V11294 is a new cyclic nucleotide phosphodiesterase type 4 (PDE4) inhibitor of the rolipram class. In this report we present the pharmacological profile of V11294. V11294 inhibited PDE4 isolated from ...human lung with IC
50 405
nM, compared to 3700
nM for rolipram. In contrast, V11294 inhibition of human PDE3 and PDE5 occurred only at concentrations greater than 100,000
nM. Like rolipram, V11294 inhibited PDE4D more potently than other PDE4 subtypes. V11294, when incubated with human anticoagulated whole blood in vitro, or administered to mice, caused increased cAMP concentration, consistent with inhibition of PDE4. V11294 inhibited lectin-induced proliferation and lipopolysaccharide-induced TNFα synthesis by human adherent monocytes in vitro and inhibited lipopolysaccharide-induced TNFα synthesis in mice. V11294 caused relaxation of guinea pig isolated trachea and inhibited allergen-induced bronchoconstriction and eosinophilia in guinea pigs at doses of 1 and 3
mg/kg, p.o. In ferrets, V11294 was not emetogenic at doses up to 30
mg/kg, p.o., despite plasma concentration reaching 10-fold the IC
50 for PDE4. In contrast, rolipram induced severe retching and vomiting at 10
mg/kg, p.o. In conclusion, V11294 is an orally active PDE4 inhibitor that exhibits antiinflammatory activity in vitro, and in vivo at doses that are not emetogenic.
One of the challenges of acupuncture research is designing appropriate control groups. To address this problem,after surgical third molar extractions 19 patients were randomly assigned to an ...acupuncture group (n=11) or a placebo acupuncture group (n=8). The length of time for reaching moderate pain and pain intensity after oral surgery were recorded by standard patient self-report. The results indicated that subjects treated with acupuncture reported longer pain-free duration times (mean, 181 versus 71 minutes;
p≤0.046) and experienced less pain intensity than those who received placebo acupuncture. This study provides a model for an acupuncture control that could examine the placebo effect in clinical acupuncture research.
The genotoxicity of low-level exposure to ethylene dichloride (EDC) and vinyl chloride monomer (VCM) in humans is not clear. We used lymphocyte sister chromatid exchange (SCE) frequency as a ...parameter to investigate the genotoxicity of low level EDC and VCM in VCM-manufacturing workers. The SCE frequency was determined for 51 male workers with exposure to VCM and/or EDC and for 20 male workers devoid of such exposure. Epidemiological data were obtained by questionnaire, and included history of smoking, drinking, and any medication taken, as well as a detailed occupational history. Personal- and area-sampling and analysis were conducted in order to calculate the time-weighted average (TWA) contaminant-exposure level corresponding to different job categories. Moderate EDC exposure around 1 ppm corresponded to a significantly greater SCE frequency than was the case for the low EDC exposure group (
p<0.01). However, VCM exposure of similar level was not associated with increased SCE. We conclude that EDC may cause genotoxicity at a relatively low level of exposure.
The purpose of this paper is to propose and study a class of quasi-interpolating operators in multivariate spline space $S_2^1(\Delta _{mn}^{2*})$ on non-uniform type-2 triangulation. Based on the ...operators, we construct cubature formula for two-dimensional hypersingular integrals. Some computing work have been done and the results are quite satisfactory.
Cyclophosphamide (177 mg/kg, IV;
n = 8) produced a biphasic emetic response in the ferret with a mean ± SE of 23.3 ± 4.0 emetic episodes during a 4-h observation period. The emetic profile of ...cyclophosphamide showed a first phase with 18.6 ± 3.9 episodes and a second phase with 4.7 ± 1.2 episodes. Ondansetron (0.07 and 0.13 mg/kg, IV) and droperidol (0.25 and 0.79 mg/kg, IV) significantly reduced the number of emetic episodes in the first phase. Metoclopramide (2.24, 4.08, and 7.07 mg/kg, IV) also significantly reduced the number of emetic episodes in the first phase, and the dose of 7.07 mg/kg completely prevented emetic episodes in the second phase. In addition, ondansetron-treated ferrets (0.04, 0.07, and 0.13 mg/kg, IV) had a significant increase in the number of emetic episodes in the second phase.
