| 1. |
- Odell, Luke R., et al.
(författare)
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Pyrimidine-Based Inhibitors of Dynamin I GTPase Activity : Competitive Inhibition at the Pleckstrin Homology Domain
- 2017
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 60:1, s. 349-361
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Tidskriftsartikel (refereegranskat)abstract
- The large GTPase dynamin mediates membrane fission during clathrin-mediated endocytosis (CME). The aminopyrimidine compounds, were reported to disrupt clynamin localization to the plasina membrane via the PH domain and,iniplicate this mechanism in the inhibition of CME. We have used a computational approach of binding site identification, docking, and interaction energy calculations to design and synthesize a new library of aminopyrimidine analogues targeting site-2 of the pleckstrin homology (PH) domain. The optimized analogues showed low micromolar inhibition against both dynamin I (IC50 = 10.6 +/- 1.3 to 1.6 +/- 0.3 mu M) and CME (IC50(CME) = 65.9 +/- 7.7 to 17 +/- 1.1 mM), which makes this. series among The more potent inhibitors of dynamin.and CME yet reported. In:CME and growth inhibition cell-based assays, the data obtained Was consistent with dynamin inhibition. CEREP ExpresS profiling identified off-.target effects at the cholecystokinin, dopamine D-2, histamine H-1 and H-2, melanocortin, rnelatonin, muscarir* M-1 and M-3 neurokinin, opioid KOP and serotonin receptors.
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| 2. |
- Aarons, G. A., et al.
(författare)
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Fostering international collaboration in implementation science and research : A concept mapping exploratory study
- 2019
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Ingår i: BMC Research Notes. - : BioMed Central Ltd.. - 1756-0500. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: International collaboration in science has received increasing attention given emphases on relevance, generalizability, and impact of research. Implementation science (IS) is a growing discipline that aims to translate clinical research findings into health services. Research is needed to identify efficient and effective ways to foster international collaboration in IS. Concept-mapping (CM) was utilized with a targeted sample for preliminary exploration of fostering international collaboration. Concept-mapping is a mixed-method approach (qualitative/quantitative) particularly suited for identifying essential themes and action items to facilitate planning among diverse stakeholders. We sought to identify key factors likely to facilitate productive and rewarding international collaborations in implementation research. Results: We identified eleven dimensions: Strategic Planning; Practicality; Define Common Principles; Technological Tools for Collaboration; Funding; Disseminate Importance of Fostering International Collaboration in IS; Knowledge Sharing; Innovative & Adaptive Research; Training IS Researchers; Networking & Shared Identity; Facilitate Meetings. Strategic Planning and Funding were highest rated for importance and Strategic Planning and Networking and Shared Identity were rated most feasible to institute. Fostering international collaboration in IS can accelerate the efficiency, relevance, and generalizability of implementation research. Strategies should be developed and tested to improve international collaborations and engage junior and experienced investigators in collaborations advancing implementation science and practice.
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| 3. |
- Amundadottir, Laufey T., et al.
(författare)
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A common variant associated with prostate cancer in European and African populations
- 2006
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Ingår i: Nature Genetics. - DeCODE Genet, IS-101 Reykjavik, Iceland. Univ Iceland, Landspitali Hosp, Dept Pathol, IS-101 Reykjavik, Iceland. Univ Iceland, Landspitali Hosp, Dept Urol, IS-101 Reykjavik, Iceland. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Orebro Univ Hosp, Dept Urol & Clin Med, Orebro, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 38:6, s. 652-658
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Tidskriftsartikel (refereegranskat)abstract
- With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.
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| 4. |
- Avritzer, A, et al.
