BACKGROUND & AIMS: :We recently showed that non-small cell lung carcinomas (NSCLCs) are of dismal prognosis when encompassing accelerated autophagic activity. The regulation of this abnormally functioning degradation system and its association with hypoxia and apoptosis in lung carcinoma patients is unexplored. In this study we used 115 NSCLC tissues to examine the immunohistochemical expression of four distinct molecules - the major regulator of autophagy Beclin 1, the anti-apoptotic and anti-autophagic protein Bcl-2, the pro-apoptotic and pro-autophagic protein BNIP3, and a marker of hypoxia and glucolysis, the glucose transporter Glut 1. Most cases showed reduced reactivity for Beclin 1 (62%) and Bcl-2 (82%) proteins, almost half of our sample revealed strong BNIP3 expression (57%), whereas most of the carcinomas strongly expressed Glut 1 antigen (71%). Beclin 1 expression showed no association with survival. Bcl-2 positivity was a marker of good prognosis (p = 0.04), whereas BNIP3 (p = 0.0004) and Glut 1 (p = 0.03) expression correlated with poor outcome in Stage I disease. Autophagic status was negatively associated with Bcl-2 (p = 0.0006), but positively with Glut 1 expression (p = 0.001). In conclusion, the accelerated autophagic status in NSCLC is unrelated to Beclin 1 and BNIP3 expression, but does show significant association with Bcl-2 reactivity. Furthermore, we showed important correlations between glucolysis and autophagy, guiding new pathways in future lung carcinoma research.

背景与目标： ：我们最近发现，非小细胞肺癌（NSCLC）包含加速自噬活性时预后不良。肺癌患者中这种功能异常的降解系统的调节及其与缺氧和细胞凋亡的关系尚待探索。在这项研究中，我们使用了115个非小细胞肺癌组织来检查四种不同分子的免疫组织化学表达-自噬Beclin 1的主要调节剂，抗凋亡和抗自噬蛋白Bcl-2，促凋亡和自噬蛋白BNIP3，葡萄糖转运蛋白Glut 1是缺氧和糖酵解的标志。大多数病例显示Beclin 1（62％）和Bcl-2（82％）蛋白的反应性降低，几乎一半的样本显示BNIP3表达强（57％），而大多数癌症强烈表达Glut 1抗原（71％）。 Beclin 1的表达与存活率无关。 Bcl-2阳性是预后良好的标志（p = 0.04），而BNIP3（p = 0.0004）和Glut 1（p = 0.03）的表达与I期疾病的不良预后相关。自噬状态与Bcl-2呈负相关（p = 0.0006），但与Glut 1表达呈正相关（p = 0.001）。总之，NSCLC中自噬状态的加速与Beclin 1和BNIP3的表达无关，但确实与Bcl-2的反应性显着相关。此外，我们显示了糖酵解与自噬之间的重要关联，为未来肺癌研究的新途径提供了指导。

BACKGROUND & AIMS: :Previously, we showed that an oligodeoxynucleotide with AAAG repeats (AAAG ODN) rescued mice from fatal acute lung injury (ALI) induced by influenza virus and inhibited production of tumor necrosis factor-α (TNF-α) in the injured lungs. However, the underlying mechanisms remain to be elucidated. Upon the bioinformatic analysis revealing that the AAAG ODN is consensus to interferon regulatory factor 5 (IRF5) binding site in the cis-regulatory elements of proinflammatory cytokines, we tried to explore whether the AAAG ODN could attenuate burn injury induced systemic inflammatory responses via inhibiting IRF5 pathway. Using the mouse model with sterile systemic inflammation induced by burn injury, we found that AAAG ODN prolonged the life span of the mice, decreased the expression of IRF5 at injured skin, reduced the production of TNF-α and IL-6 in blood and injured skin, and attenuated the ALI. Furthermore, AAAG ODN could bind IRF5 and inhibit the nuclear translocation of IRF5 in THP-1 cells. The data suggested that the AAAG ODN could act as a cytoplasmic decoy capable of interfering the function of IRF5, and be developed as a drug candidate for the treatment of inflammatory diseases.

