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Now showing items 65 - 80 of 210

  • Chronic diabetic states worsen Alzheimer neuropathology and cognitive deficits accompanying disruption of calcium signaling in leptin-deficient APP/PS1 mice

    Shuai Zhang   Rui Chai   Ying-ying Yang   Shi-Qi Guo   Shan Wang   Tian Cai Guo   Shuang-Feng Xu   Yan-hui Zhang   Zhanyou Wang   Chuang Guo  

    The coincidences between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are so compelling that it is attractive to speculate that diabetic conditions might aggravate AD pathologies by calcium dysfunction; although the understanding of the molecular mechanisms involved remains elusive. The present work was undertaken to investigate whether calcium dyshomeostasis is associated with the exacerbated Alzheimer-like cognitive dysfunction observed in diabetic conditions in APP/PS1-ob/ob mice; which were generated by crossing ob/ob mice with APP/PS1 mice. We confirmed that the diabetic condition can aggravate not only Aβ deposition but also tau phosphorylation; synaptic loss; neuronal death; and inflammation; exacerbating cognitive impairment in AD mice. More importantly; we found that the diabetic condition dramatically elevated calcium levels in APP/PS1 mice; thereby stimulating the phosphorylation of the calcium-dependent kinases. Our findings suggest that controlling over-elevation of intracellular calcium may provide novel insights for approaching AD in diabetic patients and delaying AD progression.
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  • Genome-scale identification of cell-wall related genes in Arabidopsis based on co-expression network analysis

    Shan Wang   Yanbin Yin   Qin Ma   Xiaojia Tang   Dongyun Hao   Ying Xu  

    Identification of the novel genes relevant to plant cell-wall (PCW) synthesis represents a highly important and challenging problem. Although substantial efforts have been invested into studying this problem; the vast majority of the PCW related genes remain unknown. Here we present a computational study focused on identification of the novel PCW genes in Arabidopsis based on the co-expression analyses of transcriptomic data collected under 351 conditions; using a bi-clustering technique. Our analysis identified 217 highly co-expressed gene clusters (modules) under some experimental conditions; each containing at least one gene annotated as PCW related according to the Purdue Cell Wall Gene Families database. These co-expression modules cover 349 known/annotated PCW genes and 2;438 new candidates. For each candidate gene; we annotated the specific PCW synthesis stages in which it is involved and predicted the detailed function. In addition; for the co-expressed genes in each module; we predicted and analyzed their cis regulatory motifs in the promoters using our motif discovery pipeline; providing strong evidence that the genes in each co-expression module are transcriptionally co-regulated. From the all co-expression modules; we infer that 108 modules are related to four major PCW synthesis components; using three complementary methods. We believe our approach and data presented here will be useful for further identification and characterization of PCW genes. All the predicted PCW genes; co-expression modules; motifs and their annotations are available at a web-based database: http://csbl.bmb.uga.edu/publications/materials/shanwang/CWRPdb/index.html .
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  • Heavy pollution episodes, transport pathways and potential sources of PM<sub>2.5</sub> during the winter of 2013 in Chengdu (China)

    Tingting Liao   Shan Wang   Jie Ai   Ke Gui   Bolong Duan   Qi Zhao   Xiao Zhang   Wanting Jiang   Yang Sun  