(författare)
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Monitoring for Security Intrusion using Performance Signatures
- 2010
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Ingår i: WOSP/SIPEW'10 - Proceedings of the 1st Joint WOSP/SIPEW International Conference on Performance Engineering. - New York, NY, USA : ACM. - 9781605585635 ; , s. 93-103
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Konferensbidrag (refereegranskat)abstract
- A new approach for detecting security attacks on software systems by monitoring the software system performance signatures is introduced. We present a proposed architecture for security intrusion detection using off-the-shelf security monitoring tools and performance signatures. Our approach relies on the assumption that the performance signature of the well-behaved system can be measured and that the performancesignature of several types of attacks can be identified. This assumption has been validated for operations support systems that are used to monitor large infrastructures and receive aggregated traffic that is periodic in nature. Examples of such infrastructures include telecommunications systems, transportation systems and power generation systems. In addition, significant deviation from well-behaved system performance signatures can be used to trigger alerts about new types of security attacks. We used a custom performance benchmark and five types of security attacks to deriveperformance signatures for the normal mode of operation and the security attack mode of operation. We observed that one of the types of thesecurity attacks went undetected by the off-the-shelf security monitoring tools but was detected by our approach of monitoring performance signatures. We conclude that an architecture for security intrusion detection can be effectively complemented by monitoring of performance signatures.
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| 5. |
- Chen, Kenneth, et al.
(författare)
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Recommendations for Core Outcome Domain Set for Whiplash Associated Disorders (CATWAD)
- 2019
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Ingår i: Clinical Journal of Pain. - : Lippincott Williams & Wilkins. - 0749-8047 .- 1536-5409. ; 35:9, s. 727-736
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Inconsistent reporting of outcomes in clinical trials of treatments for Whiplash Associated Disorders (WAD) hinders effective data pooling and conclusions that can be drawn about the effectiveness of tested treatments. The aim of this study was to provide recommendations for core outcome domains that should be included in clinical trials of WAD. Methods: A three-step process was used. 1) A list of potential core outcome domains were identified from the published literature; 2) Researchers, health care providers, patients and insurance personnel participated and rated the importance of each domain via a three round Delphi survey. A priori criteria for consensus were established; 3) Experts comprising researchers, health care providers and a consumer representative participated in a multidisciplinary consensus meeting that made final decisions on the recommended core outcome domains. Results: The literature search identified 63 potential core domains. 223 participants were invited to partake in the Delphi surveys with 41.7% completing Round 1, 45.3% Round 2 and 51.4% Round 3. Eleven core domains met the criteria for inclusion across the entire sample. After the expert consensus meeting, six core domains were recommended: Physical Functioning, Perceived Recovery, Work and Social Functioning, Psychological Functioning, Quality of Life and Pain. Discussion: A 3-step process was used to recommend core outcome domains for clinical trials in WAD. Six core domains were recommended: Physical Functioning, Perceived Recovery, Work and Social Functioning, Psychological Functioning, Quality of Life and Pain. The next step is to determine the outcome measurement instruments for each of these domains.
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| 6. |
- Eziama, E., et al.
(författare)
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Machine learning-based recommendation trust model for machine-to-machine communication
- 2018
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Ingår i: 2018 IEEE International Symposium on Signal Processing and Information Technology, ISSPIT 2018. - : Institute of Electrical and Electronics Engineers Inc.. - 9781538675687
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Konferensbidrag (refereegranskat)abstract
- The Machine Type Communication Devices (MTCDs) are usually based on Internet Protocol (IP), which can cause billions of connected objects to be part of the Internet. The enormous amount of data coming from these devices are quite heterogeneous in nature, which can lead to security issues, such as injection attacks, ballot stuffing, and bad mouthing. Consequently, this work considers machine learning trust evaluation as an effective and accurate option for solving the issues associate with security threats. In this paper, a comparative analysis is carried out with five different machine learning approaches: Naive Bayes (NB), Decision Tree (DT), Linear and Radial Support Vector Machine (SVM), KNearest Neighbor (KNN), and Random Forest (RF). As a critical element of the research, the recommendations consider different Machine-to-Machine (M2M) communication nodes with regard to their ability to identify malicious and honest information. To validate the performances of these models, two trust computation measures were used: Receiver Operating Characteristics (ROCs), Precision and Recall. The malicious data was formulated in Matlab. A scenario was created where 50% of the information were modified to be malicious. The malicious nodes were varied in the ranges of 10%, 20%, 30%, 40%, and the results were carefully analyzed.
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| 7. |
- Hazy, James K., et al.
