Von der Ahnung zum Wissen: Beratung in der Verwaltungsreform kleiner und mittelgroßer Kommunen

Die neuen Verheißungen des 'electronic government' werden sich nach Einschätzung des Autors nur dann erfüllen, wenn technikgetriebene Konzepte durch technisch-organisatorische Strategien ersetzt werden. Wer 'e-Government' ernst nimmt, sollte die offensichtlichen Versäumnisse in der Verwaltungsreform nicht aus den Augen verlieren, denn die Ziele, Themen und Konfliktfelder weisen hier zahlreiche Ähnlichkeiten auf. Die vorliegenden Ausführungen des Autors sind das Resultat seiner mehrjährigen Tätigkeit als externer Berater und Moderator in Kommunen mit einer Einwohnerzahl zwischen 15.000 und 45.000 Einwohnern. Er beschreibt die Situation kleiner und mittelgroßer Kommunen anhand der Ergebnisse einer im Jahre 1997 durchgeführten Befragung der Kommunalen Gemeinschaftstelle (KGSt) und diskutiert die Logiken behördlicher Veränderungsprozesse. Er skizziert vor diesem Hintergrund die Ziele und Ansätze einer (sozialwissenschaftlichen) Beratungsarbeit in kleinen und mittelgroßen Kommunen. (ICI2

Cloning and expression of activation induced cytidine deaminase from Bos taurus'

Activation induced cytidine deaminase is an enzyme crucial to somatic hypermutation and gene conversion, processes that are essential for the diversification of Ig V genes. The bovine Ig repertoire appears to be diversified by mechanisms that are significantly different to those that operate in humans and mice. This study set out to test the hypothesis that differences in the organization, coding sequence, expression or genomic location of the bovine AICDA gene enables the encoded enzyme to catalyse the unusual Ig diversification mechanism seen in cattle as well as conventional antigen-driven mutation. Characterization of bovine AICDA excluded the first two possibilities. AICDA expression was detected in lymphoid tissues from neonatal and older cattle, but AICDA cDNA could not be detected in muscle tissue. The pattern of gene expression did not therefore differ from that in other vertebrates. The AICDA cDNA was cloned and expressed successfully in Escherichia coli generating a phenotype consistent with the mutating action of this deaminase. Using a whole genome radiation hybrid panel, bovine AICDA was mapped to a region of bovine chromosome 5 syntenic with the location of human AICDA on chromosome 12. We conclude that the unusual nature of Ig diversification in cattle is unlikely to be attributable to the structure, sequence, activity or genomic location of bovine AICDA

The differentiated roles of health in the transition from work to retirement - conceptual and methodological challenges and avenues for future research

Objective:s The aim of this discussion paper is to (i) identify the differentiated roles of health in the work–retirement transition, and, with respect to these, (ii) highlight topics related to conceptual and methodological problems and challenges in research, and (iii) present avenues for future research. Methods: This discussion paper summarizes an OMEGA-NET working group discussion ongoing from November 2018 to September 2021 with face-to-face and online meetings as well as a written online discourse. Results: ‘Health’ and ‘retirement’ are ambiguous concepts. With respect to both, in retirement research, the choice of concept and indicator influences the findings. In addition, the impact of health on retirement is not necessarily a direct one, but can be influenced by further factors such as the ability, motivation and opportunity to work. The strong overall association of poor health with retiring early (path 1) bears the risk of masking distinct and deviating mechanisms in subgroups. In fact, there is evidence that also good health may lead to early retirement (path 2), while both poor health (path 3) and good health (path 4) may also make people retire later. Conclusions: An increased awareness of the differentiated roles that health may have in the work–retirement transition as outlined in this discussion paper may support research to address questions relevant for policy and practice and increase the impact of research. Recommendations for occupational health and social research are given

Loss of TMEM106B potentiates lysosomal and FTLD-like pathology in progranulin-deficient mice

Single nucleotide polymorphisms (SNPs) in TMEM106B encoding the lysosomal type II transmembrane protein 106B increase the risk for frontotemporal lobar degeneration (FTLD) of GRN (progranulin gene) mutation carriers. Currently, it is unclear if progranulin (PGRN) and TMEM106B are synergistically linked and if a gain or a loss of function of TMEM106B is responsible for the increased disease risk of patients with GRN haploinsufficiency. We therefore compare behavioral abnormalities, gene expression patterns, lysosomal activity, and TDP-43 pathology in single and double knockout animals. Grn-/- /Tmem106b-/- mice show a strongly reduced life span and massive motor deficits. Gene expression analysis reveals an upregulation of molecular signature characteristic for disease-associated microglia and autophagy. Dysregulation of maturation of lysosomal proteins as well as an accumulation of ubiquitinated proteins and widespread p62 deposition suggest that proteostasis is impaired. Moreover, while single Grn-/- knockouts only occasionally show TDP-43 pathology, the double knockout mice exhibit deposition of phosphorylated TDP-43. Thus, a loss of function of TMEM106B may enhance the risk for GRN-associated FTLD by reduced protein turnover in the lysosomal/autophagic system

Rev1 contributes to proper mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1 alpha axis

