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排序方式: 共有2227条查询结果,搜索用时 312 毫秒
1.
Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献
2.
J. B. Quinn G. E. Schumacher L. W. Schultheis 《Journal of Failure Analysis and Prevention》2004,4(1):41-46
Several days after heart surgery, a patient discovered his upper right canine tooth had broken at the root. Such tooth damage,
recognized post-operatively, is usually assumed to be caused by blunt mechanical force from an instrument used by the anesthesiologist
during placement of a breathing tube at the start of surgery.
In this case, the patient had saved the crown portion of the broken tooth, and it was possible to examine the root fracture
characteristics. The curvature and direction of the crack path and natural tooth situation suggested that failure could be
described through a cantilever beam model. This was confirmed when a whole extracted sample tooth was embedded and broken
by a measured force in a manner consistent with the model. The resulting fracture surface matched that of the patient’s broken
canine tooth. However, the high load and force direction necessary to fracture the root was inconsistent with forces applied
during the anesthesia procedure. The failure analysis and further investigation indicated tooth clenching on the breathing
tube during recovery was the likely cause of fracture.
This paper presents an alternate explanation for intubation-related dental injury, demonstrates the practicality of fractographic
analysis of biological materials, and introduces a methodology for simulating in vitro tooth settings for mechanical testing. 相似文献
3.
裂缝性油气藏采收率:100个裂缝性油气田实例的经验总结 总被引:5,自引:2,他引:3
通过对世界上100个裂缝性油气藏的综合评价,研究储集层及流体本身的性质(包括孔隙度、渗透率、黏度、可动油比例、含水饱和度、润湿性及裂缝分布特征等)和驱动机制及油藏管理战略(优化日产量和采用不同类型的提高采收率技术)对其最终采收率的影响。将裂缝性油气藏分为4类:I类的基质几乎没有孔隙度和渗透率,裂缝是储存空间和流体流动的通道;Ⅱ类的基质有较低的孔隙度和渗透率,基质提供储存空间,裂缝提供流动通道;Ⅲ类(微孔隙)的基质具有高孔隙度和低渗透率,基质提供储存空间,裂缝提供流动通道;Ⅳ类(大孔隙)的基质具有高的孔隙度和渗透率,基质提供储存空间和流动通道,裂缝仅增加渗透率。对26个Ⅱ类油气藏和20个Ⅲ类油气藏的开采历史的研究表明:Ⅱ类油气藏的采收率受水驱强度和最优日产量控制,日产量过高会很容易破坏Ⅱ类油气藏,一些Ⅱ类油气藏如果管理得当,采收率可以很高,不需要二次或三次采油;Ⅲ类油气藏的采收率主要受岩石和流体本身性质的影响,特别是基质渗透率、流体重度、润湿性以及裂缝强度等,不进行二次或三次采油不可能完全开采,往往需要采用一些提高采收率的专门技术。以往将Ⅱ类和Ⅲ类裂缝性油气藏归为一类,认识它们的区别将有助于选择更好的开发策略。 相似文献
4.
Kraft lignin (KL), a phenolic polymer formed during the kraft pulping process, is presently burned as a low value fuel. For decades, researchers have attempted to use KL as an inexpensive substitute for phenol in phenol-formaldehyde (PF) resins, but no one has produced a commercially satisfactory KL-PF resin. This paper reviews the literature on the present status of KL-PF adhesives and makes recommendations on needed research.
Kraft lignin solutions are complex mixtures which have broad molecular weight distributions, high viscosities, relatively low reactivities, and low solubilities. Attempts to overcome these inherent problems include methylolation of lignin to improve reactivity, the use of co-solvents to improve solubility, and ultrafiltration to yield more homogeneous molecular weight fractions. Future research efforts need to focus on understanding the fundamental chemical and physical properties of kraft lignin and its resins. The search for an economic lignin-based wood adhesive should continue. 相似文献
Kraft lignin solutions are complex mixtures which have broad molecular weight distributions, high viscosities, relatively low reactivities, and low solubilities. Attempts to overcome these inherent problems include methylolation of lignin to improve reactivity, the use of co-solvents to improve solubility, and ultrafiltration to yield more homogeneous molecular weight fractions. Future research efforts need to focus on understanding the fundamental chemical and physical properties of kraft lignin and its resins. The search for an economic lignin-based wood adhesive should continue. 相似文献
5.
Comparison of two methods of surfactant administration and the effect on dosing-associated hypoxemia
M Nelson JJ Nicks MA Becker LA Vrlenich V Bhatt-Mehta RE Schumacher 《Canadian Metallurgical Quarterly》1997,17(6):450-454
OBJECTIVE: The purpose of our study was to test the hypothesis that surfactant dosing through a proximal sideport adapter on an endotracheal tube leads to more dosing-associated hypoxemia compared with a method of dosing that uses a double-lumen endotracheal tube. STUDY DESIGN: Using adequate sample size to compare significant changes in O2 saturation (power > 0.8, alpha < 0.05) we enrolled 36 infants with respiratory distress syndrome in this randomized trial. A 10% change in O2 saturation was considered clinically significant. Nineteen infants received 38 doses of surfactant through the sideport adapter. Seventeen infants received 31 doses of surfactant through the nonventilation lumen of a double-lumen endotracheal tube. Two main outcome measures were assessed: time-averaged O2 saturation values 30 minutes after dosing and the largest absolute fall in O2 saturation for each patient. RESULTS AND CONCLUSIONS: Time-averaged O2 saturation measures were higher in the proximal sideport group (p = 0.02), but the magnitude of difference was probably not clinically significant. No significant difference was detected between groups when we compared largest absolute drop in O2 saturation. Secondary analyses found no effect of birth weight or dose number (second vs third dose) on either outcome measure. 相似文献
6.
