The Quality of Collaboration Process Design

Despite mixed research results, the practical value of collaboration support such as Group Support Systems (GSS) and Facilitation is well established. One of the key challenges in collaboration support is the design of collaboration processess. Such design should be based on a theory on the quality of collaboration process design. The main challenge in this research is to identify the factors that impact the quality of a collaboration process design. Collaboration Engineering (CE) is an approach to designing and deploying collaboration processes for high value recurring tasks. CE intends to enable an organization to increase the quality of collaboration for a recurring mission critical task in the organization, for which ongoing facilitation support is too expensive. Instead of a professional facilitator, a practitioner supports the group based on a short training in which he learns to execute a collaboration process design made by an expert. This design should support the group in efficiently achieving its goal through a high quality collaboration process, and needs to be transferable to the practitioner. The latter implies that the design should be clear, complete, reusable, predictable and flexible. To create such designs we need to specify the factors that foster high quality collaboration, and we need to offer support for design of a transferable high quality collaboration process design. This research will elicit these factors and offer them in a CE support tool

The Quality of Collaboration Process Design

Despite mixed research results, the practical value of collaboration support such as Group Support Systems (GSS) and Facilitation is well established. One of the key challenges in collaboration support is the design of collaboration processess. Such design should be based on a theory on the quality of collaboration process design. The main challenge in this research is to identify the factors that impact the quality of a collaboration process design. Collaboration Engineering (CE) is an approach to designing and deploying collaboration processes for high value recurring tasks. CE intends to enable an organization to increase the quality of collaboration for a recurring mission critical task in the organization, for which ongoing facilitation support is too expensive. Instead of a professional facilitator, a practitioner supports the group based on a short training in which he learns to execute a collaboration process design made by an expert. This design should support the group in efficiently achieving its goal through a high quality collaboration process, and needs to be transferable to the practitioner. The latter implies that the design should be clear, complete, reusable, predictable and flexible. To create such designs we need to specify the factors that foster high quality collaboration, and we need to offer support for design of a transferable high quality collaboration process design. This research will elicit these factors and offer them in a CE support tool

Formal ratification of subseries for the Pleistocene Series of the Quaternary System

The Pleistocene Series/Epoch of the Quaternary System/Period has been divided unofficially into three subseries/subepochs since at least the 1870s. On 30 January, 2020, the Executive Committee of the International Union of Geological Sciences ratified two proposals approved by the International Commission on Stratigraphy formalizing: 1) the Lower Pleistocene Subseries, comprising the Gelasian Stage and the superjacent Calabrian Stage, with a base defined by the GSSP for the Gelasian Stage, the Pleistocene Series, and the Quaternary System, and currently dated at 2.58 Ma; and 2) the term Upper Pleistocene, at the rank of subseries, with a base currently undefined but provisionally dated at ~129 ka. Defining the Upper Pleistocene Subseries and its corresponding stage with a GSSP is in progress. The Middle Pleistocene Subseries is defined by the recently ratified GSSP for the Chibanian Stage currently dated at 0.774 Ma. These ratifications complete the official division of the Pleistocene into three subseries/subepochs, in uniformity with the similarly subdivided Holocene Series/Epoch

Extracellular nucleotides inhibit growth of human oesophageal cancer cells via P2Y2-receptors

Extracellular ATP is known to inhibit growth of various tumours by activating specific purinergic receptors (P2-receptors). Since the therapy of advanced oesophageal cancer is unsatisfying, new therapeutic approaches are mandatory. Here, we investigated the functional expression and potential antiproliferative effects of P2-purinergic receptors in human oesophageal cancer cells. Prolonged incubation of primary cell cultures of human oesophageal cancers as well as of the squamous oesophageal cancer cell line Kyse-140 with ATP or its stable analogue ATPγS dose-dependently inhibited cell proliferation. This was due to both an induction of apoptosis and cell cycle arrest. The expression of P2-receptors was examined by RT-PCR, immunocytochemistry, and [Ca2+]i-imaging. Application of various extracellular nucleotides dose-dependently increased [Ca2+]i. The rank order of potency was ATP=UTP>ATPγS>ADP=UDP. 2-methylthio-ATP and α,β-methylene-ATP had no effects on [Ca2+]i. Complete cross-desensitization between ATP and UTP was observed. Moreover, the phospholipase C inhibitor U73122 dose-dependently reduced the ATP triggered [Ca2+]i signal. The pharmacological features strongly suggest the functional expression of G-protein coupled P2Y2-receptors in oesophageal squamous cancer cells. P2Y2-receptors are involved in the antiproliferative actions of extracellular nucleotides. Thus, P2Y2-receptors are promising target proteins for innovative approaches in oesophageal cancer therapy

High Glucose Suppresses Human Islet Insulin Biosynthesis by Inducing miR-133a Leading to Decreased Polypyrimidine Tract Binding Protein-Expression