Abstract Nucleic acids, which constitute the genetic material of all organisms, are continuously exposed to endogenous and exogenous damaging agents, representing a significant challenge to genome stability and genome integrity over the life of a cell or organism. Unrepaired DNA lesions, such as single- and double-stranded DNA breaks (SSBs and DSBs), and single-stranded gaps can block progression of the DNA replication fork, causing replicative stress and/or cell cycle arrest. However, translesion synthesis (TLS) DNA polymerases, such as Rev1, have the ability to bypass some DNA lesions, which can circumvent the process leading to replication fork arrest and minimize replicative stress. Here, we show that Rev1-deficiency in mouse embryo fibroblasts or mouse liver tissue is associated with replicative stress and mitochondrial dysfunction. In addition, Rev1-deficiency is associated with high poly(ADP) ribose polymerase 1 (PARP1) activity, low endogenous NAD+, low expression of SIRT1 and PGC1α and low adenosine monophosphate (AMP)-activated kinase (AMPK) activity. We conclude that replication stress via Rev1-deficiency contributes to metabolic stress caused by compromized mitochondrial function via the PARP-NAD+-SIRT1-PGC1α axis

Optimisation of Car Park Designs

The problem presented by ARUP to the UK Study Group 2014 was to investigate methods for maximising the number of car parking spaces that can be placed within a car park. This is particularly important for basement car parks in residential apartment blocks or offices where parking spaces command a high value. Currently the job of allocating spaces is done manually and is very time intensive. The Study Group working on this problem split into teams examining different aspects of the car park design process There were three approaches taken. These approaches include a so-called "tile-and-trim" method in which an optimal layout of cars from an `infinite car park' are overlaid onto the actual car park domain; adjustments are then made to accommodate access from one lane to the next. A second approach seeks to develop an algorithm for optimising the road within a car park on the assumption that car parking spaces should fill the space and that any space needs to be adjacent to the network. A third similar approach focused on schemes for assessing the potential capacity of a small selection of specified road networks within the car park to assist the architect in selecting the optimal road network(s). The problem is a variant of the "bin packing" problem, well known in computer science. It is further complicated by the fact that two different classes of item need to be packed (roads and cars), with both local (immediate access to a road) and global (connectivity of the road network) constraints. Bin-packing is known to be NP-hard, and hence the problem at hand has at least this level of computational complexity. None of the approaches produced a complete solution to the problem posed. Indeed, it was quickly determined by the group that this was a very hard problem (a view reinforced by the many different possible approaches considered) requiring far longer than a week to really make significant progress. All approaches rely to differing degrees on optimisation algorithms which are inherently unreliable unless designed specifically for the intended purpose. It is also not clear whether a relatively simple automated computer algorithm will be able to "beat the eye of the architect"; additional sophistication may be required due to subtle constraints. Apart from determining that the problem is hard, positive outcomes have included: Determining that parking perpendicular to the road in long aisles provides the most efficient packing of cars. Provision of code which "tiles and trims" from an infinite car park onto the given car park with interactive feedback on the number of cars in the packing. Provision of code for optimal packing in a parallel-walled car park. Methods for optimising a road within a given domain based on developing cost functions ensuring that cars fill the car park and have access to the road. Provision of code for optimising a single road in a given (square) space. Description of methods for assessing the capacity of a car park for a set of given road network in order to select optimal road networks. Some ideas for developing possible solutions further

Juvenile crust formation in the Zimbabwe Craton deduced from the O-Hf isotopic record of 3.8–3.1 Ga detrital zircons

Hafnium and oxygen isotopic compositions measured in-situ on U-Pb dated zircon from Archaean sedimentary successions belonging to the 2.9-2.8 Ga Belingwean/Bulawayan groups and previously undated Sebakwian Group are used to characterize the crustal evolution of the Zimbabwe Craton prior to 3.0 Ga. Microstructural and compositional criteria were used to minimize effects arising from Pb loss due to metamorphic overprinting and interaction with low-temperature fluids. 207 Pb/206 Pb age spectra (concordance >90%) reveal prominent peaks at 3.8, 3.6, 3.5, and 3.35 Ga, corresponding to documented geological events, both globally and within the Zimbabwe Craton. Zircon delta O-18 values from +4 to +10% point to both derivation from magmas in equilibrium with mantle oxygen and the incorporation of material that had previously interacted with water in near-surface environments. In epsilon(Hf)-time space, 3.8-3.6 Ga grains define an array consistent with reworking of a mafic reservoir ((176) Lu/(177) Hf similar to 0.015) that separated from chondritic mantle at similar to 3.9 Ga. Crustal domains formed after 3.6 Ga depict a more complex evolution, involving contribution from chondritic mantle sources and, to a lesser extent, reworking of pre-existing crust. Protracted remelting was not accompanied by significant mantle depletion prior to 3.35 Ga. This implies that early crust production in the Zimbabwe Craton did not cause complementary enriched and depleted reservoirs that were tapped by later magmas, possibly because the volume of crust extracted and stabilised was too small to influence (asthenospheric) mantle isotopic evolution. Growth of continental crust through pulsed emplacement of juvenile (chondritic mantle-derived) melts, into and onto the existing cratonic nucleus, however, involved formation of complementary depleted subcontinental lithospheric mantle since the early Archaean, indicative of strongly coupled evolutionary histories of both reservoirs, with limited evidence for recycling and lateral accretion of arc-related crustal blocks until 3.35 Ga. (C) 2017 Elsevier Ltd. All rights reserved

昆虫の生理および行動の統合性におけるセロトニン受容体の機能

博士（学術）神戸大

Processes and integration in the interaction of purchasing and marketing: considering synergy and symbiosis

Effective integration of both purchasing and marketing functions is central to effective value creation and alignment of an organization with its business environment. Rapidly changing environments create gaps in the value creation process that compromises the delivery of value to the customer and risk misalignment of value propositions to their needs. Despite the clear imperative for research in this area, the extant literature is partial and delivers limited coherence. Ours is a theoretical article that—in drawing on previous literature—introduces the new work collected in this special issue and considers this against our own empirical evidence. We present a framework that maps out the landscape of internal organizational integration with a particular emphasis on purchasing and marketing integration. Implications for theory and managers are explored