444 research outputs found
Employees’ perceptions of corporate social responsibility and ethical leadership: Are they uniquely related to turnover intention?
© 2020, Emerald Publishing Limited. Purpose: The purpose of this study is to investigate the simultaneous effect of ethical leadership (EL) and corporate social responsibility (CSR) on employees’ turnover intention and examine the mediating mechanism in these relationships. Design/methodology/approach: The authors conducted a field study of 851 employees across a variety of industries. This study applied partial least squares structural equation modelling for hypothesis testing. Findings: The results show that employees’ perceptions of CSR as well as EL are both uniquely and negatively related to turnover intention. The authors also found that employees’ job satisfaction but not commitment, mediates these relationships. Research limitations/implications: This study answers the recent call (Schminke and Sheridan, 2017) for ethics researchers to put competing explanations to the test to determine their relative importance. Research limitations have been discussed in the paper. Social implications: Through providing empirical support for the positive impact of CSR and EL on employee-related outcomes and creating a decent and empowering work environment, this study provides further support for CSR and EL. As CSR and EL require accountability, responsible management and addressing societal well-being of stakeholders, this study can contribute to the United Nations sustainable development goals. Originality/value: Previous research has found that both employees’ perceptions of supervisory EL and CSR are negatively related to employees’ turnover intentions. Yet, the authors know little about their relative importance because these relationships have not been adequately examined simultaneously
Design and realization of a frequency reconfigurable multimode antenna for ism, 5g-ub-6-ghz, and s-band applications
This paper presents the design and realization of a compact size multimode frequency reconfigurable antenna. The antenna consists of a triangular-shaped monopole radiator, originally inspired from a rectangular monopole antenna. Slots were utilized to notch the desired frequency while the PIN diodes were utilized to achieve frequency reconfigurability. The antenna can operate in wideband, dual-band, or tri-band mode depending upon the state of the diodes. To validate the simulation results, a prototype was fabricated, and various performance parameters were measured and compared with simulated results. The strong agreement between simulated and measured results along with superior performance as compared to existing works in the literature makes the proposed antenna a strong candidate for ISM, 5G-sub-6 GHz, and S-band applications
Defining the temporal evolution of gut dysbiosis and inflammatory responses leading to hepatocellular carcinoma in Mdr2 -/- mouse model.
BACKGROUND: Emerging evidence implicates the gut microbiome in liver inflammation and hepatocellular carcinoma (HCC) development. We aimed to characterize the temporal evolution of gut dysbiosis, in relation to the phenotype of systemic and hepatic inflammatory responses leading to HCC development. In the present study, Mdr2 -/- mice were used as a model of inflammation-based HCC. Gut microbiome composition and function, in addition to serum LPS, serum cytokines/chemokines and intrahepatic inflammatory genes were measured throughout the course of liver injury until HCC development. RESULTS: Early stages of liver injury, inflammation and cirrhosis, were characterized by dysbiosis. Microbiome functional pathways pertaining to gut barrier dysfunction were enriched during the initial phase of liver inflammation and cirrhosis, whilst those supporting lipopolysaccharide (LPS) biosynthesis increased as cirrhosis and HCC ensued. In parallel, serum LPS progressively increased during the course of liver injury, corresponding to a shift towards a systemic Th1/Th17 proinflammatory phenotype. Alongside, the intrahepatic inflammatory gene profile transitioned from a proinflammatory phenotype in the initial phases of liver injury to an immunosuppressed one in HCC. In established HCC, a switch in microbiome function from carbohydrate to amino acid metabolism occurred. CONCLUSION: In Mdr2 -/- mice, dysbiosis precedes HCC development, with temporal evolution of microbiome function to support gut barrier dysfunction, LPS biosynthesis, and redirection of energy source utilization. A corresponding shift in systemic and intrahepatic inflammatory responses occurred supporting HCC development. These findings support the notion that gut based therapeutic interventions could be beneficial early in the course of liver disease to halt HCC development
SPARC Deficiency Results in Improved Surgical Survival in a Novel Mouse Model of Glaucoma Filtration Surgery
Glaucoma is a disease frequently associated with elevated intraocular pressure that can be alleviated by filtration surgery. However, the post-operative subconjunctival scarring response which blocks filtration efficiency is a major hurdle to the achievement of long-term surgical success. Current application of anti-proliferatives to modulate the scarring response is not ideal as these often give rise to sight-threatening complications. SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein involved in extracellular matrix (ECM) production and organization. In this study, we investigated post-operative surgical wound survival in an experimental glaucoma filtration model in SPARC-null mice. Loss of SPARC resulted in a marked (87.5%) surgical wound survival rate compared to 0% in wild-type (WT) counterparts. The larger SPARC-null wounds implied that aqueous filtration through the subconjunctival space was more efficient in comparison to WT wounds. The pronounced increase in both surgical survival and filtration efficiency was associated with a less collagenous ECM, smaller collagen fibril diameter, and a loosely-organized subconjunctival matrix in the SPARC-null wounds. In contrast, WT wounds exhibited a densely packed collagenous ECM with no evidence of filtration capacity. Immunolocalization assays confirmed the accumulation of ECM proteins in the WT but not in the SPARC-null wounds. The observations in vivo were corroborated by complementary data performed on WT and SPARC-null conjunctival fibroblasts in vitro. These findings indicate that depletion of SPARC bestows an inherent change in post-operative ECM remodeling to favor wound maintenance. The evidence presented in this report is strongly supportive for the targeting of SPARC to increase the success of glaucoma filtration surgery
