Developmental and tissue-specific expression of the Q5k gene

Expression of the Q5k gene was examined by northern blot analysis and polymerase chain reaction (PCR) in the AKR mouse and various cell lines, each of the H-2k haplotype. Our results show that Q5k mRNA is present during the whole postimplantational development of the AKR embryo/fetus (gestation day 6 to 15). In the juvenile mouse (week 2 to 4) transcription of the Q5k gene persisted in all organs examined. In contrast, in the adult animal expression of the Q5k gene was limited to the thymus and uterus of the pregnant mouse. Upon malignant transformation, the amount of Q5k-specific mRNA increased dramatically in thymus and could also be observed in the spleen of thymoma bearing animals. Expression of the Q5k gene was also detectable in several transformed mouse cell lines. Mitogen stimulation or treatment with cytokines induced Q5k expression in primary spleen cell cultures. A possible explanation for the tissue-restricted expression in the adult AKR mouse is discussed

Human Therapies as a Successful Liaison between Chemistry and Biology

The development of novel therapies is arguably one of the most important roles of modern chemistry and biology. Here, we shed light on a particular class of human therapies in which synthetic chemical entities are attached to expressed biologicals (proteins) with the goal to enhance clinical activity. We focus our discussion on three key categories of these derivatized biologicals: proteins conjugated with biologically inert molecules, proteins conjugated with biologically active small molecules and peptides (e.g., antibody drug conjugates [ADCs]), and proteins conjugated with radio isotopes. Overall, it is apparent by the impact on clinical activity as well as the commercial success that chemical modification of recombinant proteins is becoming of increasing importance. Therefore, we argue that deeper understanding of the chemical reactions between large proteinaceous molecules and small molecule reagents will allow for more precise and elegant solutions to existing limitations in this field

A high-reflectivity high-Q micromechanical Bragg-mirror

We report on the fabrication and characterization of a micromechanical oscillator consisting only of a free-standing dielectric Bragg mirror with high optical reflectivity and high mechanical quality. The fabrication technique is a hybrid approach involving laser ablation and dry etching. The mirror has a reflectivity of 99.6%, a mass of 400ng, and a mechanical quality factor Q of approximately 10^4. Using this micromirror in a Fabry Perot cavity, a finesse of 500 has been achieved. This is an important step towards designing tunable high-Q high-finesse cavities on chip.Comment: 3 pages, 2 figure

Involvement of Egr-1/RelA Synergy in Distinguishing T Cell Activation from Tumor Necrosis Factor-α–induced NF-κB1 Transcription

NF-κB is an important transcription factor required for T cell proliferation and other immunological functions. The NF-κB1 gene encodes a 105-kD protein that is the precursor of the p50 component of NF-κB. Previously, we and others have demonstrated that NF-κB regulates the NF-κB1 gene. In this manuscript we have investigated the molecular mechanisms by which T cell lines stimulated with phorbol 12-myristate 13-acetate (PMA) and phytohemagglutin (PHA) display significantly higher levels of NF-κB1 encoding transcripts than cells stimulated with tumor necrosis factor-α, despite the fact that both stimuli activate NF-κB. Characterization of the NF-κB1 promoter identified an Egr-1 site which was found to be essential for both the PMA/ PHA-mediated induction as well as the synergistic activation observed after the expression of the RelA subunit of NF-κB and Egr-1. Furthermore, Egr-1 induction was required for endogenous NF-κB1 gene expression, since PMA/PHA-stimulated T cell lines expressing antisense Egr-1 RNA were inhibited in their ability to upregulate NF-κB1 transcription. Our studies indicate that transcriptional synergy mediated by activation of both Egr-1 and NF-κB may have important ramifications in T cell development by upregulating NF-κB1 gene expression