背景与目标： ：以前，我们显示具有AAAG重复序列的寡聚脱氧核苷酸（AAAG ODN）将小鼠从流感病毒诱导的致命性急性肺损伤（ALI）中救出，并抑制了受伤肺中肿瘤坏死因子-α（TNF-α）的产生。但是，其潜在机制仍有待阐明。生物信息学分析表明AAAG ODN是促炎细胞因子顺式调节元件中干扰素调节因子5（IRF5）结合位点的共识，我们试图探索AAAG ODN是否可以通过抑制IRF5来减轻烧伤诱导的全身性炎症反应途径。使用烧伤引起的无菌性全身性炎症的小鼠模型，我们发现AAAG ODN延长了小鼠的寿命，降低了受伤皮肤上IRF5的表达，减少了血液和受伤后血液中TNF-α和IL-6的产生皮肤，并减弱ALI。此外，AAAG ODN可以结合IRF5并抑制THP-1细胞中IRF5的核易位。数据表明，AAAG ODN可以充当能够干扰IRF5功能的胞质诱饵，并可以作为治疗炎性疾病的候选药物而开发。

BACKGROUND & AIMS: :Development of new endocrine disruption-relevant test methods has been the subject of intensive research efforts for the past several decades, prompted in part by mandates in the 1996 Food Quality Protection Act (FQPA). While scientific understanding and test methods have advanced, questions remain on whether current scientific methods are capable of adequately addressing the complexities of the endocrine system for regulatory health and ecological risk assessments. The specific objective of this article is to perform a comprehensive, detailed evaluation of the adequacy of current test methods to inform regulatory risk assessments of whether a substance has the potential to perturb endocrine-related pathways resulting in human adverse effects. To that end,  approximately 42 existing test guidelines (TGs) were considered in the evaluation of coverage for endocrine-related adverse effects. In addition to evaluations of whether test methods are adequate to capture endocrine-related effects, considerations of further enhancements to current test methods, along with the need to develop novel test methods to address existing test method gaps are described. From this specific evaluation, up to 35 test methods are capable of informing whether a chemical substance perturbs known endocrine related biological pathways. Based on these findings, it can be concluded that current validated test methods are adequate to discern substances that may perturb the endocrine system, resulting in an adverse health effect. Together, these test methods predominantly form the core data requirements of a typical food-use pesticide registration submission. It is recognized, however, that the current state of science is rapidly advancing and there is a need to update current test methods to include added enhancements to ensure continued coverage and public health and environmental protection.

背景与目标： 在过去的几十年中，新的内分泌干扰物相关测试方法的开发一直是深入研究的主题，这在一定程度上是由1996年《食品质量保护法》（FQPA）的授权推动的。尽管科学的理解和测试方法已经取得了进步，但目前的科学方法是否能够充分解决内分泌系统的复杂性，以进行监管健康和生态风险评估仍存在疑问。本文的具体目标是对当前测试方法的适当性进行全面，详细的评估，以为某种物质是否具有干扰内分泌相关途径而导致人为不良影响的潜在风险提供监管风险评估。为此，在评估内分泌相关不良反应的覆盖范围时，考虑了大约42种现有的测试指南（TG）。除了评估测试方法是否足以捕获与内分泌相关的作用外，还描述了对当前测试方法进一步增强的考虑，以及开发新型测试方法以解决现有测试方法空白的需求。通过这种特定的评估，多达35种测试方法能够告知化学物质是否干扰了与内分泌有关的生物学途径。基于这些发现，可以得出结论，当前经过验证的测试方法足以识别可能扰乱内分泌系统，对健康产生不利影响的物质。这些测试方法共同构成了典型的食品用农药注册提交文件的核心数据要求。但是，已经认识到，当前的科学状态正在迅速发展，需要更新当前的测试方法以包括更多的增强功能，以确保持续的覆盖范围以及公共卫生和环境保护。

BACKGROUND & AIMS: :Regulatory T cells (T(regs) ) are crucial in mediating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. However, in the context of cancer their role is more complex, and they are thought to contribute to the progress of many tumours. As cancer cells express both self- and tumour-associated antigens, T(regs) are key to dampening effector cell responses, and therefore represent one of the main obstacles to effective anti-tumour responses. Suppression mechanisms employed by T(regs) are thought to contribute significantly to the failure of current therapies that rely on induction or potentiation of anti-tumour responses. This review will focus on the current evidence supporting the central role of T(regs) in establishing tumour-specific tolerance and promoting cancer escape. We outline the mechanisms underlying their suppressive function and discuss the potential routes of T(regs) accumulation within the tumour, including enhanced recruitment, in-situ or local proliferation, and de-novo differentiation. In addition, we review some of the cancer treatment strategies that act, at least in part, to eliminate or interfere with the function of T(regs) . The role of T(regs) is being recognized increasingly in cancer, and controlling the function of these suppressive cells in the tumour microenvironment without compromising peripheral tolerance represents a significant challenge for cancer therapies.

