BACKGROUND & AIMS: Conformations of G-CSF and the extracellular domain of its receptor as well as their complex have been investigated by employing isotope-edited FTIR spectroscopy. To determine unambiguously the protein conformations of G-CSF and the receptor in the complex, we have prepared uniformly 13C/15N isotope labeled G-CSF to resolve its amide I' band from that of the receptor in the IR spectrum of the complex. By comparing the IR spectra of the isotope-labeled G-CSF and the receptor with that of the complex, we have provided spectral evidence that the AB loop region involving the unique 310 helix segment of G-CSF likely undergoes a conformational change to a regular alpha-helix upon binding to the receptor. The IR data also indicate a possible minor increase in alpha-helical conformation for the receptor in the complex. Furthermore, FTIR spectra of G-CSF, the receptor, and their complex demonstrate clearly that protein conformations of both G-CSF and the receptor have been dramatically stabilized by complex formation. Specifically, the melting transition (Tm value) of the alpha-helix in G-CSF is increased by nearly 30 degrees C and that of the beta-strand in the receptor by nearly 15 degrees C in the G-CSF/receptor complex. We estimate from the current FTIR data that the native conformations of approximately 15% of all receptor residues are stabilized by G-CSF binding. On the other hand, the entire alpha-helical content of G-CSF appears to be stabilized in the complex. Together, these results indicate that formation of the ligand/receptor complex results in not only conformational changes in the receptor but also significant structural changes in the ligand. This adds insight to the general consensus that binding of ligand to cytokine receptors induces mostly structural changes in the receptor which lead to receptor oligomerization and signal transduction. The current data also suggest a possible physiological role of the 310 helix present in G-CSF for its receptor binding activity.

背景与目标： G-CSF的构象及其受体的胞外域及其复合物已通过采用同位素编辑的FTIR光谱进行了研究。为明确确定复合物中G-CSF和受体的蛋白质构象，我们制备了均一的13C / 15N同位素标记的G-CSF，以从复合物的IR光谱中从其受体解析其酰胺I'谱带。通过比较同位素标记的G-CSF和受体与复合物的IR光谱，我们提供了光谱证据，证明涉及G-CSF独特310螺旋段的AB环区域可能会发生构象变化，变成规则的与受体结合后的α-螺旋。 IR数据还表明复合物中受体的α-螺旋构象可能轻微增加。此外，G-CSF，受体及其复合物的FTIR光谱清楚地表明，通过复合物的形成，G-CSF和受体的蛋白质构象均已显着稳定。具体地，在G-CSF /受体复合物中，G-CSF中的α-螺旋的熔融转变（Tm值）增加了近30℃，受体中的β-链的熔融转变增加了约15℃。我们从当前的FTIR数据估计，所有受体残基的大约15％的天然构象可通过G-CSF结合而稳定。另一方面，在复合物中G-CSF的整个α-螺旋含量似乎是稳定的。总之，这些结果表明配体/受体复合物的形成不仅导致受体的构象变化，而且导致配体的显着结构变化。这为通常的共识增加了见解，即配体与细胞因子受体的结合会在受体中诱导大部分结构变化，从而导致受体低聚和信号转导。目前的数据还表明存在于G-CSF中的310螺旋对其受体结合活性可能具有生理作用。

BACKGROUND & AIMS: Using 31phosphorus magnetic resonance spectroscopy (31P-MRS) and surface coils, we noninvasively assessed the intracellular changes in delayed skin flaps of the high-energy phosphometabolites, ATP and phosphocreatine, which are basic energy sources of living cells. In 5 rats, a 3.5 x 7.5 cm bipedicled skin flap was elevated from the dorsum and its caudal base divided after a delay period of 2 weeks. MRS spectra were collected at four timesimmediately, 1 week and 2 weeks after elevation of the bipedicled flap, and 18 hours after division of its caudal base.

From the spectra, we calculated the intracellular pH and the following ratiosPi/PCr, PCr/(PCr + Pi), ATP/(PCr + Pi) (PCr, phosphocreatine; Pi, inorganic phosphate; ATP, adenosine triphosphate). As an undelayed control group, cranially based skin flaps of the same size were elevated in another 5 rats, and MRS spectra were obtained 18 hours later. The length of the surviving area was longer in the delayed flaps than in the undelayed flaps. Intracellular pH and ATP/(PCr + Pi) showed no significant alteration in the delayed skin flaps, not only during the delay period but also after conversion of the flaps into cranially based flaps by division of their caudal base. In contrast, PCr/(PCr + Pi) decreased with each surgical procedure (bipedicled flap elevation and base division). Compared with the necrotic distal portion of the undelayed flaps, the surviving distal portion of the delayed flaps had higher levels of intracellular pH and ATP/(PCr + Pi) and lower levels of PCr/(PCr + Pi). Intracellular pH and ATP/(PCr + Pi) showed a strong correlation with the viability of the delayed and undelayed skin flaps, and they can be prognostic indices for predicting the fate of skin flaps. The reason the surviving distal portions of the delayed flaps maintained their level of ATP despite the low intracellular level of PCr may be that the accumulation of mitochondrial creatine kinase enhances the so-called 'energy transport' function of the creatine kinase/phosphocreatine system.

