1,348 research outputs found
Application of fuzzy integrated FMEA with product lifetime consideration for new product development in flexible electronics industry
Purpose: the aim of this paper is to minimize the risks of new product development and shorten time-to-market, particularly for high-tech enterprise where the complexity of the product generates vast amount of failure mode. Design/methodology/approach: first, the concept of Critical Consideration Factor (CCF) is introduced based on product-specific technical characteristics, expected lifetime, and yield requirement to identify and prioritize the critical failure mode in the subsequent Failure Mode and Effect Analysis (FMEA), followed by process characterization on the high-risk failure mode and Critical Parameter Management (CPM) practice to realize a robust mass production system of the developed technology. The application on the development of advanced flexible substrate and surface finishes fabrication technique is presented. Findings: through the proposed methodology, the risk level of each potential failure mode can be accurately quantified to identify the critical variables. With process characterization, reliability of the product is ensured. Consequently, significant reduction in development resources and time-to-market can be achieved. Practical implications: the development strategy allows high tech enterprises to achieve a balanced ecosystem in which value created through adaption of new technology/product can be thoroughly captured through commercialization in a timely manner with no field failure. Originality/value: the proposed development strategy utilizes a unique approach with thorough considerations that enables high tech enterprise to deliver new product with rapid time-to-market without sacrificing product lifetime reliability, which is key to achieve competitive advantage in the highly dynamic market.Peer Reviewe
B \to K(K^*) missing energy in Unparticle physics
In the present work we study the effects of an unparticle \unpart as the
possible source of missing energy in the decay . We find that the dependence of the differential branching ratio on
the ()-meson's energy in the presence of the vector unparticle
operators is very distinctive from that of the SM. Moreover, in using the
existing upper bound on decays, we have
been able to put more stringent constraints on the parameters of unparticle
stuff.Comment: 13 pages, 5 figure
Unparticle Physics in Single Top Signals
We study the single production of top quarks in and
collisions in the context of unparticle physics through the Flavor Violating
(FV) unparticle vertices and compute the total cross sections for single top
production as functions of scale dimension d_{\U}. We find that among all,
LHC is the most promising facility to probe the unparticle physics via single
top quark production processes.Comment: 14 pages, 10 figure
Constraints from Solar and Reactor Neutrinos on Unparticle Long-Range Forces
We have investigated the impact of long-range forces induced by unparticle
operators of scalar, vector and tensor nature coupled to fermions in the
interpretation of solar neutrinos and KamLAND data. If the unparticle couplings
to the neutrinos are mildly non-universal, such long-range forces will not
factorize out in the neutrino flavour evolution. As a consequence large
deviations from the observed standard matter-induced oscillation pattern for
solar neutrinos would be generated. In this case, severe limits can be set on
the infrared fix point scale, Lambda_u, and the new physics scale, M, as a
function of the ultraviolet (d_UV) and anomalous (d) dimension of the
unparticle operator. For a scalar unparticle, for instance, assuming the
non-universality of the lepton couplings to unparticles to be of the order of a
few per mil we find that, for d_UV=3 and d=1.1, M is constrained to be M >
O(10^9) TeV (M > O(10^10) TeV) if Lambda_u= 1 TeV (10 TeV). For given values of
Lambda_u and d, the corresponding bounds on M for vector [tensor] unparticles
are approximately 100 [3/Sqrt(Lambda_u/TeV)] times those for the scalar case.