背景与目标： ：调节性T细胞（T（regs））在介导免疫稳态和促进外周耐受的建立和维持中至关重要。但是，在癌症的背景下，它们的作用更为复杂，据认为它们可促进许多肿瘤的进展。由于癌细胞同时表达自身和肿瘤相关抗原，因此T（regs）是抑制效应细胞反应的关键，因此代表了有效抗肿瘤反应的主要障碍之一。 T（regs）所采用的抑制机制被认为对依赖抗肿瘤反应的诱导或增强的当前疗法的失败有重大贡献。这篇综述将集中在支持T（regs）在建立肿瘤特异性耐受性和促进癌症逃逸中的核心作用的当前证据上。我们概述了其抑制功能的潜在机制，并讨论了肿瘤内部T（regs）积累的潜在途径，包括增强的募集，原位或局部增殖以及新的分化。另外，我们回顾了一些至少部分起消除或干扰T（regs）功能的癌症治疗策略。 T（regs）在癌症中的作用越来越得到认可，并且在不损害周围耐受性的情况下控制肿瘤微环境中这些抑制性细胞的功能对癌症治疗提出了重大挑战。

BACKGROUND & AIMS: :As colorectal cancer remains the second highest cause of cancer-related deaths in much of the industrialised world, identifying novel strategies to prevent colorectal tumour development remains an important challenge. BAG-1 is a multi-functional protein, the expression of which is up-regulated at relatively early stages in colorectal tumorigenesis. Importantly, BAG-1 is thought to enhance colorectal tumour progression through promoting tumour cell survival. Here, we report for the first time a novel role for BAG-1, establishing it as a suppressor of transforming growth factor β (TGF-β1) expression in colorectal tumour cells. Microarray analysis first highlighted the possibility that BAG-1 may regulate TGF-β1 expression, a key cytokine in normal colonic tissue homoeostasis. Q-RT-PCR and ELISA demonstrated TGFB1 mRNA and protein expression to be significantly increased when BAG1 levels were reduced by small interfering RNA; additionally, induction of BAG-1L caused suppression of TGFB1 mRNA in colorectal tumour cells. Using reporter and chromatin immunoprecipitation assays, a direct association of BAG-1 with the TGFB1 gene regulatory region was identified. Immunohistochemistry and Weiser fraction data indicated that the levels of BAG-1 and TGF-β1 are inversely correlated in the normal colonic epithelium in vivo, consistent with a role for BAG-1-mediated repression of TGF-β1 production. In vitro studies showed that the change in TGF-β1 production following manipulation of BAG-1 is functionally relevant; through induction of anchorage-independent growth in TGF-β1-dependent normal rat kidney fibroblasts and regulation of SMAD2 phosphorylation in TGF-β1-sensitive adenoma cells. Taken together, this study identifies the anti-apoptotic protein BAG-1 as a suppressor of the inhibitory growth factor TGF-β1, suggesting that high expression of BAG-1 can impact on a number of the hallmarks of cancer, of potential importance in promoting the early stages of colorectal tumorigenesis. Establishing BAG-1 as a repressor of TGF-β1 has important biological implications, and highlights a new role for BAG-1 in colorectal tumorigenesis.

背景与目标： ：由于在大多数工业化国家中，结直肠癌仍然是与癌症相关的死亡的第二大原因，因此，确定预防结直肠肿瘤发展的新策略仍然是一项重要的挑战。 BAG-1是一种多功能蛋白，其表达在大肠肿瘤发生的相对早期阶段就被上调。重要的是，BAG-1被认为通过促进肿瘤细胞的存活来增强结直肠肿瘤的进展。在这里，我们首次报道了BAG-1的新作用，确立了它作为大肠肿瘤细胞中转化生长因子β（TGF-β1）表达的抑制剂。微阵列分析首先凸显了BAG-1可能调节TGF-β1表达的可能性，TGF-β1是正常结肠组织稳态中的关键细胞因子。 Q-RT-PCR和ELISA结果表明，当小干扰RNA降低BAG1水平时，TGFB1 mRNA和蛋白表达显着增加。另外，BAG-1L的诱导导致结直肠肿瘤细胞中TGFB1 mRNA的抑制。使用报道分子和染色质免疫沉淀测定法，鉴定了BAG-1与TGFB1基因调控区的直接关联。免疫组织化学和Weiser分数数据表明，体内正常结肠上皮中BAG-1和TGF-β1的含量呈负相关，这与BAG-1介导的抑制TGF-β1产生的作用一致。体外研究表明，操纵BAG-1后TGF-β1产生的变化在功能上相关。通过诱导TGF-β1依赖的正常大鼠肾成纤维细胞中不依赖贴壁的生长以及调节TGF-β1敏感的腺瘤细胞中SMAD2磷酸化。综上所述，这项研究确定了抗凋亡蛋白BAG-1是抑制生长因子TGF-β1的抑制剂，这表明BAG-1的高表达可以影响多种癌症，对促进癌症的发展具有潜在的重要意义。大肠癌发生的早期阶段。建立BAG-1作为TGF-β1的阻遏物具有重要的生物学意义，并突出了BAG-1在结直肠肿瘤发生中的新作用。