    Abstract Air mass concentration data from 8 environmental quality monitoring sites and meteorological data of Chengdu from 1 December 2013 to 28 February 2014 were used in this study. Chengdu suffered five continuous heavy pollutions during this winter due to the basin terrain and the meteorological conditions of low wind speed, low precipitation and high relative humidity. Analysing the hourly resolution time series of pollutants' concentrations, variation of PM 2.5 in the urban area followed a growing “saw-tooth cycle” pattern during the heavy pollution, with a daily cycle of bimodal distribution. The massive letting-off of fireworks within a short period of time on the Eve of the Lunar New Year under the unfavourable diffusion conditions resulted in an extreme pollution event. The sharply rising Longmen-Qionglai Mountains to the west of the Sichuan Basin not only acted as a huge barrier to block the air mass from the east but also favoured the formation of a local circulation. The cluster analysis of back trajectories revealed that up to 77% of them came from the inner part of the Basin. Combining the concentration data of PM 2.5 with air mass back trajectories, a potential source contribution function (PSCF) model and a concentration-weighted trajectory (CWT) method were used to evaluate the transport pathways and sources over PM 2.5 of Chengdu, revealing that the main potential sources of PM 2.5 were located in southeast cities and the western margin of the Sichuan Basin. The result provided advice for the government to take measures in improving air quality. Graphical abstract Image 1 Highlights • Chengdu suffered poor air quality in winter of 2013. • Special terrain and meteorology made great contributions to heavy pollutions. • Up to 77% of back trajectories originated from the inside of Sichuan Basin. • Air masses from southeast might be the most important potential source of PM 2.5 .
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  • An exploratory study of electronic marketplace adoption: a multiple perspective view

    Shan Wang   Archer, N.P.   Wuping Zheng  

    Many researchers have studied the adoption of business-to-business electronic marketplaces (EMs), but agreement on which factors are more important driving forces of EM adoption has not been achieved. This may be because researchers have not adopted multiple perspectives, since the importance of EM driving factors may vary when analytical perspectives change. The objective of this paper is to determine if evidence exists that this might indeed be the case. This paper explores the adoption of EMs from multiple perspectives, using case studies. Due to its parsimony, the UTAUT framework suggested by Venkatesh et al. (2003) is adopted to guide the case analysis. EM adoption factors fail into four UTAUT super-categories: performance expectancy; effort expectancy; institutional influence; and facilitating conditions. Results from the case studies indicate that performance expectancy is the most important and ease of use is the least important consideration for participating users. The importance of these factors is examined from both seller/buyer and market structure perspectives. Preliminary evidence from the case studies indicates that the importance of adoption factors does vary with different perspectives. For example, for buyers, performance expectancy appears to be the most important while, for suppliers, all factors except ease of use appear to be equally important. This implies that suppliers tend to be more passive than buyers in EM adoption.
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  • Therapeutic potential of atorvastatin-modified dendritic cells in experimental autoimmune neuritis by decreased Th1/Th17 cytokines and up-regulated T regulatory cells and NKR-P1<sup>+</sup> cells

    Hua Xu   Xiao-Li Li   Long-Tao Yue   Heng Li   Min Zhang   Shan Wang   Cong-Cong Wang   Rui-Sheng Duan  

    Abstract Statins have pleiotropic effects which include anti-inflammatory and immunomodulatory effects. In the present study, dendritic cells treated with atorvastatin (statin-DCs) could be induced into tolerogenic DCs. Administration of these tolerogenic DCs ameliorated clinical symptoms in experimental autoimmune neuritis (EAN), which was associated with reduced number of inflammatory cells in sciatic nerves, inhibited CD4 + T cells proliferation, down-regulated expression of co-stimulatory molecules (CD80 and CD86) and MHC class II, decreased levels of IFN-γ, TNF-α and IL-17A, increased number of NKR-P1 + cells (including NK and NKT cells), up-regulated number of Treg cells in lymph node MNC as well as increased Foxp3 expression in the thymus. These data indicated that statin-DCs could develop as a new therapeutic strategy to GBS in the future. Highlights • DCs treated with atorvastatin (statin-DCs) can be induced into tolerogenic DCs. • Administration of statin-DCs ameliorate the clinical symptoms in EAN. • Statin-DCs induce both central and peripheral immune tolerance in EAN.
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  • Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: implications for the performance of malaria rapid diagnostic tests

    Joanne C. Baker   Mei-Fong Ho   Anita M. Pelecanos   Michelle L. Gatton   Nanhua Chen   Salim Abdullah   Audrey Albertini   Frédéric Ariey   John W. Barnwell   David Bell   Jane Cunningham   Djibrine Djallé   Diego F. Echeverry   Dionicia Gamboa   Jeffery L Hii   Myat Phone Kyaw   Jennifer Luchavez   Christopher D Membi   Didier Ménard   Claribel Murillo   Sina Nhem   Bernhards R. Ogutu   Pamela Onyor   Wellington Aghoghovwia Oyibo   Shan Wang   James S McCarthy   Qin Cheng  

