bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Lipid Core Peptide System for Gene, Drug, and Vaccine Delivery
Authors: Zhong Wei , Skwarczynski Mariusz , Toth Istvan
Published: January 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.
ChemInform Abstract: Metagenomic Approaches to Natural Products from Free‐Living and Symbiotic Organisms
Authors: Brady Sean F. , Simmons Luke , Kim Jeffrey H. , Schmidt Eric W.
Published: January 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.
ChemInform Abstract: Electrochemical versus Heat‐Engine Energy Technology: A Tribute to Wilhelm Ostwald′s Visionary Statements
Authors: Kunze Julia , Stimming Ulrich
Published: January 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.
ChemInform Abstract: Recent Advances in Molecular Magnetic Materials
Authors: Murray Keith S.
Published: January 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.
ChemInform Abstract: The Bioconjugation of Redox Proteins to Novel Electrode Materials
Authors: Goldstein Daniel C. , Thordarson Pall , Peterson Joshua R.
Published: January 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.
ChemInform Abstract: Electrides: Early Examples of Quantum Confinement
Authors: Dye James L.
Published: January 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.
ChemInform Abstract: Two‐Dimensional Vibrational Spectroscopy of Rotaxane‐Based Molecular Machines
Authors: Bodis Pavol , Panman Matthijs R. , Bakker Bert H. , Mateo‐Alonso Aurelio , Prato Maurizio , Buma Wybren Jan , Brouwer Albert M. , Kay Euan R. , Leigh David A. , Woutersen Sander
Published: January 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.
Censored time series analysis with autoregressive moving average models
Authors: Park Jung Wook , Genton Marc G. , Ghosh Sujit K.
Published: January 2010

The authors consider time series observations with data irregularities such as censoring due to a detection limit. Practitioners commonly disregard censored data cases which often result in biased estimates. The authors present an attractive remedy for handling autocorrelated censored data based on a class of autoregressive and moving average (ARMA) models. In particular, they introduce an imputation method well suited for fitting ARMA models in the presence of censored data. They demonstrate the effectiveness of their technique in terms of bias, efficiency, and information loss. They also describe its adaptation to a specific context of meteorological time series data on cloud ceiling height, which are measured subject to the detection limit of the recording device.
Consistent testing for non‐correlation of two cointegrated ARMA time series
Authors: Saidi Abdessamad
Published: January 2010

A consistent approach to the problem of testing non‐correlation between two univariate infinite‐order autoregressive models was proposed by Hong (1996). His test is based on a weighted sum of squares of residual cross‐correlations, with weights depending on a kernel function. In this paper, the author follows Hong's approach to test non‐correlation of two cointegrated (or partially non‐stationary) ARMA time series. The test of Pham, Roy & Cédras (2003) may be seen as a special case of his approach, as it corresponds to the choice of a truncated uniform kernel. The proposed procedure remains valid for testing non‐correlation between two stationary invertible multivariate ARMA time series. The author derives the asymptotic distribution of his test statistics under the null hypothesis and proves that his procedures are consistent. He also studies the level and power of his proposed tests in finite samples through simulation. Finally, he presents an illustration based on real data.
A bayesian estimator for the dependence function of a bivariate extreme‐value distribution
Authors: Guillotte Simon , Perron François
Published: January 2010

Any continuous bivariate distribution can be expressed in terms of its margins and a unique copula. In the case of extreme‐value distributions, the copula is characterized by a dependence function while each margin depends on three parameters. The authors propose a Bayesian approach for the simultaneous estimation of the dependence function and the parameters defining the margins. They describe a nonparametric model for the dependence function and a reversible jump Markov chain Monte Carlo algorithm for the computation of the Bayesian estimator. They show through simulations that their estimator has a smaller mean integrated squared error than classical nonparametric estimators, especially in small samples. They illustrate their approach on a hydrological data set.
On population‐based measures of agreement for binary classifications
Authors: Nelson Kerrie P. , Edwards Don
Published: January 2010

