This article describes how multiple IBM PureApplication System racks can be located ingeographically distributed data centers to host business critical workloads that require thehighest levels of availability and rapid recovery following a disaster.

关键词：多站点设置；WebSphere集群模式；应用系统

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Tamoxifen, the first targeted therapy, has shown great success in treating estrogen receptor (ER) positive breast cancer. However, both acquired and de novo resistance to this therapy prevents it from being effective in all situations. Multiple lines of evidence indicate that increased signaling through growth factor pathways, such as the IGF pathway, mediates resistance to tamoxifen. The link between ER and ICGF1R leads us to hypothesize that IGF system crosstalk with the ER contributes to tamoxifen resistance. Tamoxifen resistance has thus provided researchers with a reason to investigate other growth factor pathways involved in breast cancer. As new targeted therapies are being developed, it will be important to examine their benefit with existing therapies. In order to examine the effectiveness of anti-IGF1R inhibitors in vitro, tamoxifen resistant (TamR) cells were generated by culturing MCF-7L and T47D cells in the presence of 4-OH-tamoxifen for >6 months. TamR cells had dimished levels of IGF1R, with unchanged levels of insulin receptor (IR). Further, TamR cells failed to respond to IGF-I induced p-AKT activation, while retaining responsiveness to both insulin and IGF-II. Additionally, IGF-I failed to enhance the proliferation and anchorage-independent growth of TamR cells; however, both insulin and IGF-II were able to enhance proliferation in MCF anchorage-independent growth. An IGF1R antibody was effective in inhibiting signaling, anchorage-independent growth, and proliferation in MCF-7L cells, but had no effect in TamR cells. In contract, an IGF1R/TR tyrosine kinase inhibitor was effective in both MCF-7L and TamR cells. In a xenograft model, an IGF1R antibody was able to inhibit estrogen stimulated tumor growth, but had no additive effect when combined with tamoxifen treatment. Further, tamoxifen-treated xenografts had diminished IGF1R levels.

关键词：医药；治疗技术；类胰岛素生长因子受体；抗雌激素受体

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The sympathetic nervous system (SNS) is a major pathway activated by exposure to emotional stressors. We have demonstrated SNS hard-wiring in the form of sympathetic nerve fibers in 4T1 mammary tumors, a mouse model of metastatic breast cancer. We established that 4T1 tumor cells do not express functional - or -adrenergic receptors (AR), the receptors activated by norepinephrine (NE), the neurotransmitter of the SNS. Yet, manipulation of sympathetic neurotransmission in vivo by chemical ablation of sympathetic nerves to deplete NE decreased F480+ tumor associated macrophages and reduced tumor weight. Furthermore, chronic treatment with desipramine (DMI), an antidepressant that elevates synaptic NE, increased 4T1 tumor growth, but not metastasis. DMI-induced tumor growth was not associated with increased tumor angiogenesis, and pro-tumor cytokines VEGF, IL-6, RANTES, and MIP-2 were reduced by DMI. To further dissect the tumor response to NE, mice were treated with selective AR agonists. The 2-AR agonist dexmedetomidine (DEX) increased tumor growth and metastasis in the absence of alterations in VEGF, IL-6, RANTES, and MIP-2. Treatment with the -AR agonists isoproterenol and salmeterol did not significantly alter tumor growth/metastasis. In DMI- and DEX-treated mice, tumor collagen microstructure was uniquely altered in 4T1 tumors, suggesting a novel stromal-mediated mechanism whereby elevated NE and stimulation of AR may increase tumor growth. These results suggest that NE-induced tumor growth is mediated by 2-AR activation, but other AR pathways activated by elevated synaptic NE may modulate the tumor-promoting effect of 2-AR activation. Understanding how AR pathways regulate breast tumor pathogenesis will lead to new therapies to inhibit tumor growth and metastasis.

关键词：医药；治疗技术；乳腺癌；交感神经

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While on-premise COBOL programs have been successfully transformed into Java?-basedSoftware as a Service (SaaS) applications, there are multithreading issues developers shouldwatch out for when interfacing COBOL and Java with one another in a SaaS application. Theauthor illustrates what proactive actions to take in a multithreaded SaaS failure scenario.