BACKGROUND & AIMS: INTRODUCTION:This project addresses the validation study design of a test system using a telemetered non-human primate model for cardiovascular safety pharmacology evaluation. METHODS:The validation provided by the supplier evaluated installation (IQ) and operation (OQ) qualifications. This protocol was completed with tests evaluating electronic data management and accuracy and precision of transmitter (n=4) measurements for temperature and pressure criteria with a series of tested values. As part of performance qualification, physical activity (for 24 h) as well as cardiovascular, ECG (20 complexes for each animal) and systemic arterial blood pressure (SAP, 10 different measures), data were recorded simultaneously from the same animals (n=4) using certified equipment and the telemetry system. Reliability was evaluated over 60 days. RESULTS:The IQ and OQ were completed successfully. The electronic data management was performed successfully. The ex-vivo evaluation for temperature and pressure showed high correlation (R(2)>0.99) but with a slight pressure shift, as expected, with this transmitter model. For physical activity, the correlation coefficients were good to excellent with high activity counts but the comparison demonstrated a limited sensitivity of the telemetry system with animal presenting low activity levels. ECG interval measurement using the telemetry software was considered at least equivalent to manual measurement, but with some limitations in the reading of the ECG. The comparison between both methods of SAP measurement showed adequate precision (R(2)=0.969) but no accuracy. DISCUSSION:Reference monitoring methods are important to ensure proper test system validation. Monitoring with a reference methodology and the telemetry system is important in order to evaluate precision and accuracy of the test system. Computerized analysis may lack the capability to analyze ECG complexes with abnormal morphologies. This reinforces the need to have ECG evaluation prior to telemetry implantation along with visual evaluation of ECG tracing at standard speed (e.g. 50 mm/s) at all time points.

背景与目标： 简介：该项目致力于使用遥测非人类灵长类动物模型进行心血管安全药理学评估的测试系统的验证研究设计。
方法：供应商提供的验证评估了安装（IQ）和操作（OQ）资格。通过评估电子数据管理以及变送器（n = 4）测量的温度和压力标准的准确性和精度的测试，以及一系列测试值，完成了该协议。作为性能鉴定，身体活动（持续24小时）以及心血管，心电图（每只动物20种复合物）和全身动脉血压（SAP，10种不同措施）的一部分，同时记录了来自同一只动物的数据（n = 4）使用经过认证的设备和遥测系统。在60天内评估了可靠性。
结果：智商和OQ均成功完成。电子数据管理已成功执行。温度和压力的离体评估显示出高度相关性（R（2）> 0.99），但与这种变送器模型一样，压力变化不大，正如预期的那样。对于体育活动，相关系数在具有较高活动计数的情况下很好到极好，但是比较结果表明，在动物活动水平较低的情况下，遥测系统的灵敏度有限。使用遥测软件进行的ECG间隔测量被认为至少等同于手动测量，但是在读取ECG方面存在一些限制。两种SAP测量方法之间的比较显示了足够的精度（R（2）= 0.969），但没有精度。
讨论：参考监视方法对于确保正确的测试系统验证很重要。为了评估测试系统的精度和准确性，使用参考方法和遥测系统进行监视非常重要。计算机分析可能缺乏分析形态异常的心电图复合物的能力。这加强了在遥测植入之前进行ECG评估以及在所有时间点以标准速度（例如50 mm / s）进行ECG追踪视觉评估的需求。

