38 research outputs found
A Methodology for Operationalizing Enterprise Architecture and Evaluating Enterprise IT Flexibility
We propose a network-based methodology for analyzing a firmâs enterprise architecture. Our methodology uses âDesign Structure Matricesâ (DSMs) to capture the coupling between components in the architecture, including both business and technology-related elements. It addresses the limitations of prior work, in that it i) is based upon the actual architecture âin-useâ as opposed to planned or âidealizedâ versions; ii) identifies discrete layers in a firmâs architecture associated with different technologies (e.g., applications, servers and databases); iii) reveals the main âflow of controlâ within an architecture (i.e., the set of inter-connected components); and iv) generates measures of architecture that can be used to predict performance.
We demonstrate the application of our methodology using a novel dataset developed with the division of a large pharmaceutical firm. The dataset consists of all components in the enterprise architecture, the observed dependencies between them, and estimated costs of change for software applications within this architecture. We show that measures of the architecture derived from a DSM predict the cost of change for software applications. In particular, applications that are tightly coupled to other components in the architecture cost more to change. The analysis also shows that the measure of coupling that best predicts the cost of change is one that captures all direct and indirect connections between components (i.e., it captures the potential for changes to propagate via all possible paths between components). Our work represents an important step in making the concept of enterprise architecture more operational, thereby improving a firmâs ability to understand and improve its architecture over time
Visualizing and Measuring Enterprise Application Architecture: An Exploratory Telecom Case
We test a method for visualizing and measuring enterprise application architectures. The method was designed and previously used to reveal the hidden internal architectural structure of software applications. The focus of this paper is to test if it can also uncover new facts about the applications and their relationships in an enterprise architecture, i.e., if the method can reveal the hidden external structure between software applications. Our test uses data from a large international telecom company. In total, we analyzed 103 applications and 243 dependencies. Results show that the enterprise application structure can be classified as a core-periphery architecture with a propagation cost of 25%, core size of 34%, and architecture flow through of 64%. These findings suggest that the method could be effective in uncovering the hidden structure of an enterprise application architecture
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Visualizing and Measuring Enterprise Architecture: An Exploratory BioPharma Case
We test a method that was designed and used previously to reveal the hidden internal architectural structure of software systems. The focus of this paper is to test if it can also uncover new facts about the components and their relationships in an enterprise architecture, i.e., if the method can reveal the hidden external structure between architectural components. Our test uses data from a biopharmaceutical company. In total, we analyzed 407 components and 1,157 dependencies. Results show that the enterprise structure can be classified as a core-periphery architecture with a propagation cost of 23%, core size of 32%, and architecture flow through of 67%. We also found that business components can be classified as control elements, infrastructure components as shared, and software applications as belonging to the core. These findings suggest that the method could be effective in uncovering the hidden structure of an enterprise architecture
Designing an Agile Software Portfolio Architecture: The Impact of Coupling on Performance
The modern industrial corporation encompasses a myriad of different software applications, each of which must work in concert to deliver functionality to end-users. However, the increasingly complex and dynamic nature of competition in todayâs product-markets dictates that this software portfolio be continually evolved and adapted, in order to meet new business challenges. This ability â to rapidly update, improve, remove, replace, and reimagine the software applications that underpin a firmâs competitive position â is at the heart of what has been called IT agility. Unfortunately, little work has examined the antecedents of IT agility, with respect to the choices a firm makes when designing its âSoftware Portfolio Architecture.â
We address this gap in the literature by exploring the relationship between software portfolio architecture and IT agility at the level of the individual applications in the architecture. In particular, we draw from modular systems theory to develop a series of hypotheses about how different types of coupling impact the ability to update, remove or replace the software applications in a firmâs portfolio. We test our hypotheses using longitudinal data from a large financial services firm, comprising over 1,000 applications and over 3,000 dependencies between them. Our methods allow us to disentangle the effects of different types and levels of coupling.
Our analysis reveals that applications with higher levels of coupling cost more to update, are harder to remove, and are harder to replace, than those with lower coupling. The measures of coupling that best explain differences in IT agility include all indirect dependencies between software applications (i.e., they include coupling and dependency relationships that are not easily visible to the system architect). Our results reveal the critical importance of software portfolio design decisions, in developing a portfolio of applications that can evolve and adapt over time
Controls on dissolved and particulate iron distribution in surface waters of the Western Antarctic Peninsula shelf
The Western Antarctic Peninsula (WAP) displays high but variable productivity and is also undergoing rapid change. Long-term studies of phytoplankton communities and primary production have suggested transient limitation by the micronutrient iron (Fe), but to date no data have been available to test this hypothesis. Here, we present the first spatially extensive, multi-year measurements of dissolved and particulate trace metals in surface waters to investigate the key sources and sinks of Fe in the central WAP shelf. Surface samples of dissolved and particulate metals were collected throughout the 700 Ă 200 km grid of the Palmer Long-Term Ecological Research program in three consecutive austral summers (2010 â 2012).
