BACKGROUND & AIMS: :Diverse animals can orient using geomagnetic cues, but little is known about the neurophysiological mechanisms that underlie magnetic field detection. The marine mollusc Tritonia diomedea (Bergh) has a magnetic sense and its nervous system is amenable to cellular-level electrophysiological analysis. In a semi-intact whole-animal preparation, intracellular recordings from the large, visually identifiable neurons left pedal 5 (LPe5) and right pedal 5 (RPe5) in the brain of Tritonia revealed enhanced electrical activity in response to changes in ambient earth-strength magnetic fields. No such changes in activity were observed in approximately 50 other neurons subjected to identical magnetic stimuli. The responses of LPe5 were characterized by increases in spiking frequency occurring about 6-16 min after the ambient magnetic field had been rotated to a new position. The response was abolished when the brain had been isolated from the periphery of the animal by severing nerves, a procedure that also transected prominent neurites of LPe5. We hypothesize that LPe5 is one component of a neural circuit mediating detection of the earth's magnetic field or orientation to it.

背景与目标： ：各种各样的动物可以利用地磁线索进行定向，但是对于磁场检测基础的神经生理机制知之甚少。海洋软体动物Tritonia diomedea（Bergh）具有磁性，其神经系统可进行细胞水平的电生理分析。在半完整的全动物制剂中，来自Tritonia大脑中大的，视觉上可识别的神经元左脚踏板5（LPe5）和右脚踏板5（RPe5）的细胞内记录显示出响应于周围地球力量的变化而增强的电活动。磁场。在大约50个受到相同磁刺激的其他神经元中未观察到这种活动变化。 LPe5的响应的特征是在周围磁场旋转到新位置后约6-16分钟出现尖峰频率增加。当通过切断神经将大脑与动物外周隔离时，这种反应就消失了，这种方法也可以切断LPe5的突出神经突。我们假设LPe5是神经回路的一个组成部分，它介导对地球磁场或磁场定向的检测。

BACKGROUND & AIMS: :Paracoccidioides brasiliensis isolates are not homogeneous in their patterns of pathogenicity in animals and adhesion to epithelial cells. During this investigation, genotypic differences were observed between two samples of P. brasiliensis strain 18 yeast phase (Pb18) previously cultured many times, one taken before (Pb18a) and the other after (Pb18b) animal inoculation. Random amplified polymorphic DNA analysis using the primer OPJ4 distinguished Pb18b from Pb18a by one 308 bp DNA fragment, which after cloning and sequencing was shown to encode a polypeptide sequence homologous to the protein beta-adaptin. It is suggested, by comparison to other micro-organisms, that this protein might play an important role in the virulence of P. brasiliensis. This result demonstrates the influence of in vitro subculturing on the genotype of this organism.

背景与目标： ：巴西对虾的分离株在动物中的致病性和对上皮细胞的粘附方式不均一。在这项研究过程中，观察到两次培养过多次的巴西假单胞菌菌株18酵母相（Pb18）的基因型差异，一个样品是在接种动物之前（Pb18a），另一个是在接种之后（Pb18b）。使用引物OPJ4进行的随机扩增多态性DNA分析通过一个308 bp DNA片段将Pb18b与Pb18a区别开来，该片段在克隆和测序后显示编码与蛋白质β-adaptin同源的多肽序列。与其他微生物相比，该蛋白质可能在巴西假单胞菌的毒力中起重要作用。该结果证明了体外传代培养对该生物的基因型的影响。

BACKGROUND & AIMS: BACKGROUND:Reverse engineering cellular networks is currently one of the most challenging problems in systems biology. Dynamic Bayesian networks (DBNs) seem to be particularly suitable for inferring relationships between cellular variables from the analysis of time series measurements of mRNA or protein concentrations. As evaluating inference results on a real dataset is controversial, the use of simulated data has been proposed. However, DBN approaches that use continuous variables, thus avoiding the information loss associated with discretization, have not yet been extensively assessed, and most of the proposed approaches have dealt with linear Gaussian models. RESULTS:We propose a generalization of dynamic Gaussian networks to accommodate nonlinear dependencies between variables. As a benchmark dataset to test the new approach, we used data from a mathematical model of cell cycle control in budding yeast that realistically reproduces the complexity of a cellular system. We evaluated the ability of the networks to describe the dynamics of cellular systems and their precision in reconstructing the true underlying causal relationships between variables. We also tested the robustness of the results by analyzing the effect of noise on the data, and the impact of a different sampling time. CONCLUSION:The results confirmed that DBNs with Gaussian models can be effectively exploited for a first level analysis of data from complex cellular systems. The inferred models are parsimonious and have a satisfying goodness of fit. Furthermore, the networks not only offer a phenomenological description of the dynamics of cellular systems, but are also able to suggest hypotheses concerning the causal interactions between variables. The proposed nonlinear generalization of Gaussian models yielded models characterized by a slightly lower goodness of fit than the linear model, but a better ability to recover the true underlying connections between variables.

