the secrecy of the circuit

Intelligente Prognoseverfahren für beeinflusstes Verbrauchsverhalten in Energiesystemen

Mit dem steigenden Anteil fluktuierender Einspeisung elektrischer Energie aus dezentralen Erzeugungsanlagen wie Wind und Photovoltaik wachsen auch die technischen Herausforderungen für das elektrische Energieversorgungssystem, insbesondere für die Einhaltung des permanenten Gleichgewichts von Erzeugung und Verbrauch. Für die künftige Gewährleistung der Versorgungssicherheit wird die Erschließung zusätzlicher Flexibilitäten notwendig sein. Es gibt prinzipiell zwei Möglichkeiten für den Ausgleich zwischen Erzeugung und Verbrauch: Einerseits die Anpassung der Erzeugung an den Verbrauch und andererseits die Anpassung des Verbrauchs an die Erzeugung. Letzteres ist Gegenstand der weiteren Betrachtungen. Die verbrauchsseitige Anpassung erfolgt durch die Ausnutzung verbrauchseitiger Lastverschiebepotentiale, technisch realisiert über das Demand Side Management. Mit der Bereitstellung dieser Flexibilitätspotentiale ist neben dem Vorteil auch gleichzeitig der Nachteil verbunden, dass die bisher unbeeinflussten typischen Verbrauchsmuster durch markt- und/oder erzeugungssituationsabhängige Anreizsignale verändert werden. Dies führt wiederum zur Erhöhung der Unsicherheit bei der Verbrauchsprognose und insbesondere bei autoregressiven Vorhersagemodellen zu einer Systemrückkopplung. Für eine ökonomisch und ökologisch optimale Fahrweise des elektrischen Energiesystems muss auch ein derart beeinflusstes Verbrauchsverhalten in hinreichend guter Qualität prognostizierbar sein. Herkömmliche Prognosemethoden für Standard- und Sonderkunden können diesen Beitrag durch die geänderten Anforderungen nicht leisten. Von daher sollen ggf. neue mathematische Verfahren und Modellansätze für Prognosemethoden unter Berücksichtigung von verbrauchersteuernden und -beeinflussenden Anreizsignalen entwickelt werden. Dabei sind die Auswirkungen beispielsweise von Preisanreizen auf das Verbrauchsverhalten in einem System zu berücksichtigen. Weiterhin sollen neben den Modellansätzen zur Prognose beeinflusster Verbraucher auch Modelle konzipiert und entworfen werden, mit denen auf Grundlage historischer Daten beeinflusster Verbraucher oder Verbrauchergruppen auf das unbeeinflusste Verbrauchsverhalten geschlossen werden kann. Prognosen mittels dieser Modellansätze können den Bedarf zur Lastverschiebung für einen bestimmten Zeithorizont aufgrund von ökonomischen Gesichtspunkten (aus Sicht eines Stromhändlers) oder Netzrestriktionen (aus Sicht eines Netzbetreibers) ermitteln und somit zur Entscheidungsfindung zur Lastbeeinflussung beitragen. In diesem Beitrag erfolgt eine systemtechnische Betrachtung der Problemstellung. Die Zusammenhänge zwischen der Planung für die Beeinflussung der Verbraucherseite, den resultierenden beeinflussten Lasten und den Zusammenhängen der Einflussgrößen und möglichen Systemrückkopplungen sollen aufgezeigt werden. Auf Basis dieser grundlegenden Zusammenhänge soll ein Vorgehensmodell für die Identifikation von Ansätzen für Datenanalysen und Prognosemethoden entwickelt werden, mit dessen Hilfe beeinflusstes und unbeeinflusstes Verbrauchsverhalten prognostiziert werden kann. Die Datenbasis für die Prognose der beeinflussten und unbeeinflussten Verbraucherlasten ergibt sich neben möglichen exogenen Größen nur aus historischen Werten für beeinflusstes Verbrauchsverhalten

Determinants of postnatal spleen tissue regeneration and organogenesis

Abstract The spleen is an organ that filters the blood and is responsible for generating blood-borne immune responses. It is also an organ with a remarkable capacity to regenerate. Techniques for splenic auto-transplantation have emerged to take advantage of this characteristic and rebuild spleen tissue in individuals undergoing splenectomy. While this procedure has been performed for decades, the underlying mechanisms controlling spleen regeneration have remained elusive. Insights into secondary lymphoid organogenesis and the roles of stromal organiser cells and lymphotoxin signalling in lymph node development have helped reveal similar requirements for spleen regeneration. These factors are now considered in the regulation of embryonic and postnatal spleen formation, and in the establishment of mature white pulp and marginal zone compartments which are essential for spleen-mediated immunity. A greater understanding of the cellular and molecular mechanisms which control spleen development will assist in the design of more precise and efficient tissue grafting methods for spleen regeneration on demand. Regeneration of organs which harbour functional white pulp tissue will also offer novel opportunities for effective immunotherapy against cancer as well as infectious diseases