An established means of improving the pharmacokinetics properties of oligoribonucleotides (ORNs) is to exchange their phosphodiester linkages for phosphorothioates (PSs). However, this strategy has ...not been pursued for small interfering RNAs (siRNAs), possibly because of sporadic reports that PS siRNAs show reduced inhibitory activity. The PS group is chiral at phosphorous (Rp/Sp centres), and conventional solid-phase synthesis of PS ORNs produces a population of diastereoisomers. Here we show that the choice of the activating agent for the synthesis of a PS ORN influences the Rp/Sp ratio of PS linkages throughout the strand. Furthermore, PS siRNAs composed of ORNs with a higher fraction of Rp centres show greater resistance to nucleases in serum and are more effective inhibitors in cells than their Sp counterparts. The finding that a stereochemically biased population of ORN diastereoisomers can be synthesized and exploited pharmacologically is important because uniform PS modification of siRNAs may provide a useful compromise of their pharmacokinetics and pharmacodynamics properties in RNAi therapeutics.
Context: After the Eurozone crisis unfolded a decade ago, comparative political economy has investigated reforms of public administration, labour market, welfare state and economic policy ...particularly in Southern European nations which were hit hardest by the crisis. However, analyses of skill formation reform, particularly vocational education and training (VET), have been scant, despite a common problem pressure for reforms emanating from stubbornly high rates of youth unemployment and similar legacies of statist VET. Approach: We investigate VET reforms brought underway in Greece and Italy during and in the aftermath of the crisis, asking how far apprenticeship-like forms of learning within their VET systems were strengthened. Empirically, we base our analysis on primary and secondary sources, having conducted semi-structured expert interviews in Greece and Italy in 2019. Results: We find that both countries attempted to strengthen the role of apprenticeship and work-based learning, but that politics differed across the two cases in the context of the Eurozone crisis. While in Italy, reforms were 'internalised' and shaped by domestic politics, Greek reforms were largely driven exogenously by the negotiations with the Troika. Conclusion: Although Italy and Greece have undertaken reforms to reduce the dominance of the state in VET provision by expanding apprenticeships and work-based learning, these do not amount to large scale changes to the dominant logic of school-based VET provision. In order to boost their potential in terms of practical learning both countries would need to continue on their reform pathways.
Zwischen Staat und Markt Frommberger, Dietmar; Baumann, Fabienne-Agnes
Zeitschrift für Pädagogik,
05/2016, Volume:
62, Issue:
3
Journal Article
Peer reviewed
Weltweit ist die Entwicklung kooperativer Steuerungsmechanismen zu beobachten, die der Verbindung staatlich gelenkter und marktwirtschaftlich geprägter beruflicher Qualifizierungsansätze dienen. Eine ...besondere Herausforderung liegt in der nachhaltigen Einbeziehung der Unternehmen in die Berufsbildung und von organisierten Arbeitgeber- und Arbeitnehmerinteressen. Im Beitrag werden international verbreitete Steuerungsmodelle vorgestellt, typische Ansätze zur Weiterentwicklung kooperativer Steuerungsformen in der Berufsbildung dargestellt und konkrete Erfahrungen aus zwei Schwellenländern (Brasilien und Südafrika) präsentiert. (DIPF/Orig.).
Throughout the world, we can observe the development of cooperative control mechanisms that serve the linking of state-controlled and market-oriented approaches to vocational qualification. A special challenge lies in the sustainable inclusion of companies in vocational education and in taking into account organized employer and employee interests. The contribution presents control models on an international scale, typical approaches to the development of cooperative forms of governance in vocational education, and concrete experiences gained in two emerging nations (Brazil and South Africa). (DIPF/Orig.).
