Engineered humanized diabodies for microPET imaging of prostate stem cell antigen-expressing tumors

We have previously demonstrated preclinical in vivo targeting of prostate stem cell antigen (PSCA) using a humanized anti-PSCA 2B3 monoclonal antibody (mAb). However, humanization resulted in 5-fold loss of apparent affinity relative to the parental mAb (1 nM). In this study, diabodies (scFv dimers of 55 kDa) were generated from 2B3 including variants with different linker lengths as well as back-mutations to original murine residues to improve affinity. Parental 2B3 (p2B3) and back-mutated 2B3 (bm2B3) diabodies (Dbs) with five- or eight-amino acid linkers (p2B3-Db5, p2B3-Db8, bm2B3-Db5 and bm2B3-Db8) were evaluated for binding to PSCA by flow cytometry and affinities were determined by surface plasmon resonance. Back-mutation restored the affinity from 5.4 to 1.9 nM. Stability, evaluated by size exclusion, revealed that diabodies with eight-residue linkers existed as a mixture of dimeric and monomeric species at low concentrations (相似文献   

Using Krylov‐Padé model order reduction for accelerating design optimization of structures and vibrations in the frequency domain

In many engineering problems, the behavior of dynamical systems depends on physical parameters. In design optimization, these parameters are determined so that an objective function is minimized. For applications in vibrations and structures, the objective function depends on the frequency response function over a given frequency range, and we optimize it in the parameter space. Because of the large size of the system, numerical optimization is expensive. In this paper, we propose the combination of Quasi‐Newton type line search optimization methods and Krylov‐Padé type algebraic model order reduction techniques to speed up numerical optimization of dynamical systems. We prove that Krylov‐Padé type model order reduction allows for fast evaluation of the objective function and its gradient, thanks to the moment matching property for both the objective function and the derivatives towards the parameters. We show that reduced models for the frequency alone lead to significant speed ups. In addition, we show that reduced models valid for both the frequency range and a line in the parameter space can further reduce the optimization time. Copyright © 2012 John Wiley & Sons, Ltd.     

Determination of structural building blocks in heavy petroleum systems by collision-induced dissociation Fourier transform ion cyclotron resonance mass spectrometry

Collision-induced dissociation Fourier Transform ion cyclotron resonance mass spectrometry (CID-FTICR MS) was developed to determine structural building blocks in heavy petroleum systems. Model compounds with both single core and multicore configurations were synthesized to study the fragmentation pattern and response factors in the CID reactions. Dealkylation is found to be the most prevalent reaction pathway in the CID. Single core molecules exhibit primarily molecular weight reduction with no change in the total unsaturation of the molecule (or Z-number as in chemical formula C(c)H(2c+Z)N(n)S(s)O(o)VNi). On the other hand, molecules containing more than one aromatic core will decompose into the constituting single cores and consequently exhibit both molecular weight reduction and change in Z-numbers. Biaryl linkage, C(1) linkage, and aromatic sulfide linkage cannot be broken down by CID with lab collision energy up to 50 eV while C(2)+ alkyl linkages can be easily broken. Naphthenic ring-openings were observed in CID, leading to formation of olefinic structures. Heavy petroleum systems, such as vacuum resid (VR) fractions, were characterized by the CID technology. Both single-core and multicore structures were found in VR. The latter is more prevalent in higher aromatic ring classes.     

Metabolomics: a valuable tool for stem cell monitoring in regenerative medicine

Metabolomics is a method for investigation of changes in the global metabolite profile of cells. This paper discusses the technical application of the approach, considering metabolite extraction, separation, mass spectrometry and data interpretation. A particular focus is on the application of metabolomics to the study of stem cell physiology in the context of biomaterials and regenerative medicine. Case studies are used to illustrate key points, focusing on the use of metabolomics in the examination of mesenchymal stem cell responses to titania-nanopillared substrata designed for orthopaedic applications.     

城镇污水处理工艺对紫外线消毒RED的影响

使用准平行紫外光束仪测定了重庆市3个采用不同处理工艺的城镇污水处理厂终沉池出水中粪大肠菌群(FC)的紫外线响应曲线,考察了不同处理工艺对紫外线消毒等效生物验证剂量(RED)的影响.结果表明,在15mJ/CM2的紫外线辐照剂量下,3个污水处理厂终沉池出水中的FC未发生光复活和暗复活现象;运用虚拟变量回归分析法对3个水样的试验数据进行统计分析,发现3个水样属于同一个样本空间,表明不同的二级污水处理工艺对紫外线消毒效果没有显著影响;基于数据合并处理的结果,建议新建的城镇二级污水处理厂的紫外线消毒反应器的进水FC浓度设计值取5.0×106MPN/L,以对应1.0×104和1.0×103MPN/L的两个排放标准,REDmsz分别为25和36mJ/cm2.     

Perchlorate in pleistocene and holocene groundwater in north-central New Mexico

Groundwater from remote parts of the Middle Rio Grande Basin in north-central New Mexico has perchlorate (ClO4-) concentrations of 0.12-1.8 micro/L. Because the water samples are mostly preanthropogenic in age (0-28000 years) and there are no industrial sources in the study area, a natural source of the ClO4- is likely. Most of the samples have Br-, Cl-, and SO4(2-) concentrations that are similar to those of modern bulk atmospheric deposition with evapotranspiration (ET) factors of about 7-40. Most of the ET values for Pleistocene recharge were nearly twice that for Holocene recharge. The N03-/Cl- and CIO-/Cl-ratios are more variable than those of Br-/Cl- or S04(2-)/Cl-. Samples thought to have recharged under the most arid conditions in the Holocene have relatively high N03-/Cl- ratios and low delta 15N values (+1 per mil (% per thousand)) similar to those of modern bulk atmospheric N deposition. The delta 18O values of the N03- (-4 to 0% per thousand) indicate that atmospheric N03- was not transmitted directly to the groundwater but may have been cycled in the soils before infiltrating. Samples with nearly atmospheric N03-/CI- ratios have relatively high Cl04- concentrations (1.0-1.8 ug/L) with a nearly constant Cl04-/CI- mole ratio of (1.4 +/- 0.1) x 10(-4), which would be consistent with an average Cl04-concentration of 0.093 0.005 ,ug/L in bulk atmospheric deposition during the late Holocene in north-central NM. Samples thought to have recharged under wetter conditions have higher delta 15N values (+3 to +8 % per thousando), lower NO3-/Cl- ratios, and lower ClO4-/Cl- ratios than the ones most likely to preserve an atmospheric signal. Processes in the soils that may have depleted atmospherically derived NO3-also may have depleted ClO4- to varying degrees prior to recharge. If these interpretations are correct, then ClO4- concentrations of atmospheric origin as high as 4 microg/L are possible in preanthropogenic groundwater in parts of the Southwest where ET approaches a factor of 40. Higher Cl04- concentrations in uncontaminated groundwater could occur in recharge beneath arid areas where ET is greater than 40, where long-term accumulations of atmospheric salts are leached suddenly from dry soils, or where other (nonatmospheric) natural sources of ClO4- exist.     

Continuous ice core melter system with discrete sampling for major ion, trace element and stable isotope analyses

We present a novel ice/firn core melter system that uses fraction collectors to collect discrete, high-resolution (<1 cm/sample possible), continuous, coregistered meltwater samples for analysis of eight major ions by ion chromatography (IC), >32 trace elements by inductively coupled plasma sectorfield mass spectrometry (ICP-SMS), and stable oxygen and hydrogen isotopes by isotope ratio mass spectrometry (IRMS). The new continuous melting with discrete sampling (CMDS) system preserves an archive of each sample, reduces the problem of incomplete particle dissolution in ICP-SMS samples, and provides more precise trace element data than previous ice melter models by using longer ICP-SMS scan times and washing the instrument between samples. CMDS detection limits are similar to or lower than those published for ice melter systems coupled directly to analytical instruments and are suitable for analyses of polar and mid-low-latitude ice cores. Analysis of total calcium and sulfur by ICP-SMS and calcium ion, sulfate, and methanesulfonate by IC from the Mt. Logan Prospector-Russell Col ice core confirms data accuracy and coregistration of the split fractions from each sample. The reproducibility of all data acquired by the CMDS system is confirmed by replicate analyses of parallel sections of the GISP2 D ice core.     

Verifying three types of methane fluxes from soils by testing the performance of a novel mobile photoacoustic method versus a well-established gas chromatographic one

The performance of a novel portable, tunable diode laser, resonant photoacoustic (TDL-PA) analyzer developed for field measurements of CH4 was compared to a commonly applied offline gas chromatographic (GC) method. This comparative studywas realized under normal field conditions parallel to long-term weekly GC monitoring of four different soil types with very different methane budgets. The method used for gas-exchange measurements was the well-known closed-chamber technique. The TDL-PA analyzer detects methane at 1650.957 nm [R (5) line of the 2v3 band], guaranteeing high precision without the need for correction procedures. The two techniques correlated well (R2 = 0.988) over the entire concentration range (0.15-33 ppmv CH4) tested at highly varying flux rates between -30 and -12 ppbv CH4 min(-1) for uptakes and between 2.5 and 362 ppbv CH4 min(-1) for emissions. The two analyzers proved to be interchangeable, leaving the online advantages to the TDL-PA. A suitable CH4 online GC solution for chamber measurement is not available as a portable system. Additionally, the data sampling rate of 2 Hz enables a direct coupling to other infrared gas analyzers with the high time resolution commonly required to determine plant CO2 assimilation rates or soil respiration rates.     

Esoterik

Ohne Zusammenfassung „Esoterik“, im vorliegenden Sinne: einem inneren spirituellen Personenkreis vorbehaltene Lehren (unabh?ngig von ihren Inhalten)     

High-resolution biosensor spectral peak shift estimation

In this paper, we present a maximum likelihood (ML) approach to high-resolution estimation of the shifts of a spectral signal. This spectral signal arises in application of optically based resonant biosensors, where high resolution in the estimation of signal shift is synonymous with high sensitivity to biological interactions. For the particular sensor of interest, the underlying signal is nonuniformly sampled and exhibits Poisson amplitude statistics. Shift estimation accuracies orders of magnitude finer than the sample spacing are sought. The new ML-based formulation leads to a solution approach different from typical resonance shift estimation methods based on polynomial fitting and peak (or ) estimation and tracking.