背景与目标： 使用31磷磁共振波谱（31P-MRS）和表面线圈，我们无创地评估了高能磷酸代谢产物，ATP和磷酸肌酸（它们是活细胞的基本能源）的延迟皮瓣中的细胞内变化。在5只大鼠中，在延迟2周后，从背侧抬高了一个3.5 x 7.5 cm的双蒂皮瓣，其尾基分开了。在双蒂皮瓣抬高后1周和2周以及尾鳍基底分开后18小时，分别在四次，四次收集MRS光谱。

从光谱中，我们计算了细胞内pH值和以下比率Pi / PCr，PCr /（PCr Pi），ATP /（PCr Pi）（PCr，磷酸肌酸； Pi，无机磷酸盐； ATP，三磷酸腺苷）。作为未延迟的对照组，在另外5只大鼠中抬高了相同大小的颅骨皮瓣，并在18小时后获得了MRS光谱。延迟皮瓣中存活区域的长度比未延迟皮瓣中存活区域的长度长。胞内pH和ATP /（PCr Pi）在延迟的皮瓣中没有显示出明显的变化，不仅在延迟期间，而且在皮瓣通过分割其尾基而转变为颅骨皮瓣之后。相反，PCr /（PCr Pi）随每次外科手术（双蒂皮瓣抬高和基部分裂）而降低。与未延迟皮瓣的坏死远端相比，延迟皮瓣的存活远端具有较高的细胞内pH和ATP /（PCr Pi）水平，而较低的PCr /（PCr Pi）水平。细胞内pH和ATP /（PCr Pi）与延迟和未延迟的皮瓣的生存能力密切相关，它们可以作为预测皮瓣命运的预后指标。尽管细胞内PCr水平较低，但延迟皮瓣的存活远端仍保持其ATP水平的原因可能是线粒体肌酸激酶的积累增强了肌酸激酶/磷酸肌酸系统的所谓``能量转运''功能。 br>

BACKGROUND & AIMS: For the first time, Fourier transform infrared spectroscopy has been applied to cytochrome P-450 to analyze the protein secondary structure. From Fourier self-deconvolution and fitting the infrared spectra in the amide I' region (1600-1700 cm-1), we estimate 44% alpha-helix, 31% beta-sheet, and 18% turns for substrate-free cytochrome P-450cam. In the presence of camphor, 54% alpha-helix and 310-helix, 21% beta-sheet, and 21% turns are obtained which agree with the crystallographic data of 53% alpha-helix, 19% beta-sheet, and 16% turns [Poulos, T. L., Finzel, B. C., & Howard, A. J. (1987) J. Mol. Biol. 195, 687-700]. Cytochrome P-420cam is produced from substrate-free cytochrome P-450cam in two ways(i) by temperature elevation up to 60 degrees C and (ii) by exposure to KSCN up to 1.5 M. The secondary structure composition is determined for each temperature and KSCN concentration and compared with the changes observed in the iron ligand CO stretch vibration bands appearing between 1900 and 2000 cm-1. Thermally induced cytochrome P-420 has an alpha-helix content of 19%, a beta-sheet content of 53%, 14% turns, and 5% antiparallel beta-sheets from intermolecular hydrogen bonds within protein aggregates. The formation of cytochrome P-420 as a function of the KSCN concentration indicates two types of cytochrome P-420. Up to 1 M KSCN, the induced cytochrome P-420 displays only little modification of the secondary structure, whereas at 1.5 M KSCN, larger changes are observed, resulting in 85% cytochrome P-420 without protein precipitation and containing 30% alpha-helix, 48% beta-sheet, and 17% turns. Infrared spectra in the iron ligand CO stretch region show several subconformers for cytochrome P-420. During the cytochrome P-420 formation, the CO stretch modes are shifted to higher frequencies by 3-11 cm-1, with a main feature at about 1964 cm-1, compared to those of substrate-free cytochrome P-450cam-CO.