关键词：多线程性能；多线程控制；网络专家控制

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The constraints on penetration of energy technologies are time and information, net energy, and capital cost. As D. Spreng (ORAU/IEA-78-22(R)) has pointed out, time, energy, and information constitute a triad: energy can be substituted for time, information can be substituted for energy. That energy can save time follows from irreversible thermodynamics, but the principle can be extended to the social sphere. Related to the energy/time exchange is the economic cost of intermittency of energy supply. Renewable energy sources, particularly solar sources, are characteristically intermittent. To eliminate intermittency imposes a cost that must be considered in planning energy futures based on renewable sources. Two other constraints on penetration of energy technologies - net energy and capital cost - are briefly considered. As for net energy, estimates of energy paybacks for solar thermal electric converters differ by factors of three; this introduces large uncertainties in the energy subsidy required for this technology. As for capital cost, the Peterka theory of technological change is shown to place limits on the amount of subsidy required to introduce a new energy technology

关键词：新能源；可再生能源；能源发展

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In this paper, we investigate the prediction of visual grasp affordances from 2D measurements. Appearancebased estimation of grasp affordances is desirable when 3-D scans are unreliable due to clutter or material properties.We develop a general framework for estimating grasp affordances from 2-D sources, including local texture-like measures as well as object-category measures that capture previously learned grasp strategies. Local approaches to estimating grasp positions have been shown to be effective in real-world scenarios, but are unable to impart objectlevel biases and can be prone to false positives. We describe how global cues can be used to compute continuous pose estimates and corresponding grasp point locations, using a max-margin optimization for category-level continuous pose regression.

关键词：外观；视觉；线索；3D

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This chapter will summarize current knowledge in renal replacement technologies in the treatment of critically ill patients with acute kidney injury. The mechanics of different treatment modalities with emphasis on continuous renal replacement therapies will be described, as well as the application of such technologies in the management of fluid overload and metabolic abnormalities. Appropriate composition of dialysate and replacement fluids, use of anticoagulation, choice of vascular access, and potential complications in the use of such technologies will be discussed. Finally, the chapter will compare the main features of the different currently available CRRT machines.

关键词：医药；治疗技术；肾脏；替代

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Microbiological testing plays an ever increasing role in delivering high quality drug products to patients, whether it's practiced in the pharmaceutical laboratory and in the manufacturing environment. In response to the drive for continuous improvement and further economies, a variety of new methodologies have emerged in recent years which automate existing methods, make use of surrogate markers for growth, or are based on wholly new technologies. These new methodologies offer significant improvements in terms of the speed, accuracy, precision and specificity with which testing can be performed. However, in spite of the limitations of current culture methods, acceptance of new and potentially superior methods has only started to gain momentum within the pharmaceutical, biotechnology and medical device industries. We believe this continues to be due in part to a lack of clear guidance regarding the demonstration of their equivalence to existing methods acceptable to regulatory agencies and validation of the equipment associated with the new methods. In any case, many of these new rapid methods may have a role to play in other applications including missions in space where we want to know the impact of microorganisms on space travel, as well as what microorganisms might be waiting to be discovered.

关键词：医药；药品；微生物监测；制药工业

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The broad objective of the proposed study is to empirically evaluate the efficacy of a cognitive behavioral intervention, titled, Post Admission Cognitive Therapy (PACT), for military personnel psychiatrically hospitalized due to a suicide-related event with either a recent or a lifetime suicide attempt. The primary outcomes will be incidence of repeat suicide attempt(s) and number of days until a repeat suicide attempt. Secondary outcomes include psychiatric symptoms, repeat number of psychiatric hospitalization(s), hope for one s future, and acceptability of treatment. A multi-site, single-blind, randomized controlled trial will be the research design. A total of 218 individuals will be recruited from the inpatient psychiatric and traumatic brain injury (TBI) units at the Walter Reed National Military Medical Center and Fort Belvoir Community Hospital. Participants will be randomized into one of two conditions: (1) PACT + Enhanced Usual Care (EUC) or (2) EUC. The PACT+EUC condition will consist of six 60-90 minute individual cognitive behavioral therapy sessions administered over preferably three days during the inpatient stay and up to four telephone booster sessions. The EUC condition will consist of usual psychiatric care patients receive during their hospitalization, the assessment services provided by MA and/or PhD level clinicians, and case management services provided for one year by Bachelor s level research personnel. Follow-up assessments will be conducted at 1, 3, 6, and 12-month post discharge by blind PhD level clinicians.

关键词：医药；治疗技术；认知治疗；随机实验

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关键词：建筑；应用栈；环境；信息技术

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