背景与目标： 背景技术：反向工程蜂窝网络目前是系统生物学中最具挑战性的问题之一。动态贝叶斯网络（DBN）似乎特别适用于通过对mRNA或蛋白质浓度的时间序列测量结果进行分析来推断细胞变量之间的关系。由于评估真实数据集上的推理结果存在争议，因此提出了使用模拟数据的建议。然而，尚未对使用连续变量，从而避免与离散化相关的信息丢失的DBN方法进行了广泛的评估，并且大多数提议的方法已经处理了线性高斯模型。
结果：我们提出了动态高斯网络的一般化，以适应变量之间的非线性依赖性。作为测试新方法的基准数据集，我们使用了发芽酵母中细胞周期控制数学模型的数据，真实地再现了细胞系统的复杂性。我们评估了网络描述蜂窝系统动态的能力及其在重构变量之间真正的因果关系上的精度。我们还通过分析噪声对数据的影响以及不同采样时间的影响，测试了结果的鲁棒性。
结论：结果证实具有高斯模型的DBN可以有效地用于复杂细胞系统数据的第一级分析。推断的模型是简约的，并且具有令人满意的拟合优度。此外，这些网络不仅提供了细胞系统动力学的现象学描述，而且还能够提出有关变量之间因果关系的假设。提出的高斯模型非线性泛化得出的模型的拟合优度比线性模型低，但具有恢复变量之间真正基础联系的能力。

BACKGROUND & AIMS: :We investigated the conditions under which inhomogeneity in electrical conductivity may significantly modify the magnetic evoked field (MEF) due to primary currents (i.e., neuronal currents) in the brain. In the case of an isolated turtle cerebellum immersed in a large bath of physiological saline, our theoretical analysis showed the cerebellar surface to significantly enhance the MEF due to a primary current, by a factor of as much as two, for experimentally determined values of the conductivities of the cerebellar tissue and saline. A further parametric investigation of the conductivity effect revealed that conductivity boundaries may significantly modify the MEF due to neuronal currents located within 1 mm of a conductivity boundary, as would be the case for active neurons near an edema, an anoxic fringe such as might occur during stroke, or a ventricle in the human head. For a stationary neural source, conductivity boundaries may modify the magnitude of its MEF without affecting its temporal waveform. However, this boundary effect was found to be small for a model geometry locally approximating cortical sources in a sulcus or a fissure, where the boundary effects from adjacent sulcal walls tend to cancel each other.

背景与目标： ：我们研究了由于大脑中的初级电流（即神经元电流）导致电导率不均匀会显着改变电磁诱发磁场（MEF）的情况。对于孤立的乌龟小脑浸没在生理盐水中的情况，我们的理论分析表明，由于初级电流，小脑表面由于一次电流而使MEF显着提高了2倍。小脑组织和盐水的电导率。对电导率影响的进一步参数研究表明，由于神经元电流位于电导率边界的1毫米之内，电导率边界可能会显着改变MEF，就像水肿附近的活动神经元那样，缺氧边缘可能会在中风，或人脑中的心室。对于固定的神经源，电导率边界可以在不影响其时间波形的情况下修改其MEF的大小。但是，对于局部近似于沟或裂隙中的皮质源的模型几何，发现该边界效应很小，其中相邻沟壁的边界效应往往会相互抵消。

BACKGROUND & AIMS: :A high fidelity computational fluid dynamic model is used to simulate the flow, pressure, and density fields generated in a cylindrical and a conical resonator by a vibrating end wall/piston producing high-amplitude standing waves. The waves in the conical resonator are found to be shock-less and can generate peak acoustic overpressures that exceed the initial undisturbed pressure by two to three times. A cylindrical (consonant) acoustic resonator has limitations to the output response observed at one end when the opposite end is acoustically excited. In the conical geometry (dissonant acoustic resonator) the linear acoustic input is converted to high energy un-shocked nonlinear acoustic output. The model is validated using past numerical results of standing waves in cylindrical resonators. The nonlinear nature of the harmonic response in the conical resonator system is further investigated for two different working fluids (carbon dioxide and argon) operating at various values of piston amplitude. The high amplitude nonlinear oscillations observed in the conical resonator can potentially enhance the performance of pulse tube thermoacoustic refrigerators and these conical resonators can be used as efficient mixers.