Rate coefficients (
k
4
) for the reaction of hydroxyl radicals (OH) with methyl nitrate (CH
3
ONO
2
) were measured over the temperature range 232-343 K using pulsed laser photolysis to generate OH ...and pulsed laser-induced fluorescence to detect it in real-time and under pseudo-first-order conditions. In order to optimize the accuracy of the rate coefficients obtained, the concentration of CH
3
ONO
2
(the reactant in excess) was measured on-line by absorption spectroscopy at 213.86 nm for which the absorption cross-section was also measured (
σ
213.86
= 1.65 ± 0.09 × 10
−18
cm
2
molecule
−1
). The temperature-dependent rate coefficient is described by
k
4
(
T
) = 7.5 × 10
−13
exp(−1034 ± 40)/
T
cm
3
molecule
−1
s
−1
with a room temperature rate coefficient of
k
4
(296 ± 2 K) = (2.32 ± 0.12) × 10
−14
cm
3
molecule
−1
s
−1
where the uncertainty includes the statistical error of 2
σ
and an estimation of the potential systematic bias of 5%. This new dataset helps to consolidate the database for this rate coefficient and to reduce uncertainty in the atmospheric lifetime of CH
3
ONO
2
. As part of this study, an approximate rate coefficient for the reaction of H-atoms with CH
3
ONO
2
(
k
9
) was also derived at room temperature:
k
9
(298 K) = (1.68 ± 0.45) × 10
−13
cm
3
molecule
−1
s
−1
.
Temperature dependent rate coefficients (
k
4
) for the reaction of OH with CH
3
ONO
2
.
Context: After the Eurozone crisis unfolded a decade ago, comparative political economy has investigated reforms of public administration, labour market, welfare state and economic policy ...particularly in Southern European nations which were hit hardest by the crisis. However, analyses of skill formation reform, particularly vocational education and training (VET), have been scant, despite a common problem pressure for reforms emanating from stubbornly high rates of youth unemployment and similar legacies of statist VET. Approach: We investigate VET reforms brought underway in Greece and Italy during and in the aftermath of the crisis, asking how far apprenticeship-like forms of learning within their VET systems were strengthened. Empirically, we base our analysis on primary and secondary sources, having conducted semi-structured expert interviews in Greece and Italy in 2019. Results: We find that both countries attempted to strengthen the role of apprenticeship and work-based learning, but that politics differed across the two cases in the context of the Eurozone crisis. While in Italy, reforms were 'internalised' and shaped by domestic politics, Greek reforms were largely driven exogenously by the negotiations with the Troika. Conclusion: Although Italy and Greece have undertaken reforms to reduce the dominance of the state in VET provision by expanding apprenticeships and work-based learning, these do not amount to large scale changes to the dominant logic of school-based VET provision. In order to boost their potential in terms of practical learning both countries would need to continue on their reform pathways. (DIPF/Orig.)
Backspatter is biological material that is ejected from the entry wound against the line of fire. This phenomenon was also observed in wound ballistic simulations using so called "reference cubes" ...(12 cm edge length, 10% gelatin, 4 °C, paint pad beneath the cover). High-speed video records from 102 experimental shots to these target models using full metal jacketed bullets in the calibers .32 auto, .38 special, 9 mm Luger and .357 Magnum were analyzed for chronology, morphological appearance and velocity of fluid ejection. Generally, a short tail splashing of surface material occurred when the bullet was penetrating the target. In 51 shots from distance (≥ 5 cm), regardless of caliber and shot range, a linear jet of fluid started in connection with the first collapse of the temporary cavity. The initial velocity of the jet was measured between 6 and 45 m/s. The jet was streaming on for about 60 to 100 ms with a stochastic deviation of ± 13° to the horizontal. Close range and contact shots showed earlier and faster (up to 330 m/s) backspatter depending on the cartridge and the gap between muzzle and target. Gaseous aerosol-like spray and cone-like spatter indicated an increasing influence of muzzle gases with decreasing shot range. Even under standardized experimental conditions, variations of backspatter were observed in near/contact shots.
