213 research outputs found
Business process modelling to improve incident management process
Business process management (BPM) is an approach focused on the continuous
improvement of business processes, providing for this a collection of best practices. These best
practices enable the redesign of business processes to meet the desired performance. IT service
management (ITSM) defines the management of IT operations as a service. There are several
ITSM frameworks available, consisting in best practices that propose standardizing these pro-
cesses for the respective operations. By adopting these frameworks, organisations can align IT
with their business objectives. Therefore, the objective of this research is to understand how BPM
can be used to improve of ITSM processes. An exploratory case study in a multinational company
based in Lisbon, Portugal, is conducted for the improvement of the time performance of an inci-
dent management process. Data were gained through documentation, archival records, interviews
and focus groups with a team involved in IT support service. So far, the as-is process was elicited,
and respective incongruences clarified. During the next months the authors intend to identify the
main problems and simulate the appropriate BPM heuristics to understand the impact in the busi-
ness organisation.info:eu-repo/semantics/acceptedVersio
Participation of the Cell Polarity Protein PALS1 to T-Cell Receptor-Mediated NF-κB Activation
BACKGROUND: Beside their established function in shaping cell architecture, some cell polarity proteins were proposed to participate to lymphocyte migration, homing, scanning, as well as activation following antigen receptor stimulation. Although PALS1 is a central component of the cell polarity network, its expression and function in lymphocytes remains unknown. Here we investigated whether PALS1 is present in T cells and whether it contributes to T Cell-Receptor (TCR)-mediated activation. METHODOLOGY/PRINCIPAL FINDINGS: By combining RT-PCR and immunoblot assays, we found that PALS1 is constitutively expressed in human T lymphocytes as well as in Jurkat T cells. siRNA-based knockdown of PALS1 hampered TCR-induced activation and optimal proliferation of lymphocyte. We further provide evidence that PALS1 depletion selectively hindered TCR-driven activation of the transcription factor NF-κB. CONCLUSIONS: The cell polarity protein PALS1 is expressed in T lymphocytes and participates to the optimal activation of NF-κB following TCR stimulation
Purification of Nanoparticles by Size and Shape
Producing monodisperse nanoparticles is essential to ensure consistency in biological experiments and to enable a smooth translation into the clinic. Purification of samples into discrete sizes and shapes may not only improve sample quality, but also provide us with the tools to understand which physical properties of nanoparticles are beneficial for a drug delivery vector. In this study, using polymersomes as a model system, we explore four techniques for purifying pre-formed nanoparticles into discrete fractions based on their size, shape or density. We show that these techniques can successfully separate polymersomes into monodisperse fractions
Robust Inverse Modeling of Growing Season Net Ecosystem Exchange in a Mountainous Peatland: Influence of Distributional Assumptions on Estimated Parameters and Total Carbon Fluxes
While boreal lowland bogs have been extensively studied using the eddy‐covariance (EC) technique, less knowledge exists on mountainous peatlands. Hence, half‐hourly CO2 fluxes of an ombrotrophic peat bog in the Harz Mountains, Germany, were measured with the EC technique during a growing season with exceptionally dry weather spells. A common biophysical process model for net ecosystem exchange was used to describe measured CO2 fluxes and to fill data gaps. Model parameters and uncertainties were estimated by robust inverse modelling in a Bayesian framework using a population‐based Markov Chain Monte Carlo sampler. The focus of this study was on the correct statistical description of error, i.e. the differences between the measured and simulated carbon fluxes, and the influence of distributional assumptions on parameter estimates, cumulative carbon fluxes, and uncertainties. We tested the Gaussian, Laplace, and Student's t distribution as error models. The t‐distribution was identified as best error model by the deviance information criterion. Its use led to markedly different parameter estimates, a reduction of parameter uncertainty by about 40%, and, most importantly, to a 5% higher estimated cumulative CO2 uptake as compared to the commonly assumed Gaussian error distribution. As open‐path measurement systems have larger measurement error at high humidity, the standard deviation of the error was modeled as a function of measured vapor pressure deficit. Overall, this paper demonstrates the importance of critically assessing the influence of distributional assumptions on estimated model parameters and cumulative carbon fluxes between the land surface and the atmosphere
The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction-dependent manner
The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu) mutant of syndecan-4 (SDC4). SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1) to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1-RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s) reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways
K0S and Λ production in Pb-Pb collisions at sNN−−−−√=2.76 TeV
The ALICE measurement of K0S and Λ production at midrapidity in Pb-Pb collisions at sNN−−−√=2.76 TeV is presented. The transverse momentum (pT) spectra are shown for several collision centrality intervals and in the pT range from 0.4 GeV/c (0.6 GeV/c for Λ) to 12 GeV/c. The pT dependence of the Λ/K0S ratios exhibits maxima in the vicinity of 3 GeV/c, and the positions of the maxima shift towards higher pT with increasing collision centrality. The magnitude of these maxima increases by almost a factor of three between most peripheral and most central Pb-Pb collisions. This baryon excess at intermediate pT is not observed in pp interactions at s√=0.9 TeV and at s√=7 TeV. Qualitatively, the baryon enhancement in heavy-ion collisions is expected from radial flow. However, the measured pT spectra above 2 GeV/c progressively decouple from hydrodynamical-model calculations. For higher values of pT, models that incorporate the influence of the medium on the fragmentation and hadronization processes describe qualitatively the pT dependence of the Λ/K0S ratio
C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons.