背景与目标： ：高保真计算流体动力学模型用于模拟由振动端壁/活塞产生高振幅驻波而在圆柱和圆锥形谐振器中产生的流场，压力和密度场。发现圆锥形谐振器中的波无冲击，并且可以产生峰值声学超压，其超过初始未扰动压力的2到3倍。当在另一端被声学激励时，圆柱形（辅音）声谐振器对在一端观察到的输出响应具有局限性。在圆锥形几何体（谐振声学谐振器）中，线性声学输入被转换为高能量，不受电击的非线性声学输出。使用过去在圆柱谐振器中驻波的数值结果验证了该模型。对于在活塞振幅的各种值下工作的两种不同的工作流体（二氧化碳和氩气），将进一步研究圆锥形谐振器系统中谐波响应的非线性特性。在圆锥形谐振器中观察到的高振幅非线性振荡可以潜在地增强脉冲管热声制冷机的性能，并且这些圆锥形谐振器可以用作有效的混频器。

BACKGROUND & AIMS: BACKGROUND:The expansion of science has resulted in an increased information flow and in an exponentially growing number of connections between knowledge in different research fields. In this study, we used methods of scientometric analysis to obtain a conceptual network that forms the structure of active scientific research fields in anesthesia. METHODS:We extracted from the Web of Science (Institute for Scientific Information) all original articles (n = 3275) including their references (n = 79,972) that appeared in 2003 in all 23 journals listed in the Institute for Scientific Information Journal Citation Reports under the subject heading "Anesthesiology." After identification of highly cited references (> or = 5), pairs of co-cited references were created and grouped into uniformly structured clusters of documents using a single linkage and variable level clustering method. In addition, for each such cluster of documents, we identified corresponding front papers published in 2003, each of which co-cited at least two documents of the cluster core. Active anesthetic research fields were then named by examining the titles of the documents in both the established clusters and in their corresponding front papers. These research fields were sorted according to the proportion of recent documents in their cluster core (immediacy index) and were further analyzed. RESULTS:Forty-six current anesthetic research fields were identified. The research field named "ProSeal laryngeal mask airway" showed the highest immediacy index (100%) whereas the research fields "Experimental models of neuropathic pain" and "Volatile anesthetic-induced cardioprotection" exhibited the highest level of co-citation strength (level 9). The research field with the largest cluster core, containing 12 homogeneous papers, was "Postoperative nausea and vomiting." The journal Anesthesia & Analgesia published most front papers while Anesthesiology published most of the fundamental documents used as references in the front papers. CONCLUSIONS:Using co-citation analysis, we identified distinct homogenous clusters of highly cited documents representing 46 active current anesthetic research fields and determined multiple nets of knowledge among them.

背景与目标： 背景：科学的发展导致信息流增加，不同研究领域的知识之间的联系呈指数增长。在这项研究中，我们使用了科学计量分析的方法来获得一个概念网络，该网络形成了麻醉领域活跃的科研领域的结构。
方法：我们从Web of Science（科学信息研究所）中提取了所有原始文章（n = 3275），包括其参考文献（n = 79,972），这些文章出现在2003年在《科学信息研究所期刊引文报告》下列出的所有23种期刊中主题为“麻醉学”。在识别出高引用的参考文献（>或= 5）之后，使用单链接和可变级别聚类方法创建成对的同被引用参考文献，并将其分组为结构统一的文档簇。另外，对于每个这样的文档集群，我们确定了2003年发布的相应的前文，其中每篇都共同引用了该集群核心的至少两个文档。然后，通过检查已建立的集群及其相应的前文中文件的标题来命名活跃的麻醉研究领域。这些研究领域根据其集群核心中的最新文献的比例（即时指数）进行分类，并进行了进一步分析。
结果：目前已确定了46种麻醉药研究领域。名为“ ProSeal喉罩气道”的研究领域具有最高的即时指数（100％），而“神经病理性疼痛的实验模型”和“挥发性麻醉药诱导的心脏保护”研究领域表现出最高的共被引强度（9级） ）。簇状核最大的研究领域是“术后恶心和呕吐”，其中包含12篇同类论文。 《麻醉与镇痛》杂志发表了大多数前期论文，而《麻醉学》则发表了用作前篇论文参考的大多数基本文献。
结论：使用共引分析法，我们鉴定了代表46个活跃的当前麻醉研究领域的，被高度引用的文献的不同同质簇，并在其中确定了多个知识网络。