The authors describe a model‐based kappa statistic for binary classifications which is interpretable in the same manner as Scott's pi and Cohen's kappa, yet does not suffer from the same flaws. They compare this statistic with the data‐driven and population‐based forms of Scott's pi in a population‐based setting where many raters and subjects are involved, and inference regarding the underlying diagnostic procedure is of interest. The authors show that Cohen's kappa and Scott's pi seriously underestimate agreement between experts classifying subjects for a rare disease; in contrast, the new statistic is robust to changes in prevalence. The performance of the three statistics is illustrated with simulations and prostate cancer data.
Bias reduction for nonparametric correlation coefficients under the bivariate normal copula assumption with known detection limits
Authors: Nie Lei , Chu Haitao , Korostyshevskiy Valeriy R.
Published: January 2010

The authors derive the asymptotic mean and bias of Kendall's tau and Spearman's rho in the presence of left censoring in the bivariate Gaussian copula model. They show that tie corrections for left‐censoring brings the value of these coefficients closer to zero. They also present a bias reduction method and illustrate it through two applications.
Nonparametric adaptive likelihood weights
Authors: Plante Jean‐François
Published: January 2010

The weighted likelihood can be used to make inference about one population when data from similar populations are available. The author shows heuristically that the weighted likelihood can be seen as a special case of the entropy maximization principle. This leads him to propose the minimum averaged mean squared error (MAMSE) weights. He describes an algorithm for calculating these weights and shows its convergence using the Kuhn‐Tucker conditions. He explores the performance and properties of the weighted likelihood based on MAMSE weights through simulations.
Inference in the presence of ranking error in ranked set sampling
Authors: Ozturk Omer
Published: January 2010

The author proposes inference techniques for ranked set sample data in the presence of judgment ranking errors. He bases his analysis on the models of Bohn & Wolfe (1994) and Frey (2007a, b), of which parameters are estimated by minimizing a distance measure. He then uses the fitted models to calibrate confidence intervals and tests. He shows the validity of his approach through simulation and illustrates its application through the construction of distribution‐free confidence intervals for the median area of apple tree leaves covered by a spray.
Dissecting racial disparities in the treatment of patients with locoregional pancreatic cancer
Authors: Riall Taylor S. , Townsend Courtney M. , Kuo Yong‐Fang , Freeman Jean L. , Goodwin James S.
Published: January 2010

BACKGROUND:

Previous studies have demonstrated that black patients with pancreatic cancer are less likely to undergo resection and have worse overall survival compared with white patients. The objective of this study was to determine whether these disparities occur at the point of surgical evaluation or after evaluation has taken place.

METHODS:

The authors used the Surveillance, Epidemiology, and End Results (SEER)‐Medicare linked data (1992‐2002) to compare black patients and white patients with locoregional pancreatic cancer in univariate models. Logistic regression was used to determine the effect of race on surgical evaluation and on surgical resection after evaluation. Cox proportional hazards models were used to identify which factors influenced 2‐year survival.

RESULTS:

Nine percent of 3777 patients were black. Blacks were substantially less likely than whites to undergo evaluation by a surgeon (odds ratio, 0.57; 95% confidence interval, 0.42‐0.77) when the model was adjusted for demographics, tumor characteristics, surgical evaluation, socioeconomic status, and year of diagnosis. Patients who were younger and who had fewer comorbidities, abdominal imaging, and a primary care physician were more likely to undergo surgical evaluation. Once they were seen by a surgeon, blacks still were less likely than whites to undergo resection (odds ratio, 0.64; 95% confidence interval, 0.49‐0.84). Although black patients had decreased survival in an unadjusted model, race no longer was significant after accounting for resection.