背景与目标： 第一次，傅里叶变换红外光谱已应用于细胞色素P-450，以分析蛋白质的二级结构。通过傅立叶自解卷积并拟合酰胺I'区域（1600-1700 cm-1）中的红外光谱，我们估计无底物的细胞色素P-占44％的α-螺旋，31％的β-折叠和18％的匝数。 450cam。在存在樟脑的情况下，获得了54％的α-螺旋和310螺旋，21％的β-折叠和21％的折光，这与53％的α-螺旋，19％的β-折叠和16％的晶体学数据相符[Poulos，TL，Finzel，BC，and Howard，AJ（1987）J. Mol。生物学195，687-700]。由无底物的细胞色素P-450cam产生细胞色素P-420cam的方法有两种（i）通过升高温度达到60摄氏度和（ii）通过暴露于KSCN达到1.5 M.在每个温度下确定二级结构组成和KSCN浓度，并与在1900至2000cm-1之间出现的铁配体CO拉伸振动带中观察到的变化进行比较。热诱导的细胞色素P-420具有19％的α-螺旋含量，53％的β-折叠层含量，14％匝数和5％的蛋白质聚集体中分子间氢键反平行的β-折叠层。细胞色素P-420的形成随KSCN浓度的变化指示出两种类型的细胞色素P-420。高达1 M KSCN时，诱导的细胞色素P-420仅显示出二级结构的修饰，而在1.5 M KSCN时，观察到较大的变化，导致85％的细胞色素P-420没有蛋白质沉淀并且含有30％的α-螺旋，48％的Beta版表和17％的匝数。铁配体CO延伸区的红外光谱显示了细胞色素P-420的多个亚构型。在细胞色素P-420形成过程中，与无底物的细胞色素P-450cam-CO相比，CO拉伸模式向更高的频率移动了3-11 cm-1，主要特征在大约1964 cm-1。

BACKGROUND & AIMS: :In this study, a new nondestructive technique for passport examination is proposed. In this technique, linearly polarized light is used to measure Fourier transform infrared (FT-IR) reflectance spectra of films on the biographical data page. Thirty genuine and thirty-five counterfeit Japanese passports and five marketed films pasted on name cards were examined. The measured spectra were analyzed as follows. The absorption spectra were obtained by the Kramers-Kronig transformations of reflectance spectra. The peak ratios were then calculated from the absorption spectra by adding the peak areas at 1126 and 1263 cm(-1) and dividing the result by the peak area at 1727 cm(-1). When nonpolarized light was used, the samples could not be distinguished by comparing the peak ratios. However, when polarized light was used, they were successfully distinguished by the comparison. Therefore, polarized light is useful for the forensic discrimination of passport films by the measurement of FT-IR spectra.

背景与目标： ：在这项研究中，提出了一种新的护照无损检测技术。在此技术中，线偏振光用于测量传记数据页面上胶片的傅立叶变换红外（FT-IR）反射光谱。检查了三十三本伪造的日本护照和三十五本伪造的日本护照，以及五张贴在名片上的市售影片。所测量的光谱如下分析。通过反射光谱的Kramers-Kronig变换获得吸收光谱。然后，通过将1126和1263 cm（-1）处的峰面积相加并将结果除以1727 cm（-1）处的峰面积，从吸收光谱中计算出峰比。使用非偏振光时，无法通过比较峰比率来区分样品。然而，当使用偏振光时，通过比较成功地将它们区分开。因此，偏振光可用于通过FT-IR光谱的测量来鉴别护照薄膜。

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: Purpose:To compare the intermodality and interreader agreement for geographic atrophy (GA) lesion size quantification in green-light fundus autofluorescence (GAF; excitation = 518 nm) versus combined blue-light fundus autofluorescence (BAF; excitation = 488 nm) and near-infrared reflectance (NIR; 820 nm) -based grading. Methods:Confocal scanning laser ophthalmoscopy (cSLO) GAF, BAF, and NIR images of 40 eyes from 29 patients (mean age 79.7 years) with GA secondary to AMD were recorded according to a standardized protocol. GA areas were analyzed in GAF, BAF combined with NIR (BAF+NIR), or BAF alone, by four independent readers using semiautomated software (RegionFinder; Heidelberg Engineering, Heidelberg, Germany). A mixed-effects model was used to assess the effect of image modality on the measured square-root lesion area. The coefficient of repeatability (CR) and intraclass correlation coefficient (ICC) were assessed for the square-root lesion area, lesion perimeter, and circularity. Results:GAF-based measurements were on average 0.062 mm (95% confidence interval [CI] 0.04-0.08 mm) larger than BAF+NIR-based measurements and 0.077 mm (95% CI 0.06 - 0.10 mm) larger than BAF-based measurements. Interreader agreement was highest for GAF-based analysis ([CR, ICC] 0.196 mm, 0.995) followed by BAF+NIR (0.232 mm, 0.992) and BAF alone (0.263 mm, 0.991). The same was noted for the lesion perimeter and circularity. Post hoc review revealed that interreader differences were associated with media opacification interfering with lesion boundary demarcation to a larger extent in BAF than in GAF. Conclusions:cSLO-based GAF and combined BAF+NIR imaging with semiautomated lesion delineation allow for an accurate and reproducible quantification of GA. The slightly better interreader agreement using cSLO GAF suggests that its use may be preferable in clinical trials examining the change in lesion size as a clinical endpoint.