BACKGROUND & AIMS: :The respective use of random (RPC) and apheresis (APC) platelet concentrates is highly heterogeneous among countries, ranging from 10 to 98% RPC in countries supposed to provide a similar transfusion service to patients. Moreover, when considering each country in the past 10 years, one can observe that some have changed their policy, switching from a majority of APC to RPC or vice versa. This presentation intends to analyse which factors may impact such decisions. For many years, the only available platelet component was a RPC obtained from whole blood donation by a two centrifugation steps process, the "platelet rich plasma" or PRP method. Since the beginning of the 1970s, APCs became available, with in fact many different techniques leading to many APCs that may not be equivalent. Since the end of the 1980s, a new method of RPC preparation was developed, using the buffy-coat (BC-PC), providing a blood component with highly preserved platelet functions as compared to RPCs prepared by the PRP technique. Finally, the use of each of these components either native, or leuco-reduced, or suspended in a storage solution, or processed with a pathogen inactivation technique adds new layers of complexity to compare them. Innumerable references can be found in the literature describing in vitro functional parameters of platelet concentrates. Although it is clear that BC-RPC retain much more their in vitro functions than PRP-RPC, indicating that no one should use the latter any more, it is much more difficult to distinguish differences between other PCs. Conversely, only a very few studies have been published related to a comparison of clinical efficacy of RPC versus APC, the endpoints being mainly CCI. Similarly to the in vitro studies, although RPC prepared with the PRP method show the lowest CCIs, no clear difference exists between "modern" RPC and APC. Another factor that may impact policy decision is the occurrence of adverse reactions in recipients. When considering only comparable data, for example leuco-reduced RPC versus leuco-reduced APC, there is now evidence that the latter is more associated with adverse reactions in recipients: data from hemovigilance in France show that, although no difference is noted for febrile non haemolytic transfusion reactions, nor for bacteria contamination, the incidence of allergic adverse reactions is about four times higher with APC as compared with RPC. Other aspects may impact the decision: the fact that using APC in place of RPC reduces the total donor exposure of patients was considered critical in some countries to reduce the risk of transmission of blood transmissible disease. Finally, the cost of the components, much higher for APC may be considered.

背景与目标： ：随机（RPC）和单采血液（APC）血小板浓缩液的使用在各国之间是高度异质的，在应该向患者提供类似输血服务的国家中，RPC的使用范围从10％到98％不等。此外，在过去10年中考虑每个国家时，可以观察到一些国家改变了其政策，从大多数APC转换为RPC，反之亦然。本演示文稿旨在分析哪些因素可能影响此类决策。多年来，唯一可用的血小板成分是通过两个离心步骤过程（“富含血小板的血浆”或PRP方法）从全血中获得的RPC。自1970年代初以来，APC便已问世，实际上有许多不同的技术导致许多APC可能不等效。自1980年代末以来，使用血沉棕黄层（BC-PC）开发了一种新的RPC制备方法，与通过PRP技术制备的RPC相比，该血液组分具有高度保留的血小板功能。最后，使用这些天然成分或无色成分减少的成分，或悬浮在存储溶液中或使用病原体灭活技术处理的成分，都增加了新的复杂度来比较它们。在描述血小板浓缩物的体外功能参数的文献中可以找到无数的参考文献。尽管很明显BC-RPC比PRP-RPC保留了更多的体外功能，这表明没有人可以再使用PRP-RPC，但是要区分其他PC之间的差异要困难得多。相反，只有很少的研究发表过与RPC和APC的临床疗效比较相关的研究，其终点主要是CCI。与体外研究相似，尽管用PRP方法制备的RPC显示出最低的CCI，但“现代” RPC和APC之间没有明显的区别。可能影响政策决策的另一个因素是受助者中发生的不良反应。当仅考虑可比较的数据时，例如白细胞减少的RPC与白细胞减少的APC，现在有证据表明后者与接受者的不良反应相关：法国的血液警惕性数据表明，尽管对于发热性非酒精性脂肪性肝炎没有观察到差异。与RPC相比，APC的溶血性输血反应或细菌污染的变态反应性不良反应的发生率大约高四倍。其他方面可能会影响该决策：在某些国家，使用APC代替RPC可以减少患者的总供体暴露这一事实对于减少血液传播疾病的传播风险至关重要。最后，可以考虑组件的成本，对于APC而言，成本要高得多。