CONCLUSIONS:

Twenty‐nine percent of black patients with potentially resectable pancreatic cancers never received surgical evaluation. Without surgical evaluation, patients cannot make an informed decision and will not be offered resection. Attaining higher rates of surgical evaluation in black patients would be the first step to eliminating the observed disparity in the resection rate. Cancer 2010. © 2010 American Cancer Society
Epstein‐Barr virus latent membrane protein 1 mRNA is expressed in a significant proportion of patients with chronic lymphocytic leukemia
Authors: Tarrand Jeffrey J. , Keating Michael J. , Tsimberidou Apostolia M. , O'Brien Susan , LaSala Rocco P. , Han Xiang‐Yang , Bueso‐Ramos Carlos E.
Published: January 2010

BACKGROUND:

Epstein‐Barr virus (EBV) infection has been associated with Richter transformation in patients with chronic lymphocytic leukemia (CLL).

METHODS:

A direct isothermal mRNA amplification method was developed for detection of EBV latent membrane protein 1 (LMP1) mRNA transcriptional activity in the peripheral blood of 135 chronic lymphocytic leukemia patients and 98 hematologically healthy control subjects.

RESULTS:

EBV LMP1 mRNA transcripts were found in 19 of 135 (14%) of the CLL cases, but only 1% of the healthy controls (P < .0001). In contrast, 23 solid tumor patients tested negative for EBV LMP1 transcripts. In a later cohort of patients after hematopoietic stem cell transplantation, 4 of 7 patients with Hodgkin lymphoma or Burkitt lymphoma had EBV LMP1 detected. In a preliminary analysis, outcome data were available for 88 of the 135 patients with CLL. EBV LMP1 mRNA positivity was associated with a significantly increased degree of histologically demonstrated bone marrow involvement by CLL (P = .003, Mann‐Whitney U test).

CONCLUSIONS:

EBV LMP1 mRNA transcriptional activity was observed in a significant proportion of CLL patients. Transcription of the EBV LMP1, a late gene with known transforming potential in vitro, suggests that EBV activation plays a role in CLL disease progression. Thus, EBV LMP1 expression in CLL patients may be a factor involved in the genesis of refractory disease. Cancer 2010. © 2010 American Cancer Society.
p53 and MDM2 in renal cell carcinoma
Authors: Noon Aidan P. , Vlatković Nikolina , Polański Radosław , Maguire Maria , Shawki Howida , Parsons Keith , Boyd Mark T.
Published: January 2010

Renal cell carcinoma (RCC) is the most common type of kidney cancer and follows an unpredictable disease course. To improve prognostication, a better understanding of critical genes associated with disease progression is required. The objective of this review was to focus attention on 2 such genes, p53 and murine double minute 2 (MDM2), and to provide a comprehensive summary and critical analysis of the literature regarding these genes in RCC. Information was compiled by searching the PubMed database for articles that were published or e‐published up to April 1, 2009. Search terms included renal cancer, renal cell carcinoma, p53, and MDM2. Full articles and any supplementary data were examined; and, when appropriate, references were checked for additional material. All studies that described assessment of p53 and/or MDM2 in renal cancer were included. The authors concluded that increased p53 expression, but not p53 mutation, is associated with reduced overall survival/more rapid disease progression in RCC. There also was evidence that MDM2 up‐regulation is associated with decreased disease‐specific survival. Two features of RCC stood out as unusual and will require further investigation. First, increased p53 expression is tightly linked with increased MDM2 expression; and, second, patients who have tumors that display increased p53 and MDM2 expression may have the poorest overall survival. Because there was no evidence to support the conclusion that p53 mutation is associated with poorer survival, it seemed clear that increased p53 expression in RCC occurs independent of mutation. Further investigation of the mechanisms leading to increased p53/MDM2 expression in RCC may lead to improved prognostication and to the identification of novel therapeutic interventions. Cancer 2010. © 2010 American Cancer Society.
Nonsynonymous single nucleotide polymorphisms in DNA damage repair pathways and lung cancer risk
Authors: Tanaka Yugo , Maniwa Yoshimasa , Bermudez Vladimir P. , Doi Takefumi , Nishio Wataru , Ohbayashi Chiho , Okita Yutaka , Hurwitz Jerard , Hayashi Yoshitake , Yoshimura Masahiro
Published: January 2010

BACKGROUND:

Several reports have revealed the association between single nucleotide polymorphisms (SNPs) and the development of cancer. Although many SNPs have been investigated, they were tested individually. In this study, nonsynonymous SNPs present in DNA damage response genes were comprehensively analyzed for lung cancer susceptibility.

