bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactivity of Transition Metal–Phosphorus Triple Bonds towards Triply Bonded [{CpMo(CO)2}2]: Formation of Heteronuclear Cluster Compounds
Authors: Scheer Manfred , Himmel Daniel , Kuntz Christian , Zhan Shuzhong , Leiner Eva
Published: August 2008

Thermolysis of [Cp*P{W(CO)5}2] (1) in the presence of [{CpMo(CO)2}2] leads to the novel complexes [{(CO)2Cp*W}{CpMo(CO)2}(μ,η2:η1:η1‐P2{W(CO)5}2)] (6; Cp=η5‐C5H5, Cp*=η5‐C5Me5), [{(μ‐O)(CpMoWCp*)W(CO)4}{μ3‐PW(CO)5}2] (7), [{CpMo(CO)2}2{Cp*W(CO)2}{μ3‐PW(CO)5}] (8) and [{CpMo(CO)2}2{Cp*W(CO)2}(μ3‐P)] (9). The structural framework of the main products 8 and 9 can be described as a tetrahedral Mo2WP unit that is formed by a cyclisation reaction of [{CpMo(CO)2}2] with an [Cp*(CO)2WP→W(CO)5] intermediate containing a WP triple bond and subsequent metal–metal and metal–phosphorus bond formation. Photolysis of 1 in the presence of [{CpMo(CO)2}2] gives 8, 9 and phosphinidene complex [(μ3‐PW(CO)5){CpMo(CO)2W(CO)5}] (10), in which the P atom is in a nearly trigonal‐planar coordination environment formed by one {CpMo(CO)2} and two {W(CO)5} units. Comprehensive structural and spectroscopic data are given for the products. The reaction pathways are discussed for both activation procedures, and DFT calculations reveal the structures with minimum energy along the stepwise Cp* migration process under formation of the intermediate [Cp*(CO)2WP→W(CO)5].
[2]Borametallocenophanes of Group 4 Metals: Synthesis and Structure
Authors: Braunschweig Holger , Gross Manuela , Hammond Kai , Friedrich Maria , Kraft Mario , Oechsner Andreas , Radacki Krzysztof , Stellwag Sascha
Published: August 2008

We report a series of [2]borametallocenophanes of Ti, Zr, and Hf with various ligand systems. The ligands have been synthesized in high yields starting from 1,2‐dibromo‐1,2‐bis(dimethylamino)diborane(4) upon reaction with Na[C5H5] and Li[C13H9], respectively. All compounds were fully characterized by multinuclear NMR spectroscopy and, for selected examples, by X‐ray analysis.
High Stability of the Polyproline II Helix in Polypeptide Bottlebrushes
Authors: Zhang Afang , Guo Yifei
Published: August 2008

Polymer bottlebrushes with monodisperse oligoproline side chains were efficiently synthesized, and the conformation of the peptide side chains in different solvents was investigated. Polymers with number‐average degrees of polymerization (DPn) of 89 and 366 were obtained by polymerization of the macromonomer in iPrOH/MeCN (1:1) and hexafluoroisopropanol, respectively. Circular dichroism (CD) spectra of the bottlebrush polymers in the neutral and charged states reveal that the oligoproline side chains attain stable polyproline II (PPII) helical conformations not only in aqueous solution, but also in aliphatic alcohol solutions. Dense attachment of oligopeptides onto a linear polymer chain did not lead to an increase in helix content. The possible effects of the main‐chain length on the conformational stability were examined. The switching between the polyproline I (PPI) and PPII helical conformations for the oligoproline side chains in aliphatic alcohol solutions is believed to be inhibited by the overcrowded structure in the polymer bottlebrushes.
Selektive Filtration – Eine Sortierung im Magnetfeld
Authors: Eichholz C. , Stolarski M. , Nirschl H.
Published: August 2008

Die Kombination von klassischer Filtration und Sortierprozessen im Magnetfeld ermöglicht eine selektive Separation von magnetischen und unmagnetischen Komponenten bei gleichzeitig überlagerter Flüssigkeitsabtrennung aus dem System. Diese Arbeit zeigt den Einfluss von magnetischer Feldstärke und der Wahl des Filtermediums auf die Selektivität der Trennung eines Modellsystems aus Magnetit und Quarzmehl. Zudem wird mit der mehrstufigen selektiven Filtration eine mögliche Prozessvariante demonstriert.
Prostate‐specific antigen screening among young men in the United States
Authors: Scales Charles D. , Antonelli Jodi , Curtis Lesley H. , Schulman Kevin A. , Moul Judd W.
Published: August 2008

BACKGROUND.

Disagreement exists on the use of prostate‐specific antigen (PSA) tests for cancer‐risk stratification in young men in the United States. Little is known about the use of PSA testing in these men. To understand policy implications of risk stratification, the authors sought to characterize PSA use among young men.

METHODS.

The authors used the 2002 Behavioral Risk Factor Surveillance System to study prostate‐cancer screening in a representative sample of men aged 40 years and older (n = 58,511). The primary outcome was self‐report of a PSA test in the previous year.

RESULTS.

Among men aged 40 to 49 years, 22.5% (95% confidence interval [CI], 21.5‐23.5) reported having had a PSA test in the previous year, compared with 53.7% (95% CI, 52.8‐54.7; P < .001) of men aged ≥50 years. When sociodemographic characteristics were statistically controlled, young, black, non‐Hispanic men were more likely than young, white, non‐Hispanic men to report having had a PSA test in the previous year (odds ratio [OR], 2.42; 95% CI, 1.95‐3.01; P < .001). In young men, annual household income ≥$35,000 (OR, 1.50; 95% CI, 1.26‐1.78; P < .001) and an ongoing relationship with a physician (OR, 2.52; 95% CI, 2.06‐3.07; P < .001) were associated with PSA testing.