    Accurate diagnosis is essential for prompt and appropriate treatment of malaria. While rapid diagnostic tests (RDTs) offer great potential to improve malaria diagnosis; the sensitivity of RDTs has been reported to be highly variable. One possible factor contributing to variable test performance is the diversity of parasite antigens. This is of particular concern for Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-detecting RDTs since PfHRP2 has been reported to be highly variable in isolates of the Asia-Pacific region. The pfhrp2 exon 2 fragment from 458 isolates of P. falciparum collected from 38 countries was amplified and sequenced. For a subset of 80 isolates; the exon 2 fragment of histidine-rich protein 3 (pfhrp3) was also amplified and sequenced. DNA sequence and statistical analysis of the variation observed in these genes was conducted. The potential impact of the pfhrp2 variation on RDT detection rates was examined by analysing the relationship between sequence characteristics of this gene and the results of the WHO product testing of malaria RDTs: Round 1 (2008); for 34 PfHRP2-detecting RDTs. Sequence analysis revealed extensive variations in the number and arrangement of various repeats encoded by the genes in parasite populations world-wide. However; no statistically robust correlation between gene structure and RDT detection rate for P. falciparum parasites at 200 parasites per microlitre was identified. The results suggest that despite extreme sequence variation; diversity of PfHRP2 does not appear to be a major cause of RDT sensitivity variation.
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  • Polypyrrole-Grafted Coconut Shell Biological Carbon as a Potential Adsorbent for Methyl Tert-Butyl Ether Removal: Characterization and Adsorption Capability

    Shanshan Li   Keke Qian   Shan Wang   Kaiqiang Liang   Wei Yan  

    Methyl tert-butyl ether (MTBE) has been used as a common gasoline additive worldwide since the late twentieth century; and it has become the most frequently detected groundwater pollutant in many countries. This study aimed to synthesize a novel microbial carrier to improve its adsorptive capacity for MTBE and biofilm formation; compared to the traditional granular activated carbon (GAC). A polypyrrole (PPy)-modified GAC composite (PPy/GAC) was synthesized; and characterized by Fourier transform infrared spectroscopy (FT-IR) and Brunauer-Emmett-Teller (BET) surface area analysis. The adsorption behaviors of MTBE were well described by the pseudo-second-order and Langmuir isotherm models. Furthermore; three biofilm reactors were established with PPy/GAC; PPy; and GAC as the carriers; respectively; and the degradation of MTBE under continuous flow was investigated. Compared to the biofilm reactors with PPy or GAC (which both broke after a period of operation); the PPy/GAC biofilm column produced stable effluents under variable treatment conditions with a long-term effluent MTBE concentration <20 μg/L. Pseudomonas aeruginosa and Acinetobacter pittii may be the predominant bacteria responsible for MTBE degradation in these biofilm reactors.
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  • Analysis on the Practice of Marxist View of Journalism in Local Media During the COVID-19 Epidemic

    Based on the important principles of Marxist view of journalism-party spirit, affinity to the people and authenticity as the axis, the local media carried out journalistic practice in the coverage during the COVID-19 epidemic. Through in-depth interviews, it is found that the details and experiences of local media in implementing journalistic practices guided by the key principles of Marxist view of journalism in the face of the crisis were able to be understood and meet the people's need for truthfulness to a certain extent, achieving the dialectical unity of party spirit,affinity to the people and authenticity.
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  • Hydroelastic analysis of a rectangular plate subjected to slamming loads