背景与目标： 目的：比较绿光眼底自发荧光（GAF；激发= 518 nm）与蓝光眼底自发荧光（BAF；激发= 488 nm）和近-基于红外反射率（NIR; 820 nm）的分级。
方法：按照标准方案记录29例年龄平均为79.7岁，继发于AMD的GA患者的40只眼的椎间扫描激光检眼镜（cSLO）GAF，BAF和NIR图像。四个独立的读者使用半自动化软件（RegionFinder； Heidelberg Engineering，Heidelberg，Germany），在GAF，BAF与NIR（BAF NIR）结合或单独使用BAF中分析了GA区域。使用混合效应模型来评估图像模态对所测量的平方根病变区域的影响。对平方根病变面积，病变周长和圆度评估了重复性系数（CR）和组内相关系数（ICC）。
结果：基于GAF的测量值比基于BAF NIR的测量值平均大0.062 mm（95％置信区间[CI] 0.04-0.08 mm），比基于BAF的测量值大0.077 mm（95％CI 0.06-0.10 mm）。基于GAF的分析（[CR，ICC] 0.196 mm，0.995）的阅读器间协议最高，其次是BAF NIR（0.232 mm，0.992）和单独的BAF（0.263 mm，0.991）。病变周长和圆形度也相同。事后审查显示，与GAF相比，BAF中阅读者之间的差异与媒介混浊干扰病灶边界的程度更大。
结论：基于cSLO的GAF以及结合BAF NIR成像和半自动病变描述，可以对GA进行准确且可重复的定量。使用cSLO GAF的阅读器之间的协议稍好，这表明在临床研究中（病灶大小变化作为临床终点）可能更可取。

BACKGROUND & AIMS: :The key component in the so-called EPRI effective dose equivalent (EDE) methodology is an algorithm that utilizes two dosimeters (instead of multiple dosimeters) to predict the EDE for external photon exposures. The exposure scenarios that were previously studied in deriving the algorithm include parallel photon beams and point sources 33 cm from the body surface. The motivation for this study was the need to investigate source locations within 33 cm from the body so the method is more widely applicable. The ORNL stylized mathematical human phantoms and the MCNP code were used to calculate organ doses in this study. This paper presents the EDE data for point gamma sources at 0.3, 1.0, and 1.5 MeV, respectively, which are located at 10 cm from the surface of the body. The results and analyses show that the locations ranging from the overhead to the foot have resulted in conservative ratios except for two general regions near the front upper thigh and directly overhead. If all locations considered in this study were averaged for each photon energy, the overall ratio is on the conservative side. These data suggest that the EPRI EDE methodology is still valid for sources located 10 cm from the body, although the chance for resulting in a non-conservative estimate of the EDE has increased in comparison with the sources located at 30 cm from the body. Finally, this paper provides recommendations on how to apply the EPRI EDE methodology.

背景与目标： ：所谓的EPRI有效剂量当量（EDE）方法中的关键组件是一种算法，该算法利用两个剂量计（而不是多个剂量计）来预测外部光子暴露的EDE。先前在推导算法时曾研究过的曝光场景包括平行光子束和距体表33 cm的点光源。这项研究的动机是需要调查距人体33厘米以内的放射源位置，因此该方法更广泛地适用。在本研究中，使用了ORNL程式化的数学人体模型和MCNP代码来计算器官剂量。本文介绍了分别位于距人体表面10 cm处的0.3 MeV，1.0 MeV和1.5 MeV的点伽马源的EDE数据。结果和分析表明，从头顶到脚的位置范围导致了保守的比率，除了大腿前上方和直接头顶附近的两个一般区域。如果在本研究中考虑的所有位置均针对每种光子能量求平均值，则总体比率处于保守的一面。这些数据表明，EPRI EDE方法对于距离人体10厘米处的放射源仍然有效，尽管与位于人体30厘米处的放射源相比，导致EDE非保守估计的机会有所增加。最后，本文提供了有关如何应用EPRI EDE方法的建议。

BACKGROUND & AIMS: OBJECTIVE:Functional near-infrared spectroscopy (fNIRS) is a non-invasive optical technique for bedside evaluation of cerebral metabolism that has clinical potential for monitoring the efficacy of pharmacological treatment. In this pilot study, we investigated the cognitive effects of methylphenidate (MP) on prefrontal function using fNIRS in healthy subjects. METHODS:Thirteen right-handed healthy subjects underwent working memory tasks (0-back and 2-back) after a single oral dose of MP (20 mg) or placebo administered in a double-blind crossover design on two different days separated by 1-3 days. We measured changes in oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) concentrations during the tasks in bilateral prefrontal regions after MP or placebo administration using two-channel fNIRS. RESULTS:There were significantly more correct responses and fewer missed responses during the 2-back task performance after MP treatment as compared with placebo. Baseline-corrected oxy-Hb was significantly decreased after MP treatment compared with the placebo in the 2-back task in the right frontal region but was not different in the 0-back task. Baseline-corrected deoxy-Hb and total-Hb concentrations were not significant between MP and placebo conditions in either of the cognitive tasks. CONCLUSIONS:These data are consistent with previous positron emission tomography findings of MP-mediated reduction in lateral prefrontal activity accompanied by improved cognitive performance.

背景与目标： 目的：功能性近红外光谱法（fNIRS）是一种非侵入性光学技术，可在床头评估脑部新陈代谢，具有监测药理学疗效的临床潜力。在这项初步研究中，我们调查了健康受试者中使用fNIRS的哌醋甲酯（MP）对前额叶功能的认知作用。
方法：13名右撇子健康受试者在双盲交叉设计中，在两天内分别以双盲交叉设计给予单次口服MP（20 mg）或安慰剂，进行了工作记忆任务（0背和2背）。 3天。我们在使用双通道fNIRS进行MP或安慰剂给药后，测量了双侧前额叶区域任务期间氧合血红蛋白（oxy-Hb）和脱氧血红蛋白（deoxy-Hb）浓度的变化。
结果：与安慰剂相比，MP治疗后的2背任务执行过程中，正确的反应明显多，漏掉的反应少。与安慰剂相比，MP处理后基线校正的oxy-Hb在右额叶区域的2后卫任务中较安慰剂显着降低，但在0后卫任务中无差异。在任一认知任务中，MP和安慰剂条件之间经基线校正的脱氧血红蛋白和总血红蛋白浓度均不显着。
结论：这些数据与以前的正电子发射断层扫描所发现的MP介导的侧前额叶活动减少以及认知能力改善相一致。

BACKGROUND & AIMS: :This study sought to investigate the relationship between going outdoor daily and prefrontal cortex activation during execution of the VFT using near-infrared spectroscopy (NIRS) in community-dwelling older adults. Blood oxygenation changes in left and right prefrontal cortices were measured in twenty older adults (mean age 76.1 ± 6.7 years) by NIRS during VFT performance. In this task, participants were required to pronounce as many nouns as possible beginning with the letters "Shi," "I," and "Re." Changes in oxygenated hemoglobin (oxy-Hb) levels during the VFT were compared between two groups defined by the frequency of going outdoors: daily or non-daily within a week. Participants in both groups exhibited significantly increased oxy-Hb levels in the left and right prefrontal cortices during the VFT compared to a resting baseline condition. After controlling for age and gender, there were significant group-by-condition interactions on oxy-Hb levels with less activation during the execution of the VFT over both cortices in the non-daily group (left: F=4.76, p=0.04; right: F=6.32, p=0.02). These findings indicate that going outdoors daily is associated with increased activation in the prefrontal cortices during VFT performance in community-dwelling older adults.

背景与目标： ：这项研究旨在调查居住在社区的老年人中，每天进行户外运动与使用近红外光谱（NIRS）进行VFT期间前额叶皮层激活之间的关系。在VFT表现期间，通过NIRS对20名老年人（平均年龄76.1±6.7岁）测量了左前额叶皮层和右前额叶皮层中的血液氧合变化。在此任务中，要求参与者以字母“ Shi”，“ I”和“ Re”开头的尽可能多的名词发音。在VFT期间，比较了两组由户外活动频率定义的两组之间的氧化血红蛋白（oxy-Hb）水平的变化：每天或一周内的非每天一次。与静止的基线状态相比，两组的参与者在VFT期间左，右前额叶皮层的氧合血红蛋白水平均显着升高。在控制了年龄和性别之后，非每日组的两个皮层在执行VFT时，氧合血红蛋白水平存在显着的组间条件交互作用，而激活较少（左：F = 4.76，p = 0.04；右：F = 6.32，p = 0.02）。这些发现表明，在社区居住的老年人中，每天进行户外运动与在VFT表现中前额叶皮层的激活增加有关。

BACKGROUND & AIMS: :The structures of d(GCAATTGC)2 and its complex with berenil in solution were analyzed by two-dimensional 1H NMR spectroscopy. Intra- and internucleotide nuclear Overhauser effect (NOE) connectivities demonstrate that the octanucleotide duplex is primarily in the B conformation. Binding with berenil stabilizes the duplex with respect to thermal denaturation by about 10 degrees C, based on the appearance of the imino proton signals. The berenil-d(GCAATTGC)2 system is in fast exchange on the NMR time scale. The two-dimensional NMR data reveal that berenil binds in the minor groove of d(GCAATTGC)2. The aromatic drug protons are placed within 5 A of the H2 proton of both adenines, the H1', H5', and H5" of both thymidines, and the H4', H5', and H5" of the internal guanosine. The amidine protons on berenil are also close to the H2 proton of both adenines. The duplex retains an overall B conformation in the complex with berenil. At 18 degrees C, NOE contacts at longer mixing times indicate the presence of end-to-end association both in the duplex alone and also in its complex with berenil. These intermolecular contacts either vanished or diminished substantially at 45 degrees C. Two molecular models are proposed for the berenil-(GCAATTGC)2 complex; one has hydrogen bonds between the berenil amidine protons and the carbonyl oxygen, O2, of the external thymines, and the other has hydrogen bonds between the drug amidine protons and the purine nitrogen, N3, of the internal adenines. Quantitative analysis of the NOE data favors the second model.

背景与目标： ：用二维1H NMR光谱分析了d（GCAATTGC）2的结构及其与苯磺酸的络合物。核苷酸内和核苷酸间核豪沃效应（NOE）的连通性表明，八核苷酸双链体主要位于B构象中。基于亚氨基质子信号的出现，与苯磺酸酯的结合相对于热变性使双链体稳定约10℃。 berenil-d（GCAATTGC）2系统在NMR时标上可以快速交换。二维NMR数据表明，苯胺醇结合在d（GCAATTGC）2的小沟中。芳香族药物质子位于两个腺嘌呤的H2质子，两个胸苷的H1'，H5'和H5”以及内部鸟苷的H4'，H5'和H5”的5 A之内。苯甲腈上的质子也接近两个腺嘌呤的H2质子。该双链体在与贝内尔的复合物中保留了整体的B构象。在18摄氏度时，NOE在较长混合时间下的接触表明在双链体中及其与苯甲腈的复合物中不仅存在端对端缔合。这些分子间的接触在45摄氏度时基本消失或减弱。对于berenil-（GCAATTGC）2配合物，提出了两种分子模型。一个在苯胺基am质子与外部胸腺嘧啶的羰基氧O2之间具有氢键，另一个在药物am质子与内部腺嘌呤的嘌呤氮N3之间具有氢键。 NOE数据的定量分析有利于第二种模型。

BACKGROUND & AIMS: :We evaluated the differences in strength of the associations of prevalent cardiovascular disease and lower extremity arterial atherosclerosis to common carotid intima-media thickness, assessed by near wall measurements only, by far wall measurements only, and by the average of near and far wall measurements. The study was based on data from 1500 participants of the Rotterdam Study, a single-center-population-based prospective follow-up study among 7983 subjects, aged 55 years or over. Comparison of the strength of the associations of near wall intima-media thickness and of combined near and far wall intima-media thickness to cardiovascular disease and lower extremity arterial atherosclerosis revealed significantly stronger associations compared to associations observed for far wall intima-media thickness, in particular for stroke and lower extremity arterial disease. We conclude that near wall common carotid intima-media thickness measurement provides at least as good an indicator of atherosclerosis elsewhere and of cardiovascular risk as the far wall intima-media thickness measurement.