Intronic hexanucleotide expansions in C9ORF72 are common in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but it is unknown whether loss of function, toxicity by the expanded RNA or dipeptides from non-ATG-initiated translation are responsible for the pathophysiology. We determined the interactome of C9ORF72 in motor neurons and found that C9ORF72 was present in a complex with cofilin and other actin binding proteins. Phosphorylation of cofilin was enhanced in C9ORF72-depleted motor neurons, in patient-derived lymphoblastoid cells, induced pluripotent stem cell-derived motor neurons and post-mortem brain samples from ALS patients. C9ORF72 modulates the activity of the small GTPases Arf6 and Rac1, resulting in enhanced activity of LIM-kinases 1 and 2 (LIMK1/2). This results in reduced axonal actin dynamics in C9ORF72-depleted motor neurons. Dominant negative Arf6 rescues this defect, suggesting that C9ORF72 acts as a modulator of small GTPases in a pathway that regulates axonal actin dynamics
Involvement of Girdin in the Determination of Cell Polarity during Cell Migration
Cell migration is a critical cellular process that determines embryonic development and the progression of human diseases. Therefore, cell- or context-specific mechanisms by which multiple promigratory proteins differentially regulate cell migration must be analyzed in detail. Girdin (girders of actin filaments) (also termed GIV, Gα-interacting vesicle associated protein) is an actin-binding protein that regulates migration of various cells such as endothelial cells, smooth muscle cells, neuroblasts, and cancer cells. Here we show that Girdin regulates the establishment of cell polarity, the deregulation of which may result in the disruption of directional cell migration. We found that Girdin interacts with Par-3, a scaffolding protein that is a component of the Par protein complex that has an established role in determining cell polarity. RNA interference-mediated depletion of Girdin leads to impaired polarization of fibroblasts and mammary epithelial cells in a way similar to that observed in Par-3-depleted cells. Accordingly, the expression of Par-3 mutants unable to interact with Girdin abrogates cell polarization in fibroblasts. Further biochemical analysis suggests that Girdin is present in the Par protein complex that includes Par-3, Par-6, and atypical protein kinase C. Considering previous reports showing the role of Girdin in the directional migration of neuroblasts, network formation of endothelial cells, and cancer invasion, these data may provide a specific mechanism by which Girdin regulates cell movement in biological contexts that require directional cell movement
Organization of multiprotein complexes at cell–cell junctions
The formation of stable cell–cell contacts is required for the generation of barrier-forming sheets of epithelial and endothelial cells. During various physiological processes like tissue development, wound healing or tumorigenesis, cellular junctions are reorganized to allow the release or the incorporation of individual cells. Cell–cell contact formation is regulated by multiprotein complexes which are localized at specific structures along the lateral cell junctions like the tight junctions and adherens junctions and which are targeted to these site through their association with cell adhesion molecules. Recent evidence indicates that several major protein complexes exist which have distinct functions during junction formation. However, this evidence also indicates that their composition is dynamic and subject to changes depending on the state of junction maturation. Thus, cell–cell contact formation and integrity is regulated by a complex network of protein complexes. Imbalancing this network by oncogenic proteins or pathogens results in barrier breakdown and eventually in cancer. Here, I will review the molecular organization of the major multiprotein complexes at junctions of epithelial cells and discuss their function in cell–cell contact formation and maintenance
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