BACKGROUND & AIMS: The recent ratification of the World Trade Organisation Agreement will arguably be the most important factor in developing new sanitary measures for the international trade in food over the next decade. There is a markedly increased desire for quantitative data on the microbial risks associated with different classes of foods, and traditional good manufacturing practice (GMP)-based food hygiene requirements are coming under increasing challenge. As the risk assessment paradigm is increasing applied and as decision-making criteria for risk management become established, more emphasis will be placed on predictive microbiology as a means of generating exposure data and establishing critical limits for Hazard Analysis Critical Control Point (HACCP) plans. In this respect, developing international guidelines for risk management arguably presents the greatest challenge in establishing and maintaining quantitative Sanitary and Phytosanitary (SP) measures for food in international trade, and for judging their equivalence. Where specific industry sectors and regulators do not have jurisdiction over the entire food chain, from production of raw materials through to consumption, it will be difficult to apply the risk assessment paradigm in the design of HACCP plans. Thus, it appears that default to food safety objectives for many segments of food production chains subject to application of HACCP plans is inevitable in the medium term.

背景与目标： 可以说，最近批准《世界贸易组织协定》将是在未来十年为国际食品贸易制定新的卫生措施的最重要因素。对于与不同类别食品相关的微生物风险的定量数据的需求显着增加，并且基于传统的良好生产规范（GMP）的食品卫生要求正面临越来越大的挑战。随着风险评估范式的日益应用以及建立风险管理的决策标准，将更加重视预测微生物学，作为生成暴露数据和确定危害分析关键控制点（HACCP）计划的关键限值的一种方法。在这方面，制定国际风险管理准则可以说是在建立和维持国际贸易中食品的卫生检疫和植物检疫定量措施以及判断其等效性方面面临的最大挑战。如果特定的行业部门和监管机构没有对从原料生产到消费的整个食品链进行管辖，那么将很难在HACCP计划的设计中应用风险评估范式。因此，在中期看来，不可避免地要遵循HACCP计划，在食品生产链的许多环节都违背食品安全目标。

BACKGROUND & AIMS: :The effect of immobilization on cell physiology and how this determines cell metabolic performance is an important concern for developing bioprocess. This is particularly true for genetically modified microorganisms and their genetic stability. For this reason the stability and physiological state of plasmid-bearing E. coli cells were ascertained by flow cytometry. Differences in the cellular DNA and protein content (15-20%) permit discrimination of control and plasmid-bearing cells, as well as adaptation to continuous cultivation conditions in both freely suspended and immobilized states to be monitored. Moreover, the observed metabolic burden due to maintenance and over-expression of plasmid-coded genetic material and slow cell growth in poorly-viable immobilized cells were found to be the main factors contributing to strain stabilization.

背景与目标： ：固定化对细胞生理的影响以及这如何决定细胞代谢性能是发展生物过程的重要考虑因素。对于转基因微生物及其遗传稳定性尤其如此。因此，通过流式细胞术确定了带有质粒的大肠杆菌细胞的稳定性和生理状态。细胞DNA和蛋白质含量的差异（15-20％）可以区分对照细胞和带有质粒的细胞，并可以监测自由悬浮和固定状态下连续培养条件的适应性。此外，已发现由于质粒编码的遗传物质的维持和过表达以及在存活率低的固定化细胞中缓慢的细胞生长而导致的观察到的代谢负担是促成菌株稳定的主要因素。

BACKGROUND & AIMS: :Extracellular magnesium ions [Mg2+]o are known to regulate functions of endothelial cells, but whether [Mg2+]o can alter intracellular free ionized magnesium [Mg2+]i in these cells remains unknown. The present studies, using digital imaging microscopy and the Mg2+ fluorescent probe, mag-fura-2, determined effects of elevation of [Mg2+]o on [Mg2+]i in cultured human aortic endothelial cells. With normal Mg2+(1.2 mM)-containing incubation media, [Mg2+]i was 0.51+/-0.04 mM with a heterogeneous distribution. The ratio of [Mg2+]i/[Mg2+]o was 0.52+/-0.07. Elevation of [Mg2+]o up to 4.8 mM increased [Mg2+]i to 0.80+/-0.07 mM in 2-10 min and lowered the ratio of [Mg2+]i/[Mg2+]o to 0.16+/-0.02. Irrespective of the observed increments of [Mg2+]i, a subcellular heterogeneous distribution of [Mg2+]i was always evident in all cells tested. Our results suggest that [Mg2+]o can regulate [Mg2+]i more rapidly than heretofore believed, supporting the hypothesis that extracellular Mg2+ can exert regulatory effects on endothelial cell functions and probably act as extracellular regulatory cations