BACKGROUND: Prolonged periods of high glucose exposure results in human islet dysfunction in vitro. The underlying mechanisms behind this effect of high glucose are, however, unknown. The polypyrimidine tract binding protein (PTB) is required for stabilization of insulin mRNA and the PTB mRNA 3'-UTR contains binding sites for the microRNA molecules miR-133a, miR-124a and miR-146. The aim of this study was therefore to investigate whether high glucose increased the levels of these three miRNAs in association with lower PTB levels and lower insulin biosynthesis rates. METHODOLOGY/PRINCIPAL FINDINGS: Human islets were cultured for 24 hours in the presence of low (5.6 mM) or high glucose (20 mM). Islets were also exposed to sodium palmitate or the proinflammatory cytokines IL-1beta and IFN-gamma, since saturated free fatty acids and cytokines also cause islet dysfunction. RNA was then isolated for real-time RT-PCR analysis of miR-133a, miR-124a, miR-146, insulin mRNA and PTB mRNA contents. Insulin biosynthesis rates were determined by radioactive labeling and immunoprecipitation. Synthetic miR-133a precursor and inhibitor were delivered to dispersed islet cells by lipofection, and PTB was analyzed by immunoblotting following culture at low or high glucose. Culture in high glucose resulted in increased islet contents of miR-133a and reduced contents of miR-146. Cytokines increased the contents of miR-146. The insulin and PTB mRNA contents were unaffected by high glucose. However, both PTB protein levels and insulin biosynthesis rates were decreased in response to high glucose. The miR-133a inhibitor prevented the high glucose-induced decrease in PTB and insulin biosynthesis, and the miR-133a precursor decreased PTB levels and insulin biosynthesis similarly to high glucose. CONCLUSION: Prolonged high-glucose exposure down-regulates PTB levels and insulin biosynthesis rates in human islets by increasing miR-133a levels. We propose that this mechanism contributes to hyperglycemia-induced beta-cell dysfunction

Ireland: Submerged Prehistoric Sites and Landscapes

Evidence of Ireland's drowned landscapes and settlements presently comprises 50 sites spread across the entire island. These comprise mainly intertidal find spots or small collections of flint artefacts. A handful of fully subtidal sites are known, generally from nearshore regions and consisting, with one exception, of isolated single finds. Evidence of organic remains is also sparse, with the exception of Mesolithic and Neolithic wooden fish traps buried in estuarine sediments under Dublin. The relatively small number of sites is probably due to lack of research as much as taphonomic issues, and thus the current evidence hints at the potential archaeological record which may be found underwater. Such evidence could contribute to knowledge of the coastal adaptations and seafaring abilities of Ireland's earliest inhabitants. Nonetheless, taphonomic considerations, specifically relating to Ireland's history of glaciation, sea-level change and also modern oceanographic conditions likely limit the preservation of submerged landscapes and their associated archaeology. Realistically, the Irish shelf is likely characterised by pockets of preservation, which makes detection and study of submerged landscapes difficult but not impossible. A range of potential routes of investigation are identifiable, including site-scale archaeological survey, landscape-scale seabed mapping, archival research and community engagement

Inspired or foolhardy: sensemaking, confidence and entrepreneurs' decision-making.

The purpose of this paper is to investigate the role of confidence in how both new and experienced entrepreneurs interpret and make sense of their business environment to inform decision-making. We illustrate our conceptual arguments with descriptive results from a large-scale (n = 6289) survey on entrepreneurs' perception of business performance and their decisions taken at a time of uncertainty in an economic downturn. Quantitative findings are stratified along experiential lines to explore heterogeneity in entrepreneurial decision-making and directly inform our conceptual arguments, while qualitative data from open questions are used to explain the role of confidence. Newer entrepreneurs are found to be more optimistic in the face of environmental risk, which impacts on their decision-making and innovative capabilities. However, the more experienced entrepreneurs warily maintain margin and restructure to adapt to environmental changes. Instead of looking directly at the confidence of individuals, we show how confidence impacts sensemaking, and ultimately, decision-making. These insights inform research on the behaviour of novice and experienced entrepreneurs in relation to innovative business activities. Specifically, blanket assumptions on the role of confidence may be misplaced as its impact changes with experience to alter how entrepreneurs make sense of their environment

Gene expression profiling revealed novel mechanism of action of Taxotere and Furtulon in prostate cancer cells

BACKGROUND: Both Taxotere and Capecitabine have shown anti-cancer activity against various cancers including prostate cancer. In combination, Taxotere plus Capecitabine has demonstrated higher anti-cancer activity in advanced breast cancers. However, the molecular mechanisms of action of Taxotere and Capecitabine have not been fully elucidated in prostate cancer. METHODS: The total RNA from PC3 and LNCaP prostate cells untreated and treated with 2 nM Taxotere, 110 μM Furtulon (active metabolite of Capecitabine), or 1 nM Taxotere plus 50 μM Furtulon for 6, 36, and 72 hours, was subjected to Affymetrix Human Genome U133A Array analysis. Real-time PCR and Western Blot analysis were conducted to confirm microarray data. RESULTS: Taxotere and Furtulon down-regulated some genes critical for cell proliferation, cell cycle progression, transcription factor, cell signaling, and oncogenesis, and up-regulated some genes related to the induction of apoptosis, cell cycle arrest, and differentiation in both cell lines. Taxotere and Furtulon also up-regulated some genes responsible for chemotherapeutic resistance, suggesting the induction of cancer cell resistance to these agents. CONCLUSIONS: Taxotere and Furtulon caused the alternation of a large number of genes, many of which may contribute to the molecular mechanisms by which Taxotere and Furtulon inhibit the growth of prostate cancer cells. This information could be utilized for further mechanistic research and for devising optimized therapeutic strategies against prostate cancer