The social consequences of using agent-based systems

The starting point of this paper is that the proper functioning of agent-based systems depends on the understanding of their societal effects on us.Only by understanding the inter-relationship between the agent-based systems and their resources can we ensure that such systems are not designed anddeveloped in isolation of the social context in wich they find their purposes. However, the consequences of deploying agent-based systems are not welldefined in het current literature. The aim of this paper is to contribute to the understanding of this issue by investigating the possibilities of using theorganizational semiotic framework which is founded on sound and theoreticalunderpinnings to structure our discourse of some of these consequences. The semioticframework will help us to draw deep insights from the phenomena under examination

An empirical study of auditors switching, corporate governance and financial performances of Malaysian Public Listed Companies (PLCs)

In the past years, regulators and the business communities had expressed worries about the alarming rate at which firms or corporations collapse due to the mismanagement and manipulation of resources as seen in the cases of Enron, WorldCom in the United States of America; and to be specific in Malaysia, the cases of Megan Media Holdings Berhad and Transmile Group. Auditor switching is evident and the disorder of auditor switching often takes place in Malaysia; however, as time goes by, it is decreasing. Thus, this paper seeks to empirically examine the effect of auditor switching and corporate governance on financial performance of Malaysian PLCs. Secondary data on a total number of 100 PLCs from years 2009 to 2013 are used. The results reveal that the effect of auditor switching on performance does not vary with duality role and the board size. However, the independent director does not cause a good firm performance. Nonetheless, auditors do not have a direct effect on financial performance since they are not directly involved with the management of the firms which negates the results of previous study. Therefore, this paper has vital impact in that regulators and the public need to be educated through awareness campaigns to emphasize on the auditors’ roles as agents in understanding the impact of the association between corporate governance and financial performance. Furthermore, auditor switching should embrace not only rotation of audit partners, but rotation of audit firms as well in view that this will help in infusing discipline from the top to the bottom of the audit firms and the companies

Augmenting recombinant antibody production in HEK293E cells: Optimizing transfection and culture parameters

Background: Optimizing recombinant antibody production is important for cost-effective therapeutics and diagnostics. With impact on commercialization, higher productivity beyond laboratory scales is highly sought, where efficient production can also accelerate antibody characterizations and investigations. Methods: Investigating HEK293E cells for mammalian antibody production, various transfection and culture parameters were systematically analyzed for antibody light chain production before evaluating them for whole antibody production. Transfection parameters investigated include seeding cell density, the concentration of the transfection reagent and DNA, complexation time, temperature, and volume, as well as culture parameters such as medium replacement, serum deprivation, use of cell maintenance antibiotic, incubation temperature, medium volume, post-transfection harvest day, and common nutrient supplements. Results: Using 2 mL adherent HEK293E cell culture transfections with 25 kDa linear polyethylenimine in the most optimized parameters, we demonstrated a ~2-fold production increase for light chain alone and for whole antibody production reaching 536 and 49 μg, respectively, in a cost-effective manner. With the addition of peptone, κ light chain increased by ~4-fold to 1032 μg, whereas whole antibody increased to a lesser extent by ~2.5-fold to 51 μg, with benefits potentially for antibodies limited by their light chains in production. Conclusions: Our optimized findings show promise for a more efficient and convenient antibody production method through transfection and culture optimizations that can be incorporated to scale-up processes and with potential transferability to other mammalian-based recombinant protein production using HEK293E

Molecular insights of nickel binding to therapeutic antibodies as a possible new antibody superantigen

The binding of nickel by immune proteins can manifest as Type IV contact dermatitis (Ni-specific T cells mediated) and less frequently as Type I hypersensitivity with both mechanisms remaining unknown to date. Since there are reports of patients co-manifesting the two hypersensitivities, a common mechanism may underlie both the TCR and IgE nickel binding. Focusing on Trastuzumab and Pertuzumab IgE variants as serendipitous investigation models, we found Ni-NTA interactions independent of Her2 binding to be due to glutamine stretches. These stretches are both Ni-inducible and in fixed pockets at the antibody complementarity-determining regions (CDRs) and framework regions (FWRs) of both the antibody heavy and light chains with influence from the heavy chain constant region. Comparisons with TCRs structures revealed similar interactions, demonstrating the possible underlying mechanism in selecting for Ni-binding IgEs and TCRs respectively. With the elucidation of the interaction, future therapeutic antibodies could also be sagaciously engineered to utilize such nickel binding for biotechnological purposes

Meta-analysis shows both congruence and complementarity of DNA and eDNA metabarcoding to traditional methods for biological community assessment