Conversely, these results can be translated into severe constraints on
universality violation of the fermion couplings to unparticle operators with
scales which can be accessible at future colliders.Comment: 13 pages, 3 figures. Minor changes due to precision in numerical
factors and correction in figure labels. References added. Conclusions remain
unchange
Genomic Sequencing and Comparative Analysis of Epstein-Barr Virus Genome Isolated from Primary Nasopharyngeal Carcinoma Biopsy
Whether certain Epstein-Barr virus (EBV) strains are associated with pathogenesis of nasopharyngeal carcinoma (NPC) is still an unresolved question. In the present study, EBV genome contained in a primary NPC tumor biopsy was amplified by Polymerase Chain Reaction (PCR), and sequenced using next-generation (Illumina) and conventional dideoxy-DNA sequencing. The EBV genome, designated HKNPC1 (Genbank accession number JQ009376) is a type 1 EBV of approximately 171.5 kb. The virus appears to be a uniform strain in line with accepted monoclonal nature of EBV in NPC but is heterogeneous at 172 nucleotide positions. Phylogenetic analysis with the four published EBV strains, B95-8, AG876, GD1, and GD2, indicated HKNPC1 was more closely related to the Chinese NPC patient-derived strains, GD1 and GD2. HKNPC1 contains 1,589 single nucleotide variations (SNVs) and 132 insertions or deletions (indels) in comparison to the reference EBV sequence (accession number NC007605). When compared to AG876, a strain derived from Ghanaian Burkitt's lymphoma, we found 322 SNVs, of which 76 were non-synonymous SNVs and were shared amongst the Chinese GD1, GD2 and HKNPC1 isolates. We observed 88 non-synonymous SNVs shared only by HKNPC1 and GD2, the only other NPC tumor-derived strain reported thus far. Non-synonymous SNVs were mainly found in the latent, tegument and glycoprotein genes. The same point mutations were found in glycoprotein (BLLF1 and BALF4) genes of GD1, GD2 and HKNPC1 strains and might affect cell type specific binding. Variations in LMP1 and EBNA3B epitopes and mutations in Cp (11404 C>T) and Qp (50134 G>C) found in GD1, GD2 and HKNPC1 could potentially affect CD8+ T cell recognition and latent gene expression pattern in NPC, respectively. In conclusion, we showed that whole genome sequencing of EBV in NPC may facilitate discovery of previously unknown variations of pathogenic significance
Structural studies of (rac)-BIPHEN organomagnesiates and intermediates in the halogen-metal exchange of 2-Bromopyridine
Four lithium magnesiate complexes (2−5) containing the dianionic (rac)-BIPHEN ligand have been prepared and characterized using X-ray crystallography and NMR spectroscopy. (THF)3·Li2Mg{(rac)-BIPHEN}nBu2, 2, (THF)3·Li2Mg{(rac)-BIPHEN}(CH2SiMe3)2, 3, and (THF)2·Li2Mg{(rac)-BIPHEN}neoPe2, 4, have been prepared by complexation of the appropriate dialkylmagnesium compound with in situ prepared Li(rac)-BIPHEN in a mixture of hydrocarbon/THF. For all structures, the Mg centers are four-coordinate (and retain the alkyl groups); however, in 2 and 3 the two Li centers have different coordination spheres (one binding to one THF molecule, the other to two). The solid-state structures of 2 and 3 are essentially isostructural with that of 4 except that both Li atoms in this molecule have equivalent coordination spheres. The solution behaviors of these three molecules have been studied by 1H, 13C, and DOSY NMR spectroscopy. During the synthesis of 2, it was discovered that a (rac)-BIPHEN-rich (or n-butyl-free) lithium magnesiate, (THF)4Li2Mg{(rac)-BIPHEN}fo2, 2b, could be isolated. The lithium precursor to 2−5, (THF)4·Li4{(rac)-BIPHEN)}2, 1, has also been isolated. Within the molecular structure of this tetranuclear complex, there are three different Li coordination environments. Finally, 2 has already shown promise as a reagent in a halogen−metal exchange reaction with 2-bromopyridine. The structural chemistry at play in this reaction was probed by X-ray crystallography and NMR spectroscopy. The organometallic intermediate pyridyl-magnesiated 5, (THF)2·Li2Mg{(rac)-BIPHEN}(2-pyridyl)2, was isolated in high yield
Genome-Wide Transcriptomic Analysis of Intestinal Tissue to Assess the Impact of Nutrition and a Secondary Nematode Challenge in Lactating Rats
Gastrointestinal nematode infection is a major challenge to the health and welfare of mammals. Although mammals eventually acquire immunity to nematodes, this breaks down around parturition, which renders periparturient mammals susceptible to re-infection and an infection source for their offspring. Nutrient supplementation reduces the extent of periparturient parasitism, but the underlying mechanisms remain unclear. Here, we use a genome wide approach to assess the effects of protein supplementation on gene expression in the small intestine of periparturient rats following nematode re-infection.The use of a rat whole genome expression microarray (Affymetrix Gene 1.0ST) showed significant differential regulation of 91 genes in the small intestine of lactating rats, re-infected with Nippostrongylus brasiliensis compared to controls; affected functions included immune cell trafficking, cell-mediated responses and antigen presentation. Genes with a previously described role in immune response to nematodes, such as mast cell proteases, and intelectin, and others newly associated with nematode expulsion, such as anterior gradient homolog 2 were identified. Protein supplementation resulted in significant