    Shan Wang   C. Guedes Soares  

    A hydroelastic analysis of a rectangular plate subjected to slamming loads is presented. An analytical model based on Wagner theory is used for calculations of transient slamming load on the ship plate. A thin isotropic plate theory is considered for determining the vibration of a rectangular plate excited by an external slamming force. The forced vibration of the plate is calculated by the modal expansion method. Analytical results of the transient response of a rectangular plate induced by slamming loads are compared with numerical calculations from finite element method. The theoretical slamming pressure based on Wagner model is applied on the finite element model of a plate. Good agreement is obtained between the analytical and numerical results for the structural deflection of a rectangular plate due to slamming pressure. The effects of plate dimension and wave profile on the structural vibration are discussed as well. The results show that a low impact velocity and a small wetted radial length of wave yield negligible effects of hydroelasticity.
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  • α-Lipoic acid improves abnormal behavior by mitigation of oxidative stress, inflammation, ferroptosis, and tauopathy in P301S Tau transgenic mice

    Yan-Hui Zhang   Da-Wei Wang   Shuang-Feng Xu   Shuai Zhang   Yong-Gang Fan   Ying-Ying Yang   Shi-Qi Guo   Shan Wang   Tian Guo   Zhan-You Wang   Chuang Guo  

    Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by neurofibrillary tangles (NFTs) composed of Tau protein. α-Lipoic acid (LA) has been found to stabilize the cognitive function of AD patients, and animal study findings have confirmed its anti-amyloidogenic properties. However, the underlying mechanisms remain unclear, especially with respect to the ability of LA to control Tau pathology and neuronal damage. Here, we found that LA supplementation effectively inhibited the hyperphosphorylation of Tau at several AD-related sites, accompanied by reduced cognitive decline in P301S Tau transgenic mice. Furthermore, we found that LA not only inhibited the activity of calpain1, which has been associated with tauopathy development and neurodegeneration via modulating the activity of several kinases, but also significantly decreased the calcium content of brain tissue in LA-treated mice. Next, we screened for various modes of neural cell death in the brain tissue of LA-treated mice. We found that caspase-dependent apoptosis was potently inhibited, whereas autophagy did not show significant changes after LA supplementation. Interestingly, Tau-induced iron overload, lipid peroxidation, and inflammation, which are involved in ferroptosis, were significantly blocked by LA administration. These results provide compelling evidence that LA plays a role in inhibiting Tau hyperphosphorylation and neuronal loss, including ferroptosis, through several pathways, suggesting that LA may be a potential therapy for tauopathies.
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  • Long-circulating and liver-targeted nanoassemblies of cyclic phosphoryl N-dodecanoyl gemcitabine for the treatment of hepatocellular carcinoma

    Lina Du   Baolei Zhang   Youjie Lei   Shan Wang   Yiguang Jin  

    Graphical abstract Abstract Hepatocellular carcinoma (HCC) is a serious cancer with high mortality worldwide. Gemcitabine (GEM) is easily degraded in the circulation and has no tumor-targeted effect. In our previous research, an amphiphilic GEM derivative, cyclic phosphoryl N- dodecanoyl gemcitabine (CPDG) was prepared based on the techniques of HepDirect prodrug and self-assembled drug delivery systems (SADDS), which self-assembled into the stable nanoassemblies in water. In this study, the long-circulating nanoassemblies of CPDG/CHS-PEG1500 (9:1, mol/mol) were prepared for HCC treatment. In vitro and in vivo studies of the long-circulating CPDG nanoassemblies were explored. The degradation rates of CPDG depended on the media. CPDG showed much faster degradation in the acidic environment (pH 2.0) than the weak acidic and neutral media (pH 5.0, pH 7.4). However, the degradation half-life ( t 1/2 ) of CPDG was about 43 h in the mouse plasma, longer than the t 1/2 at pH 2.0. Therefore, the long-circulating CPDG nanoassemblies could keep stable before reaching the targets in vivo . In the biodistribution study, the long-circulating CPDG nanoassemblies were bolus intravenously ( i.v. ) injected into the hepatocellular tumor-bearing mice. The distribution of CPDG in the tumors was much higher than that in the blood, indicating the tumor targeting of the long-circulating nanoassemblies. In the pharmacodynamic study, the long-circulating CPDG nanoassemblies were i.v. injected into the tumor-bearing mice with doses of (37.5, 75 μmol/kg) compared with GEM (150 μmol/kg). The mice were injected once every 3 days for totally 3 times. The long-circulating nanoassemblies nearly always showed the higher anti-cancer effects than GEM. The tumor inhibitory rates of GEM, the long circulating CPDG nanoassemblies (37.5, 75 μmol/kg) were 49.54, 42.97, 65.10%, respectively. Therefore, the long-circulating CPDG nanoassemblies had the much higher anti-cancer effect than GEM. The long-circulating CPDG nanoassemblies are promising nanomedicines to treat HCC. The combination design of tumor-targeted nanoassemblies based on HepDirect prodrug technique and SADDS theory is an effective method to modify the pharmacologically active nucleosides to treat some liver diseases.
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  • 909 - Mucosal Stem Cell Heterogeneity in Pediatric Crohn's Disease

