Zug der Israeliten mit der Bundeslade um Jericho und Fall der Mauern. Jos., 6

Signatur des Originals: S 36/G02602

Der Fall unserer ersten Eltern Adams und Evä : ... Nach Endigung dieser Admirabelen mit so vielfältigen Theatralischen Auszierungen … Les Fourberies du Scapin Oder Des Lustigen Knechts Scabins listige Betrügerei ; den 4. Juni [1698] ; [Theaterzettel]

Die Königliche Polnische und Churfürstl. Sächsische Hoff-Comoedianten

The differential staurosporine mediated G1 arrest in normal versus tumor cells is dependent on the retinoblastoma and Chk1 proteins

The ability to regulate cell cycle progression is one of the differences that separates normal from tumor cells. A protein, which is frequently mutated or deleted in a majority of tumor cells, is the retinoblastoma protein (pRb). Previously, we reported that normal cells, which have a wild-type Rb pathway, can be reversibly arrested in the G1 phase of the cell cycle by staurosporine (ST), while tumor cells were unaffected by this treatment. As a result, ST may be used to protect normal cells against the toxic affects of chemotherapy. Here we set out to determine the mechanism(s) by which ST can mediate a reversible G1 arrest in pRb positive cells. To this end, we used an isogenic cell model system of normal human mammary epithelial cells (HMEC) with either intact pRb+ (p53-) or p53+ (pRb-) treated with ST. Our results show that pRb+ cells treated with low concentrations of ST, arrested in the G1 phase of the cell cycle; however, in pRb - cells there was no response. This was verified as a true G 1 arrest in pRb+ cells by two different methods for monitoring cell cycle kinetics and in two additional model systems for Rb (i.e. pRb -/- mouse embryo fibroblasts, and downregulation of RB with siRNA). Our results indicated that ST-mediated G1 arrest required pRb, which in turn initiated a cascade of events leading to inhibition of CDK4 and CDK2 activities and up-regulation of p21 protein. Further assessment of this pathway revealed the novel finding that Chk1 expression and activity were required for the Rb-dependent, ST-mediated G1 arrest. In fact, overexpression of Chk1 facilitated recovery from ST-mediated G1 arrest, an effect only observed in RB+ cells. Collectively, our data suggest pRb is able to cooperate with Chk1 to mediate a G1 arrest in pRb+ cells, but not in pRb- cells. The elucidation of this pathway can help identify novel agents that can be used to protect cancer patients against the debilitating affects of chemotherapy, by targeting only the normal proliferating cells in the body that are otherwise destroyed. ^

Particle fluxes and in-situ particle properties measured with sediment traps and a moored camera system from 2008 - 2010 in region off Cape Blanc / NW-Africa

We compared particle data from a moored video camera system with sediment trap derived fluxes at ~1100 m depth in the highly dynamic coastal upwelling system off Cape Blanc, Mauritania. Between spring 2008 and winter 2010 the trap collected settling particles in 9-day intervals, while the camera recorded in-situ particle abundance and size-distribution every third day. Particle fluxes were highly variable (40-1200 mg m**-2 d**-1) and followed distinct seasonal patterns with peaks during spring, summer and fall. The particle flux patterns from the sediment traps correlated to the total particle volume captured by the video camera, which ranged from1 to 22 mm**3 l**-1. The measured increase in total particle volume during periods of high mass flux appeared to be better related to increases in the particle concentrations, rather than to increased average particle size. We observed events that had similar particle fluxes, but showed clear differences in particle abundance and size-distribution, and vice versa. Such observations can only be explained by shifts in the composition of the settling material, with changes both in particle density and chemical composition. For example, the input of wind-blown dust from the Sahara during September 2009 led to the formation of high numbers of comparably small particles in the water column. This suggests that, besides seasonal changes, the composition of marine particles in one region underlies episodical changes. The time between the appearance of high dust concentrations in the atmosphere and the increase lithogenic flux in the 1100 m deep trap suggested an average settling rate of 200 m d**-1, indicating a close and fast coupling between dust input and sedimentation of the material.