CONCLUSIONS.

One‐fifth of young men reported having had a PSA test within the previous year. Young, black, non‐Hispanic men are more likely than young, white, non‐Hispanic men to report having had a PSA test, although screening in this high‐risk group remains suboptimal. Cancer 2008. © 2008 American Cancer Society.
Cancer health disparities among Indian and Pakistani immigrants in the United States
Authors: Hossain Akm , Sehbai Aasim , Abraham Rachel , Abraham Jame
Published: August 2008

BACKGROUND.

Immigrants from India and Pakistan comprise about 1.5% of the total United States population. To the author' knowledge, this is the first study analyzing epidemiologic data on Indian and Pakistani patients with newly diagnosed cancer.

METHODS.

The Surveillance, Epidemiology, and End Results (SEER) database has reported cancer incidence from 1973 to 2003. Since 1988, the Indian and Pakistani population has been reported separately under race and ethnicity. Frequency and survival analyses with SEER data were performed, and descriptive parameters were calculated along with overall survival in common cancers.

RESULTS.

In total, 6889 cases were reported between 1988 and 2003, and those cases included 51% men and 49% women (P = .821). Among men, 30% of cases were prostate cancers, 10% of cases were lung cancers, and 9% of cases were colorectal cancers. Among women, 38% of cases were breast cancers, 15% of cases were genital cancers, and 7% of cases were colorectal cancers. When overall survival with common cancer was compared between immigrants and non‐Hispanic whites in the United States, it was better among Indian and Pakistani immigrants.

CONCLUSIONS.

In a United States‐based Indian and Pakistani population, prostate and breast cancers were the most common malignancies in men and women, respectively. This differed from the incidence in India and Pakistan, where oral cavity cancer in men and breast and cervical cancers in women were the most common. These immigrant cancer patients also had better survival. This change in demographics may be attributed to multiple factors, and the current data have implications on cancer screening and intervention. Cancer 2008. © 2008 American Cancer Society.
Oriented Nanostructures for Energy Conversion and Storage
Authors: Liu Jun , Cao Guozhong , Yang Zhenguo , Wang Donghai , Dubois Dan , Zhou Xiaodong , Graff Gordon L. , Pederson Larry R. , Zhang Ji‐Guang
Published: August 2008

Recently, the role of nanostructured materials in addressing the challenges in energy and natural resources has attracted wide attention. In particular, oriented nanostructures demonstrate promising properties for energy harvesting, conversion, and storage. In this Review, we highlight the synthesis and application of oriented nanostructures in a few key areas of energy technologies, namely photovoltaics, batteries, supercapacitors, and thermoelectrics. Although the applications differ from field to field, a common fundamental challenge is to improve the generation and transport of electrons and ions. We highlight the role of high surface area to maximize the surface activity and discuss the importance of optimum dimension and architecture, controlled pore channels, and alignment of the nanocrystalline phase to optimize the transport of electrons and ions. Finally, we discuss the challenges in attaining integrated architectures to achieve the desired performance. Brief background information is provided for the relevant technologies, but the emphasis is focused mainly on the nanoscale effects of mostly inorganic‐based materials and devices.
Low‐frequency noise analysis and minimization in Gilbert‐cell‐based mixers for direct‐conversion (zero‐IF) low‐power front‐ends
Authors: Alvarado U. , Berenguer R. , Adín I. , Mayordomo I. , Vaz A. , Bistué G.
Published: August 2008

Low‐frequency (flicker) noise is one of the most important issues in the design of direct‐conversion zero‐IF front‐ends. Within the front‐end building blocks, the direct‐conversion mixer is critical in terms of flicker noise, since it performs the signal down‐conversion to baseband. This paper analyzes the main sources of low‐frequency noise in Gilbert‐cell‐based direct‐conversion mixers, and several issues for minimizing the flicker noise while keeping a good mixer performance in terms of gain, noise figure and power consumption are introduced in a quantitative manner. In order to verify these issues, a CMOS Gilbert‐cell‐based zero‐IF mixer has been fabricated and measured. A flicker noise as low as 10.4 dB is achieved (NF at 10 kHz) with a power consumption of only 2 mA from a 2.7 V power supply. More than 14.6 dB conversion gain and noise figure lower than 9 dB (DSB) are obtained from DC to 2.5 GHz with an LO power of −10 dBm, which makes this mixer suitable for a multi‐standard low‐power zero‐IF front‐end. Copyright © 2008 John Wiley & Sons, Ltd.
Continuous‐time filter featuring Q and frequency on‐chip automatic tuning
Authors: Otin A. , Celma S. , Aldea C.
Published: August 2008

The on‐chip automatic tuning of digitally programmable continuous‐time Gm‐C filters with a wide operation range employing a hybrid analog‐digitalmaster‐slavescheme is reported in this work. Themastersystem is implemented with a voltage‐controlled filter (VCF) with the same programmable transconductance cells as the main filter to enhance the matching betweenmasterandslave. The frequency tuning method, for both analog and digital control, is based on a digital phase comparator included in the phase‐locked loop achieving high‐precision tunability. The digital frequency tuning is obtained with an error of ±4% and the maximum settling time when changing between two consecutive digital words is 0.3 µs. Once the digital word is fixed, the analog tuning finely adjusts the value of the characteristic frequency to the reference and corrects for possible temperature variations with a settling time of 0.2 µs. The analog frequency control covers the whole discrete step with a maximum error of ±5%. Furthermore, a magnitude‐locked loop (MLL) Q‐tuning block is simultaneously applied to the system in order to precisely control the quality factor of the Gm‐C filter by using an appropriate envelope detector. According to the obtained results, both post‐layout simulation and experimental results, the adopted scheme has resulted as a useful and adequate solution to implement the complete auto‐tuning system of digitally programmable continuous‐time filters, including frequency and Q‐control. Copyright © 2008 John Wiley & Sons, Ltd.
Analysis and design of common‐gate low‐noise amplifier for wideband applications
Authors: Kaukovuori Jouni , Kaltiokallio Mikko , Ryynänen Jussi
Published: August 2008