    Frank McKeon   Wa Xian   Yutao Qi   Rahul Neupane   Shan Wang   Yusuke Yamamoto   Rajasekaran Mahalingam   Marcin Duleba   Christopher Crum   Francisco Sylvester   Jason K. Hou   Jeffrey S. Hyams   Khek-Yu Ho  

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  • Inhibition of Cancer Cell Proliferation by PPARγ Is Mediated by a Metabolic Switch that Increases Reactive Oxygen Species Levels

    Nishi Srivastava   Rahul K. Kollipara   Dinesh K. Singh   Jessica Sudderth   Zeping Hu   Hien Nguyen   Shan Wang   Caroline G. Humphries   Ryan Carstens   Kenneth E. Huffman   Ralph J. DeBerardinis   Ralf Kittler  

    Summary The nuclear receptor peroxisome-proliferation-activated receptor gamma (PPARγ), a transcriptional master regulator of glucose and lipid metabolism, inhibits the growth of several common cancers, including lung cancer. In this study, we show that the mechanism by which activation of PPARγ inhibits proliferation of lung cancer cells is based on metabolic changes. We found that treatment with the PPARγ agonist pioglitazone triggers a metabolic switch that inhibits pyruvate oxidation and reduces glutathione levels. These PPARγ-induced metabolic changes result in a marked increase of reactive oxygen species (ROS) levels that lead to rapid hypophosphorylation of retinoblastoma protein (RB) and cell-cycle arrest. The antiproliferative effect of PPARγ activation can be prevented by suppressing pyruvate dehydrogenase kinase 4 (PDK4) or β-oxidation of fatty acids in vitro and in vivo. Our proposed mechanism also suggests that metabolic changes can rapidly and directly inhibit cell-cycle progression of cancer cells by altering ROS levels. Graphical Abstract Highlights • PPARγ activates an antiproliferative gene regulatory program in lung adenocarcinoma • PPARγ agonists induce a metabolic switch that reduces glutathione levels • Reduced glutathione levels increase ROS levels, which mediate cell-cycle arrest The nuclear receptor PPARγ inhibits the growth of several common cancers. Srivastava et al. show that the PPARγ agonist diabetic drug pioglitazone triggers a metabolic switch that inhibits pyruvate oxidation and reduces glutathione levels, leading to increase in ROS levels, which account for the antitumorigenic effects of PPARγ in lung cancer.
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  • The natural compound codonolactone impairs tumor induced angiogenesis by downregulating BMP signaling in endothelial cells

    Shan Wang   Rui Cai   Junchao Ma   Ting Liu   Xiaoqin Ke   Hong Lu   Jianjiang Fu  