(författare)
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Reconceptualizing value creation with limited resources
- 2008
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Ingår i: Journal of Technology Management & Innovation. - Sweden. - 0718-2724. ; 3:3, s. 45-54
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Tidskriftsartikel (refereegranskat)abstract
- In traditional economics and finance the notion of value creation is virtually synonymous with the net present value of cash flows. Such a characterization implies that all of the uses of resource inputs, such as raw material and energy, are known and that their value is priced into commodities markets. It also fails to allow for the opportunity cost associated with the depletion of resources which, with advancing technology, might reasonably have future uses far greater in value than can be achieved at present with current technology. Stated differently, in traditional valuation analysis the option value associated with scarce resources -when new technology or knowledge can be applied to them- is not addressed. In the present work, we define technology leverage as representative of this effect. We then address the problem of sustainability of organizations by stating four propositions and examining their implications for government policy and for firm governance.
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| 8. |
- Hazy, James K., et al.
(författare)
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Technology Leverage and Sustainable Society Systems : A Call for Technology Forecasting that Anticipates Innovation
- 2011
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Ingår i: International Journal of Society Systems Science. - 1756-2511. ; 3:1-2, s. 5-20
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Tidskriftsartikel (refereegranskat)abstract
- We argue that economic value to society is created by converting input resources into valued outputs though the application of technology. To support this argument, the concept of technology leverage is introduced, and it is noted that the same input resource can be converted into different output values depending upon the technology employed in the conversion process and the state of technical innovation at the time the conversion occurs. This implies that through as yet unrealised innovations, future generations may create greater value for the same amount of resource than is currently possible. This difference has significant ramifications for current day resource allocation decisions. In addition to more conventional conservation arguments, technology leverage also recognises that the future value of retaining resources, especially non-renewable ones, may be evaluated using real option valuation techniques. These concepts are helpful in determining more comprehensive policies relating to resource allocation decisions.
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| 9. |
- Hazy, James K., et al.
(författare)
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Unfolding the Future : Bifurcation in Organizing Form and Emergence in Social Systems
- 2011
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Ingår i: Emergence. - 1521-3250 .- 1532-7000. ; 13:3, s. 57-79
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a complexity science informed theory to describe how organizing forms emerge and foster innovation. The theory explores the bidirectional linkages between fine-grained interactions among human beings in a complex adaptive system and the emergent coarse-grained properties that characterize qualitatively distinct and yet stable organizing forms in social systems. By exploiting a mathematical foundation that has been successfully employed in analogous cases in the natural sciences, it opens the door to a rigorous theory of performance and adaptation in human systems by relating changing local rules of interaction to qualitative changes in emerging organizing forms. This process is mediated by evolving models of the system in the environment developed and shared among individuals. Finally, the paper explores whether this model can be used canonically and does so in the context of axiomatic hurdles that must be overcome if a practical mathematical theory of human organizing is to be realized.
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| 10. |
- Pesämaa, Ossi, 1970-, et al.
(författare)
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Secret ties as a way to succeed : describing and exploring relations among successful tourism managers
- 2004
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Ingår i: Tourism in peripheries. - Wallingford, Oxfordshire : CABI Publishing. - 9781845931773
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Konferensbidrag (refereegranskat)abstract
- Managers and owners of successful companies act with deliberate purpose in order to succeed (Penrose, 1959; Nelson and Winter, 1982; Aldrich and Zimmer, 1986; Edquist, 1997; Metcalfe, 1997). Understanding the issue of success and failure has received great interest among practitioners, policymakers and researchers. This study considers a region understood as a rural, sparsely populated area. In this region, traditional industries such as mining, agriculture and forest products are suffering under pressure for sustainable replacement industries. Reconstruction of such areas involves structural processes facilitating the entry of new industries, such as tourism (Petterson, 2002). The replacement industries often demand a shift in terms of tangible assets and also in terms of finding decision routines adapted to sensitive customer needs. In order to understand the complexity of this industrial shift, this paper intends to describe and explore (as moderators for understanding success) present decision routines in tourism industry, at three levels, and to chart the decision paths.
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