The design of a common‐gate (CG) LNA for the wideband applications is discussed in this paper. The effect of the different components in matching network is analyzed in detail. The design of a wideband input matching and output signal current for the input stage is presented. In addition, the effect of the matching network on the linearity and noise of a CG stage is studied. A design example is given to demonstrate the effectiveness of the presented theory. Copyright © 2008 John Wiley & Sons, Ltd.
Analog calibration of channel mismatches in time‐interleaved ADCs
Authors: Harpe P. J. A. , Hegt J. A. , van Roermund A. H. M.
Published: August 2008

This paper presents a method for the on‐chip measurement and correction of gain errors, offsets and time‐skew errors in time‐interleaved ADCs. With the proposed method, the errors can be measured and processed in the digital domain. Then, this information is used to optimize several digitally controlled analog parameters of the circuit, which minimize the effect of aforementioned mismatch errors. After optimization, the digital logic can be switched off completely in order to save power. Simulation results on a full‐transistor implementation of the time‐interleaved sampling structure show that the channel matching errors can be accurately compensated. Copyright © 2008 John Wiley & Sons, Ltd.
T1/E1/J1 receiver in CMOS
Authors: Sobot Robert , Guo Haizheng
Published: August 2008

Behavioural model, simulation and testing results of a mixed‐signal short‐/long‐haul receiver suitable for high‐speed T1/E1/J1 application in CMOS are presented. The measured results demonstrate successful recovery of distorted incoming signals attenuated from 0 to 44 dB (max). The mixed‐signal part of the receiver chip occupies area of 1.2 mm × 1.8 mm in CMOS 0.35 µm process and requires typically 120 mW of power at 3.3 V power supply. Digital framer supports the operation of the receiver whereas local RAM is used for storing the unshielded twisted pair cable models that can be easily reprogrammed. Copyright © 2008 John Wiley & Sons, Ltd.
High‐resolution continuous‐time interface for micromachined capacitive accelerometer
Authors: Aaltonen Lasse , Rahikkala Pasi , Saukoski Mikko , Halonen Kari
Published: August 2008

A continuous‐time accelerometer interface is feasible when high dynamic range together with wide signal band is required. In this paper, design of interface electronics for a capacitive sensor is presented. The interface design is focused on attaining resolutions up to 120 dB together with a signal bandwidth of 300 Hz. The essential circuit structures of the interface will be presented and analyzed in detail. Important sources of instabilities and issues that affect the dynamic properties of the sensor are discussed. Measured and simulated results of the closed‐loop sensor will be provided to support the theory. Copyright © 2008 John Wiley & Sons, Ltd.
For better or for worse: the congruence of personal and group outcomes on targets' responses to discrimination
Authors: Stroebe Katherine , Ellemers Naomi , Barreto Manuela , Mummendey Amélie
Published: August 2008

This paper reports two studies examining how (in‐) congruence between personal and group outcomes affects emotional well‐being, outcome attributions and procedural justice perceptions of individuals who are exposed to subtle discrimination. In Study 1 (N = 82) participants are either accepted or rejected in a (bogus) job application procedure, and either do or do not receive additional information indicating group‐level disadvantage. In Study 2 (N  = 79), participants were either accepted or rejected, and received information indicating either advantage or disadvantage for members of their group. Results of both studies reveal that not only emotional well‐being and outcome attributions, but also procedural justice perceptions are primarily guided by personal outcomes. That is, being informed of group‐level disadvantage does not intensify but can instead alleviate negative affect resulting from personal rejection. Furthermore, group disadvantage is only seen as an indicator of an unjust procedure by individual group members who have personally suffered rejection. Results are discussed in relation to current insights on discrimination, tokenism and social justice. Copyright © 2008 John Wiley & Sons, Ltd.
Independent benefits of contact and friendship on attitudes toward homosexuals among authoritarians and highly identified heterosexuals
Authors: Hodson Gordon , Harry Hannah , Mitchell Andrea
Published: August 2008

Although intergroup contact is generally associated with positive intergroup attitudes, little is known about whether individual differences moderate these relations, or how contact might operate among prejudice‐prone individuals. The present investigation explores Person × Contact and Person × Friendship interaction patterns among heterosexual university students. As expected, the positive relations of right‐wing authoritarianism (RWA) and heterosexual identification with prejudice against homosexuals were weakened when participants reported increased contact, more positive contact, direct (personal) friendships, or indirect friendships (i.e., ingroup friends with outgroup friends) with homosexuals. These patterns held after controlling statistically for each person or situation variable. Contact and friendship exerted smaller or negligible effects among low authoritarians or low identifiers. Tests of indirect effects revealed that among high authoritarians or high identifiers, contact and friendship exerted influence on attitudes through group‐level perceptions that homosexuals promote societal values and through increased self–other overlap with gay friends, each otherwise resisted by these individuals. Overall these results suggest that: (a) intergroup contact and intergroup friendship are related but distinct constructs; and (b) past findings underestimate contact effects by collapsing across levels of personal biases. Copyright © 2008 John Wiley & Sons, Ltd.
Influence of line routing and terminations on transient overvoltages in LV power installations
Authors: Metwally Ibrahim A. , Heidler Fridolin H.
Published: August 2008

