A comparative study of the proventricular structure in twenty Chinese Tettigoniidae (Orthoptera) species

This study focuses on the proventriculus and the alimentary canal of twenty Tettigoniidae species among three subfamilies, Tettigoniinae, Phaneropterinae and Conocephalinae. Each part of the alimentary canal and the inner structure of proventriculus were examined under optic microscope and scanning electron microscopy. As a result, the length of each part of the alimentary canal and the inner structure of proventriculus were highly associated with feeding habits. Carnivorous species always had a short foregut and long cilia on the base of the sclerotized appendix in proventriculus, whereas herbivorous species always had a longer foregut and a highly sclerotized proventriculus. These results increase understanding of the alimentary canal in Tettigoniidae and will be useful in future studies of their feeding habits

Strategic Analysis of Dual Sourcing and Dual Channel with an Unreliable Alternative Supplier

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148383/1/poms12938_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148383/2/poms12938.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148383/3/poms12938-sup-0001-AppendixS1.pd

Target-driven sustainable product development

Figuring in sustainability in product development requires a profound understanding of the cause and effect of engineering decisions along the full spectrum of the product lifecycle and the triple bottomline of sustainability. Sustainability design targets can contribute to mitigating the complexity involved, by means of a formalised problem description. This article discusses how sustainability design targets can be defined and presents methods for systematically implementing these targets into the design process. To that end, different means of decision support mechanisms are presented. They comprise (a) use cases of target breakdowns in subsystems, (b) systematic reduction of solution space and (c) assistance in design activities to ensure achievement of sustainability design targets. This paper explains how interfaces to engineering tools such as Computer Aided Design/Engineering (CAD/CAE) or Product Data/Lifecycle Management (PDM/PLM) can be put in place to make the process of retrieving information and providing decision support more seamless

Quantifying Reproducibility in Computational Biology: The Case of the Tuberculosis Drugome

How easy is it to reproduce the results found in a typical computational biology paper? Either through experience or intuition the reader will already know that the answer is with difficulty or not at all. In this paper we attempt to quantify this difficulty by reproducing a previously published paper for different classes of users (ranging from users with little expertise to domain experts) and suggest ways in which the situation might be improved. Quantification is achieved by estimating the time required to reproduce each of the steps in the method described in the original paper and make them part of an explicit workflow that reproduces the original results. Reproducing the method took several months of effort, and required using new versions and new software that posed challenges to reconstructing and validating the results. The quantification leads to “reproducibility maps” that reveal that novice researchers would only be able to reproduce a few of the steps in the method, and that only expert researchers with advance knowledge of the domain would be able to reproduce the method in its entirety. The workflow itself is published as an online resource together with supporting software and data. The paper concludes with a brief discussion of the complexities of requiring reproducibility in terms of cost versus benefit, and a desiderata with our observations and guidelines for improving reproducibility. This has implications not only in reproducing the work of others from published papers, but reproducing work from one’s own laboratory

Mesenchymal Stem Cells Modified with Heme Oxygenase-1 Have Enhanced Paracrine Function and Attenuate Lipopolysaccharide-Induced Inflammatory and Oxidative Damage in Pulmonary Microvascular Endothelial Cells

Background/Aims: Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has therapeutic effects on endothelial damage during acute lung injury (ALI). Heme oxygenase-1 (HO-1) can restore homeostasis and implement cytoprotective defense functions in many pathologic states. Therefore, we explored whether transduction of HO-1 into BM-MSCs (MSCs-HO-1) would have an increased beneficial effect on lipopolysaccharide (LPS)-induced inflammatory and oxidative damage in human pulmonary microvascular endothelial cells (PVECs). Methods: MSCs were isolated from rat bone marrow and transfected with the HO-1 gene by a lentivirus vector. The phenotype and multilineage differentiation of MSCs were assessed. MSCs or MSCs-HO-1 were co-cultured with PVECs using a transwell system, and LPS was added to induce PVEC injury. The production of reactive oxygen species (ROS), and the activities of lipid peroxide (LPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in PVECs were determined by flow cytometry and colorimetric assays, respectively. The levels of human PVEC-derived tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in the supernatants of the co-culture system, and the activity of nuclear transcription factor-κB and NF-E2-related factor 2 (Nrf2) in PVECs were examined by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of TNF-α, IL-1β and IL-6 in PVECs was detected by quantitative real-time polymerase chain reaction (qRT-PCR), HO-1 expression and enzymatic activity in PVECs and the influence of zinc protoporphyrin (ZnPP) or HO-1 small interfering RNA on the above inflammatory and oxidative stress markers were evaluated. In addition, the expression of rat MSC-derived hepatocyte growth factor (HGF) and IL-10 was determined by ELISA and qRT-PCR. Results: MSCs showed no significant changes in phenotype or multilineage differentiation after transduction. LPS strongly increased the production of inflammatory and oxidative stress indicators, as well as decreased the levels of antioxidant components and the activity of Nrf2 in PVECs. MSC co-cultivation ameliorated these detrimental effects in PVECs and MSCs-HO-1 further improved the damage to PVECs induced by LPS when compared with MSCs alone. The beneficial effects of MSCs-HO-1 were dependent on HO-1 overexpression and may be attributed to the enhanced paracrine production of HGF and IL-10. Conclusion: MSCs-HO-1 have an enhanced ability to improve LPS-induced inflammatory and oxidative damage in PVECs, and the mechanism may be partially associated with the enhanced paracrine function of the stem cells. These data encourage further testing of the beneficial effects of MSCs-HO-1 in ALI animal models