BACKGROUND & AIMS: :Platelet concentrates are routinely manufactured from whole blood by differential centrifugation (random donor platelets-RDP) or by plateletpheresis (single donor platelets-SDP). These platelet concentrates have a storage period of 5 days and many different approaches exist to measure the condition of platelets during their storage. In this study, platelet aggregation testing using adenosine diphosphate (ADP) and collagen and flow cytometric platelet activation analysis using CD41 FITC and CD62 PE before and after ADP was performed on days 1, 3 and 5 of storage of platelet preparations. Thirty three RDPs, stored in Baxter and Kansuk blood bags and 18 SDPs stored in Fresenius blood bags were evaluated. In RDPs and in SDPs; ADP and collagen induced PA responses were decreased significantly on the 3rd and 5th days compared to 1st day. CD62 positive platelet percentage after ADP were decreased significantly on the 3rd and 5th days compared to the 1st day in Kansuk bags. Flow cytometric analysis revealed minor changes in CD41 expression after ADP on the 3rd day compared to 1st day and on the 5th day compared to 3rd day. Differences in CD62 positive platelet percentage were not significant between the RDPs and SDPs. Our results suggest that: (1) ADP and collagen induced PA responses decrease both in RDPs and SDPs during storage. (2) Flow cytometric analysis does not show major significant changes in platelet activation after ADP during storage. (3) Continous shaking on the agitator does not cause a significant change in CD62 positive platelet percentage during storage. (4) Platelet aggregation responses in RDPs stored in Baxter and Kansuk blood bags do not differ during storage.

背景与目标： 血小板浓缩物通常通过全血通过差速离心（随机供体血小板-RDP）或血小板分离（单供体血小板-SDP）制成。这些血小板浓缩物的储存期为5天，并且存在许多不同的方法来测量血小板在储存过程中的状况。在这项研究中，在血小板制品储存的第1、3和5天进行了使用二磷酸腺苷（ADP）和胶原蛋白进行的血小板聚集测试，以及在使用ADP之前和之后使用CD41 FITC和CD62 PE进行的流式细胞术血小板活化分析。对存储在Baxter和Kansuk血袋中的33个RDP和存储在费森尤斯血袋中的18个SDP进行了评估。在RDP和SDP中；与第一天相比，第三天和第五天ADP和胶原蛋白诱导的PA反应显着降低。与Kansuk袋中的第1天相比，ADP后第3天和第5天的CD62阳性血小板百分比显着下降。流式细胞仪分析显示，与第一天相比，ADP后第3天和第3天与第5天相比，CD41的表达有轻微变化。 RDP和SDP之间CD62阳性血小板百分比的差异不显着。我们的结果表明：（1）在储存过程中，ADP和胶原诱导的PA反应在RDP和SDP中均降低。 （2）流式细胞仪分析未显示ADP储存后血小板活化的主要显着变化。 （3）在储存过程中，在搅拌器上连续摇动不会引起CD62阳性血小板百分比的显着变化。 （4）储存在Baxter和Kansuk血袋中的RDP中的血小板聚集反应没有差异。

BACKGROUND & AIMS: :Tyrosine phenol-lyase (Tpl), which can synthesize 3, 4-dihydroxyphenylalanine from pyruvate, ammonia, and catechol, is a tyrosine-inducible enzyme. Previous studies demonstrated that the tpl promoter of Erwinia herbicola is activated by the TyrR protein of Escherichia coli. In an attempt to create a high-Tpl-expressing strain, we cloned the tyrR gene of E. herbicola and then randomly mutagenized it. Mutant TyrR proteins with enhanced ability to activate tpl were screened for by use of the lac reporter system in E. coli. The most increased transcription of tpl was observed for the strain with the mutant tyrR allele involving amino acid substitutions of alanine, cysteine, and glycine for valine-67, tyrosine-72, and glutamate-201, respectively. A tyrR-deficient derivative of E. herbicola was constructed and transformed with a plasmid carrying the mutant tyrR allele (V67A Y72C E201G substitutions). The resultant strain expressed Tpl without the addition of tyrosine to the medium and produced as much of it as was produced by the wild-type strain grown under tyrosine-induced conditions. The regulatory properties of the mutant TyrR(V67A), TyrR(Y72C), TyrR(E201G), and TyrR(V67A Y72C E201G) proteins were examined in vivo. Interestingly, as opposed to the wild-type TyrR protein, the mutant TyrR(V67A) protein had a repressive effect on the tyrP promoter in the presence of phenylalanine as the coeffector.