differential regulation of 64 genes; affected functions included protein synthesis, cellular function and maintenance. It increased cell metabolism, evident from the high number of non-coding RNA and the increased synthesis of ribosomal proteins. It regulated immune responses, through T-cell activation and proliferation. The up-regulation of transcription factor forkhead box P1 in unsupplemented, parasitised hosts may be indicative of a delayed immune response in these animals.This study provides the first evidence for nutritional regulation of genes related to immunity to nematodes at the site of parasitism, during expulsion. Additionally it reveals genes induced following secondary parasite challenge in lactating mammals, not previously associated with parasite expulsion. This work is a first step towards defining disease predisposition, identifying markers for nutritional imbalance and developing sustainable measures for parasite control in domestic mammals
Modeling Within-Host Dynamics of Influenza Virus Infection Including Immune Responses
Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and substantial viral decline (about 2 to 4 logs within 1 day) after the peak can be explained by the killing of infected cells mediated by interferon activated cells, such as natural killer cells, during the innate immune response. After the viral load declines to a lower level, the loss of interferon-induced antiviral effect and an increased availability of target cells due to loss of the antiviral state can explain the observed short phase of viral plateau in which the viral level remains unchanged or even experiences a minor second peak in some animals. An adaptive immune response is needed in our model to explain the eventual viral clearance. This study provides a quantitative understanding of the biological factors that can explain the viral and interferon kinetics during a typical influenza virus infection
Multi-Modality Therapeutics with Potent Anti-Tumor Effects: Photochemical Internalization Enhances Delivery of the Fusion Toxin scFvMEL/rGel
BACKGROUND: There is a need for drug delivery systems (DDS) that can enhance cytosolic delivery of anti-cancer drugs trapped in the endo-lysosomal compartments. Exposure of cells to specific photosensitizers followed by light exposure (photochemical internalization, PCI) results in transfer of agents from the endocytic compartment into the cytosol. METHODOLOGY AND PRINCIPAL FINDINGS: The recombinant single-chain fusion construct scFvMEL/rGel is composed of an antibody targeting the progenitor marker HMW-MAA/NG2/MGP/gp240 and the highly effective toxin gelonin (rGel). Here we demonstrate enhanced tumor cell selectivity, cytosolic delivery and anti-tumor activity by applying PCI of scFvMEL/rGel. PCI performed by light activation of cells co-incubated with scFvMEL/rGel and the endo-lysosomal targeting photosensitizers AlPcS(2a) or TPPS(2a) resulted in enhanced cytotoxic effects against antigen-positive cell lines, while no differences in cytotoxicity between the scFvMEL/rGel and rGel were observed in antigen-negative cells. Mice bearing well-developed melanoma (A-375) xenografts (50-100 mm(3)) were treated with PCI of scFvMEL/rGel. By 30 days after injection, approximately 100% of mice in the control groups had tumors>800 mm(3). In contrast, by day 40, 50% of mice in the PCI of scFvMEL/rGel combination group had tumors<800 mm(3) with no increase in tumor size up to 110 days. PCI of scFvMEL/rGel resulted in a synergistic effect (p<0.05) and complete regression (CR) in 33% of tumor-bearing mice (n = 12). CONCLUSIONS/SIGNIFICANCE: This is a unique demonstration that a non-invasive multi-modality approach combining a recombinant, targeted therapeutic such as scFvMEL/rGel and PCI act in concert to provide potent in vivo efficacy without sacrificing selectivity or enhancing toxicity. The present DDS warrants further evaluation of its clinical potential
Critical Role of Constitutive Type I Interferon Response in Bronchial Epithelial Cell to Influenza Infection
Innate antiviral responses in bronchial epithelial cells (BECs) provide the first line of defense against respiratory viral infection and the effectiveness of this response is critically dependent on the type I interferons (IFNs). However the importance of the antiviral responses in BECs during influenza infection is not well understood. We profiled the innate immune response to infection with H3N2 and H5N1 virus using Calu-3 cells and primary BECs to model proximal airway cells. The susceptibility of BECs to influenza infection was not solely dependent on the sialic acid-bearing glycoprotein, and antiviral responses that occurred after viral endocytosis was more important in limiting viral replication. The early antiviral response and apoptosis correlated with the ability to limit viral replication. Both viruses reduced RIG-I associated antiviral responses and subsequent induction of IFN-β. However it was found that there was constitutive release of IFN-β by BECs and this was critical in inducing late antiviral signaling via type I IFN receptors, and was crucial in limiting viral infection. This study characterizes anti-influenza virus responses in airway epithelial cells and shows that constitutive IFN-β release plays a more important role in initiating protective late IFN-stimulated responses during human influenza infection in bronchial epithelial cells
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