Towards Structural Systems Pharmacology to Study Complex Diseases and Personalized Medicine

Genome-Wide Association Studies (GWAS), whole genome sequencing, and high-throughput omics techniques have generated vast amounts of genotypic and molecular phenotypic data. However, these data have not yet been fully explored to improve the effectiveness and efficiency of drug discovery, which continues along a one-drug-one-target-one-disease paradigm. As a partial consequence, both the cost to launch a new drug and the attrition rate are increasing. Systems pharmacology and pharmacogenomics are emerging to exploit the available data and potentially reverse this trend, but, as we argue here, more is needed. To understand the impact of genetic, epigenetic, and environmental factors on drug action, we must study the structural energetics and dynamics of molecular interactions in the context of the whole human genome and interactome. Such an approach requires an integrative modeling framework for drug action that leverages advances in data-driven statistical modeling and mechanism-based multiscale modeling and transforms heterogeneous data from GWAS, high-throughput sequencing, structural genomics, functional genomics, and chemical genomics into unified knowledge. This is not a small task, but, as reviewed here, progress is being made towards the final goal of personalized medicines for the treatment of complex diseases

Calculated Epithelial/Absorbed Power Density for Exposure from Antennas at 10–90 GHz: Intercomparison Study Using a Planar Skin Model

International audienceInternational organizations have collaborated to revise standards and guidelines for human protection from exposure to electromagnetic fields. In the frequency range of 6-300 GHz, the permissible spatially averaged epithelial/absorbed power density, which is primarily derived from thermal modeling, is considered as the basic restriction. However, for the averaging methods of the epithelial/absorbed power density inside human tissues, only a few groups have presented calculated results obtained using different exposure conditions and numerical methods. Because experimental validation is extremely difficult in this frequency range, this paper presents the first intercomparison study of the calculated epithelial/absorbed power density inside a human body model exposed to different frequency sources ranging from 10-90 GHz. This intercomparison aims to clarify the difference in the calculated results caused by different numerical electromagnetic methods in dosimetry analysis from 11 research groups using planar skin models. To reduce the comparison variances caused by various key parameters, computational conditions (e.g., the antenna type, dimensions, and dielectric properties of the skin models) were unified. The results indicate that the maximum relative standard deviation (RSD) of the peak spatially averaged epithelial/absorbed power densities for one- and three-layer skin models are less than 17.49% and 17.39%, respectively, when using a dipole antenna as the exposure source. For the dipole array antenna, the corresponding maximum RSD increases to 32.49% and 42.55%, respectively. Under the considered exposure scenarios, the RSD in the spatially averaged epithelial/absorbed power densities decrease from 42.55% to 16.7% when the frequency is increased from 10-90 GHz. Furthermore, the deviation from the two equations recommended by the exposure guidelines for deriving the spatially averaged epithelial/absorptive power density is mostly within 1 dB. The fair agreement in the intercomparison results demonstrates that the variances of the spatially averaged epithelial/absorbed power densities calculated using planar skin models are marginal

Synthesis of a Dual Functional Anti-MDR Tumor Agent PH II-7 with Elucidations of Anti-Tumor Effects and Mechanisms

Multidrug resistance mediated by P-glycoprotein in cancer cells has been a major issue that cripples the efficacy of chemotherapy agents. Aimed for improved efficacy against resistant cancer cells, we designed and synthesized 25 oxindole derivatives based on indirubin by structure-activity relationship analysis. The most potent one was named PH II-7, which was effective against 18 cancer cell lines and 5 resistant cell lines in MTT assay. It also significantly inhibited the resistant xenograft tumor growth in mouse model. In cell cycle assay and apoptosis assay conducted with flow cytometry, PH II-7 induced S phase cell cycle arrest and apoptosis even in resistant cells. Consistently revealed by real-time PCR, it modulates the expression of genes related to the cell cycle and apoptosis in these cells, which may contributes to its efficacy against them. By side-chain modification and FITC-labeling of PH II-7, we were able to show with confocal microscopy that not only it was not pumped by P-glycoprotein, it also attenuated the efflux of Adriamycin by P-glycoprotein in MDR tumor cells. Real-time PCR and western blot analysis showed that PH II-7 down-regulated MDR1 gene via protein kinase C alpha (PKCA) pathway, with c-FOS and c-JUN as possible mediators. Taken together, PH II-7 is a dual-functional compound that features both the cytotoxicity against cancer cells and the inhibitory effect on P-gp mediated drug efflux