Tunable Probes with Direct Fluorescence Signals for the Constitutive and Immunoproteasome

Electrophiles are commonly used for the inhibition of proteases. Notably, inhibitors of the proteasome, a central determinant of cellular survival and a target of several FDA‐approved drugs, are mainly characterized by the reactivity of their electrophilic head groups. We aimed to tune the inhibitory strength of peptidic sulfonate esters by varying the leaving groups. Indeed, proteasome inhibition correlated well with the pK_a of the leaving group. The use of fluorophores as leaving groups enabled us to design probes that release a stoichiometric fluorescence signal upon reaction, thereby directly linking proteasome inactivation to the readout. This principle could be applicable to other sulfonyl fluoride based inhibitors and allows the design of sensitive probes for enzymatic studies.     

Wander of a Gaussian-Beam Wave Propagated Through a Non-Kolmogorov Turbulent Atmosphere

Both increasing experimental evidence and some results of theoretical investigation have shown that there exist two kinds of turbulence in the aerosphere, Kolmogorov and non-Kolmogorov turbulence. Thus, it is necessary to improve the theory of optical wave propagation through atmospheric turbulence, namely, study the laser-beam propagation in non-Kolmogorov turbulence, before analyzing the joint influence of the Kolmogorov turbulence and non-Kolmogorov one on satellite laser communication. The beam wander will lead to the performance degradation of satellite laser communication systems and exert an influence on the achievement and stability of its links. In this paper, we consider a theoretical power spectrum of refractive-index fluctuations with a generalized power law in order to derive the variance of Gaussian-beam wave wander in weak turbulence for a horizonal path and analyze the influence of spectral power-law variations on the beam wander. We show that the expression for the beam-wander variance is of concise closed form and independent of the optical wavelength.     

Phase retrieval from fringe pattern with 1-D discrete wavelet transform

This paper proposes a novel method to obtain frequency modulation (FM) signals from a single fringe pattern for phase retrieval. First, a 1D discrete Meyer wavelet is employed to decompose the pattern image signal row by row and the soft-thresholding approach is applied to remove noise. The low frequency coefficients of the wavelet decomposition are then set to 0, and the signal is reconstructed. Moreover, the optimal wavelet decomposition level is adaptively determined using a cost function-based method. The reconstructed signal, which no longer contains a background component, is normalized using a nonlinear and piecewise normalization method. The proposed method is faster and more accurate than some other phase retrieval approaches, which is illustrated with two test cases.     

阿尔茨海默病诊断的自适应BP神经网络模型

阿尔茨海默病(AD)和轻度认知功能损伤(MCI)具有患者多、诊断难的特点,改进BP神经网络,提出自适应BP神经网络(ABP)进行100次AD和MCI诊断模拟,ABP神经网络的诊断正确率显著高于BP和RBF神经网络.采用留一法将101例正常人、200例MCI和90例AD患者的样本分为训练集和检测集,用ABP神经网络对其进行诊断模拟,总正确率达到73.91%.     

Complementary MS Methods Assist Conformational Characterization of Antibodies with Altered S–S Bonding Networks

As therapeutic monoclonal antibodies (mAbs) become a major focus in biotechnology and a source of the next-generation drugs, new analytical methods or combination methods are needed for monitoring changes in higher order structure and effects of post-translational modifications. The complexity of these molecules and their vulnerability to structural change provide a serious challenge. We describe here the use of complementary mass spectrometry methods that not only characterize mutant mAbs but also may provide a general framework for characterizing higher order structure of other protein therapeutics and biosimilars. To frame the challenge, we selected members of the IgG2 subclass that have distinct disulfide isomeric structures as a model to evaluate an overall approach that uses ion mobility, top-down MS sequencing, and protein footprinting in the form of fast photochemical oxidation of proteins (FPOP). These three methods are rapid, sensitive, respond to subtle changes in conformation of Cys?→?Ser mutants of an IgG2, each representing a single disulfide isoform, and may be used in series to probe higher order structure. The outcome suggests that this approach of using various methods in combination can assist the development and quality control of protein therapeutics.      

Synthesis, structure, and activity evaluation of two silver(I) complexes as Helicobacter pylori urease inhibitors

Two silver(I) compounds, [Ag(R,R-hxn)](C₇H₄BrO₂) · 2H₂O (I) (Chxn = 1,2-diaminocyclohexane) and [Ag(C₅H₆N₂)₂]₂(C₈H₄O₄) · 10H₂O (II), were synthesized and complex I was structurally characterized by X-ray crystallography. Compound I contains a catena-(trans-1,2-diaminocyclohexane) silver polycation ([Ag(Chxn)]_∞) in a roughly linear fashion, while II possesses a linear-type silver monocation. Compounds I and II were evaluated for their inhibitory activities against Helicobacter pylori urease in vitro. Both were found to have strong inhibitory activities against H. pylori urease comparable to that of acetohydroxamic acid.     

Biochemical and Structural Studies of Conserved Maf Proteins Revealed Nucleotide Pyrophosphatases with a Preference for Modified Nucleotides

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Study on the structure and reactivity of COREX coal

COREX is the primary process in the current smelting reduction method. The process has strict coal quality standards. Combustion processes of coal used in the COREX operating system were analyzed using a synchronous thermogravimetric analyzer combined with a mass spectrometer. The microcosmic structure and macerals were observed by an electronic scanning microscope. The qualitative and quantitative determinations of oxygen functional groups, such as phenolic hydroxyl, carboxyl, carbonyl, and methoxy groups were detected by the Fourier Transform Infrared spectrometer (FT-IR) and through chemical analysis methods. In addition, the evolution of the chemical structure and transformation mechanism of organic oxygen functional groups during COREX coal combustion have been thoroughly investigated. This study proposes a new coal-requirement index system and coal blending method, which will increase the expansion of coal selection and decrease the overall usage of coal during COREX.     

Preparation and characterization of an active catalyst

As an active catalyst to promote thermolysis of ammonium perchlorate (AP), potassium lead hexanitrocobaltate(II) complex (K₂Pb[Co(NO₂)₆]) was synthesized by the direct deposition method and inverse microemulsion method. Its submicron, size, cube morphology, and crystal structure were investigated by SEM, TEM, and XRD analysis, respectively. Thermal decomposition of K₂Pb[Co(NO₂)₆] was studied by the TG/DSC-IR online system and XRD analysis. The catalyst was decomposed at about 300 °C; its gaseous products were NO₂, NO, and N₂O and its solid products were Pb₃O₄, Co₃O₄, PbO, CoO, and KNO₂. Because thermal decomposition of the catalyst was synchronous with low temperature decomposition of AP, thermolysis of AP was promoted remarkably. In particular, the gaseous products (NO _x ) could directly oxidize the absorbed NH₃. As a result, compared to the data of pure AP, the integral heat of AP added 3.0 wt% of the catalyst multiplied by 280 %, the maximum rate of heat release increased by 634 %. The decomposition of catalyzed AP ended at about 317 °C, at which only less than 30 % of pure AP decomposed.