S Schumacher H Volkmer F Buck A Otto A Tarnók S Roth FG Rathjen 《Canadian Metallurgical Quarterly》1997,136(4):895-906
Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB) was identified by combining binding assays with immunological screens in the chicken nervous system as a novel member of the EGF family of differentiation factors. cDNA cloning indicates that CALEB is a multidomain protein that consists of an NH2-terminal glycosylation region, a leucine-proline-rich segment, an acidic box, a single EGF-like domain, a transmembrane, and a short cytoplasmic stretch. In the developing nervous system, CALEB is associated with glial and neuronal surfaces. CALEB is composed of a 140/130-kD doublet, an 80-kD band, and a chondroitinsulfate-containing 200-kD component. The latter two components are expressed in the embryonic nervous system and are downregulated in the adult nervous system. CALEB binds to the extracellular matrix glycoproteins tenascin-C and -R. In vitro antibody perturbation experiments reveal a participation of CALEB in neurite formation in a permissive environment. 相似文献
7.
We investigated changes in the anterior tibial muscle during lengthening of the lower leg in rabbits. In 37 rabbits, an osteotomy of the right middle tibia was performed and was fixed by a unilateral external fixator. The rabbits were randomized into 6 groups. In groups 1, 2, and 3 the tibiae were distracted 0.5 mm/day. In groups 1 and 2, the rabbits were killed after 14 and 28 days of distraction, respectively, and in group 3 after 28 days of distraction, followed by 14 days of rest. Groups 1a, 2a, and 3a served as controls. They were treated similarly as groups 1, 2, and 3, but no distraction was performed. Proliferating cell nuclei were labeled with 5-bromo-2-deoxyuridine and were identified by immunohistochemical staining. The weight of the muscle was measured. During bone lengthening the muscle showed signs of growth, as indicated by increasing weight and number of proliferating cell nuclei. This was observed only during lengthening and it ceased when the lengthening was stopped. 相似文献
8.
The gates of GaAs MESFETS rely on the formation of a Schottky diode between the semiconductor surface and a deposited metal and so are extremely sensitive to the nature of this interface. For this reason an investigation of surface damage and contamination by the various processing stages involved in IC fabrication has been undertaken. This paper outlines the results obtained from processes involved in activation of ion implantation through annealing with a dielectric encapsulant, wet chemical etching, and metallization. Methods for removing or minimizing the effects of processing damage or contamination are also investigated. 相似文献
9.
Measurement of Energy Expenditure in Elite Athletes Using MEMS-Based Triaxial Accelerometers 总被引:1,自引:0,他引:1
Andrew J. Wixted David V. Thiel Allan G. Hahn Christopher J. Gore David B. Pyne Daniel A. James 《IEEE sensors journal》2007,7(4):481-488
Fitness development and performance assessment of elite athletes requires an understanding of many physiological factors, many of these are direct and indirect measures of athlete energy expenditure. Many methods are physiological factor assessments and require the athlete to be constrained by laboratory equipment or periodic interruption of activity to take measurements such as blood samples are required to be taken. This paper presents a method that is entirely ambulatory and noninvasive, using microelectromechanical systems (MEMS) accelerometers. The commonly used output of commercial accelerometer-based devices (known as "counts") cannot discriminate activity intensity for the activities of interest. This, in conjunction with variability in output from different systems and lack of commonality across manufacturers, limits the usefulness of commercial devices. This paper identifies anthropometric and kinematic sources of inter-athlete variability in accelerometer output, leading to an alternate energy expenditure estimator based mainly on step frequency modified by anthropometric measures. This energy expenditure estimator is more robust and not influenced by many sources of variability that affect the currently used estimator. In this system, low-power signal processing was implemented to extract both the energy estimator and other information of physiological and statistical interest 相似文献
10.
Mazzocco Michèle M. M.; Freund Lisa S.; Baumgardner Thomas L.; Forman Lisa; Reiss Allan L. 《Canadian Metallurgical Quarterly》1995,9(4):470
An extensive evaluation was conducted with 16-yr-old monozygotic twins concordant for the fragile X full mutation but discordant for mental retardation. The clearly affected twin had an IQ score of 47; 77% of her neuropsychological z scores were at least 2 SDs below average. Her sister had an IQ score of 105 and average neuropsychological performance. However, each girl demonstrated relative verbal strengths and visual-spatial weaknesses. Their parents rated each girl as having significant problems with attention, conduct, anxiety-withdrawal, and hyperactivity. The girls did not rate themselves as having significant anxiety. These findings are consistent with group data on females with fragile X and demonstrate the wide range of effects associated with the fragile X full mutation. This case report implicates the importance of a psychosocial phenotype of fragile X independent of cognitive ability level. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献