Markers of Oxidative Damage Are Not Elevated in Otherwise Healthy Individuals With the Metabolic Syndrome
OBJECTIVE- The role of oxidative damage in the pathogenesis of metabolic syndrome is poorly understood. RESEARCH DESIGN AND METHODS- A detailed cross-sectional study was performed to assess the relationship between lipid oxidation products, γ-glutamyltransferase, highsensitivity C-reactive protein (hs-CRP), and phospholipase activities with respect to the metabolic status in a cohort of otherwise healthy individuals. RESULTS- A total of 179 individuals (87 men and 92 women) aged 43 ± 14 years (mean ± SD) participated in this study. There were no differences in the levels of plasma F 2-isoprostanes, hydroxyeicosatetraenoic acids, cholesterol oxidation products, and phospholipase activities in individuals with features of metabolic syndrome. In multivariate analyses, serum hs-CRP was a consistent independent predictor of metabolic syndrome. CONCLUSIONS- Minimal changes were observed in multiple markers of oxidative damage in a well-characterized cohort of individuals with features of metabolic syndrome. © 2010 by the American Diabetes Association.link_to_subscribed_fulltex
IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System
PURPOSE:
To improve persistence of adoptively transferred T-cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application.
EXPERIMENTAL DESIGN:
HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were coadministered to myelodepleted HLA-A2/Kb mice within a formal Good Laboratory Practice (GLP)-compliant study to demonstrate safety, persistence, and HSC differentiation into all blood lineages. Non-GLP experiments included assessment of transgene immunogenicity and in vitro viral insertion safety studies. Furthermore, Good Manufacturing Practice (GMP)-compliant cell production qualification runs were performed to establish the manufacturing protocols for clinical use.
RESULTS:
TCR genetically modified and ex vivo-cultured HSCs differentiated into all blood subsets in vivo after HSC transplantation, and coadministration of TCR-transduced T cells did not result in increased toxicity. The expression of NY-ESO-1 TCR and sr39TK transgenes did not have a detrimental effect on gene-modified HSC's differentiation to all blood cell lineages. There was no evidence of genotoxicity induced by the lentiviral vector. GMP batches of clinical-grade transgenic cells produced during qualification runs had adequate stability and functionality.
CONCLUSIONS:
Coadministration of HSCs and T cells expressing an NY-ESO-1 TCR is safe in preclinical models. The results presented in this article led to the FDA approval of IND 17471
New insights about host response to smallpox using microarray data
<p>Abstract</p> <p>Background</p> <p>Smallpox is a lethal disease that was endemic in many parts of the world until eradicated by massive immunization. Due to its lethality, there are serious concerns about its use as a bioweapon. Here we analyze publicly available microarray data to further understand survival of smallpox infected macaques, using systems biology approaches. Our goal is to improve the knowledge about the progression of this disease.</p> <p>Results</p> <p>We used KEGG pathways annotations to define groups of genes (or modules), and subsequently compared them to macaque survival times. This technique provided additional insights about the host response to this disease, such as increased expression of the cytokines and ECM receptors in the individuals with higher survival times. These results could indicate that these gene groups could influence an effective response from the host to smallpox.</p> <p>Conclusion</p> <p>Macaques with higher survival times clearly express some specific pathways previously unidentified using regular gene-by-gene approaches. Our work also shows how third party analysis of public datasets can be important to support new hypotheses to relevant biological problems.</p
Ethanolamine phosphoglycerol attachment to eEF1A is not essential for normal growth of Trypanosoma brucei
Eukaryotic elongation factor 1A (eEF1A) is the only protein modified by ethanolamine phosphoglycerol (EPG). In mammals and plants, EPG is attached to conserved glutamate residues located in eEF1A domains II and III, whereas in the unicellular eukaryote, Trypanosoma brucei, a single EPG moiety is attached to domain III. A biosynthetic precursor of EPG and structural requirements for EPG attachment to T. brucei eEF1A have been reported, but the role of this unique protein modification in cellular growth and eEF1A function has remained elusive. Here we report, for the first time in a eukaryotic cell, a model system to study potential roles of EPG. By down-regulation of EF1A expression and subsequent complementation of eEF1A function using conditionally expressed exogenous eEF1A (mutant) proteins, we show that eEF1A lacking EPG complements trypanosomes deficient in endogenous eEF1A, demonstrating that EPG attachment is not essential for normal growth of T. brucei in culture
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