DNA metabarcoding is increasingly used for the assessment of aquatic communities, and numerous studies have investigated the consistency of this technique with traditional morpho-taxonomic approaches. These individual studies have used DNA metabarcoding to assess diversity and community structure of aquatic organisms both in marine and freshwater systems globally over the last decade. However, a systematic analysis of the comparability and effectiveness of DNA-based community assessment across all of these studies has hitherto been lacking. Here, we performed the first meta-analysis of available studies comparing traditional methods and DNA metabarcoding to measure and assess biological diversity of key aquatic groups, including plankton, microphytobentos, macroinvertebrates, and fish. Across 215 data sets, we found that DNA metabarcoding provides richness estimates that are globally consistent to those obtained using traditional methods, both at local and regional scale. DNA metabarcoding also generates species inventories that are highly congruent with traditional methods for fish. Contrastingly, species inventories of plankton, microphytobenthos and macroinvertebrates obtained by DNA metabarcoding showed pronounced differences to traditional methods, missing some taxa but at the same time detecting otherwise overseen diversity. The method is generally sufficiently advanced to study the composition of fish communities and replace more invasive traditional methods. For smaller organisms, like macroinvertebrates, plankton and microphytobenthos, DNA metabarcoding may continue to give complementary rather than identical estimates compared to traditional approaches. Systematic and comparable data collection will increase the understanding of different aspects of this complementarity, and increase the effectiveness of the method and adequate interpretation of the results

Regulated Interfacial Proton and Water Activity Enhances Mn2+/MnO2 Platform Voltage and Energy Efficiency

Electrolytic MnO2 batteries store charges via the Mn2+/MnO2 two-electron transfer process with higher capacity and voltage than conventional one-electron (Zn2+ or H+) intercalation reactions. Yet, the opposite effect of interfacial H+ on the dissolution/deposition processes and the role of interfacial H2O are rarely discussed. Here we introduce tetrafluoroborate (BF4-) into the sulfate-based electrolyte to regulate interfacial H+ and H2O activity. First, BF4- hydrolysis increases the electrolyte’s acidity, promoting MnO2 dissolution. Second, BF4- forms H-bond networks with interfacial H2O that assist H+ diffusion while retaining a sufficient H2O supply to facilitate MnO2 deposition. As a result, the cathode-free Zn//MnO2 electrolytic cell achieves a high platform of ∼1.92 V and energy efficiency of ∼84.23%. Significantly, the cell delivers 1000 cycles at 1 C with ∼100% Coulombic efficiency and a high energy efficiency retention of 93.65%. Our findings disclose a new strategy to promote Mn2+/MnO2 platform voltage and energy efficiency

Reduced LIMK2 expression in colorectal cancer reflects its role in limiting stem cell proliferation

Objective: Colorectal cancer (CRC) is a major contributor to cancer mortality and morbidity. LIM kinase 2 (LIMK2) promotes tumour cell invasion and metastasis. The objectives of this study were to determine how LIMK2 expression is associated with CRC progression and patient outcome, and to use genetically modified Drosophila and mice to determine how LIMK2 deletion affects gastrointestinal stem cell regulation and tumour development.<p></p> Design: LIMK2 expression and activity were measured by immunostaining tumours from CRC-prone mice, human CRC cell lines and 650 human tumours. LIMK knockdown in Drosophila or Limk2 deletion in mice allowed for assessment of their contributions to gastrointestinal stem cell homeostasis and tumour development.<p></p> Results: LIMK2 expression was reduced in intestinal tumours of cancer-prone mice, as well as in human CRC cell lines and tumours. Reduced LIMK2 expression and substrate phosphorylation were associated with shorter patient survival. Genetic analysis in Drosophila midgut and intestinal epithelial cells isolated from genetically modified mice revealed a conserved role for LIMK2 in constraining gastrointestinal stem cell proliferation. Limk2 deletion increased colon tumour size in a colitis-associated colorectal mouse cancer model.<p></p> Conclusions: This study revealed that LIMK2 expression and activity progressively decrease with advancing stage, and supports the hypothesis that there is selective pressure for reduced LIMK2 expression in CRC to relieve negative constraints imposed upon gastrointestinal stem cells.<p></p&gt

Variable-heavy (VH) families influencing IgA1&2 engagement to the antigen, FcαRI and superantigen proteins G, A, and L

Interest in IgA as an alternative antibody format has increased over the years with much remaining to be investigated in relation to interactions with immune cells. Considering the recent whole antibody investigations showing significant distal effects between the variable (V) and constant (C)- regions that can be mitigated by the hinge regions of both human IgA subtypes A1 and A2, we performed an in-depth mechanistic investigation using a panel of 28 IgA1s and A2s of both Trastuzumab and Pertuzumab models. FcαRI binding were found to be mitigated by the differing glycosylation patterns in IgA1 and 2 with contributions from the CDRs. On their interactions with antigen-Her2 and superantigens PpL, SpG and SpA, PpL was found to sterically hinder Her2 antigen binding with unexpected findings of IgAs binding SpG at the CH2-3 region alongside SpA interacting with IgAs at the CH1. Although the VH3 framework (FWR) is commonly used in CDR grafting, we found the VH1 framework (FWR) to be a possible alternative when grafting IgA1 and 2 owing to its stronger binding to antigen Her2 and weaker interactions to superantigen Protein L and A. These findings lay the foundation to understanding the interactions between IgAs and microbial superantigens, and also guide the engineering of IgAs for future antibody applications and targeting of superantigen-producing microbes