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21.
Stover  V. 《Potentials, IEEE》1991,10(2):25-28
The use of a central repository for data and a database management system that enables programs to share data more efficiently and ensures the consistency of the data across the system is discussed. Relational databases, which represent both entities and relationships using tables, are described. It is shown that by proper design of the relational tables, the redundancy and wasted space of many ad hoc databases can be eliminated. Data are retrieved from a relational database through the use of a procedural query language. The leading query language for relational databases, the Structured Query Language (SQL), is examined  相似文献   
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Indoleamine 2,3-dioxygenase 1 (IDO1) is a promising therapeutic target in cancer immunotherapy and neurological disease. Thus, searching for highly active inhibitors for use in human cancers is now a focus of widespread research and development efforts. In this study, we report the structure-based design of 2-(5-imidazolyl)indole derivatives, a series of novel IDO1 inhibitors which have been designed and synthesized based on our previous study using N1-substituted 5-indoleimidazoles. Among these, we have identified one with a strong IDO1 inhibitory activity (IC50=0.16 μM, EC50=0.3 μM). Structural-activity relationship (SAR) and computational docking simulations suggest that a hydroxyl group favorably interacts with a proximal Ser167 residue in Pocket A, improving IDO1 inhibitory potency. The brain penetrance of potent compounds was estimated by calculation of the Blood Brain Barrier (BBB) Score and Brain Exposure Efficiency (BEE) Score. Many compounds had favorable scores and the two most promising compounds were advanced to a pharmacokinetic study which demonstrated that both compounds were brain penetrant. We have thus discovered a flexible scaffold for brain penetrant IDO1 inhibitors, exemplified by several potent, brain penetrant, agents. With this promising scaffold, we provide herein a basis for further development of brain penetrant IDO1 inhibitors.  相似文献   
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Previously, we showed that chemotherapy paradoxically exacerbated cancer cell colonization at the secondary site in a manner dependent on Atf3, a stress-inducible gene, in the non-cancer host cells. Here, we present evidence that this phenotype is established at an early stage of colonization within days of cancer cell arrival. Using mouse breast cancer models, we showed that, in the wild-type (WT) lung, cyclophosphamide (CTX) increased the ability of the lung to retain cancer cells in the vascular bed. Although CTX did not change the WT lung to affect cancer cell extravasation or proliferation, it changed the lung macrophage to be pro-cancer, protecting cancer cells from death. This, combined with the initial increase in cell retention, resulted in higher lung colonization in CTX-treated than control-treated mice. In the Atf3 knockout (KO) lung, CTX also increased the ability of lung to retain cancer cells. However, the CTX-treated KO macrophage was highly cytotoxic to cancer cells, resulting in no increase in lung colonization—despite the initial increase in cell retention. In summary, the status of Atf3 dictates the dichotomous activity of macrophage: pro-cancer for CTX-treated WT macrophage but anti-cancer for the KO counterpart. This dichotomy provides a mechanistic explanation for CTX to exacerbate lung colonization in the WT but not Atf3 KO lung.  相似文献   
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It has been reported that alteration of deletion of critical residues within one of the two homologous protein tyrosine phosphatase (PTPase)-like domains of CD45 completely abolishes all activity, suggesting that only the more N-terminal domain is catalytically active. However, we now demonstrate, by two independent techniques, that the second (C-terminal) domain is also a viable phosphatase. Limited proteolysis by endoproteinase Lys-C or trypsin increased the phosphatase activity toward reduced, carboxymethylated, and maleylated lysozyme approximately 8-fold. A 50-kDa fragment, isolated by ion exchange chromatography, was found to be responsible for this activity. N-terminal sequencing revealed that this fragment includes less than half of the first phosphatase domain and most, if not all, of the second. In a second experiment, 109 residues, including the presumed catalytic region, were removed from domain I by site-directed mutagenesis. Expression of this construct in a mammalian cell line resulted in increased PTPase activity over nontransfected control cells. Isolation of the recombinant CD45 by immunoprecipitation and immunoaffinity chromatography revealed that it had phosphatase activity. Both of these experimental approaches demonstrate that the second conserved PTPase domain of CD45 is a functioning PTPase, but that external regulation may be required to express its activity in the context of the native molecule.  相似文献   
27.