背景与目标： ：已知细胞外镁离子[Mg2] o调节内皮细胞的功能，但是[Mg2] o是否可以改变这些细胞中的细胞内游离离子化镁[Mg2] i，仍然未知。本研究使用数字成像显微镜和Mg2荧光探针mag-fura-2，确定了培养的人主动脉内皮细胞中[Mg2] o升高对[Mg2] i的影响。在正常的含Mg2（1.2 mM）的培养培养基中，[Mg2] i为0.51 / 0.04 mM，分布不均。 [Mg 2] i / [Mg 2] o的比例为0.52 / -0.07。 [Mg2] o升高至4.8 mM会使[Mg2] i在2-10分钟内增加到0.80 /-0.07 mM，并使[Mg2] i / [Mg2] o的比率降低到0.16 /-0.02。不管观察到的[Mg2] i增量如何，在所有测试的细胞中[Mg2] i的亚细胞异质分布总是很明显的。我们的结果表明，[Mg2] o可以比以前认为的更快地调节[Mg2] i，支持以下假设：细胞外Mg2可以对内皮细胞功能发挥调节作用，并且可能充当细胞外调节阳离子

BACKGROUND & AIMS: Histochemical, immunohistochemical, and biochemical evidence is reported showing that the ink gland of the cuttlefish Sepia officinalis contains a calcium-dependent isoform of nitric oxide synthase as well as an NMDA R1 receptor subunit localized for the most part in the immature inner cells of the epithelial layer of the gland. These results may be taken to implicate a hitherto unrecognized regulatory role of the glutamate-nitric oxide pathway in the maturation and metabolic activity of melanin-producing cells in the cephalopod defense system.

背景与目标： 据组织化学，免疫组织化学和生物化学证据显示，墨鱼乌贼墨the的墨腺含有一氧化氮合酶的钙依赖性同工型，以及大部分位于上皮未成熟内细胞中的NMDA R1受体亚基。腺体层。这些结果可能暗示了迄今为止尚未认识到的谷氨酸一氧化氮途径在头足防御系统中黑色素生成细胞的成熟和代谢活性中的作用。

BACKGROUND & AIMS: :'Citizen participation' includes various participatory techniques and is frequently viewed as an unproblematic and important social good when used as part of the regulation of the innovation and implementation of science and technology. This is perhaps especially evident in debates around 'anticipatory governance' or 'upstream engagement'. Here, we interrogate this thesis using the example of the European Union's regulation of emerging health technologies (such as nanotechnology). In this case, citizen participation in regulatory debate is concerned with innovative objects for medical application that are considered to be emergent or not yet concrete. Through synthesising insights from law, regulatory studies, critical theory, and science and technology studies, we seek to cast new light on the promises, paradoxes, and pitfalls of citizen participation as a tool or technology of regulation in itself. As such we aim to generate a new vantage point from which to view the values and sociotechnical imaginaries that are both 'designed-in' and 'designed-out' of citizen participation. In so doing, we show not only how publics (do not) regulate technologies, but also how citizens themselves are regulated through the techniques of participation.

背景与目标： ：“公民参与”包括各种参与性技术，在用作科学技术创新和实施的一部分时，通常被认为是毫无问题且重要的社会公益。在有关“预期治理”或“上游参与”的辩论中，这一点尤其明显。在这里，我们以欧洲联盟对新兴卫生技术（例如纳米技术）的监管为例，对本论文进行审讯。在这种情况下，公民参与监管辩论与医疗应用的创新对象有关，这些对象被认为是新兴的或尚未具体的。通过综合来自法律，监管研究，批判理论以及科学和技术研究的见解，我们寻求对公民参与作为其自身的工具或技术的承诺，悖论和陷阱进行新的阐释。因此，我们旨在产生一个新的视角，从中可以查看“参与式”设计和“参与式”设计的公民参与的价值观和社会技术想象力。通过这样做，我们不仅展示了公众如何（不）规范技术，而且还展示了如何通过参与技术来规范公民自身。

BACKGROUND & AIMS: :Long term bioassays in animals cannot reliably forecast unknown potential but distant human risks, and especially cancer risks. The genetic, anatomic, physiologic, behavioral and environmental adaptations of rats and mice - the officially prescribed animals - are not relevant to humans. Even bioassay results for the two prescribed species are not mutually predictive. The dearth of human relevance is augmented by arbitrary and incongruous default assumptions, also officially prescribed for the conduct and interpretation of bioassays in rats and mice. Moreover, and contrary to publicized perceptions, bioassay results are freely evaded in the markup of regulations, with the imposition of arbitrary safety factors and the guided opinions of ad hoc appointed advisory committees. Regardless of bioassay results, actual regulations of unknowable distant risks end up allowing those minimum exposures that are still compatible with uses deemed necessary or useful for the common welfare. Thus it would seem sensible to do away with very costly long-term bioassays irrelevant to humans and whose results are anyway bypassed, and to focus regulations on short-term effects relevant to humans, and on transparent cost and benefit considerations toward minimizing useful exposures.

