30 research outputs found
Survival and Growth in Entrepreneurial Ecosystems: An Integration with Resource Dependence Theory and Entrepreneurial Orientation
The emergence of entrepreneurial systems has become a global phenomenon in the last decade (Cao & Shi, 2021). Entrepreneurial ecosystems are groups of interdependent actors and factors that formally and informally coalesce to connect, mediate, and enable entrepreneurship within a regional entrepreneurial environment (Mason & Brown, 2014; Spigel & Harrison, 2018; Stam, 2015). Researchers on entrepreneurial ecosystems have proposed different entrepreneurial ecosystem models comprising various components and elements. However, despite the popularity of the emergence of entrepreneurial ecosystems, there is a lack of measurement scales to respond to the high demand for empirical research, and the domain of entrepreneurial systems remains under-theorized. The limited research also has not explored the value of resource dependence theory and entrepreneurial behavior integration into entrepreneurial ecosystems. Therefore, this study fills in the above gaps by making four meaningful contributions. First, the study integrates resources dependency theory into the entrepreneurial ecosystems research domain. Second, the study illuminates the interaction between entrepreneurs and entrepreneurial ecosystems. Third, the entrepreneurial behavior approach of entrepreneurial orientation is explored as an enhancement to the entrepreneurial ecosystem. Fourth, this study will extend and improve current measurement scales for entrepreneurial ecosystems. Survey data will be collected from participants located in different regions of the United States. Partial least squares x structural equation modeling will be used to analyze the data and test the hypotheses. Given these considerations, the current investigation will likely have numerous implications for management research and practice
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Impact of Th1 CD4 Follicular Helper T Cell Skewing on Antibody Responses to an HIV-1 Vaccine in Rhesus Macaques.
Generating durable humoral immunity through vaccination depends upon effective interactions of follicular helper T (Tfh) cells with germinal center (GC) B cells. Th1 polarization of Tfh cells is an important process shaping the success of Tfh-GC B cell interactions by influencing costimulatory and cytokine-dependent Tfh help to B cells. However, the question remains as to whether adjuvant-dependent modulation of Tfh cells enhances HIV-1 vaccine-induced antienvelope (anti-Env) antibody responses. We investigated whether an HIV-1 vaccine platform designed to increase the number of Th1-polarized Tfh cells enhances the magnitude and quality of anti-Env antibodies. Utilizing a novel interferon-induced protein 10 (IP-10)-adjuvanted HIV-1 DNA prime followed by a monophosphoryl lipid A and QS-21 (MPLA+QS-21)-adjuvanted Env protein boost (DIP-10 PALFQ) in macaques, we observed higher anti-Env serum IgG titers with greater cross-clade reactivity, specificity for V1V2, and effector functions than in macaques primed with DNA lacking IP-10 and boosted with MPLA-plus-alum-adjuvanted Env protein (DPALFA) The DIP-10 PALFQ vaccine regimen elicited higher anti-Env IgG1 and lower IgG4 antibody levels in serum, showing for the first time that adjuvants can dramatically impact the IgG subclass profile in macaques. The DIP-10 PALFQ regimen also increased vaginal and rectal IgA antibodies to a greater extent. Within lymph nodes, we observed augmented GC B cell responses and the promotion of Th1 gene expression profiles in GC Tfh cells. The frequency of GC Tfh cells correlated with both the magnitude and avidity of anti-Env serum IgG. Together, these data suggest that adjuvant-induced stimulation of Th1-Tfh cells is an effective strategy for enhancing the magnitude and quality of anti-Env antibody responses.IMPORTANCE The results of the RV144 trial demonstrated that vaccination could prevent HIV transmission in humans and that longevity of anti-Env antibodies may be key to this protection. Efforts to improve upon the prime-boost vaccine regimen used in RV144 have indicated that booster immunizations can increase serum anti-Env antibody titers but only transiently. Poor antibody durability hampers efforts to develop an effective HIV-1 vaccine. This study was designed to identify the specific elements involved in the immunological mechanism necessary to produce robust HIV-1-specific antibodies in rhesus macaques. By clearly defining immune-mediated pathways that improve the magnitude and functionality of the anti-HIV-1 antibody response, we will have the foundation necessary for the rational development of an HIV-1 vaccine
Improved Medical Treatment and Surgical Surveillance of Children and Adolescents with Ulcerative Colitis in the United Kingdom
This is a pre-copyedited, author-produced version of an article accepted for publication in Inflammatory Bowel Diseases following peer review. The version of record, Auth, M. K.-K., et al. (2018). "Improved Medical Treatment and Surgical Surveillance of Children and Adolescents with Ulcerative Colitis in the United Kingdom." Inflammatory Bowel Diseases: izy042-izy042. is available online at:https://doi.org/10.1093/ibd/izy042Background: Pediatric ulcerative colitis (UC) presents at an earlier age and increasing prevalence. Our aim was to examine morbidity, steroid sparing strategies, and surgical outcome in children with active UC. Methods: A national prospective audit was conducted for the inpatient period of all children with UC for medical or surgical treatment in the United Kingdom (UK) over 1 year. Thirty-two participating centers recruited 224 children in 298 admissions, comparisons over 6 years were made with previous audits. Results: Over 6 years, recording of Paediatric Ulcerative Colitis Activity Index (PUCAI) score (median 65)(23% to 55%, P < 0.001), guidelines for acute severe colitis (43% to 77%, P < 0.04), and ileal pouch surgery registration (4% to 56%, P < 0.001) have increased. Corticosteroids were given in 183/298 episodes (61%) with 61/183 (33%) not responding and requiring second line therapy or surgery. Of those treated with anti-TNFalpha (16/61, 26%), 3/16 (18.8%) failed to respond and required colectomy. Prescription of rescue therapy (26% to 49%, P = 0.04) and proportion of anti-TNFalpha (20% to 53%, P = 0.03) had increased, colectomy rate (23.7% to 15%) was not significantly reduced (P = 0.5). Subtotal colectomy was the most common surgery performed (n = 40), and surgical complications from all procedures occurred in 33%. In 215/224 (96%) iron deficiency anemia was detected and in 51% treated, orally (50.2%) or intravenously (49.8%). Conclusions: A third of children were not responsive to steroids, and a quarter of these were treated with anti-TNFalpha. Colectomy was required in 41/298 (13.7%) of all admissions. Our national audit program indicates effectiveness of actions taken to reduce steroid dependency, surgery, and iron deficiency. 10.1093/ibd/izy042_video1izy042.video15769503407001.Dr Richard K Russell is supported by an NHS Scotland Research Senior fellowship.