Studied 36 hyperkinetic and 36 control boys, ages 8-11, on a rapid-tapping task. Ss were divided into 3 incentive groups: 1 allowed to respond freely (U), 1 encouraged to tap rapidly (S), and 1 given pennies for increasing their tapping rate (R). As expected, the R and S groups tapped more rapidly than the U groups. When analyzed separately, no significant incentive group differences were found for hyperkinetics. The moderately fast tapping of the hyperkinetics, regardless of group, resulted in U hyperkinetics tapping more rapidly than U controls, but when incentive was introduced (S and R groups), controls were able to tap faster than the hyperkinetics. This inability of the hyperkinetics to adaptively adjust to the changing incentive conditions is suggested to be a function of defects in brain structures regulating arousal and concentration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
28.
In the present investigation elemental powder mixtures with nominal composition of Nb-25at. % Al and Ru-50at.% Al corresponding to Nb3Al and RuAl intermetallic phases were prepared. Green compacts from these mixtures were reactive sintered in vacuum or hot isostatically pressed after being encapsulated and reacted in quartz capsules. In the absence of pressure, reactive sintering at temperatures up to 1800 °C did not lead to densification, and swelling effects were observed. Reactions of formation of Nb3Al and RuAl were found to take place at different temperature regions characteristic for each aluminide system, with clear dependence of the reaction temperature on the heating rate of the powder mixtures. Dilatometry studies showed that swelling occurred instantaneously at temperatures corresponding to the reaction temperature and led to a volume increase of about 25% and 42% for Nb3Al and RuAl, respectively. The activation energy for the reactions was estimated from the differential thermal analysis. Similar data for the NiAl intermetallic phase were also obtained for comparison. The densification behavior and the phase composition of the reaction products were investigated and correlated with the heating rate, the mutual solubility of the reactants, and the amount of liquid phase available during the reaction.  相似文献   
29.
Reduced bone mineral density (BMD), termed diabetic osteopenia, has been reported in patients with insulin-dependent (Type 1) diabetes mellitus (IDDM). To examine BMD in long-term IDDM patients with normal kidney function, but with different degrees of urinary albumin excretion rate (UAER), compared to that of patients with elevated plasma creatinine, 36 IDDM male patients (mean duration 27 years) were subdivided according to UAER (<30, 30-300, >300, >300 mg 24 h(-1) and plasma creatinine 0.120-0.350 mmol l(-1)) and 15 controls were recruited. BMD was measured by dual energy X-ray absorptiometry and UAER by enzyme linked immunosorbent assay. BMD was normal in IDDM patients with normal UAER and reduced in the femoral neck, the trochanter major, and the Wards triangle in patients with increased UAER (p < 0.01, p < 0.05, p < 0.02). BMD correlated to creatinine clearance in both cortical and cancellous bone sites (p < 0.001, p < 0.0001), and inversely to the levels of plasma PTH (p < 0.0005). We conclude that BMD is normal in long-term IDDM male patients with normal kidney function and normal UAER and reduced in patients with increased UAER. Diabetic osteopenia seems to be a progressive phenomenon related to diabetic nephropathy and associated with the decrease in creatinine clearance and with the resulting rise in plasma PTH.  相似文献   
30.
The objective of this article was to survey available intimate partner violence (IPV) treatment studies with (a) randomized case assignment, and (b) at least 20 participants per group. Studies were classified into 4 categories according to primary treatment focus: perpetrator, victim, couples, or child-witness interventions. The results suggest that extant interventions have limited effect on repeat violence, with most treatments reporting minimal benefit above arrest alone. There is a lack of research evidence for the effectiveness of the most common treatments provided for victims and perpetrators of IPV, including the Duluth model for perpetrators and shelter–advocacy approaches for victims. Rates of recidivism in most perpetrator- and partner-focused treatments are approximately 30% within 6 months, regardless of intervention strategy used. Couples treatment approaches that simultaneously address problems with substance abuse and aggression yield the lowest recidivism rates, and manualized child trauma treatments are effective in reducing child symptoms secondary to IPV. This review shows the benefit of integrating empirically validated substance abuse and trauma treatments into IPV interventions and highlights the need for more work in this area. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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