背景与目标： ：动物的长期生物测定不能可靠地预测潜在的未知因素，但有遥远的人类风险，尤其是癌症风险。大鼠和小鼠（官方指定的动物）的遗传，解剖，生理，行为和环境适应与人类无关。甚至两个规定物种的生物测定结果也不是相互预测的。人类相关性的缺乏由于任意和不协调的默认假设而加剧，默认假设也被正式规定用于在大鼠和小鼠中进行和进行生物测定。而且，与公开的看法相反，生物测定的结果在规章的标记中被随意规避，施加了任意的安全系数和特设咨询委员会的指导意见。不管生物测定的结果如何，最终的不可知的远距离风险的实际规定最终都允许那些仍与认为对共同福利必要或有用的用途兼容的最低暴露量。因此，取消与人类无关，成本高昂的长期生物测定方法，无论如何都要避免其结果，而将法规重点放在与人类有关的短期影响上，以及将透明的成本和收益考虑因素集中到最大限度地减少有用的暴露量上，似乎是明智的。

BACKGROUND & AIMS: :To maximize the biomass and lipid production for applications in food or biofuel feedstock, nine stress conditions were tested considering N and/or P limitations, light intensity & quality, for Haematococcus pluvialis SCCAP K-0084 cultivation. Photosynthetically active radiation (PAR), warm white light emitting diode (WWLED), and white light emitting diode (WLED) at illumination of 240 μmol photons m(-2) sec(-1) were the best stress-regulatory factors. PAR without P & low N conditions yielded high biomass with 33% lipids containing increased C16:0 and C18:0 saturated fatty acids, and reduced unsaturated fatty acids (UFAs) (oleic, linoleic, and α/γ-linolenic). WWLED and WLED without P conditions also yielded high biomass, but 25% lipids with increased amounts of UFAs. Red light emitting diode (RLED) without P & low N conditions yielded 46% lipids with lowest biomass. PAR and WWLED & WLED illuminated conditions were found suitable respectively for biodiesel feedstock lipids and UFA-rich lipids for multiple applications.

背景与目标： ：为了使生物质和脂质的生产最大化以用于食品或生物燃料原料，测试了九种胁迫条件，考虑了氮和/或磷的限制，光强度和质量，适用于雨生红球菌SCCAP K-0084的培养。在240μmol光子m（-2）sec（-1）的光照下，光合有效辐射（PAR），暖白光发光二极管（WWLED）和白光发光二极管（WLED）是最佳的应力调节因子。没有P和低N条件的PAR产生了高生物量，其中33％的脂质包含增加的C16：0和C18：0饱和脂肪酸，以及减少的不饱和脂肪酸（UFAs）（油酸，亚油酸和α/γ-亚麻酸）。没有P条件的WWLED和WLED也产生高生物量，但是25％的脂质具有增加的UFA含量。没有P和低N条件的红色发光二极管（RLED）产生了46％的脂质，具有最低的生物量。发现PAR和WWLED和WLED照明的条件分别适合于生物柴油原料脂质和富含UFA的脂质的多种应用。