IEC 62305‐4 gives the rules for the selection and the installation of surge protective devices (SPDs), where the maximum enhancement factor is considered to be equal to 2 in the worst case of open‐circuit condition. The objective of the present paper is to check this relation for equipment connected to low‐voltage (LV) power system. The LV power system is considered as TN‐S system with different routings in three‐ and six‐storey buildings. The terminals of apparatus are substituted by a variety of different loads, namely, resistances, inductances, and capacitances. All Maxwell's equations are solved by the method of moments (MoM) and the voltage is calculated at the apparatus terminals. The SPD itself is simulated by a voltage source at the ground floor. The results reveal that the voltage at the apparatus terminals may overshoot the SPD protection level by a factor of 3 irrespective of the number of floors and loops. Copyright © 2008 John Wiley & Sons, Ltd.
Simulating turbulent Dean flow in Cartesian coordinates
Authors: El Khoury George K. , Andersson Helge I. , Pettersen Bjørnar
Published: August 2008

A simplified approach to simulate turbulent flows in curved channels is proposed. A set of governing equations of motion in Cartesian coordinates is derived from the full Navier–Stokes equations in cylindrical coordinates. Terms to first order in the dimensionless curvature parameter are retained, whereas higher‐order terms are neglected. The curvature terms are implemented in a conventional Navier–Stokes code using Cartesian coordinates. Direct numerical simulations (DNS) of turbulent flow in weakly curved channels are performed. The pronounced asymmetries in the mean flow and the turbulence statistics observed in earlier DNS studies are faithfully reproduced by the present simplified Navier–Stokes model. It is particularly rewarding that also distinct pairs of counter‐rotating streamwise‐oriented vortices are embedded in the simulated flow field. Copyright © 2008 John Wiley & Sons, Ltd.
CpG island hypermethylation of E‐cadherin (CDH1) and integrin α4 is associated with recurrence of early stage esophageal squamous cell carcinoma
Authors: Lee Eun Ju , Lee Bo Bin , Han Joungho , Cho Eun Yoon , Shim Young Mog , Park Joobae , Kim Duk‐Hwan
Published: August 2008

The prognosis of esophageal squamous cell carcinoma (ESCC) patients remains very poor, which is partially due to a high rate of recurrence. This study was aimed at identifying a recurrence‐associated epigenetic prognostic marker in patients with ESCC. We retrospectively analyzed the CpG island hypermethylation of the p16, Wif‐1, sFRP1, integrin α4, CDH1, DAP kinase and RARβ2 genes in 251 ESCCs. The methylation status was determined by methylation‐specific PCR. Hypermethylation was detected in 52% for p16, 25% for RARβ2, 43% for CDH1, 21% for integrin α4, 57% for sFRP1, 38% for DAP kinase and 35% for Wif‐1. Recurrence was observed in 131 (52%) of the 251 cases. For stage I cancers, CDH1 methylation was associated with a high risk of recurrence (OR = 5.26, 95% CI = 1.48–18.67; p = 0.01) and a poor recurrence‐free survival after surgery (HR = 3.13, 95% CI = 1.21–8.09; p = 0.02). The hazard of failure after recurrence was about 13.17 (95% CI = 2.46–70.41; p = 0.003) times higher in patients with Wif‐1 methylation than in those without. For stage II cancers, integrin α4 methylation was associated with an increased risk of recurrence (OR = 3.03, 95% CI = 1.09–8.37; p = 0.03) and a poor recurrence‐free survival (HR = 2.12, 95% CI = 1.13–3.98; p = 0.03). In conclusion, the present study suggests that hypermethylation of CDH1 and integrin α4 genes may be used as recurrence‐associated prognostic indicators in stage I and stage II ESCCs, respectively. © 2008 Wiley‐Liss, Inc.
Ras‐driven proliferation and apoptosis signaling during rat liver carcinogenesis is under genetic control
Authors: Calvisi Diego F. , Pinna Federico , Pellegrino Rossella , Sanna Valeria , Sini Marcella , Daino Lucia , Simile Maria M. , De Miglio Maria R. , Frau Maddalena , Tomasi Maria L. , Seddaiu Maria A. , Muroni Maria R. , Feo Francesco , Pascale Rosa M.
Published: August 2008

Fast growth and deregulation of G1 and S phases characterize preneoplastic and neoplastic liver lesions of genetically susceptible F344 rats, whereas a G1‐S block in lesions of resistant BN rats explains their low progression capacity. However, signal transduction pathways responsible for the different propensity of lesions from the 2 rat strains to evolve to malignancy remain unknown. Here, we comparatively investigated the role of Ras/Erk pathway inhibitors, involved in growth restraint and cell death, in the acquisition of a phenotype resistant or susceptible to hepatocarcinogenesis. Moderate activation of Ras, Raf‐1 and Mek proteins was paralleled in both rat models by strong induction of Dab2 and Rkip inhibitors. Levels of Dusp1, a specific ERK inhibitor, increased only in BN rat lesions, leading to modest ERK activation, whereas a progressive Dusp1 decline occurred in corresponding lesions from F344 rats and was accompanied by elevated ERK activation. Furthermore, a gradual increase of Rassf1A/Nore1A/Mst1‐driven apoptosis was detected in both rat strains, with highest levels in BN hepatocellular carcinoma (HCC), whereas loss of Dab2IP, a protein implicated in ASK1‐dependent cell death, occurred only in F344 rat HCC, resulting in significantly higher apoptosis in BN than F344 HCC. Taken together, our results indicate a control of the Ras/Erk pathway and the pro‐apoptotic Rassf1A/Nore1A and Dab2IP/Ask1 pathways by HCC susceptibility genes. Dusp1 possesses a prominent role in the acquisition of the phenotype resistant to HCC by BN rats, whereas late activation of RassF1A/Nore1A and Dab2IP/Ask1 axes is implicated in the highest apoptosis characteristic of BN HCC. © 2008 Wiley‐Liss, Inc.
Lactotransferrin: A candidate tumor suppressor—Deficient expression in human nasopharyngeal carcinoma and inhibition of NPC cell proliferation by modulating the mitogen‐activated protein kinase pathway
Authors: Zhou Yanhong , Zeng Zhaoyang , Zhang Wenling , Xiong Wei , Wu Minghua , Tan Yixin , Yi Wei , Xiao Lan , Li Xiaoling , Huang Chen , Cao Li , Tang Ke , Li Xiayu , Shen Shourong , Li Guiyuan
Published: August 2008