METHODS:

The authors selected 37 nonsynonymous SNPs in 23 genes involved in DNA damage repair pathways. Fifty lung adenocarcinoma patients resected at their institution between 2002 and 2005 and 50 individuals without any known history of cancer were recruited for a case‐control study.

RESULTS:

Three variants (XRCC1 194Trp homozygotes, POLδ1 119His homozygotes, and RAD9 239Arg heterozygotes) tended to coassociate with lung cancer risk. The authors analyzed and calculated whether the association between combinations of these 3 SNPs significantly affected the risk of lung cancer. Compared with carriers of either XRCC1 194Trp homozygote or RAD9 239Arg heterozygote variants, noncarriers were at a significantly decreased risk for lung cancer (odds ratio [OR], 0.282; confidence interval [CI], 0.089‐0.893). The same results were found for the combination of POLδ1 119His homozygotes and RAD9 239Arg heterozygotes (OR, 0.277; CI, 0.077‐0.993). Moreover, compared with carriers that had at least 1 of the 3 variants, noncarriers showed a more significant decrease in risk (OR, 0.263; CI, 0.090‐0.767).

CONCLUSIONS:

Analysis of the presence of XRCC1 194Trp homozygote, POLδ1 119His homozygote, and RAD9 239Arg heterozygote variants revealed that their coassociation leads to a significant risk for the development of lung adenocarcinoma. Inclusive analyses of different SNPs were important in this cancer risk study. Cancer 2010. © 2010 American Cancer Society.
N1S3: A revised staging system for head and neck cutaneous squamous cell carcinoma with lymph node metastases
Authors: Forest Veronique‐Isabelle , Clark Jonathan J. , Veness Michael J. , Milross Chris
Published: January 2010

BACKGROUND.

A staging system was designed for metastatic cutaneous squamous cell carcinoma (SCC) that would incorporate the parotid as a regional level and facilitate a better prognostic discrimination between subgroups.

METHODS.

A retrospective review of clinical and pathological information of patients treated for metastatic cutaneous SCC to the parotid and/or neck was conducted. Potential prognostic factors were analyzed using univariate and multivariate analyses. A staging system was elaborated and externally validated.

RESULTS.

Two hundred fifteen patients were included. All patients had surgery as their primary treatment; 148 had parotidectomy with neck dissection, 50 parotidectomy alone, and 18 neck dissection alone. One hundred seventy‐five patients received postoperative radiotherapy. On univariate analysis, the number of involved lymph nodes (P < .001), maximal size (P = .01), and extracapsular spread (P = .003) were found to be significant predictors of survival. On Cox regression, the number of involved lymph nodes as single or multiple (P = .006) was significant. The N1S3 staging system incorporates involved lymph nodes from parotid and neck (single or multiple) and the size (< or >3 cm). This system demonstrates significant predictive capacity for locoregional control (P < .001), disease‐specific survival (P<.0001), and overall survival (P<.0001). N1S3 was tested on a different cohort of 250 patients, and the results confirmed those obtained from our primary analyses.

CONCLUSIONS.