BACKGROUND & AIMS: PURPOSE:After the Fontan procedure, children exhibit reduced peak exercise capacity, yet their submaximal exercise response remains unclear. This study sought to determine the relationship between submaximal and peak exercise capacity and physical activity in Fontan patients. METHODS:This cross-sectional study recruited 50 Fontan patients (59% males) with a median age of 9 yr (range = 6-12 yr). The median age at Fontan procedure was 2.9 yr (range = 1.6-9.1 yr). Study assessments included medical history, exercise testing, and accelerometry. RESULTS:Significantly lower submaximal oxygen consumption (V˙O2) and HR in response to a standardized workload than published values for healthy children (mean ± SD) of -1.72 ± 5.24 (P < 0.001) and -1.45 ± 1.98 (P < 0.001), respectively, suggest enhanced submaximal work efficiency in this group of patients after Fontan. Higher submaximal V˙O2 z-score was associated with higher submaximal HR z-score (P = 0.02) and lower body mass index z-score (P = 0.01). Higher V˙O2peak was associated with higher submaximal V˙O2 z-score (P < 0.01), male sex (P = 0.03), higher RER (P = 0.02), lower submaximal HR z-score (P < 0.01), and higher chronotropic responsiveness (P < 0.0001). Exercise test duration z-score was associated with lower submaximal HR z-score (P = 0.02) and higher chronotropic responsiveness (P = 0.02). CONCLUSIONS:Fontan patients exhibited a lower submaximal V˙O2 and HR responsiveness at a given workload than healthy controls did during standardized exercise testing. Thus, they may be better adapted to perform submaximal exercise. Although peak exercise capacity is limited, Fontan patients are able to perform submaximal physical activities at the same level as their healthy peers.

背景与目标： 目的：进行丰坦手术后，儿童的峰值运动能力下降，但其次最大运动反应仍不清楚。这项研究试图确定丰坦患者亚最大和最大运动能力与身体活动之间的关系。
方法：这项横断面研究招募了50名Fontan患者（男性占59％），中位年龄为9岁（范围= 6-12岁）。丰坦手术的中位年龄为2.9岁（范围= 1.6-9.1岁）。研究评估包括病史，运动测试和加速度计。
结果：标准化工作量下的最大摄氧量（V˙O2）和HR显着低于健康儿童的公布值（平均值±SD）的-1.72±5.24（P <0.001）和-1.45±1.98（P <0.001） ）分别表明，在接受Fontan治疗后，该组患者的工作效率得到了提高。较高的V subO2 z评分较高与较高的HR z评分较低（P = 0.02）和较低的体重指数z评分（P = 0.01）相关。较高的V˙O2peak与较高的V˙O2z分数较高（P <0.01），男性（P = 0.03），较高的RER（P = 0.02），较低的最大HR z分数（P <0.01）和更高的变时响应性（P <0.0001）。运动测试持续时间z分数与较低的最大心率z分数（P = 0.02）和较高的变时反应性（P = 0.02）相关。
结论：在标准的运动测试中，与健康对照组相比，在一定的工作量下，Fontan患者表现出低于最大的V˙O2和HR反应性。因此，它们可能更好地适于进行次最大运动。尽管峰值运动能力有限，但Fontan患者能够以与健康同龄人相同的水平进行次最大的体育锻炼。

BACKGROUND & AIMS: :Interactions between transcription factors and target genes form regulatory networks that control target gene expression. Regulatory networks contain canonical motifs, including the feed forward loop (FFL), single input module (SIM), and multiple input module (MIM) (Fig. 1). A challenge for network analysis is to identify and enumerate the motifs, required to illuminate their biological significance. Although there is consensus about the definition of the FFL, published definitions of the SIM and MIM are unclear and often used inconsistently. Here, we provide, for the first time, a complete and consistent definition of SIM and MIM, and algorithms for enumerating SIMs and MIMs in any network. From the algorithmic point of view, enumeration of SIMs and MIMs is substantially harder than enumerating FFLs. We compare the distributions of motifs in the Yeast regulatory network under different physiological conditions, reported earlier by the landmark paper of Luscombe et al. (Nature 2004, 431: 308-312). Our reanalysis shows major differences in the number of motifs compared with the results of those authors, requiring significant revision of some of their conclusions.

背景与目标： 转录因子与靶基因之间的相互作用形成控制靶基因表达的调节网络。监管网络包含规范主题，包括前馈环路（FFL），单输入模块（SIM）和多输入模块（MIM）（图1）。网络分析的一个挑战是识别并枚举阐明其生物学意义所需的基序。尽管对FFL的定义已达成共识，但已发布的SIM和MIM的定义尚不清楚，并且经常使用不一致。在这里，我们首次提供了完整和一致的SIM卡和MIM定义，以及用于枚举任何网络中的SIM卡和MIM的算法。从算法的角度来看，SIM和MIM的枚举比枚举FFL的难度大得多。我们比较了不同生理条件下酵母调节网络中基序的分布，这是由Luscombe等人的地标性论文较早报道的。 （Nature 2004，431：308-312）。我们的重新分析表明，与那些作者的结果相比，母题的数量存在重大差异，需要对他们的某些结论进行重大修改。