Left and Right Pathlengths in Random Binary Trees

We study the difference between the left and right total pathlengths in a random binary tree. The results include exact and asymptotic formulas for moments and an asymptotic distribution that can be expressed in terms of either the Brownian snake or ISE. The proofs are based on computing expectations for a subcritical binary Galton-Watson tree, and studying asymptotics as the Galton-Watson process approaches a critical one.     

Determination of somatostatin receptor subtype 2 in carcinoid tumors by immunohistochemical investigation with somatostatin receptor subtype 2 antibodies

We have shown previously that expression of mRNA for somatostatin receptor subtype 2 (sst2) detected by in situ hybridization correlates to therapeutic outcome in patients with carcinoid tumors treated with somatostatin analogues. However, in situ hybridization is laborious and not practical in clinical routine work. We have, therefore, developed polyclonal antibodies directed against sst2 that may be used for immunohistochemistry on tissue specimens. The staining is specific and is highly correlated to expression of mRNA for sst2 (P < 0.01) as well as to tracer uptake at somatostatin receptor scintigraphy (P < 0.01). There is also a good correlation to the therapeutic response in carcinoid patients treated with somatostatin analogues (P < 0.05). Of 35 patients with carcinoid tumors included in this investigation, 25 stained positive with the antibodies. Twenty-two of these were investigated by somatostatin receptor scintigraphy and showed tracer uptake in metastases. An additional two patients that did not stain with the antibodies showed pathological uptake of the tracer in metastases, which might indicate binding to somatostatin receptor subtype 5. None of the 10 patients without positive immunostaining responded to somatostatin analogue treatment, whereas patients with a positive stain had a biochemical response or remained stable during treatment. Thus, these antibodies may be used to determine the presence of sst2 in carcinoid tumors and to select patients suitable for somatostatin analogue treatment. The method is easily applicable in clinical practice.     

A new block-based method for copy move forgery detection under image geometric transforms

Copy move forgery detection (CMFD) is one of the most active subtopic in forgery scheme. The methods of CMFD are divided into to block-based method and keypoint-based method in general. Compared with keypoint-based method, block-based method can detect undetectable detail without morphology segmentation. But many block-based methods detect the plain copy-move forgeries only. They have been incompetent to detect the post-processing operations such as various geometrical distortions, and then fail to detect the forgery regions accurately. Therefore, this paper presents an improved block-based efficient method for CMFD. Firstly, after pre-processing, an auxiliary overlapped circular block is presented to divide the forged image into overlapped circular blocks. The local and inner image feature is extracted by the Discrete Radial Harmonic Fourier Moments (DRHFMs) with the overlapped circular block from the suspicious image. Then, the similar feature vectors of blocks are searched by 2 Nearest Neighbors (2NN) test. Euclidean distance and correlation coefficient is employed to filter these features and then remove the false matches. Morphologic operation is employed to delete the isolated pixels. A series of experiments are done to analyze the performance for CMFD. Experimental results show that the new DRHFMs can obtain outstanding performance even under image geometrical distortions.     

A common network flow formulation for several civil engineering problems

This paper discusses a common network flow problem that arises in four areas of civil engineering. The problem is one of identifying arc flows that simultaneously satisfy the circuit and node law constraints for a given network. Applications and computational procedures in the areas of elastic structural analysis, hydraulic network analysis, traffic equilibrium and construction task scheduling are described. The interpretation of decision variables and mathematical functions will vary depending on the application, but the general priblem formulation and solution technique for each application remains essentially unchanged. Analogies between the different applications may enhance the conceptual understanding and intuition of engineers working in each area.     

Bivalent EGFR-Targeting DARPin-MMAE Conjugates

Epidermal growth factor receptor (EGFR) is a validated tumor marker overexpressed in various cancers such as squamous cell carcinoma (SSC) of the head and neck and gliomas. We constructed protein-drug conjugates based on the anti-EGFR Designed Ankyrin Repeat Protein (DARPin) E01, and compared the bivalent DARPin dimer (DD1) and a DARPin-Fc (DFc) to the monomeric DARPin (DM) and the antibody derived scFv425-Fc (scFvFc) in cell culture and a mouse model. The modular conjugation system, which was successfully applied for the preparation of protein-drug and -dye conjugates, uses bio-orthogonal protein-aldehyde generation by the formylglycine-generating enzyme (FGE). The generated carbonyl moiety is addressed by a bifunctional linker with a pyrazolone for a tandem Knoevenagel reaction and an azide for strain-promoted azide-alkyne cycloaddition (SPAAC). The latter reaction with a PEGylated linker containing a dibenzocyclooctyne (DBCO) for SPAAC and monomethyl auristatin E (MMAE) as the toxin provided the stable conjugates DD1-MMAE (drug-antibody ratio, DAR = 2.0) and DFc-MMAE (DAR = 4.0) with sub-nanomolar cytotoxicity against the human squamous carcinoma derived A431 cells. In vivo imaging of Alexa Fluor 647-dye conjugates in A431-xenografted mice bearing subcutaneous tumors as the SCC model revealed unspecific binding of bivalent DARPins to the ubiquitously expressed EGFR. Tumor-targeting was verified 6 h post-injection solely for DD1 and scFvFc. The total of four administrations of 6.5 mg/kg DD1-MMAE or DFc-MMAE twice weekly did not cause any sequela in mice. MMAE conjugates showed no significant anti-tumor efficacy in vivo, but a trend towards increased necrotic areas (p = 0.2213) was observed for the DD1-MMAE (n = 5).     