The N1S3 system stages patients according to the number of involved lymph nodes and size, and incorporates parotid as 1 of the regional levels. These 2 predictors are easily applied on both clinical and pathological data. Cancer 2010. © 2010 American Cancer Society.
Impact of smoking on patients with stage III colon cancer
Authors: McCleary Nadine Jackson , Niedzwiecki Donna , Hollis Donna , Saltz Leonard B. , Schaefer Paul , Whittom Renaud , Hantel Alexander , Benson Al , Goldberg Richard , Meyerhardt Jeffrey A.
Published: January 2010

BACKGROUND:

Cigarette smoking has been shown to increase the risk of developing colorectal cancer, particularly smoking early in life. Little is known about the impact of tobacco use on colon cancer recurrence among colon cancer survivors.

METHODS:

The authors prospectively collected lifetime smoking history from stage III colon cancer patients enrolled in a phase 3 trial via self‐report questionnaires during and 6 months after completion of adjuvant chemotherapy. Smoking status was defined as never, current, or past. Lifetime pack‐years were defined as number of lifetime packs of cigarettes. Patients were followed for recurrence or death.

RESULTS:

Data on smoking history were captured on 1045 patients with stage III colon cancer receiving adjuvant therapy (46% never smokers; 44% past; 10% current). The adjusted hazard ratio (HR) for disease‐free survival (DFS) was 0.99 (95% confidence interval [CI], 0.70‐1.41), 1.17 (95% CI 0.89‐1.55), and 1.22 (95% CI 0.92‐1.61) for lifetime pack‐years 0‐10, 10‐20, and 20+, respectively, compared with never smoking (P = .16). In a preplanned exploratory analysis of smoking intensity early in life, the adjusted HR for 12+ pack‐years before age 30 years for DFS was 1.37 (95% CI, 1.02‐1.84) compared with never smoking (P = .04). The adjusted HR for DFS was 1.18 (95% CI, 0.92‐1.50) for past smokers and 1.10 (95% CI, 0.73‐1.64) for current smokers, compared with never smokers.

CONCLUSIONS:

Total tobacco usage early in life may be an important, independent prognostic factor of cancer recurrences and mortality in patients with stage III colon cancer. Cancer 2010. © 2010 American Cancer Society.
A randomized phase 2 trial comparing 3‐hour versus 96‐hour infusion schedules of paclitaxel for the treatment of metastatic breast cancer
Authors: Moulder Stacy L. , Holmes Frankie A. , Tolcher Anthony W. , Thall Peter , Broglio Kristine , Valero Vicente , Buzdar Aman U. , Arbuck Susan G. , Seidman Andrew , Hortobagyi Gabriel N.
Published: January 2010

BACKGROUND:

This study was performed to compare efficacy and toxicity profiles of paclitaxel using 3‐hour versus 96‐hour infusion schedules.

METHODS:

Patients with metastatic breast cancer (MBC) were randomly assigned to receive paclitaxel starting at a dose of 250 mg/m2intravenously (iv) over 3 hours every 21 days or paclitaxel starting at a dose of 140 mg/m2iv over 96 hours every 21 days. Stratification variables included number of prior chemotherapy regimens and previous response to anthracyclines. Response was assessed every 2 cycles using bidimensional measurements. Patients were allowed to cross over at disease progression or therapy intolerance.

RESULTS:

A total of 214 patients received therapy (107 patients per arm). Response rates were similar: 23.4% in the 3‐hour arm and 29.9% in the 96‐hour arm (P= .28). The median duration of response (8.9 months vs 5.7 months;P= .75) and progression‐free survival (5.0 months vs 3.8 months;P= .17) slightly favored the 96‐hour arm. Overall survival was slightly longer in the 3‐hour arm (14.2 months vs 12.7 months;P= .57). One patient who crossed over to the 96‐hour arm (N = 18) developed a partial response; no response was noted with crossover to the 3‐hour arm (N = 10). Myalgia/arthralgia and neuropathy were more frequent in the 3‐hour arm, whereas mucositis, neutropenic fever/infection, and diarrhea were more common in the 96‐hour arm.