Lactotransferrin (LTF) has been shown to regulate tumorogenesis. However, little is known about the role of LTF in regulating the development of human nasopharyngeal carcinoma (NPC). The aim of our study was to investigate whether LTF could regulate the development of NPC by characterizing the pattern of LTF expression in human NPC tissues using cDNA and tissue microarrays. Loss of LTF expression was observed in a significantly higher frequency of NPC tissues compared to that in nontumor nasopharyngeal epithelial tissues. While 61.25% of NPC tissues at the T1/T2 stage were positive for LTF expression, only 40.82% of NPC at the T3/T4 stage were stained by anti‐LTF. Similarly, 41.58% of NPC with local lymph node metastasis displayed LTF expression, a value significantly lower than the 46.36% in primary tumors (p < 0.05). These findings suggest that LTF may negatively regulate the development and metastasis of NPC in vivo. Furthermore, overexpression of or treatment with LTF inhibited the proliferation of NPC cells and promoted cell cycle arrest at the G0/G1 phase in vitro. While LTF treatment downregulated expression of cyclin D1 and phosphorylation of retinoblastoma protein (Rb), expression of p21 and p27 in 5–8F NPC cells was enhanced. Moreover, LTF treatment modulated the mitogen‐activated protein kinase (MAPK) pathway, but did not affect p53 and STAT3 expression in 5–8F NPC cells. Thus LTF is likely to be a candidate tumor suppressor and downregulates the development of NPC by inhibiting NPC proliferation through induction of cell cycle arrest and modulation of the MAPK signaling pathway. Therefore, our findings provide new insights in understanding the mechanism(s) underlying the action of LTF in regulating the development of human NPC. © 2008 Wiley‐Liss, Inc.
Chemotherapeutic drugs and human tumor cells cytokine network
Authors: Levina Vera , Su Yunyun , Nolen Brian , Liu Xiaoning , Gordin Yuri , Lee Melissa , Lokshin Anna , Gorelik Elieser
Published: August 2008

The ability of human tumor cell lines to produce various cytokines, chemokines, angiogenic and growth factors was investigated using Luminex multiplex technology. Media conditioned by tumor cells protected tumor cells from drug‐induced apoptosis and stimulated tumor cell proliferation. Antibodies neutralizing IL‐6, CXCL8, CCL2 and CCL5 blocked this stimulation. Treatment of tumor cells with doxorubicin and cisplatin resulted in a substantial increase in the production of IL‐6, CXCL8, CCL2, CCL5, BFGF, G‐CSF and VEGF. This stimulation was associated with drug‐induced activation of NF‐κB, AP‐1, AP‐2, CREB, HIF‐1, STAT‐1, STAT‐3, STAT‐5 and ATF‐2 transcription factors and upregulation ofIL‐6, CXCL8, FGF‐2, CSF‐3andCCL5gene expression. Treatment of tumor cells with doxorubicin and antibodies neutralizing G‐CSF, CCL2 or CCL5 had higher inhibitory effects than each modality used alone. These results indicate that chemokines and growth factors produced by tumor by binding to the cognate receptors on tumor and stroma cells could provide proliferative and antiapoptotic signals helping tumor to escape drug‐mediated destruction. Clinical studies showed that antibodies neutralizing VEGF (Avastin/Bevacizumab) or blocking HER2/neu signaling (Herceptin/Trastuzumab) could increase the efficacy of chemotherapy, although these beneficial effects have been limited. It is possible that drug‐stimulated production of growth and proangiogenic factors could counterbalance the effects of antibody therapy. In addition, numerous growth factors and chemokines share angiogenic and growth‐stimulating properties, and thus reduction of a single factor is insufficient to completely block tumor growth. Thus, a broad disruption of tumor cytokine network is needed to further increase the efficacy of cancer therapy. © 2008 Wiley‐Liss, Inc.
Kinetics of repression by modified p53 on the PDGF β‐receptor promoter
Authors: Yang Weiwen , Wetterskog Daniel , Matsumoto Yoshiki , Funa Keiko
Published: August 2008

Herein, we show that both exogenously transfected and endogenously activated p53 repress promoter activity and expression of PDGFRB. p53 binds the proximal promoter containing the CCAAT motif as examined by EMSA and chromatin immunoprecipitation. However, gradual induction of p53 in tet‐onSAOS2 cells resulted in a transient increase of the PDGFRB‐promoter activity and its expression. As binding of p53 to the promoter increased, previously bound p73, ΔNp73, c‐Myc, HDAC1 and HDAC4 were dismissed from the repressed promoter, and p300 was recruited. The transient increase of the promoter activity was therefore induced by the release of the p73, Myc and HDACs, previously shown to act as repressors to this promoter. Along with further increase of p53, p300 was replaced by HDAC1 and HDAC4, resulting in decreased PDGFRB expression. For the repression, acetylation of the C‐terminal lysines of p53 is important, and both acetyl‐K373p53 and methyl‐K370p53 became bound to the promoter. The acetyl‐K373p53 was accumulated in the nucleus and colocalized with promyelocytic leukemia protein. Mitomycin treatment of MEF induced similar epigenetic modification of p53 and its binding to the promoter chromatin. Addition of a PDGFR tyrosine‐kinase inhibitor to p53‐inducing tet‐onSAOS2 increased the number of apoptotic cells. These results suggest that p53 represses the PDGFRB promoter, facilitating the p53‐induced apoptosis, whereas tumor cells with p53 mutation or a high level of ΔNp73 or Myc could become refractory to the regulation. © 2008 Wiley‐Liss, Inc.
Angiostatic immune reaction in colorectal carcinoma: Impact on survival and perspectives for antiangiogenic therapy
Authors: Naschberger Elisabeth , Croner Roland S. , Merkel Susanne , Dimmler Arno , Tripal Philipp , Amann Kerstin U. , Kremmer Elisabeth , Brueckl Wolfgang M. , Papadopoulos Thomas , Hohenadl Christine , Hohenberger Werner , Stürzl Michael
Published: August 2008