背景与目标： 酪氨酸酚裂解酶（Tpl）可以从酪氨酸，氨水和邻苯二酚合成3，4-二羟基苯丙氨酸，是一种酪氨酸诱导酶。先前的研究表明，草食欧文氏菌的tpl启动子被大肠杆菌的TyrR蛋白激活。为了创建高表达Tpl的菌株，我们克隆了E. herbicola的tyrR基因，然后对其进行了随机诱变。通过使用大肠杆菌中的lac报告系统筛选具有增强的tpl激活能力的突变TyrR蛋白。对于具有突变tyrR等位基因的菌株，观察到tpl的转录增加最多，所述突变体分别涉及丙氨酸，半胱氨酸和甘氨酸的氨基酸取代缬氨酸67，酪氨酸72和谷氨酸201。构建了E. herbicola的tyrR缺陷型衍生物，并用携带突变型tyrR等位基因（V67A Y72C E201G替代）的质粒转化。所得菌株在不向培养基中添加酪氨酸的情况下表达Tpl，并产生与在酪氨酸诱导的条件下生长的野生型菌株所产生的一样多的菌株。在体内检查了突变体TyrR（V67A），TyrR（Y72C），TyrR（E201G）和TyrR（V67A Y72C E201G）蛋白的调控特性。有趣的是，与野生型TyrR蛋白相反，突变型TyrR（V67A）蛋白在存在苯丙氨酸作为协同增效剂的情况下对tyrP启动子具有抑制作用。

BACKGROUND & AIMS: BACKGROUND:Organ motion during treatment delivery in radiotherapy (RT) may lead to deterioration of the planned dose, but can be mitigated by dynamic multi-leaf collimator (DMLC) tracking. The purpose of this study was to implement and experimentally validate a method for time-resolved motion including dose reconstruction for volumetric modulated arc therapy (VMAT) treatments delivered with and without DMLC tracking. MATERIAL AND METHODS:Tracking experiments were carried out on a linear accelerator (Trilogy, Varian) with a prototype DMLC tracking system. A motion stage carrying a biplanar dosimeter phantom (Delta4PT, Scandidos) reproduced eight representative clinical tumor trajectories (four lung, four prostate). For each trajectory, two single-arc 6 MV VMAT treatments with low and high modulation were delivered to the moving phantom with and without DMLC tracking. An existing in-house developed program that adds target motion to treatment plans was extended with the ability to split an arc plan into any number of sub-arcs, allowing the calculated dose for different parts of the treatment to be examined individually. For each VMAT sub-arc, reconstructed and measured doses were compared using dose differences and 3%/3 mm γ-tests. RESULTS:For VMAT sub-arcs the reconstructed dose distributions had a mean root-mean-square (rms) dose difference of 2.1% and mean γ failure rate of 2.0% when compared with the measured doses. For final accumulated doses the mean rms dose difference was 1.6% and the γ failure rate was 0.7%. CONCLUSION:The time-resolved motion including dose reconstruction was experimentally validated for complex tracking and non-tracking treatments with patient-measured tumor motion trajectories. The reconstructed dose will be of high value for evaluation of treatment plan robustness facing organ motion and adaptive RT.

背景与目标： 背景：放射治疗（RT）进行治疗期间的器官运动可能会导致计划剂量的恶化，但可以通过动态多叶准直仪（DMLC）跟踪来缓解。这项研究的目的是实施并通过实验验证一种用于时间分辨运动的方法，包括采用和不采用DMLC跟踪进行体积调制电弧治疗（VMAT）治疗的剂量重建。
材料与方法：跟踪实验是在具有原型DMLC跟踪系统的线性加速器（Trilogy，Varian）上进行的。携带双平面剂量计体模（Delta4PT，Scandidos）的运动台可再现八种代表性的临床肿瘤轨迹（四肺，四前列腺）。对于每个轨迹，在有和没有DMLC跟踪的情况下，将具有低调制和高调制的两种单弧6 MV VMAT处理传递给运动体模。现有的内部开发程序可以将目标运动添加到治疗计划中，并且可以将电弧计划划分为任意数量的子弧线，从而可以单独检查治疗不同部分的计算出的剂量，从而扩展了功能。对于每个VMAT子电弧，使用剂量差异和3％/ 3 mmγ测试比较重建和测量的剂量。
结果：对于VMAT亚弧，与测量剂量相比，重建的剂量分布的平均均方根（rms）剂量差异为2.1％，平均γ失效率为2.0％。对于最终累积剂量，平均均方根剂量差异为1.6％，γ失效率为0.7％。
结论：包括剂量重建在内的时间分辨运动已通过实验验证，可用于采用患者测量的肿瘤运动轨迹进行复杂的跟踪和非跟踪治疗。重建的剂量对于评估面向器官运动和适应性RT的治疗计划的鲁棒性将具有很高的价值。

BACKGROUND & AIMS: :Brief exposure to moderate intensity static magnetic fields has been shown to produce a transient alteration in physiological function in a variety of biological systems, primarily those related to changes in intracellular Ca(2+). In the present study GH3 cells were cultured during continuous exposure to a 0.5 T field, for periods of up to 5 weeks. Following a 1-week exposure, cell growth declined by 22% and returned to control levels in 1 week. This was not statistically significant but, with a 4-week exposure, a statistically significant decline in growth of 51% was observed and return to control levels did not occur for 4 weeks. Cell diameter, on the other hand, significantly increased following 3 weeks of exposure and did not return to control levels for 3 weeks after termination of exposure. Ca(2+)-dependent changes in the dynamic reorganization of the actin cytoskeleton are suggested as the probable explanation for these observations.