Structure-based design of cathepsin K inhibitors containing a benzyloxy-substituted benzoyl peptidomimetic

Peptidomimetic cathepsin K inhibitors have been designed using binding models which were based on the X-ray crystal structure of an amino acid-based, active site-spanning inhibitor complexed with cathepsin K. These inhibitors, which contain a benzyloxybenzoyl group in place of a Cbz-leucine moiety, maintained good inhibitory potency relative to the amino acid-based inhibitor, and the binding models were found to be very predictive of relative inhibitor potency. The binding mode of one of the inhibitors was confirmed by X-ray crystallography, and the crystallographically determined structure is in close qualitative agreement with the initial binding model. These results strengthen the validity of a strategy involving iterative cycles of structure-based design, inhibitor synthesis and evaluation, and crystallographic structure determination for the discovery of peptidomimetic inhibitors.     

Prospering in a transition economy through information technology-supported organizational learning

Abstract.  This paper presents the findings of a longitudinal study of the Slovenian company Sava during its 1995–2004 transition period when it adapted to and prospered in a free market economy. The company is particularly interesting because of its successful transition from a socialist company operating in a protected market to a privatized company operating in a capitalist global market, as well as the pivotal role of information technology (IT)-supported organizational learning that brought about radical change and successful transition. Our investigation of Sava's experiences demonstrates how the company's increasing attention to organizational learning, integration of working and learning, and its constant innovation of products and processes created new needs for IT support that motivated the adoption of new IT systems (such as Lotus Notes, document management systems, SAP), which in turn increased Sava's capacity to learn. Furthermore, our study reveals how the role of IT systems in organizational learning depends on the nature of learning (single-loop, double-loop or triple-loop learning) and the organizational level at which learning takes place (individual, group/department or organization). By providing insight into the emergence of distinct types of IT-supported learning and their vital role in Sava's successful transition, the paper contributes to a deeper understanding of the relationship between IT and organizational learning that is relevant and inspiring to other companies, especially those operating in transition economies.     

Trace metal concentrations in the North-western Mediterranean atmospheric aerosol between 1986 and 2008: Seasonal patterns and decadal trends

Climatic and anthropogenic changes are able to engender modifications in the aerosol composition at different geographical and temporal scales. The present study addresses this question for the trace metal concentrations (TM = Al, Fe, Mn, Co, Ni, Cu, Pb, Cd and Zn) of aerosol from the North-western Mediterranean coast of France (Cap Ferrat, nearby Nice) between 1986 and 2008. From seasonal variations (2006-08) and decadal trends (1986-2008) of TM concentrations, three groups of elements can be distinguished. They consist of different aerosol sources: crustal-derived elements (Al, Fe, Mn and Co), trace metals of anthropogenic origin (Pb, Cd and Zn) and a third, intermediate, group of trace metals that presented both anthropogenic and natural/crustal influences (Ni and Cu). Reproducible seasonal patterns were observed for crustal and intermediate elements with highest concentrations between May and November, while anthropogenic trace metals did not show a pronounced seasonal cycle. Nevertheless, highest concentrations of anthropogenic trace metals occurred mostly in autumn/winter. Aerosol concentrations of anthropogenic TMs decreased remarkably over the last two decades, while crustal trace metals did not show any evolution. Nickel and copper aerosol concentrations remained constant, as well. Lead concentrations decreased from 1986 (29.34 ng m^− 3) to 2008 (3.33 ng m^− 3), overall by 90%. Cadmium and zinc aerosol concentrations decreased by 66 and 54%, respectively, between 1998 and 2006-08, from 0.27 to 0.09 ng m^− 3 and from 23.9 to 10.9 ng m^− 3, respectively. These findings demonstrate the response of the atmospheric environment to the implementation of antipollution policies. Possible changes of trace metal emissions sources and local influences are discussed.     

疏水相互作用与亲水相互作用组合色谱纯化缩宫素

将疏水相互作用色谱与亲水相互作用色谱结合,建立了用于化学合成缩宫素粗品分离纯化的两步纯化工艺.先以纯水为流动相,采用Nylon6疏水相互作用色谱对粗品进行脱盐与富集,后以Superose12亲水相互作用色谱进行进一步纯化,两步纯化后,峰面积纯度达93.5%,提高了5.96倍,总回收率为50.1%,与用C18为介质的传统两步反相色谱纯化的结果相当.本方法有机溶剂用量仅为传统反相色谱的1/7,且两种介质都能耐受极端pH值清洗条件,重复利用率高.