Evapotranspiration of grapevine trained to a gable trellis system under netting and black plastic mulching

The evapotranspiration (ET c) of a table grape vineyard (Vitis vinifera, cv. Red Globe) trained to a gable trellis under netting and black plastic mulching was determined under semiarid conditions in the central Ebro River Valley during 2007 and 2008. The netting was made of high-density polyethylene (pores of 12 mm2) and was placed just above the ground canopy about 2.2 m above soil surface. Black plastic mulching was used to minimize soil evaporation. The surface renewal method was used to obtain values of sensible heat flux (H) from high-frequency temperature readings. Later, latent heat flux (LE) values were obtained by solving the energy balance equation. For the May–October period, seasonal ET c was about 843 mm in 2007 and 787 mm in 2008. The experimental weekly crop coefficients (K cexp) fluctuated between 0.64 and 1.2. These values represent crop coefficients adjusted to take into account the reduction in ET c caused by the netting and the black plastic mulching. Average K cexp values during mid- and end-season stages were 0.79 and 0.98, respectively. End-season K cexp was higher due to combination of factors related to the precipitation and low ET o conditions that are typical in this region during fall. Estimated crop coefficients using the Allen et al. (1998) approach adjusting for the effects of the netting and black plastic mulching (K cFAO) showed a good agreement with the experimental K cexp values.

An universal system to de-orbit satellites at end of life

A 3-year Project financed by the European Commission is aimed at developing a universal system to de-orbit satellites at their end of life, as a fundamental contribution to limit the increase of debris in the Space environment. The operational system involves a conductive tapetether left bare to establish anodic contact with the ambient plasma as a giant Langmuir probe. The Project will size the three disparate dimensions of a tape for a selected de-orbit mission and determine scaling laws to allow system design for a general mission. Starting at the second year, mission selection is carried out while developing numerical codes to implement control laws on tether dynamics in/off the orbital plane; performing numerical simulations and plasma chamber measurements on tether-plasma interaction; and completing design of subsystems: electronejecting plasma contactor, power module, interface elements, deployment mechanism, and tether-tape/end-mass. This will be followed by subsystems manufacturing and by currentcollection, free-fall, and hypervelocity impact tests.

Self-antigen does not accelerate immature B cell apoptosis, but stimulates receptor editing as a consequence of developmental arrest

In pre-B lymphocytes, productive rearrangement of Ig light chain genes allows assembly of the B cell receptor (BCR), which selectively promotes further developmental maturation through poorly defined transmembrane signaling events. Using a novel in vitro system to study immune tolerance during development, we find that BCR reactivity to auto-antigen blocks this positive selection, preventing down-regulation of light chain gene recombination and promoting secondary light chain gene rearrangements that often alter BCR specificity, a process called receptor editing. Under these experimental conditions, self-antigen induces secondary light chain gene rearrangements in at least two-thirds of autoreactive immature B cells, but fails to accelerate cell death at this stage. These data suggest that in these cells the mechanism of immune tolerance is receptor selection rather than clonal selection.

DNA damage and p53-mediated cell cycle arrest: A reevaluation

Most mammalian cells exhibit transient delays in the G1 and G2 phases of the cell cycle after treatment with radiation or radiomimetic compounds. p53 is required for the arrest in G1, which provides time for DNA repair. Recently, a role of p53 in the G2/M transition has also been suggested. However, it has been reported that the presence of functional p53 does not always correlate with the induction of these checkpoints. To precisely assess the role of p53 in activating cell cycle checkpoints and in cell survival after radiation, we studied the response of two isogenic human fibrosarcoma cell lines differing in their p53 status (wild type or mutant). We found that when irradiated cells undergo a wild-type p53-dependent G1 arrest, they do not subsequently arrest in G2. Moreover, wild-type p53 cells irradiated past the G1 checkpoint arrest in G2 but do not delay in the subsequent G1 phase. Furthermore, in these cell lines, which do not undergo radiation-induced apoptosis, the wild-type p53 cell line exhibited a greater radioresistance in terms of clonogenic survival. These results suggest that the two checkpoints may be interrelated, perhaps through a control system that determines, depending on the extent of the damage, whether the cell needs to arrest cell cycle progression at the subsequent checkpoint for further repair. p53 could be a crucial component of this control system.

Arrest of endotoxin-induced hypotension by transforming growth factor beta1.