背景与目标： ：短暂暴露于中等强度的静磁场已显示在多种生物系统中，主要是与细胞内Ca（2）的变化有关的生理功能中，产生暂时性的生理变化。在本研究中，在连续暴露于0.5 T场的过程中培养GH3细胞长达5周。暴露1周后，细胞生长下降了22％，并在1周内恢复到对照水平。这在统计学上不显着，但是在暴露4周后，观察到生长增长在统计学上显着下降51％，并且在4周内未出现恢复到对照水平的情况。另一方面，细胞直径在接触3周后显着增加，并且在接触终止后3周未恢复到对照水平。 Ca（2）依赖变化的肌动蛋白细胞骨架的动态重组被建议为这些观察结果的解释。

BACKGROUND & AIMS: :The inhomogeneous Markov chain model is used to discriminate acceptor and donor sites in genomic DNA sequences. It outperforms statistical methods such as homogeneous Markov chain model, higher order Markov chain and interpolated Markov chain models, and machine-learning methods such as k-nearest neighbor and support vector machine as well. Besides its high accuracy, another advantage of inhomogeneous Markov chain model is its simplicity in computation. In the three states system (acceptor, donor, and neither), the inhomogeneous Markov chain model is combined with a three-layer feed forward neural network. Using this combined system 3175 primate splice-junction gene sequences have been tested, with a prediction accuracy of greater than 98%.

背景与目标： ：非均匀马尔可夫链模型用于区分基因组DNA序列中的受体和供体位点。它优于统计方法，例如齐次马尔可夫链模型，高阶马尔可夫链和插值马尔可夫链模型，以及k-最近邻和支持向量机等机器学习方法。非均质马尔可夫链模型除了具有很高的准确性外，它的另一个优点是计算简单。在三态系统（受体，供体和两者都不是）中，不均匀的马尔可夫链模型与三层前馈神经网络结合在一起。使用该组合系统，已经测试了3175个灵长类动物剪接连接基因序列，其预测精度大于98％。

BACKGROUND & AIMS: :Experiments from flight- and ground-based model systems suggest that unexpected alterations of the human lymphoblastoid cell line Jurkat, as well as effects on cell growth, metabolism, and apoptosis, can occur in altered gravity conditions. Using a desktop random positioning machine (RPM), we investigated the effects of simulated microgravity on Jurkat cells and their multidrug-resistant subline, Jurkat/A4 cells. The viability of Jurkat/A4 cells decreased after simulated microgravity in contrast with the Jurkat cells. At the same time, the viability between the experimental Jurkat cells and control Jurkat cells was not significantly different. Of note, Jurkat cells appeared as less susceptible to apoptosis than their multidrug-resistant clone Jurkat/A4 cells, whereas cell-cycle analysis showed that the percentage of Jurkat/A4 cells in the S-phase was increased after 72 and 96 h of RPM-simulated microgravity relative to their static counterparts. The differences in Jurkat cells at all phases between static and simulated microgravity were not significant. The surface expression of the intercellular adhesion molecule 3 (ICAM-3)-also known as cluster of differentiation (CD)50-protein was changed for Jurkat/A4 cells following exposure to the RPM. Changes in cell morphology were observed in the Jurkat/A4 cells after 96 h of RPM-simulated microgravity. Thus, we concluded that Jurkat/A4 cells are more sensitive to RPM-simulated microgravity as compared with the parental Jurkat cell line. We also suggest that intercellular adhesion molecule 3 may be an important adhesion molecule involved in the induction of leukocyte apoptosis. The Jurkat/A4 cells with an acquired multidrug resistance phenotype could be a useful model for studying the effects of simulated microgravity and testing anticancer drugs.

