127 research outputs found

    A blast-tolerant sandwich plate design with a polyurea interlayer

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    AbstractThis paper presents a study of both conventional and modified sandwich plate designs subjected to blast loads. The conventional sandwich Design (1) consists of thin outer (loaded side) and inner facesheets made of fibrous laminates, separated by a layer of structural foam core. In the modified Design (2), a thin polyurea interlayer is inserted between the outer facesheet and the foam core. Comparisons of the two designs are made during a long time period of 5.0ms, initiated by a pressure impulse lasting 0.05ms applied to a single span of a continuous plate. In the initial response period the overall deflections are limited and significant foam core crushing is caused in the conventional design by the incident compression wave. This type of damage is much reduced in the modified design, by stiffening of the polyurea interlayer under shock compression, which provides support to the outer facesheet and alters propagation of stress waves into the foam core. This benefits the long term, bending response and leads to significant reductions in facesheet strains and overall deflection. The total kinetic energy of the modified sandwich plate is much lower than that of a conventionally designed plate, and so is the stored and dissipated strain energy. Similar reductions are found when the conventional and the enhanced sandwich plates have equal overall thickness or equal total mass

    Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab

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    Pharmacological inhibition of VEGF-A has proven to be effective in inhibiting angiogenesis and vascular leak associated with cancers and various eye diseases. However, little information is currently available on the binding kinetics and relative biological activity of various VEGF inhibitors. Therefore, we have evaluated the binding kinetics of two anti-VEGF antibodies, ranibizumab and bevacizumab, and VEGF Trap (also known as aflibercept), a novel type of soluble decoy receptor, with substantially higher affinity than conventional soluble VEGF receptors. VEGF Trap bound to all isoforms of human VEGF-A tested with subpicomolar affinity. Ranibizumab and bevacizumab also bound human VEGF-A, but with markedly lower affinity. The association rate for VEGF Trap binding to VEGF-A was orders of magnitude faster than that measured for bevacizumab and ranibizumab. Similarly, in cell-based bioassays, VEGF Trap inhibited the activation of VEGFR1 and VEGFR2, as well as VEGF-A induced calcium mobilization and migration in human endothelial cells more potently than ranibizumab or bevacizumab. Only VEGF Trap bound human PlGF and VEGF-B, and inhibited VEGFR1 activation and HUVEC migration induced by PlGF. These data differentiate VEGF Trap from ranibizumab and bevacizumab in terms of its markedly higher affinity for VEGF-A, as well as its ability to bind VEGF-B and PlGF

    Current understanding of the relationship between cervical manipulation and stroke: what does it mean for the chiropractic profession?

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    The understanding of the relationship between cervical manipulative therapy (CMT) and vertebral artery dissection and stroke (VADS) has evolved considerably over the years. In the beginning the relationship was seen as simple cause-effect, in which CMT was seen to cause VADS in certain susceptible individuals. This was perceived as extremely rare by chiropractic physicians, but as far more common by neurologists and others. Recent evidence has clarified the relationship considerably, and suggests that the relationship is not causal, but that patients with VADS often have initial symptoms which cause them to seek care from a chiropractic physician and have a stroke some time after, independent of the chiropractic visit

    Aerosol Delivery of Small Hairpin Osteopontin Blocks Pulmonary Metastasis of Breast Cancer in Mice

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    Metastasis to the lung may be the final step in the breast cancer-related morbidity. Conventional therapies such as chemotherapy and surgery are somewhat successful, however, metastasis-related breast cancer morbidity remains high. Thus, a novel approach to prevent breast tumor metastasis is needed.Aerosol of lentivirus-based small hairpin osteopontin was delivered into mice with breast cancer twice a week for 1 or 2 months using a nose-only inhalation system. The effects of small hairpin osteopontin on breast cancer metastasis to the lung were evaluated using near infrared imaging as well as diverse molecular techniques. Aerosol-delivered small hairpin osteopontin significantly decreased the expression level of osteopontin and altered the expression of several important metastasis-related proteins in our murine breast cancer model.Aerosol-delivered small hairpin osteopontin blocked breast cancer metastasis. Our results showed that noninvasive targeting of pulmonary osteopontin or other specific genes responsible for cancer metastasis could be used as an effective therapeutic regimen for the treatment of metastatic epithelial tumors

    Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage

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    The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells