Prognostic Metabolite Biomarkers for Soft Tissue Sarcomas Discovered by Mass Spectrometry Imaging

Metabolites can be an important read-out of disease. The identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients is one of the main current research aspects. Mass spectrometry has become the technique of choice for metabolomics studies, and mass spectrometry imaging (MSI) enables their visualization in patient tissues. In this study, we used MSI to identify prognostic metabolite biomarkers in high grade sarcomas; 33 high grade sarcoma patients, comprising osteosarcoma, leiomyosarcoma, myxofibrosarcoma, and undifferentiated pleomorphic sarcoma were analyzed. Metabolite MSI data were obtained from sections of fresh frozen tissue specimens with matrix-assisted laser/desorption ionization (MALDI) MSI in negative polarity using 9-aminoarcridine as matrix. Subsequent annotation of tumor regions by expert pathologists resulted in tumor-specific metabolite signatures, which were then tested for association with patient survival. Metabolite signals with significant clinical value were further validated and identified by high mass resolution Fourier transform ion cyclotron resonance (FTICR) MSI. Three metabolite signals were found to correlate with overall survival (m/z 180.9436 and 241.0118) and metastasis-free survival (m/z 160.8417). FTICR-MSI identified m/z 241.0118 as inositol cyclic phosphate and m/z 160.8417 as carnitine.

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The synthesis and high optical birefringence of nematogens incorporating 2,6-disubstituted naphthalenes and terminal cyano-substituent

A range of nematogenic materials which incorporate a 2,6-disubstituted naphthyl moiety and a terminal cyano-substituent have been synthesized by using palladium-catalysed cross-coupling procedures involving arylboronic acids and alkynylzinc reagents with aryl iodides, bromides and trifluoromethanesulphonates (triflates). The compounds have very high nematic phase stability, but their melting points are also quite high. The birefringences were measured using an extrapolation technique and the values were found to be between 0·26 and 0·42.     

ChemInform Abstract: Theoretical Study of Mg+—X and [X—Mg—Y]+ Complexes Important in the Chemistry of Ionospheric Magnesium (X,Y: H2O,CO2, N2, O2, and O).

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.     

Analysis of chemical shift changes reveals the binding modes of isoindolinone inhibitors of the MDM2-p53 interaction

In this study we present a method for defining the binding modes of a set of structurally related isoindolinone inhibitors of the MDM2-p53 interaction. This approach derives the location and orientation of isoindolinone binding, based on an analysis of the patterns of magnitude and direction of chemical shift perturbations for a series of inhibitors of the MDM2-p53 interaction. The MDM2-p53 complex is an attractive target for therapeutic intervention in cancer cells with intact tumor suppressor p53, as it offers the possibility of releasing p53 by blocking the MDM2-p53 binding site with a small molecule antagonist to promote apoptosis. Isoindolinones are a novel class of MDM2-antagonists of moderate affinity, which still require the development of more potent candidates for clinical applications. As the applicability of conventional structural methods to this system is limited by a number of fundamental factors, the exploitation of the information contained in chemical shift perturbations has offered a useful route to obtaining structural information to guide the development of more potent compounds. For a set of 12 structurally related isoindolinones, the data suggests 4 different orientations of binding, caused by subtle changes in the chemical structure of the inhibitors.     

Auxiliary probe design adaptable to existing probes for remote detection NMR, MRI, and time-of-flight tracing

A versatile, detection-only probe design is presented that can be adapted to any existing NMR or MRI probe with the purpose of making the remote detection concept generally applicable. Remote detection suggests freeing the NMR experiment from the confinement of using the same radio frequency (RF) coil and magnetic field for both information encoding and signal detection. Information is stored during the encoding step onto a fluid sensor medium whose magnetization is later measured in a different location. The choice of an RF probe and magnetic field for encoding can be made based solely on the size and characteristics of the sample and the desired information quality without considering detection sensitivity, as this aspect is dealt with by a separate detector. While early experiments required building probes that included two resonant circuits, one for encoding and one for detection, a modular approach with a detection-only probe as presented here can be used along with any existing NMR probe of choice for encoding. The design of two different detection-only probes is presented, one with a saddle coil for milliliter-sized detection volumes, and the other one with a microsolenoid coil for sub-microliter fluid quantities. As example applications, we present time-of-flight (TOF) tracing of hyperpolarized (129)Xe spins in a gas mixture through coiled tubing using the microsolenoid coil detector and TOF flow imaging through a nested glass container where the gas flow changes its direction twice between inlet and outlet using the saddle coil detector.     

基于箭形累积损伤的裂纹尖端力学:奇异性分级和多尺度分段

在适度的空间和时间尺度组合下,裂纹既可在几个月中蠕变几个纳米,也能在几秒钟内扩展10km.虽然裂纹的尖端没有实际的质量,但是它能通过激活周围的物质而处于高能量状态.依赖于材料的损伤方向,激活质量的减少和增加可发生在尺度转变之前或之后.每个尺度区的分段阈值被假定为与裂纹尖端速度的平方a~2和激活质量密度M的乘积有关:W=M_(↓↑)a_(↑↓)~2和D=M~(↓↑)a_(↑↓)~2.W和D分别被称为直接吸收和自耗散能量密度.正如下标/上标符号所示,激活的质量密度M_(↓↑)和M~(↓↑)与裂纹尖端速度a变化趋势相反,既可增加也可减少.a~2和M的互补效应隐含着常用于宇宙物理学建模的膨胀和/或收缩的物理过程.在用于尺度敏感的裂纹尖端的行为时,激活的质量密度有相同的解释.分段时的多尺度可以由…皮观、纳观、微观和宏观…组成.因此,形象地说,材料损伤过程可以通过裂纹扩展过程中非均匀的总体和局部能量的传递来模拟.疲劳裂纹扩展引起的材料损伤被用来阐释由大到小和由慢到快的尺度/时间序,热力学中的冷→热和有序→无序转换.这一过程正巧与宇宙演化的箭形方向相反,宇宙演化遵循小→大和快→慢,而热力学相反,遵循热→冷和无序→有序.为了表示由损伤萌生所造成的类裂缝型缺陷的不均匀性,提出了一个被称为裂纹尖端力学(crack tip mechanics,CTM)的新模式.涉及的范围是模拟原子列之间的界面裂纹或连续体中分叉的切口.假如需要的话,尺寸和时间的范围可以复盖从皮观到宏观甚至更大.虽然采用疲劳裂纹来说明CTM的基本原理,在宇宙物理学背景中与直接吸收和自耗散相关的膨胀和收缩的情况可以描述裂纹周围激活质量的行为,它们可看为能量的汇或源.奇异性被用来捕获能量的源或汇的特性,物理上,两者作为界面的一部分,从数学上看则是不连续的线的一部分.能量从一种形式变为另一种形式取决于能量吸收或耗散的箭形损伤时间,这之中牵涉到尺度分段和奇异性强度的联合应用.材料组分随时间的劣化是根据指定的设计寿命导出的,从而使材料的响应与加载率的时间历史匹配.2024-T3铝板的皮观/纳观/微观/宏观开裂模型用来说明什么地方可以增加结构的寿命部分.皮观/纳观/微观/宏观/结构系统的性能随时间劣化可以用9个尺度转变物理参数来描述:纳观/微观区有3个(μ_(na/mi)~*,σ_(na/mi)~*,d_(na/mi)~*),微观/宏观区有3个(μ_(mi/ma)~*,σ_(mi/ma)~*,d_(mi/ma)~*),皮观/纳观区有3个(μ_(pi/na)~*,σ_(pi/na)~*,d_(pi/na)~*).下标pi,na,mi,ma和struc分别表示皮观、纳观、微观、宏观和结构.只要知道两个相连的尺度敏感参数,在较低尺度的时间相关的局部物理参数就完成了分析连续体的形式论,虽然它们并不需要用实验来知道.更具体地说,根据皮观→纳观→微观→宏观分别有1.25/1.00/0.75/0.50的λ奇异性强度,皮观裂纹、纳观裂纹、微观裂纹和宏观裂纹的转变特征是从时间箭形的指定的寿命预期来确定的.附加的0.25强度的奇异性可用于结构元件.回想起来,λ=0.5相应于断裂力学中的应力分量与r~(0.5)成反比,r是与宏观裂纹尖端的距离.微观裂纹、纳观裂纹和皮观裂纹分别赋予r~(-0.75),r~(-1.0),r~(-1.25)的奇异性.箭形时间(以年为单位)取决于问题的定义.设备的关键部件可用1.5~±/2.5~±/3.5~±/5.5~±寿命分布和总寿命为13~±年(a)的皮观/纳观/微观/宏观尺度来设计运行.上标±表示多于或少于实际运行的时间.累进损伤被假定为发生在皮观→纳观→微观→宏观方向.同样的方案用于20年总寿命的2024-T3铝板的疲劳损伤,按照1.5~±/2.5~±/3.5~±/5.5~±/7.0~±的方式将它的寿命分布在皮观、纳观、微观、宏观和结构的尺度上,这样的指定只是满足在每个尺度范围内损伤内部材料结构所用的能量匹配,因此可以强制执行在总寿命的跨度内精确的时间相关的材料性能劣化过程.     

On the electric current from electrodes in a magnetized semiconductor film

The problem on the electric current from electrodes in a magnetizedsemiconductor film is reduced to the skew derivative problemfor the Laplace equation outside cuts in a plane. The problemfor the Laplace equation is studied under different conditionsat infinity, which have a certain physical meaning. With thehelp of potential theory, the skew derivative problem is reducedto a Fredholm integral equation of the second kind, which isuniquely solvable. The Neumann problem for the Laplace equationin the exterior of cuts in a plane is a particular case of ourproblem.     

阻抗谱法确定扩散系数

给出了阻抗谱法确定扩散系数的理论和方法;以钒酸盐阴极材料Na_(1+x)V_3O_(?)(L.T.)为例,应用本方法计算给出了Li~+在阴极中的扩散系数为10~(?)-10~(-9)cm~2·s~(-1);最后还对误差来源进行了讨论. 关键词：