Angiogenesis and inflammation are the 2 major stroma reactions in colorectal carcinoma (CRC). Guanylate binding protein‐1 (GBP‐1) is a key mediator of angiostatic effects of inflammation. Therefore, we hypothesized that GBP‐1 may be a biomarker of intrinsic angiostasis associated with an improved outcome in CRC patients. GBP‐1 was strongly expressed in endothelial cells and immune cells in the desmoplastic stroma of 32% of CRC as determined by immunohistochemical investigation of 388 sporadic CRC. Cancer‐related 5‐year survival was highly significant (p < 0.001) increased (16.2%) in patients with GBP‐1‐positive CRC. Multivariate analysis showed that GBP‐1 is an independent prognostic factor indicating a reduction of the relative risk of cancer‐related death by the half (p = 0.032). A comparative transcriptome analysis (22,215 probe sets) of GBP‐1‐positive (n = 12) and ‐negative (n = 12) tumors showed that particularly IFN‐γ‐induced genes including the major antiangiogenic chemokines CXCL9, CXCL10 and CXCL11 were coexpressed with GBP‐1. Altogether our findings indicated that GBP‐1 may be a novel biomarker and an active component of a Th‐1‐like angiostatic immune reaction in CRC. This reaction may affect patient's response to antiangiogenic therapy and the identification of such tumors may provide a novel criterion for patient selection. Moreover, the induction of a Th‐1‐like angiostatic immune reaction may be a promising approach for the clinical treatment of CRC. © 2008 Wiley‐Liss, Inc.
Combined NMR three‐bond scalar coupling measurements and QM calculations to calculate OH‐rotamer equilibrium of polyalcohols
Authors: Kövér Katalin E. , Beke Tamás , Lipták András , Perczel András
Published: August 2008

A combined but independently applied NMR and QM procedure has been used to investigate the conformational properties of the exchangeable hydroxyl protons of polyalcohols. In this study, to demonstrate the applicability of such a strategy, we investigated a simple monosaccharide, i.e. α‐ and β‐anomers of a D‐glucopyranoside derivative. The redundant set of experimental vicinal homonuclear and heteronuclear scalar couplings involving the OH‐protons obtained for both anomers of our model compound were simultaneously analyzed to yield the preferred OH‐rotamer populations and moreover to parametrize a new Karplus‐type equation for 3JC(i−1)OH(i) coupling. The populations of the lowest energy conformers and the conformational‐averaged coupling constants were independently calculated using the QM approach in both vacuum and chloroform. The similarity of the estimated rotamer populations obtained by two very different techniques and the similarity of the experimental and calculated coupling constants suggest that these approaches can be used in conjunction and in a fully integrated way to determine a more accurate atomic level description of molecular conformers. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Stable water isotope simulation in different reservoirs of Manaus, Brazil, by Community Land Model incorporating stable isotopic effect
Authors: Zhang Xin‐Ping , Yang Zong‐Liang , Niu Guo‐Yue , Wang Xiao‐Yun
Published: August 2008

The daily and monthly variations of stable water isotopes in different reservoirs at Manaus, Brazil, are simulated and inter‐compared in an equilibrium year, using the Community Land Model (CLM) involving the stable isotopic effects as a diagnostic tool for an in‐depth understanding of the hydrometeorological processes. On the daily scale, the δ18O in precipitation, vapour and surface runoff have clear seasonality, with marked negative correlations with the corresponding water amount. However, the δ18O in surface dew displays marked positive correlation with dew amount. On the diurnal time scale, the δ18O in precipitation displays an unclear diurnal variation and an unmarked correlation with the precipitation amount. However, the δ18O in vapour keeps consistency with specific humidity. On the monthly time scale, the δ18O in precipitation and surface runoff displays distinct bimodal seasonality, with two maxima in January and in July, and two minima in April and in October; Vapor displays a similar bimodal pattern, two maxima appear in January and August, and two minima in April and November. The amount effect simulated on the monthly time scale has consistency with the actual survey result at the Manaus station, from 1965 to 1990, set up by International Atomic Energy Agency (IAEA)/World Meteorological Organization (WMO). In addition, the slope (7.49) and the intercept (6.25) of the simulated meteoric water line (MWL) are all smaller than those of the actual mean MWL. However, compared with the annual MWL, the simulated MWL lies within the variation range of actual MWLs. Copyright © 2008 Royal Meteorological Society
Mixed‐mode ion‐exchangers and their comparative chromatographic characterization in reversed‐phase and hydrophilic interaction chromatography elution modes
Authors: Lämmerhofer Michael , Richter Martin , Wu Junyan , Nogueira Raquel , Bicker Wolfgang , Lindner Wolfgang
Published: August 2008