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Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Functionalized oligoribonucleotides are essential tools in RNA chemical biology. Various synthetic routes have been developed over recent years to conjugate functional groups to oligoribonucleotides. ...However, the presence of the functional group on the oligoribonucleotide backbone can lead to partial or total loss of biological function. The limited knowledge concerning the positioning of functional groups therefore represents a hurdle for the development of oligoribonucleotide chemical tools. Here we describe a systematic investigation of site‐specific labeling of pre‐miRNAs to identify positions for the incorporation of functional groups, in order not to hinder their processing into active mature miRNAs.
Location, location, location! Functionalized oligoribonucleotides are essential tools in RNA chemical biology. Depending on its position, a label on the oligoribonucleotide backbone can lead to loss of biological function. Here we describe a systematic investigation of site‐specific labeling of pre‐miRNAs to identify positions for functional groups that do not hinder their processing into active mature miRNAs.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
8.
Zwischen Staat und Markt Frommberger, Dietmar; Baumann, Fabienne-Agnes
Zeitschrift für Pädagogik,
2016
3
Journal Article
Peer reviewed
Zusammenfassung: Weltweit ist die Entwicklung kooperativer Steuerungsmechanismen zu beobachten, die der Verbindung staatlich gelenkter und marktwirtschaftlich geprägter beruflicher ...Qualifizierungsansätze dienen. Eine besondere Herausforderung liegt in der nachhaltigen Einbeziehung der Unternehmen in die Berufsbildung und von organisierten Arbeitgeber- und Arbeitnehmerinteressen. Im vorliegenden Beitrag werden international verbreitete Steuerungsmodelle vorgestellt, typische Ansätze zur Weiterentwicklung kooperativer Steuerungsformen in der Berufsbildung dargestellt und konkrete Erfahrungen aus zwei Schwellenländern (Brasilien und Südafrika) präsentiert.
Schlagworte: Berufsbildung, Governance, Kooperative Steuerung, Brasilien, Südafrika
Abstract: Throughout the world, we can observe the development of cooperative control mechanisms that serve the linking of state-controlled and market-oriented approaches to vocational qualification. A special challenge lies in the sustainable inclusion of companies in vocational education and in taking into account organized employer and employee interests. The present contribution presents control models on an international scale, typical approaches to the development of cooperative forms of governance in vocational education, and concrete experiences gained in two emerging nations (Brazil and South Africa).
Keywords: Vocational Education, Governance, Cooperative Governance, Brasil, Republic of South Africa
The pathogenesis of diabetic retinopathy is closely associated with the breakdown of the neurovascular unit including the glial cells. Deficiency of nucleoside diphosphate kinase B (NDPK-B) results ...in retinal vasoregression mimicking diabetic retinopathy. Increased retinal expression of Angiopoietin-2 (Ang-2) initiates vasoregression. In this study, Müller cell activation, glial Ang-2 expression, and the underlying mechanisms were investigated in streptozotocin-induced diabetic NDPK-B deficient (KO) retinas and Müller cells isolated from the NDPK-B KO retinas. Müller cells were activated and Ang-2 expression was predominantly increased in Müller cells in normoglycemic NDPK-B KO retinas, similar to diabetic wild type (WT) retinas. Diabetes induction in the NDPK-B KO mice did not further increase its activation. Additionally, cultured NDPK-B KO Müller cells were more activated and showed higher Ang-2 expression than WT cells. Müller cell activation and Ang-2 elevation were observed upon high glucose treatment in WT, but not in NDPK-B KO cells. Moreover, increased levels of the transcription factor forkhead box protein O1 (FoxO1) were detected in non-diabetic NDPK-B KO Müller cells. The siRNA-mediated knockdown of FoxO1 in NDPK-B deficient cells interfered with Ang-2 upregulation. These data suggest that FoxO1 mediates Ang-2 upregulation induced by NDPK-B deficiency in the Müller cells and thus contributes to the onset of retinal vascular degeneration.
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