    Abstract Background Angiogenesis, the recruitment of new blood vessels, was demonstrated that is an essential component of the growth of a tumor beyond a certain size and the metastatic pathway. The potential use of angiogenesis-based agents, such as those involving natural and synthetic inhibitors as anticancer drugs is currently under intense investigation. In this study, the anti-angiogenic properties of codonolactone (CLT), a sesquiterpene lactone from Atractylodes lancea , were examined in endothelial cells. Purpose Our published study reported that CLT shows significant anti-metastatic properties in vitro and in vivo . In order to determine whether angiogenic–involved mechanisms contribute to the anti-metastatic effects of CLT, we checked the anti-angiogenic properties of CLT and its potential mechanisms. Study design/methods Human umbilical vein endothelial cells (HUVECs) and EA.hy 926 cells were involved in this study. Immunofluorescence assay for cells and immunohistochemistry assay for tissues were used to check the expression of angiogenic markers. In vitro migration and invasion of endothelial cells treated with and without CLT were analyzed. Protein expressions were measured by Western blot analysis. For MMPs activity assay, fluorescence resonance energy transfer-based MMPs activity assay and gelatin zymography assay were involved in this study. Results Here we demonstrated that CLT exhibited inhibition on cancer cell induced angiogenesis in vivo , and direct inhibited migration and invasion of endothelial cells in vitro . Moreover, we observed that the down-regulation of MMPs and VEGF-VEGFR2 was involved in the anti-angiogenic effects of CLT. Data from Western blotting showed that, in endothelial cells, CLT reduced Runx2 activation and BMP signaling. Conclusion Our findings demonstrated that CLT impaired the development of angiogenesis both in vitro and in vivo by direct inhibition on endothelial cells. These inhibitory effects were depended on its ability to interference with BMP signaling in endothelial cells, which may cause inhibition of MMPs expression and VEGF secretion by down-regulating Runx2 activation. Graphical abstract Image, graphical abstract
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  • Insights into the working mechanism of cathode interlayers in polymer solar cells via [(C8H17)4N]4[SiW12O40]

    Youchun Chen   Shan Wang   Lingwei Xue   Zhiguo Zhang   Haolong Li   Lixin Wu   Yue Wang   Fenghong Li   Fengling Zhang   Yongfang Li  

    A low-cost (<$1 per g), high-yield (>90%), alcohol soluble surfactant-encapsulated polyoxometalate complex [(C8H17)4N]4[SiW12O40] has been synthesized and utilized as a cathode interlayer (CIL) in polymer solar cells (PSCs). A power conversion efficiency of 10.1% can be obtained for PSCs based on PTB7-Th (poly[[2,60-4,8-di(5-ethylhexylthienyl)benzo[1,2-b;3,3-b]-dithiophene][3-fluoro-2[(2-ethylhexyl) carbonyl] thieno [3,4-b]-thiophenediyl]]):PC71BM ([6,6]-phenyl C71-butyric acidmethyl ester) due to the incorporation of [(C8H17)4N]4[SiW12O40]. Combined measurements of current density–voltage characteristics, transient photocurrent, charge carrier mobility and capacitance–voltage characteristics demonstrate that [(C8H17)4N]4[SiW12O40] can effectively increase the built-in potential, charge carrier density and mobility and accelerate the charge carrier extraction in PSCs. Most importantly, the mechanism of using [(C8H17)4N]4[SiW12O40] as the CIL is further brought to light by X-ray photoemission spectroscopy (XPS) and ultraviolet photoemission spectroscopy (UPS) of the metal/ [(C8H17)4N]4[SiW12O40] interface. The findings suggest that [(C8H17)4N]4[SiW12O40] not only decreased the work function of the metal cathodes but also was n-doped upon contact with the metals, which provide insights into the working mechanism of the CILs simultaneously improving the open circuit voltage, short circuit current and fill factor in the PSCs.
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  • How Does Organizational Culture Affect IS Effectiveness: A Culture-Information System Fit Framework

    Shan Wang   William Yeoh  

    Previous research has examined the impactof organizational culture(OC) on the implementation ofmany information systems. However, there is a lack ofoverall picture on how OC affects the effectiveness ofdifferent information systems differently. Based on theCompeting Value Framework, this paper proposes acomprehensive framework to explain how the fit betweenorganizational culture and types of IS results in differenttypes of IS effectiveness. This framework can be used bymanagers to create a proper organizational culture that iscompatible with the use of specific information systems.
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