CONCLUSIONS:

Paclitaxel given by 3‐hour or 96‐hour infusion was active in MBC. The 96‐hour paclitaxel regimen did not significantly improve response or time to disease progression, was more cumbersome to administer, and was associated with greater myelosuppression (but less neuropathy and myalgia) compared with the 3‐hour schedule. Cancer 2010. © 2010 American Cancer Society.
An Electrochemical and Photophysical Study of a Covalently Linked Inorganic–Organic Dyad
Authors: Kahnt Axel , Heiniger Leo‐Philipp , Liu Shi‐Xia , Tu Xiaoyan , Zheng Zhiping , Hauser Andreas , Decurtins Silvio , Guldi Dirk M.
Published: January 2010

A molecular donor–acceptor dyad comprising a hexarhenium cluster core, [Re6(μ3‐Se)8]2+, and a fullerene moiety which are covalently linked through a pyridine ligand was synthesized and fully characterized. The electrochemical and photophysical properties are reported. The detailed study includes cyclic voltammetry, steady‐state absorption and fluorescence spectroscopy, radiation chemistry and transient absorption spectroscopy. A light‐induced electron transfer between the inorganic cluster moiety and the fullerene can be excluded. However, a light‐induced energy transfer from the rhenium cluster to the fullerene is proposed.
Tetranuclear Copper(II) Complexes Bearing Cu4O6 and Cu4O4 Cores: Synthesis, Structure, Magnetic Properties, and DFT Study
Authors: Banerjee Atanu , Singh Reena , Mondal Pallab , Colacio Enrique , Rajak Kajal Krishna
Published: January 2010

The reaction of Cu(ClO4)2·6H2O with N4O3 coordinating heptadentate (H3L1) and N2O coordinating tridentatereduced Schiff base (HL2) ligands yielded copper(II) tetranuclear complexes [Cu4(L1)2](ClO4)2 (1) and [Cu4(L2)4](ClO4)4 (2), respectively. Complex 1 crystallizes in the cubic system, space group Fd$\bar {3}$c, with unit‐cell parameters a = b = c = 43.124(5) Å, Z = 48, whereas complex 2 crystallizes in the space group P41212 in the tetragonal crystal system with Z = 8 and unit‐cell parameters a = b = 17.113(4) Å, c = 44.150(4) Å. The X‐ray structures of 1 and 2 have revealed a Cu4O6 core in 1 and a Cu4O4 core in 2. Complexes 1 and 2 show intramolecular antiferromagnetic interaction with moderate |J| values (104.2 cm–1 for 1 and 155.1 cm–1 for 2). The moderate |J| value can be explained by the existence of only one bridging alkoxido group between each pair of copper(II) atoms and the out‐of‐plane displacement of the alkoxido carbon atom from the Cu–O–Cu plane. Broken‐symmetry density functional theory (BSDFT) has been used to justify the exchange pathways.
Tetranuclear N‐Heterocyclic Carbene Mercury(II) Complexes Containing Triply Deprotonated Acetonitrile: Synthesis and Structural Studies
Authors: Liu Qing‐Xiang , Li Shu‐Juan , Zhao Xiao‐Jun , Zang Yan , Song Hai‐bin , Guo Jian‐Hua , Wang Xiu‐Guang
Published: January 2010