Septic shock is a cytokine-mediated process typically caused by a severe underlying infection. Toxins generated by the infecting organism trigger a cascade of events leading to hypotension, to multiple organ system failure, and frequently to death. Beyond supportive care, no effective therapy is available for the treatment of septic shock. Nitric oxide (NO) is a potent vasodilator generated late in the sepsis pathway leading to hypotension; therefore, NO represents a potential target for therapy. We have previously demonstrated that transforming growth factor (TGF) beta1 inhibits inducible NO synthase (iNOS) mRNA and NO production in vascular smooth muscle cells after its induction by cytokines critical in the sepsis cascade. Thus, we hypothesized that TGF-beta1 may inhibit iNOS gene expression in vivo and be beneficial in the treatment of septic shock. In a conscious rat model of septic shock produced by Salmonella typhosa lipopolysaccharide (LPS), TGF-beta1 markedly reduced iNOS mRNA and protein levels in several organs. In contrast, TGF-beta1 did not decrease endothelium-derived constitutive NOS mRNA in organs of rats receiving LPS. We also performed studies in anesthetized rats to evaluate the effect of TGF-beta1 on the hemodynamic compromise of septic shock; after an initial 25% decrease in mean arterial pressure, TGF-beta1 arrested LPS-induced hypotension and decreased mortality. A decrease in iNOS mRNA and protein levels in vascular smooth muscle cells was demonstrated by in situ hybridization and NADPH diaphorase staining in rats treated with TGF-beta1. Thus these studies suggest that TGF-beta1 inhibits iNOS in vivo and that TGF-beta1 may be of future benefit in the therapy of septic shock.

Induction of a retinoblastoma phosphatase activity by anticancer drugs accompanies p53-independent G1 arrest and apoptosis.

DNA-damaging agents induce accumulation of the tumor suppressor and G1 checkpoint protein p53, leading cells to either growth arrest in G1 or apoptosis (programmed cell death). The p53-dependent G1 arrest involves induction of p21 (also called WAF1/CIP1/SDI1), which prevents cyclin kinase-mediated phosphorylation of retinoblastoma protein (RB). Recent studies suggest a p53-independent G1 checkpoint as well; however, little is known about its molecular mechanisms. We report that induction of a protein-serine/threonine phosphatase activity by DNA damage signals is at least one of the mechanisms responsible for p53-independent, RB-mediated G1 arrest and consequent apoptosis. When two p53-null human leukemic cell lines (HL-60 and U-937) were treated with a variety of anticancer agents, RB became hypophosphorylated, accompanied with G1 arrest. This was followed immediately (in less than 30 min) by apoptosis, as determined by the accumulation of pre-G1 apoptotic cells and the internucleosomal fragmentation of DNA. Addition of calyculin A or okadaic acid (specific serine/threonine phosphatase inhibitors) or zinc chloride (apoptosis inhibitor) prevented the G1 arrest- and apoptosis-specific RB dephosphorylation. The levels of cyclin E- and cyclin A-associated kinase activities remained high during RB dephosphorylation, supporting the involvement of a chemotherapy-induced serine/threonine phosphatase(s) rather than p21. Furthermore, the induced phosphatase activity coimmunoprecipitated with the hyperphosphorylated RB and was active in a cell-free system that reproduced the growth arrest- and apoptosis-specific RB dephosphorylation, which was inhibitable by calyculin A but not zinc. We propose that the RB phosphatase(s) might be one of the p53-independent G1 checkpoint regulators.

Sovereignty and Intervention in the Middle East: From the Fall of the Ottoman Empire to the Arab Spring

This research provides an institutional explanation of the practices of external intervention in the Arab state system from the fall of the Ottoman Empire in 1922 to the Arab Spring. My explanation consists of two institutional variables: sovereignty and inter-state borders. I examine the changes in regional and international norms of sovereignty and their impact on the practices of external intervention in the Arab state system. I also examine the impact of the level of institutionalization of inter-state borders in the Arab World on the practices of external intervention. I argue that changes in regional and international norms of sovereignty and changes in the level of institutionalization of inter-state borders have constituted the significant variation over time in both the frequency and type of external intervention in the Arab state system from 1922 to the present. My institutional explanation and findings seriously challenge the traditional accounts of sovereignty and intervention in the Arab World, including the cultural perspectives that emphasize the conflict between sovereignty, Arabism, and Islam, the constructivist accounts that emphasize the regional norm of pan-Arabism, the comparative politics explanations that focus on the domestic material power of the Arab state, the post-colonial perspectives that emphasize the artificiality of the Arab state, and the realist accounts that focus on great powers and the regional distribution of power in the Middle East. This research also contributes to International Relations Theory. I construct a new analytical framework to study the relations between sovereignty, borders, and intervention, combining theoretical elements from the fields of Role Theory, Social Constructivism, and Institutionalization. Methodologically, this research includes both quantitative and qualitative analysis. I conduct content analysis of official documents of Arab states and the Arab League, Arabic press documents, and Arab political thought. I also utilize quantitative data sets on international intervention.