A set of particulate silica‐supported mixed‐mode RP/weak anion‐exchangers (RP/WAX) (obtained by bonding of N‐undecenoylated 3‐aminoquinuclidine, 3‐aminotropane and 2‐dimethylaminoethylamine as well as of N‐butenoyl‐(2S,4S,5R)‐2‐aminomethyl‐5‐[(2‐octylthio)ethyl]‐quinuclidine to thiol‐modified silica) were chromatographically characterized in comparison to selected commercially available columns using two distinct isocratic elution modes, viz. an aqueous‐rich RP‐type elution mode (with 40% ACN and 60% buffer) as well as an organic solvent‐rich hydrophilic interaction chromatography (HILIC)‐type elution mode (95 and 90% ACN). The mixed‐mode RP/WAX phases showed multimodal applicability, unlike a polar embedded RP material (Synergi Fusion RP), amino phases (Luna NH2, BioBasic AX) or typical HILIC packings (ZIC‐HILIC, TSKGel Amide‐80). Principal component analysis (PCA) of the RP test data confirmed that the in‐house developed RP/WAX columns as well as the Acclaim Mixed‐Mode WAX‐1 phase resemble each other in their chromatographic characteristics having slightly lower hydrophobic selectivity (αCH2 of 1.5) than the tested Synergi Fusion RP (αCH2 ∼︁1.8). In contrast, a decrease in mixed‐mode character due to lowered ion‐exchange capacity and concomitantly increased RP‐like behavior could be identified for other mixed‐mode phases in the order of Obelisc R > Primesep B2 > Uptisphere MM3. PCA on HILIC data revealed that the RP/WAX phases behave dissimilar to TSKGel Amide‐80, ZIC‐HILIC and polysulfoethyl A under the chosen elution conditions. Hence, they may be regarded as complementary to these commercial stationary phases with applicability profiles for hydrophilic but also hydrophobic solutes.
Fingerprinting of human bile during liver transplantation by capillary electrophoresis
Authors: Papaspyridonos Konstantina , Garcia‐Perez Isabel , Angulo Santiago , Domann Paula J. , Vilca‐Melendez Hector , Heaton Nigel , Murphy Gerard M. , Holmes Elaine , Barbas Coral , Legido‐Quigley Cristina
Published: August 2008

Increasing rates of success in liver transplantation have increased the number of cases considered. However, liver post‐transplant graft dysfunction of liver transplants (TXs) is not fully understood and by applying holistic approaches we can investigate metabolic change deriving from confounding factors such as liver fat content, ischaemia time, donor age, recipient's health,etc.Twenty‐six hepatic bile samples taken from liver donors and recipients were retrieved from a total of six TXs, from these one recipient underwent post‐graft dysfunction. CE was employed to fingerprint bile collected at 10 min increments in the donors and in the recipients. The electropherograms of these samples were aligned and normalised using correlation optimised warping algorithms and modelled with multivariate techniques. The resulting metabolic signatures were compared; in general donors and recipients showed distinct fingerprints and clustered separately. When a partial least square discriminant analysis (PLS‐DA) model was constructed between donor and recipient's samples, a recipient of a 32 year old liver with normal steatosis, and shortest cold ischaemia time showed as the observation nearest to its donor observation, denoting minimal metabolic change. This study proposes CE fingerprinting of human bile as a promising technique to help unravel the complex metabolic pathways involved during transplantation.
Separation and HPLC analysis of 15 benzodiazepines in human plasma
Authors: Mercolini Laura , Mandrioli Roberto , Amore Mario , Raggi Maria Augusta
Published: August 2008

Benzodiazepines (BZDs) are often prescribed to schizophrenic or depressed patients, as a part of polypharmacy regimens. An HPLC method has been developed for the simultaneous determination of 15 BZDs in human plasma. Separation was obtained by using a C8 RP column and a mobile phase composed of 65% aqueous phosphate buffer at pH 3.0 and 35% ACN. The UV detector was set at 220 nm and clomipramine was used as the internal standard. A careful pretreatment procedure of plasma samples was developed, using SPE with C1 cartridges, which gives high extraction yields (> 97%). The LOQs were always lower than 7.6 ng/mL and the LODs always lower than 2.6 ng/mL for all analytes. The method was successfully applied to plasma samples from depressed and schizophrenic patients undergoing polypharmacy with one or more BZDs. Precision data, as well as accuracy results, were satisfactory and no interference from other drugs was found. Hence, the method seems to be suitable for the therapeutic drug monitoring (TDM) of patients undergoing therapy with one or more BZDs.
Identification of RFLP G6PD mutations by using microcapillary electrophoretic chips (ExperionTM)
Authors: Minucci Angelo , Delibato Elisabetta , Castagnola Massimo , Concolino Paola , Ameglio Franco , Zuppi Cecilia , Giardina Bruno , Capoluongo Ettore
Published: August 2008

Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is one of the most well‐known human genetic defects, identified in more than 400 million individuals in the world. To date, no commercial kits are available for the mutation screening of this disease. Seventy G6PD‐deficient Italian individuals admitted to the Laboratory of Clinical Molecular Biology of Hospital “Agostino Gemelli” of Rome were screened for the most frequent Italian mutations, by means of allele‐specific PCR, followed by restriction fragment length electrophoresis. The present study compares two techniques for the identification of restriction patterns: agarose gel electrophoresis versus Experion system. When the first screening was negative, the entire G6PD gene was sequenced using the ABI 3100 Avant Instrumentation. The G6PD variants identified and their frequencies were the following: G6PD Mediterranean (75.7%), G6PD Seattle (7.1%), G6PD A– 202 + 376 (7.1%), and G6PD Cassano (2.8%). In addition, we identified by direct sequencing two new mutations, namely Buenos Aires and Rignano. With the Experion method, the size band determination was more accurate than that obtained by gel electrophoresis. The Experion system resulted as a valid, easy, and reproducible diagnostic method for the screening of G6PD mutation as compared with the agarose electrophoretic analysis.
Proteome analysis of human dorsolateral prefrontal cortex using shotgun mass spectrometry
Authors: Martins‐de‐Souza Daniel , Gattaz Wagner F. , Schmitt Andrea , Rewerts Christiane , Maccarrone Giuseppina , Dias‐Neto Emmanuel , Turck Christoph W.
Published: August 2008