In the presence of KOtBu, bis[N‐(nPr)benzimidazoliumylmethyl]durene bromide (1a) and bis[N‐(nBu)benzimidazoliumylmethyl]durene bromide (1b) were treated with HgBr2 in CH3CN, respectively, to afford two novel tetranuclear NHC–mercury(II) complexes, [durene(CH2bimynPr)2Hg2(CCN)Hg2Br5] (2a) and [durene(CH2bimynBu)2Hg2(CCN)Hg2Br5] (2b; durene = 1,2,4,5‐tetramethylbenzene, bimy = benzimidazol‐2‐ylidene, CCN = triply deprotonated acetonitrile). In 2a or 2b, a funnel‐like molecular structure is formed by a triply deprotonated acetonitrile, a bidentate biscarbene ligand, the HgII ions, and the bromide ions. Additionally, analysis of the crystal packings of 2a or 2b reveals that the double‐stranded 1D supramolecular chains are formed through intermolecular weak interactions, including π–π stacking interactions, C–H···Br hydrogen bonds, and weak O···Hg bonds.
Mimics of a R22(8) Hydrogen‐Bond Dimer Motif: Synthesis and Influence on the Crystallisation of Sulfathiazole and Sulfapyridine
Authors: Lawrence Simon E. , McAuliffe Marie T. , Moynihan Humphrey A.
Published: January 2010

The bis[4‐(hydroxyamino)phenylsulfonyl]piperazine 5, diketopiperazine 10 and benzene 14 were synthesised as mimics of an R22(8) motif, which occurs in one crystal polymorph of sulfathiazole and in several polymorphs of sulfapyridine. When present in crystallisations of sulfathiazole and sulfapyridine, these mimics were found to have little or no effect under crystallisation conditions that favour the formation of polymorphs not containing R22(8) motifs. However, the mimics were found to completely or partially inhibit the formation of form I sulfathiazole, which contains the R22(8) dimer, in crystallisations of sulfathiazole from 1‐propanol. In crystallisations of sulfapyridine, the mimics were found to promote the formation of form III, which does not contain the R22(8) motif. These compounds therefore appear to act as “tailor‐made” additives, displaying polymorph‐selective crystal nucleation inhibition based on interaction with hydrogen‐bond network motifs.
The function of GluR1 and GluR2 in cerebellar and hippocampal LTP and LTD is regulated by interplay of phosphorylation andO‐GlcNAc modification
Authors: Din Nasirud , Ahmad Ishtiaq , ul Haq Ikram , Elahi Sana , Hoessli Daniel C. , Shakoori Abdul Rauf
Published: January 2010

Long‐term potentiation (LTP) and long‐term depression (LTD) are the current models of synaptic plasticity and widely believed to explain how different kinds of memory are stored in different brain regions. Induction of LTP and LTD in different regions of brain undoubtedly involve trafficking of AMPA receptor to and from synapses. Hippocampal LTP involves phosphorylation of GluR1 subunit of AMPA receptor and its delivery to synapse whereas; LTD is the result of dephosphorylation and endocytosis of GluR1 containing AMPA receptor. Conversely the cerebellar LTD is maintained by the phosphorylation of GluR2 which promotes receptor endocytosis while dephosphorylation of GluR2 triggers receptor expression at the cell surface and results in LTP. The interplay of phosphorylation andO‐GlcNAc modification is known as functional switch in many neuronal proteins. In this study it is hypothesized that a same phenomenon underlies as LTD and LTP switching, by predicting the potential of different Ser/Thr residues for phosphorylation,O‐GlcNAc modification and their possible interplay. We suggest the involvement ofO‐GlcNAc modification of dephosphorylated GluR1 in maintaining the hippocampal LTD and that of dephosphorylated GluR2 in cerebral LTP. J. Cell. Biochem. 109: 585–597, 2010. © 2010 Wiley‐Liss, Inc.
RB gene family: Genome‐wide ChIP approaches could open undiscovered roads
Authors: Rizzolio Flavio , Esposito Luca , Muresu Debora , Fratamico Robert , Jaraha Ranna , Caprioli Gianluca Vosa , Giordano Antonio
Published: January 2010