Linda J Williams has been supported by the Royal College of Physicians
Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.
Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways
Algorithmic approach to warehouse consolidation and optimization
This thesis presents a new methodology for warehouse consolidation to optimize the capacity, throughput, and overall efficiency of the warehouse. The application of the methodology allows an organization to become more competitive by reducing real estate and inventory holding costs. The algorithms use various quantitative techniques including statistical inference and integer programming, and apply them to material handling and facilities layout issues. The proposed methodology is independent of the warehouse management system in use. It was implemented by a Fortune 500 company, and resulted in significant cost, capacity and productivity improvements
Technology Forecasting of Google Data Centers
The purpose of this research paper is to measure improvement rate of Power Usage Efficiency (PUE) with Information Technology (IT) equipment power and Total Facility Power (TP) in order to forecast the data center performance. We examined eleven Google Data Centers located in different geographical regions within the United States between 2005 and 2011. We used two mathematical approaches, Malmquist Index and the concept of Technology Forecast Data Envelope Analysis (TFDEA). The results were analyzed to determine the trend of PUE and used to forecast the PUE performance for the Google data centers for the next 10 years
A Mechanistic Description of the Sensitized N-substituted Maleimide Initiated Photopolymerization of an Acrylate Monomer
N-substituted maleimides have been investigated for their use as photoinitiators for free-radical polymerization. The mechanism of initiation in the presence of sensitizers and coinitiators is postulated to involve chemical and energy transfer sensitization processes. Photo-DSC and laser-flash photolysis results provide photophysical data supporting the proposed mechanisms
Photoinitiation of Acrylates Via Sensitized Phthalimide Derivatives
When isopropylthioxanthone is used as a coinitiator for substituted N-phenylphthalimide photoinitiators, rapid rates of acrylate polymerization are attained if a tertiary amine is present as a hydrogen source. N-Phenylphthalimide with electron withdrawing substituents on the N-phenyl ring in the presence of a combination of isopropylthioxanthone and N-methyl-N,N-diethanolamine results in an increase in the maximum rate of polymerization of 1,6-hexanedioldiacrylate by a factor of as much as twice that attained when only the coinitiator and N-methyl-N,N-diethanolamine are present
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Radiologic-pathologic analysis of quantitative 3D tumour enhancement on contrast-enhanced MR imaging: a study of ROI placement
ObjectivesTo investigate the influence of region-of-interest (ROI) placement on 3D tumour enhancement [Quantitative European Association for the Study of the Liver (qEASL)] in hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE).MethodsPhase 1: 40 HCC patients had nine ROIs placed by one reader using systematic techniques (3 ipsilateral to the lesion, 3 contralateral to the lesion, and 3 dispersed throughout the liver) and qEASL variance was measured. Intra-class correlations were computed. Phase 2: 15 HCC patients with histosegmentation were selected. Six ROIs were systematically placed by AC (3 ROIs ipsilateral and 3 ROIs contralateral to the lesion). Three ROIs were placed by 2 radiologists. qEASL values were compared to histopathology by Pearson's correlation, linear regression, and median difference.ResultsPhase 1: The dispersed method (abandoned in phase 2) had low consistency and high variance. Phase 2: qEASL correlated strongly with pathology in systematic methods [Pearson's correlation coefficient = 0.886 (ipsilateral) and 0.727 (contralateral)] and in clinical methods (0.625 and 0.879). However, ipsilateral placement matched best with pathology (median difference: 5.4 %; correlation: 0.89; regression CI: [0.904, 0.1409]).ConclusionsqEASL is a robust method with comparable values among tested placements. Ipsilateral placement showed high consistency and better pathological correlation.Key pointsIpsilateral and contralateral ROI placement produces high consistency and low variance. Both ROI placement methods produce qEASL values that correlate well with histopathology. Ipsilateral ROI placement produces best correlation to pathology along with high consistency