背景与目标： ：我们评估了常见心血管疾病和下肢动脉粥样硬化与颈总动脉内膜中层厚度之间的关联强度差异，仅通过近壁测量，仅远壁测量以及近壁和远壁测量的平均值来评估。该研究基于来自鹿特丹研究的1500名参与者的数据，鹿特丹研究是一项基于单中心人群的前瞻性随访研究，涉及对象为7983名年龄在55岁以上的受试者。比较近壁内膜-中层厚度和近，远壁内膜-中层厚度联合对心血管疾病和下肢动脉粥样硬化的强度，发现与远壁内膜-中层厚度相关的关联明显更强。特别适用于中风和下肢动脉疾病。我们得出的结论是，近壁普通颈动脉内膜中层厚度测量至少可以提供与远壁内膜中层厚度测量一样好的动脉粥样硬化和心血管风险的指标。

BACKGROUND & AIMS: :This research firstly investigated the inhibitory effect of isoquercitrin (ISQ) on Ovalbumin (OVA) glycation. The mechanism was elucidated through the interaction between OVA and ISQ, and changes in glycation sites and degree of each site as deduced by spectroscopy, spectrometry and molecular docking. ISQ significantly inhibited OVA glycation by attenuating the conformational change induced by glycation. It quenched the fluorescence of Trp via static mechanism, and exposed Trp residues to a more hydrophobic surroundings. Formation of OVA-ISQ complex was a endothermic processing driven by hydrophobic interactions, van der Waals forces and hydrogen bonds. LC-Orbitrap-MS/MS revealed that ISQ altered the location of glycation and alleviated the glycation degree of most sites. Molecular docking results indicated that ISQ inserted into the hydrophobic pocket of OVA with six hydrogen bonds and one π-π stacking formed between ISQ and the amino acid residues of OVA, leading to the altered glycation activity of some sites.

背景与目标： ：本研究首先研究了异槲皮苷（ISQ）对卵清蛋白（OVA）糖基化的抑制作用。通过OVA和ISQ之间的相互作用以及通过光谱学，光谱学和分子对接推导的糖基化位点和每个位点的程度的变化阐明了该机理。 ISQ通过减弱糖基化诱导的构象变化来显着抑制OVA糖基化。它通过静态机制淬灭了Trp的荧光，并使Trp残基暴露于疏水性更高的环境中。 OVA-ISQ复合物的形成是由疏水相互作用，范德华力和氢键驱动的吸热过程。 LC-Orbitrap-MS / MS表明，ISQ改变了糖基化的位置并减轻了大多数位点的糖基化程度。分子对接结果表明，ISQ以六个氢键插入到OVA的疏水口袋中，在ISQ与OVA的氨基酸残基之间形成一个π-π堆积，从而导致某些位点的糖基化活性发生了改变。

BACKGROUND & AIMS: :A decoupling structure using an additional LC resonant configuration for NMR transmit coils is analysed and the probe sensitivity of the receive coil with the decoupled transmit coil is calculated using simple circuit models. An adjustment-free technique for the decoupling circuit under different loading conditions is proposed using the calculated results and demonstrated by experiments. The proposed method can simplify the probe operation.

背景与目标： ：分析了使用附加LC谐振配置的NMR发送线圈的去耦结构，并使用简单的电路模型计算了具有去耦发送线圈的接收线圈的探头灵敏度。利用计算结果，提出了一种在不同负载条件下去耦电路的免调整技术，并通过实验进行了验证。所提出的方法可以简化探测操作。

BACKGROUND & AIMS: :We are reporting a case of pyrethroid poisoning with atypical presentation in a 21-month-old toddler who was transferred to us from a peripheral center. Signs and symptoms at presentation were predominantly of cardiopulmonary dysfunction contrary to more common presenting features of gastrointestinal and neurological impairment. The reason for this seems to be the aspiration pneumonitis as a consequence of vomiting induced by parents at home, rather than the toxin itself even though a rather rapid progression of lung injury does not rule out the possibility. He had developed decreased level of consciousness and increased work of breathing after ingestion, which had progressed to Acute Respiratory Distress Syndrome, septic shock, and multi organ failure. He even had a brief cardiac arrest with Return of Spontaneous Circulation after 5 min of cardiopulmonary resuscitation, immediately after arrival at our unit, which seemed more likely to be a consequence of inappropriate management during transfer of the child. In addition to antibiotics and vasopressors, he required high frequency oscillatory ventilation and prone positioning initially, and lung-protective conventional ventilation later. His cardiopulmonary status improved gradually and he was successfully extubated after 12 days. Other organ systems also showed complete recovery. Even though Magnetic Resonance Imaging of brain done a few days after cardiac arrest showed features suggestive of hypoxic-ischemic encephalopathy he showed complete neurological recovery. He was thriving well at three-month follow-up with no neurological deficits, good exercise tolerance, and normal renal and liver function. Atypical presentation of pyrethroid poisoning is associated with significant morbidities and there seems to no reliable parameters in children to identify the risk of the same. Considering that there is no specific antidote, prompt, and aggressive supportive therapy is necessary for a favorable outcome. This case highlights several important aspects in the care of the pediatric patient after ingestion of insecticides. First, attempt to induce emesis, especially outside of a healthcare facility is not only ineffective but also highly dangerous, and should not be done. Second, unstable patients require inter and intrahospital transfer by experienced and trained personnel; and lastly, management for these complex and atypical cases should be done as early as possible in a center which is equipped to provide high level of circulatory and ventilatory support while prioritizing neuro-protective measures, and neurologic recovery and rehabilitation.