Self-cooling of a micro-mirror by radiation pressure

We demonstrate passive feedback cooling of a mechanical resonator based on radiation pressure forces and assisted by photothermal forces in a high-finesse optical cavity. The resonator is a free-standing high-reflectance micro-mirror (of mass m=400ng and mechanical quality factor Q=10^4) that is used as back-mirror in a detuned Fabry-Perot cavity of optical finesse F=500. We observe an increased damping in the dynamics of the mechanical oscillator by a factor of 30 and a corresponding cooling of the oscillator modes below 10 K starting from room temperature. This effect is an important ingredient for recently proposed schemes to prepare quantum entanglement of macroscopic mechanical oscillators.Comment: 11 pages, 9 figures, minor correction

The primary cilium influences interleukin-1 beta-induced NF kappa B signalling by regulating IKK activity

AbstractThe primary cilium is an organelle acting as a master regulator of cellular signalling. We have previously shown that disruption of primary cilia assembly, through targeting intraflagellar transport, is associated with muted nitric oxide and prostaglandin responses to the inflammatory cytokine interleukin-1β (IL-1β). Here, we show that loss of the primary cilium disrupts specific molecular signalling events in cytosolic NFκB signalling. The induction of cyclooxygenase 2 (COX2) and inducible nitrous oxide synthase (iNOS) protein is abolished. Cells unable to assemble cilia exhibit unaffected activation of IκB kinase (IKK), but delayed and reduced degradation of IκB, due to diminished phosphorylation of inhibitor of kappa B (IκB) by IKK. This results in both delayed and reduced NFκB p65 nuclear translocation and nuclear transcript binding. We also demonstrate that heat shock protein 27 (hsp27), an established regulator of IKK, is localized to the ciliary axoneme and cellular levels are dramatically disrupted with loss of the primary cilium. These results suggest that the primary cilia compartment exerts influence over NFκB signalling. We propose that the cilium is a locality for regulation of the molecular events defining NFκB signalling events, tuning signalling as appropriate

Optimierung des Informations-, Kommunikations- und Wissenschaftsmanagements im Bereich Vertrieb After Sales bei der VW AG: eine netzwerkanalytische Untersuchung

Dimensionen des I-K-W-Managements und Möglichkeiten der Optimierung dieses Konzepts. Unter der Prämisse einer grundlegenden Kohärenz von Information, Kommunikation und Wissen konnte demonstriert werden, wie die Netzwerkkonzepte diesen Integrationsversuch befruchten. So wurde im ersten Kapitel aufgezeigt, dass Wissen und Organisation als soziale Phänomene betrachtet werden sollen, die sich als Vernetzung von Informationen manifestieren lassen. Dadurch dass Wissen in Organisationen einen kollektiven Charakter aufweist, ist jede Organisation auf die Interaktion von sozialen Gruppen, d. h. auf die Kommunikation angewiesen. Die Annahme, dass die Kommunikation im Unternehmen (in einer Organisation) über soziale Netzwerke erfolgt, erwies sich ausschlaggebend für die These, dass jede Organisation auf die Netzwerkkommunikation angewiesen ist. Diese Feststellung war wiederum entscheidend für die Ableitung des Zusammenhangs zwischen Informations-, Kommunikations- und Wissensmanagement. Da Wissensmanagement nur im Rahmen einer Organisation (eines Organisationssystems) denkbar ist, konnte mit dem obigen Gedankengang belegt werden, dass Wissensmanagement auf Kommunikation in sozialen Netzwerken (Vernetzung) angewiesen ist. Das Netzwerkphänomen erschien somit der entscheidende Grund zu sein, warum in der vorliegenden Untersuchung die Rede stets vom integrativen Konzept des Informations-, Kommunikations- und Wissensmanagements ist. Im zweiten Kapitel wurde aufgezeigt, inwieweit die allgegenwärtige Vernetzung zum Globalisierungsphänomen erklärt werden kann. Das Konzept des I-K-W-Managements, das sich weitgehend auf das Vernetzungsparadigma ausrichtet, bekam dabei eine unmittelbare Legitimationsgrundlage