In 1981, the authors' company initiated a loss measurement study involving the collection of a large amount of loss data on older distribution transformers. The objective was to better characterize ...their losses for such studies as economic replacement, voltage conversion and economic loading. This paper is a discussion and analysis of that data.
The creation of three‐dimensional (3D) structures from two‐dimensional (2D) nanomaterial building blocks enables novel chemical, mechanical or physical functionalities that cannot be realized with ...planar thin films or in bulk materials. Here, we review the use of emerging 2D materials to create complex out‐of‐plane surface topographies and 3D material architectures. We focus on recent approaches that yield periodic textures or patterns, and present four techniques as case studies: (i) wrinkling and crumpling of planar sheets, (ii) encapsulation by crumpled nanosheet shells, (iii) origami folding and kirigami cutting to create programmed curvature, and (iv) 3D printing of 2D material suspensions. Work to date in this field has primarily used graphene and graphene oxide as the 2D building blocks, and we consider how these unconventional approaches may be extended to alternative 2D materials and their heterostructures. Taken together, these emerging patterning and texturing techniques represent an intriguing alternative to conventional materials synthesis and processing methods, and are expected to contribute to the development of new composites, stretchable electronics, energy storage devices, chemical barriers, and biomaterials.
Emerging approaches to fabrication of 3D architectures are discussed, emphasizing creation of textural patterns by directed assembly of nanosheet building blocks: i) wrinkling and crumpling of 2D material films; ii) wrapping and crumpling of 2D materials around curved objects; iii) folding (origami) and cutting (kirigami) using 2D materials; and iv) 3D printing from 2D nanosheet suspensions.
Lymphangiogensis is involved in various pathological conditions, such as arthritis and cancer metastasis. Although many factors have been identified to stimulate lymphatic vessel growth, little is ...known about lymphangiogenesis inhibitors. Here we report that membrane type 1-matrix metalloproteinase (MT1-MMP) is an endogenous suppressor of lymphatic vessel growth. MT1-MMP-deficient mice exhibit spontaneous corneal lymphangiogenesis without concomitant changes in angiogenesis. Mice lacking MT1-MMP in either lymphatic endothelial cells or macrophages recapitulate corneal lymphangiogenic phenotypes observed in Mmp14(-/-) mice, suggesting that the spontaneous lymphangiogenesis is both lymphatic endothelial cells autonomous and macrophage associated. Mechanistically, MT1-MMP directly cleaves LYVE-1 on lymphatic endothelial cells to inhibit LYVE-1-mediated lymphangiogenic responses. In addition, MT1-MMP-mediated PI3Kδ signalling restrains the production of VEGF-C from prolymphangiogenic macrophages through repressing the activation of NF-κB signalling. Thus, we identify MT1-MMP as an endogenous inhibitor of physiological lymphangiogenesis.
This paper presents the current state of understanding of the factors that limit the continued scaling of Si complementary metal-oxide-semiconductor (CMOS) technology and provides an analysis of the ...ways in which application-related considerations enter into the determination of these limits. The physical origins of these limits are primarily in the tunneling currents, which leak through the various barriers in a MOS field-effect transistor (MOSFET) when it becomes very small, and in the thermally generated subthreshold currents. The dependence of these leakages on MOSFET geometry and structure is discussed along with design criteria for minimizing short-channel effects and other issues related to scaling. Scaling limits due to these leakage currents arise from application constraints related to power consumption and circuit functionality. We describe how these constraints work out for some of the most important application classes: dynamic random access memory (DRAM), static random access memory (SRAM), low-power portable devices, and moderate and high-performance CMOS logic. As a summary, we provide a table of our estimates of the scaling limits for various applications and device types. The end result is that there is no single end point for scaling, but that instead there are many end points, each optimally adapted to its particular applications.
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