背景与目标： ：我们正在报告一例21岁大的婴儿中从典型的外围中心转移给我们的拟除虫菊酯中毒事件。表现时的体征和症状主要是心肺功能障碍，与胃肠道和神经功能障碍的更常见表现特征相反。造成这种情况的原因似乎是由父母在家中引起的呕吐引起的吸入性肺炎，而不是毒素本身，即使肺损伤的迅速发展并不排除了这种可能性。摄入后，他的意识水平下降，呼吸工作增加，已发展为急性呼吸窘迫综合症，败血性休克和多器官衰竭。他在到达我们单位后立即进行了5分钟的心肺复苏，甚至在短暂的心脏骤停后恢复了自发性循环，这似乎更可能是由于孩子转移过程中处理不当造成的。除了抗生素和血管升压药外，他还需要高频振荡通气和俯卧位，之后需要常规的肺保护通气。他的心肺状态逐渐好转，并在12天后成功拔管。其他器官系统也显示出完全恢复。即使心脏骤停后几天进行的脑磁共振成像显示出提示缺氧缺血性脑病的特征，他仍显示出完全的神经功能恢复。在三个月的随访中，他表现良好，没有神经功能缺损，良好的运动耐受性以及正常的肾和肝功能。拟除虫菊酯中毒的非典型表现与高发病率相关，儿童中似乎没有可靠的参数可确定其危险性。考虑到没有特定的解毒剂，迅速而积极的支持疗法对于取得良好的结果是必要的。该病例突出显示了在摄入杀虫剂后对小儿患者进行护理的几个重要方面。首先，尝试引起呕吐，尤其是在医疗机构外部进行呕吐，不仅效果不佳，而且非常危险，因此不应该这样做。其次，不稳定的患者需要经验丰富且训练有素的人员进行医院内部和医院之间的转移；最后，应对这些复杂和非典型病例的治疗应尽早在中心进行，该中心应提供高水平的循环和通气支持，同时优先考虑神经保护措施以及神经系统的恢复和康复。

BACKGROUND & AIMS: :Precision spectroscopy of atomic systems1 is an invaluable tool for the study of fundamental interactions and symmetries2. Recently, highly charged ions have been proposed to enable sensitive tests of physics beyond the standard model2-5 and the realization of high-accuracy atomic clocks3,5, owing to their high sensitivity to fundamental physics and insensitivity to external perturbations, which result from the high binding energies of their outer electrons. However, the implementation of these ideas has been hindered by the low spectroscopic accuracies (of the order of parts per million) achieved so far6-8. Here we cool trapped, highly charged argon ions to the lowest temperature reported so far, and study them using coherent laser spectroscopy, achieving an increase in precision of eight orders of magnitude. We use quantum logic spectroscopy9,10 to probe the forbidden optical transition in 40Ar13+ at a wavelength of 441 nanometres and measure its excited-state lifetime and g-factor. Our work unlocks the potential of highly charged ions as ubiquitous atomic systems for use in quantum information processing, as frequency standards and in highly sensitive tests of fundamental physics, such as searches for dark-matter candidates11 or violations of fundamental symmetries2.

背景与目标： ：原子系统的精密光谱学1是研究基本相互作用和对称性2的宝贵工具。最近，由于高电离的离子对基本物理的高敏感性和对外部扰动的不敏感性，已提出了高电荷的离子以实现超出标准模型2-5的物理敏感性测试和实现高精度原子钟3,5。它们的外电子具有很高的结合能。但是，到目前为止，这些思想的实现受到了低光谱精度（百万分之几）的阻碍[6-8]。在这里，我们将捕获的高电荷氩离子冷却到迄今为止报告的最低温度，并使用相干激光光谱法对其进行研究，从而将精度提高了八个数量级。我们使用量子逻辑光谱法9,10来探测40Ar13在441纳米波长处的禁止光学跃迁，并测量其激发态寿命和g因子。我们的工作释放了高电荷离子作为量子信息处理，频率标准和基础物理的高度敏感测试（如搜索暗物质候选物11或违反基本对称性2）中无处不在的原子系统的潜力。