Fall River, Massachusetts 15 Minute Digital Raster Graphic

This layer is a digital raster graphic of the historic 15-minute USGS topographic map of the Fall River, Massachusetts quadrangle. The survey date (ground condition) of this map is 1885. A digital raster graphic (DRG) is a scanned image of a U.S. Geological Survey (USGS) standard series topographic map, including all map collar information. The image inside the map neatline is geo-referenced to the surface of the earth and fit to the Universal Transverse Mercator projection. The horizontal positional accuracy and datum of the DRG matches the accuracy and datum of the source map. The names of quadrangles which border this one appear on the map collar in their respective positions (N,S,E,W) in relation to this map.

A Minor Change?: A Case Study of Carleton Place's Integration of Minor Variance Procedures into Ontario's Development Permit System

The Development Permit System has been introduce with minimal directives for establishing a decision making process. This is in opposition to the long established process for minor variances and suggests that the Development Permit System does not necessarily incorporate all of Ontario’s fundamental planning principles. From this concept, the study aimed to identify how minor variances are incorporated into the Development Permit System. In order to examine this topic, the research was based around the following research questions: • How are ‘minor variance’ applications processed within the DPS? • To what extent do the four tests of a minor variance influence the outcomes of lower level applications in the DPS approval process? A case study approach was used for this research. The single-case design employed both qualitative and quantitative research methods including a review of academic literature, court cases, and official documents, as well as a content analysis of Class 1, 1A, and 2 Development Permit application files from the Town of Carleton Place that were decided between 2011 and 2015. Upon the completion of the content analysis, it was found that minor variance issues were most commonly assigned to Class 1 applications. Planning staff generally met approval timelines and embraced their delegated approval authority, readily attaching conditions to applications in order to mitigate off-site impacts. While staff met the regulatory requirements of the DPS, ‘minor variance’ applications were largely decided on impact alone, demonstrating that the principles established by the four tests, the defining quality of the minor variance approval process, had not transferred to the Development Permit System. Alternatively, there was some evidence that the development community has not fully adjusted to the requirements of the new approvals process, as some applications were supported using a rationale containing the four tests. Subsequently, a set of four recommendations were offered which reflect the main themes established by the findings. The first two recommendations are directed towards the Province, the third to municipalities and the fourth to developers and planning consultants: 1) Amend Ontario Regulation 608/06 so that provisions under Section 4(3)(e) fall under Section 4(2). 2) Change the rhetoric from “combining elements of minor variances” to “replacing minor variances”. 3) Establish clear evaluation criteria. 4) Understand the evaluative criteria of the municipality in which you are working.

Banking system soundness is the key to more SME financing. Bruegel Policy Contribution 2013/10, July 2013

The SME access-to-finance problem is not universal in the European Union and there are reasons for the fall in credit aggregates and higher SME lending rates in southern Europe. Possible market failures, high unemployment and externalities justify making greater and easier access to finance for SMEs a top priority. Previous European initiatives were able to support only a tiny fraction of Europe’s SMEs; merely stepping-up these programmes is unlikely to result in a breakthrough. Without repairing bank balance sheets and resuming economic growth, initiatives to help SMEs get access to finance will have limited success. The European Central Bank can foster bank recapitalisation by performing in the toughest possible way the asset quality review before it takes over the single supervisory role. Of the possible initiatives for fostering SME access to finance, a properly designed scheme for targeted central bank lending seems to be the best complement to the banking clean-up, but other options, such as increased European Investment Bank lending and the promotion of securitisation of SME loans, should also be explored.