The prefrontal cortex executes important functions such as differentiation of conflicting thoughts, correct social behavior and personality expression, and is directly implicated in different neurodegenerative diseases. We performed a shotgun proteome analysis that included IEF fractionation, RP‐LC, and MALDI‐TOF/TOF mass spectrometric analysis of tryptic digests from a pool of seven human dorsolateral prefrontal cortex protein extracts. In this report, we present a catalog of 387 proteins expressed in these samples, identified by two or more peptides and high confidence search scores. These proteins are involved in different biological processes such as cell growth and/or maintenance, metabolism/energy pathways, cell communication/signal transduction, protein metabolism, transport, regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism, and immune response. This analysis contributes to the knowledge of the human brain proteome by adding sample diversity and protein expression data from an alternative technical approach. It will also aid comparative studies of different brain areas and medical conditions, with future applications in basic and clinical research.
Determination of acid–base dissociation constants of azahelicenes by capillary zone electrophoresis
Authors: Ehala Sille , Míšek Jiří , Stará Irena G. , Starý Ivo , Kašička Václav
Published: August 2008

CZE was employed to determine acid–base dissociation constants (pKa) of ionogenic groups of azahelicenes in methanol (MeOH). Azahelicenes are unique 3‐D aromatic systems, which consist of ortho‐fused benzene/pyridine units and exhibit helical chirality. The pKa values of pyridinium groups of the studied azahelicenes were determined from the dependence of their effective electrophoretic mobility on pH by a nonlinear regression analysis. The effective mobilities of azahelicenes were determined by CZE at pH range between 2.1 and 10.5. Thermodynamic pKa values of monobasic 1‐aza[6]helicene and 2‐aza[6]helicene in MeOH were determined to be 4.94 ± 0.05 and 5.68 ± 0.05, respectively, and pKa values of dibasic 1,14‐diaza[5]helicene were found to be equal to 7.56 ± 0.38 and 8.85 ± 0.26. From these values, the aqueous pKa of these compounds was estimated.
Preparation of a high‐performance multi‐lectin affinity chromatography (HP‐M‐LAC) adsorbent for the analysis of human plasma glycoproteins
Authors: Kullolli Majlinda , Hancock William S. , Hincapie Marina
Published: August 2008

We report on the preparation of an improved multi‐lectin affinity support for HPLC separations. We combined the selectivity of three different lectins: concanavalin A (ConA), wheat germ agglutinin (WGA), and jacalin (JAC). Each lectin was first covalently immobilized onto a polymeric matrix and then the three lectin media were combined in equal ratios. The beads were packed into a column to produce a mixed‐bed multi‐lectin HPLC column (high‐performance multi‐lectin affinity chromatography (HP‐M‐LAC)) for fast chromatographic affinity separations. The support was characterized with respect to kinetics of immobilization, ligand density, and binding capacity for human plasma glycoproteins. A high lectin density (15 mg/mL of beads) was found to be optimal for the binding of glycoproteins from human plasma. A single clinical sample can be fractionated in less than 10 min per run, making this a useful sample preparation tool for proteomics/glycoproteomics studies associated with disease abormalities.
Characterization of biodiesel and biodiesel blends using comprehensive two‐dimensional gas chromatography
Authors: Tiyapongpattana Warawut , Wilairat Prapin , Marriott Philip J.
Published: August 2008

In this work the development of a comprehensive 2‐D GC flame ionization detection (GC×GC FID) method for biodiesel fuels is reported. This method is used for the analysis of fatty acid methyl esters (FAMEs) in both biodiesel (B100) and biodiesel blend (B5) samples. The separation of FAME was based on component boiling point in the first dimension and polarity in the second dimension by using a BPX5/BP20 column set to provide a measure of ‘orthogonality’ in the 2‐D space. Here the columns are coupled with a cryogenic modulator operating in a novel temperature programmed mode (TM) whereby the cryotrap is progressively incremented in temperature as the oven temperature is increased. The final method employs eight cryotrap temperature settings. The developed GC×GC method is able to successfully characterize and identify both B100 and B5 FAME components, which are produced from a variety of vegetable oils, animal fats and waste cooking oils, with high precision. The method is capable of analysing FAME with carbon numbers C4–C24, and is particularly suitable to characterize various types of biodiesel, making it possible to differentiate the origin and type of FAME used in the biodiesel samples.
Liposome electrokinetic capillary chromatography in the study of analyte–phospholipid membrane interactions. Application to pesticides and related compounds
Authors: Wiedmer Susanne K. , Kulovesi Pipsa , Riekkola Marja‐Liisa
Published: August 2008

Interactions between low‐molar mass analytes and phospholipid membranes were studied by liposome electrokinetic capillary chromatography (LEKC). The analytes were pesticides, some degradation products, and compounds associated with the manufacture of pesticides. Negatively charged liposome dispersions with different zwitterionic lipids (PC) were applied to the determination of retention factors (k) of 15 charged and uncharged compounds. The liposome dispersions consisted of 80:20 mol% of 1,2‐dilauroyl‐sn‐glycero‐3‐phosphocholine (DLPC)/1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phospho‐L‐serine (POPS), 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphocholine (DMPC)/POPS, and 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine (POPC)/POPS. Retention factors were calculated from the effective electrophoretic mobilities of the analytes under LEKC and CZE conditions and from the effective electrophoretic mobilities of the liposomes, determined by CZE with a polyacrylamide‐coated capillary. Determining the liposome mobilities in this way proved to be a good alternative to the conventional method employing a liposome marker compound. The log k values of the analytes for the different liposome dispersed phases were correlated with one another. In addition, correlation curves were determined between log k and calculated octanol–water partition coefficients. The results showed that the zwitterionic phospholipid in the liposome has a major impact on the interactions between the tested compounds and the lipid membranes.