背景与目标： ：基于飞行和地面的模型系统的实验表明，人的淋巴母细胞样细胞系Jurkat发生意想不到的改变，以及对细胞生长，代谢和细胞凋亡的影响，都可能在重力条件改变的情况下发生。我们使用台式随机定位机（RPM），研究了模拟微重力对Jurkat细胞及其耐多药亚系Jurkat / A4细胞的影响。与Jurkat细胞相比，模拟微重力作用后Jurkat / A4细胞的活力降低。同时，实验Jurkat细胞和对照Jurkat细胞之间的生存力没有显着差异。值得注意的是，Jurkat细胞似乎比耐多药的克隆Jurkat / A4细胞更不容易凋亡，而细胞周期分析显示，RPM分别在72和96 h后，S期的Jurkat / A4细胞百分比增加了-模拟相对于其静态对应物的微重力。静态和模拟微重力之间所有阶段的Jurkat细胞差异均不显着。暴露于RPM后，Jurkat / A4细胞的细胞间粘附分子3（ICAM-3）（也称为分化簇（CD）50-蛋白）的表面表达发生了变化。 RPM模拟微重力96 h后，在Jurkat / A4细胞中观察到细胞形态的变化。因此，我们得出的结论是，与亲本Jurkat细胞系相比，Jurkat / A4细胞对RPM模拟的微重力更敏感。我们还建议细胞间粘附分子3可能是参与白细胞凋亡诱导的重要粘附分子。具有获得的多药耐药表型的Jurkat / A4细胞可能是研究模拟微重力作用和测试抗癌药物的有用模型。

BACKGROUND & AIMS: :Discrete bounded outcome scores (BOS), i.e. discrete measurements that are restricted on a finite interval, often occur in practice. Examples are compliance measures, quality of life measures, etc. In this paper we examine three related random effects approaches to analyze longitudinal studies with a BOS as response: (1) a linear mixed effects (LM) model applied to a logistic transformed modified BOS; (2) a model assuming that the discrete BOS is a coarsened version of a latent random variable, which after a logistic-normal transformation, satisfies an LM model; and (3) a random effects probit model. We consider also the extension whereby the variability of the BOS is allowed to depend on covariates. The methods are contrasted using a simulation study and on a longitudinal project, which documents stroke rehabilitation in four European countries using measures of motor and functional recovery.

背景与目标： ：离散有界结果分数（BOS），即在有限的时间间隔内进行的离散测量，通常在实践中会出现。示例包括合规性措施，生活质量措施等。在本文中，我们研究了三种相关的随机效应方法，以BOS作为响应来分析纵向研究：（1）将线性混合效应（LM）模型应用于经逻辑转换的改良BOS ; （2）假设离散BOS是潜在随机变量的粗化版本的模型，在对数正态变换之后，该模型满足LM模型； （3）随机效应概率模型。我们还考虑了扩展，即BOS的可变性取决于协变量。通过模拟研究和一个纵向项目对这些方法进行了对比，该项目记录了四个欧洲国家中运动恢复和功能恢复的卒中康复情况。

BACKGROUND & AIMS: :We have recently shown that low intensity, intermediate frequency, electric fields inhibit by an anti-microtubule mechanism of action, cancerous cell growth in vitro. Using implanted electrodes, these fields were also shown to inhibit the growth of dermal tumors in mice. The present study extends these findings to additional cell lines [human breast carcinoma; MDA-MB-231, and human non-small-cell lung carcinoma (H1299)] and to animal tumor models (intradermal B16F1 melanoma and intracranial F-98 glioma) using external insulated electrodes. These findings led to the initiation of a pilot clinical trial of the effects of TTFields in 10 patients with recurrent glioblastoma (GBM). Median time to disease progression in these patients was 26.1 weeks and median overall survival was 62.2 weeks. These time to disease progression and OS values are more than double the reported medians of historical control patients. No device-related serious adverse events were seen after >70 months of cumulative treatment in all of the patients. The only device-related side effect seen was a mild to moderate contact dermatitis beneath the field delivering electrodes. We conclude that TTFields are a safe and effective new treatment modality which effectively slows down tumor growth in vitro, in vivo and, as demonstrated here, in human cancer patients.

背景与目标： ：我们最近发现，低强度，中频电场会通过抗微管作用机制抑制体外癌细胞的生长。使用植入的电极，还显示了这些电场可抑制小鼠皮肤肿瘤的生长。本研究将这些发现扩展到其他细胞系[人乳腺癌； MDA-MB-231和人非小细胞肺癌（H1299）]和动物肿瘤模型（皮内B16F1黑色素瘤和颅内F-98胶质瘤）使用外部绝缘电极。这些发现导致了TTFields在10例复发性胶质母细胞瘤（GBM）患者中的临床试验试验的启动。这些患者疾病进展的中位时间为26.1周，中位总生存期为62.2周。这些疾病进展时间和OS值是历史对照组患者报告中位数的两倍以上。在所有患者中，> 70个月的累积治疗后，均未发现与器械相关的严重不良事件。看到的唯一与设备相关的副作用是在电场传递电极下方的轻度至中度接触性皮炎。我们得出的结论是，TTFields是一种安全有效的新治疗方式，可有效减缓体外，体内以及人类癌症患者体内肿瘤的生长。