Iron concentrations varied widely. Both dissolved and particulate Fe were high in coastal waters (up to 8 nmol kgâ 1 and 42 nmol kgâ 1, respectively). In contrast, very low Fe concentrations (< 0.1 nmol kgâ 1) were widespread in mid- to outer-shelf surface waters, especially in the northern half of the sampling grid, suggesting possible Fe limitation of primary production on the shelf. Sea ice and dust inputs of Fe were minor, although their relative importance increased with distance from shore due to the larger near-shore sources. Sedimentary inputs were inferred from manganese distributions; these were more significant in the northern portion of the grid, and showed interannual variation in intensity. Overall, the interannual distribution of Fe was most closely correlated to that of meteoric water (glacial melt and precipitation). Although the Fe concentrations and relative contributions of dissolved and particulate Fe attributed to meltwater were variable throughout the sampling region, increasing glacial meltwater flux can be expected to increase the delivery of Fe to surface waters of the coastal WAP in the future
Electronic sculpting of ligand-GPCR subtype selectivity:the case of angiotensin II
GPCR subtypes possess distinct functional
and pharmacological profiles,
and thus development of subtype-selective ligands has immense therapeutic
potential. This is especially the case for the angiotensin receptor
subtypes AT1R and AT2R, where a functional negative control has been
described and AT2R activation highlighted as an important cancer drug
target. We describe a strategy to fine-tune ligand selectivity for
the AT2R/AT1R subtypes through electronic control of ligand aromatic-prolyl
interactions. Through this strategy an AT2R high affinity (<i>K</i><sub>i</sub> = 3 nM) agonist analogue that exerted 18,000-fold
higher selectivity for AT2R versus AT1R was obtained. We show that
this compound is a negative regulator of AT1R signaling since it is
able to inhibit MCF-7 breast carcinoma cellular proliferation in the
low nanomolar range
The Adhesion GPCR GPR125 is specifically expressed in the choroid plexus and is upregulated following brain injury
<p>Abstract</p> <p>Background</p> <p>GPR125 belongs to the family of <it>Adhesion </it>G protein-coupled receptors (GPCRs). A single copy of GPR125 was found in many vertebrate genomes. We also identified a <it>Drosophila </it>sequence, DmCG15744, which shares a common ancestor with the entire Group III of <it>Adhesio</it>n GPCRs, and also contains Ig, LRR and HBD domains which were observed in mammalian GPR125.</p> <p>Results</p> <p>We found specific expression of GPR125 in cells of the choroid plexus using <it>in situ </it>hybridization and protein-specific antibodies and combined <it>in situ</it>/immunohistochemistry co-localization using cytokeratin, a marker specific for epithelial cells. Induction of inflammation by LPS did not change GPR125 expression. However, GPR125 expression was transiently increased (almost 2-fold) at 4 h after traumatic brain injury (TBI) followed by a decrease (approximately 4-fold) from 2 days onwards in the choroid plexus as well as increased expression (2-fold) in the hippocampus that was delayed until 1 day after injury.</p> <p>Conclusion</p> <p>These findings suggest that GPR125 plays a functional role in choroidal and hippocampal response to injury.</p
The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members
The Interferon induced transmembrane proteins (IFITM) are a family of transmembrane proteins that is known to inhibit cell invasion of viruses such as HIV-1 and influenza. We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure. We mined the Dispanins in 36 eukaryotic species, covering all major eukaryotic groups, and investigated their evolutionary history using Bayesian and maximum likelihood approaches to infer a phylogenetic tree. We identified ten human genes that together with the known IFITM genes form the Dispanin family. We show that the Dispanins first emerged in eukaryotes in a common ancestor of choanoflagellates and metazoa, and that the family later expanded in vertebrates where it forms four subfamilies (AâD). Interestingly, we also find that the family is found in several different phyla of bacteria and propose that it was horizontally transferred to eukaryotes from bacteria in the common ancestor of choanoflagellates and metazoa. The bacterial and eukaryotic sequences have a considerably conserved protein structure. In conclusion, we introduce a novel family, the Dispanins, together with a nomenclature based on the evolutionary origin
The Origin of GPCRs: Identification of Mammalian like Rhodopsin, Adhesion, Glutamate and Frizzled GPCRs in Fungi
G protein-coupled receptors (GPCRs) in humans are classified into the five main families named Glutamate, Rhodopsin, Adhesion, Frizzled and Secretin according to the GRAFS classification. Previous results show that these mammalian GRAFS families are well represented in the Metazoan lineages, but they have not been shown to be present in Fungi. Here, we systematically mined 79 fungal genomes and provide the first evidence that four of the five main mammalian families of GPCRs, namely Rhodopsin, Adhesion, Glutamate and Frizzled, are present in Fungi and found 142 novel sequences between them. Significantly, we provide strong evidence that the Rhodopsin family emerged from the cAMP receptor family in an event close to the split of Opisthokonts and not in Placozoa, as earlier assumed. The Rhodopsin family then expanded greatly in Metazoans while the cAMP receptor family is found in 3 invertebrate species and lost in the vertebrates. We estimate that the Adhesion and Frizzled families evolved before the split of Unikonts from a common ancestor of all major eukaryotic lineages. Also, the study highlights that the fungal Adhesion receptors do not have N-terminal domains whereas the fungal Glutamate receptors have a broad repertoire of mammalian-like N-terminal domains. Further, mining of the close unicellular relatives of the Metazoan lineage, Salpingoeca rosetta and Capsaspora owczarzaki, obtained a rich group of both the Adhesion and Glutamate families, which in particular provided insight to the early emergence of the N-terminal domains of the Adhesion family. We identified 619 Fungi specific GPCRs across 79 genomes and revealed that Blastocladiomycota and Chytridiomycota phylum have Metazoan-like GPCRs rather than the GPCRs specific for Fungi. Overall, this study provides the first evidence of the presence of four of the five main GRAFS families in Fungi and clarifies the early evolutionary history of the GPCR superfamily
Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts
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