Many in vitro and reporter assays have helped to clarify how transcription factors regulate gene transcription. Today, it is important to decode the map of all transcription factor binding sites in the genome context. Chromatin immunoprecipitation followed by genome‐wide analyses have tremendously opened new ways to analyze the mechanisms of action of DNA binding factors, cofactors and epigenetic modifications. It is now possible to correlate these regulatory mechanisms with genomic features such as the promoter, enhancer, silencer, intragenic, and intergenic DNA sequences. These approaches help to clarify the complex rules that govern many biological processes. In this review we discuss the genome‐wide approaches applied to the retinoblastoma gene family (RBF), the central player of cell cycle control. There are also new, possible directions that are suggested within the review that can be followed to further explore the role of each pRb members in the transcriptional networks of the cell. J. Cell. Biochem. 109: 839–843, 2010. © 2010 Wiley‐Liss, Inc.
TAp63 is a transcriptional target of NF‐κB
Authors: Wu Junfeng , Bergholz Johann , Lu Jinin , Sonenshein Gail E. , Xiao Zhi‐Xiong Jim
Published: January 2010

The p53 homologue p63 encodes multiple protein isoforms either with (TA) or without (ΔN) the N‐terminal transactivation domain. Accumulating evidence indicates that TAp63 plays an important role in various biological processes, including cell proliferation, differentiation, and apoptosis. However, how TAp63 is regulated remains largely unclear. In this study, we demonstrate that NF‐κB induces TAp63 gene expression. The responsible elements for NF‐κB‐mediated TAp63 induction are located within the region from −784 to −296 bp in the TAp63 promoter, which contains two NF‐κB binding sites. Ectopic expression of RelA stimulates TAp63 promoter‐driven reporter activity and increases endogenous TAp63 mRNA levels. Inhibition of NF‐κB by IκBα super‐repressor or with a chemical inhibitor leads to down regulation of TAp63 mRNA expression and activity. In addition, mutations in the critical NF‐κB‐binding sites significantly abolish the effects of NF‐κB on TAp63. Activation of NF‐κB by TNFα enhances p50/RelA binding to the NF‐κB binding sites. Furthermore, we show that an Sp1 site adjacent to the NF‐κB sites plays a role in NF‐κB‐mediated upregulation of TAp63. Taken together, these data reveal that TAp63 is a transcriptional target of NF‐κB, which may play a role in cell proliferation, differentiation and survival upon NF‐κB activation by various stimuli. J. Cell. Biochem. 109: 702–710, 2010. © 2010 Wiley‐Liss, Inc.
Bifidobacteria inhibit the inflammatory response induced by gliadins in intestinal epithelial cells via modifications of toxic peptide generation during digestion
Authors: Laparra J.M. , Sanz Y.
Published: January 2010

Celiac disease (CD) is a chronic enteropathy triggered by intake of gliadin, the toxic component of gluten. This study aims at evaluating the capacity of different Bifidobacterium strains to counteract the inflammatory effects of gliadin‐derived peptides in intestinal epithelial (Caco‐2) cells. A commercial extract of several gliadin (Gld) types (α, β, γ, ϖ) was subjected to in vitro gastrointestinal digestion (pepsin at pH 3, pancreatin‐bile at pH 6), inoculated or not with cell suspensions (108 colony forming units/ml) of either B. animalis IATA‐A2, B. longum IATA‐ES1, or B. bifidum IATA‐ES2, in a bicameral system. The generated gliadin‐derived peptides were identified by reverse phase‐HPLC–ESI‐MS/MS. Caco‐2 cell cultures were exposed to the different gliadin peptide digestions (0.25 mg protein/ml), and the mRNA expression of nuclear factor kappa‐B (NF‐κB), tumor necrosis factor α (TNF‐α), and chemokine CXCR3 receptor were analyzed by semi‐quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) in stimulated cells. The production of the pro‐inflammatory markers NF‐κB p50, TNF‐α, and IL‐1β (interleukine 1β) by Caco‐2 cells was also determined by ELISA. The peptides from gliadin digestions inoculated with bifidobacteria did not exhibit the toxic amino acid sequences identified in those noninoculated (α/β‐Gld [158–164] and α/β‐Gld [122‐141]). The RT‐PCR analysis evidenced a down‐regulation in mRNA expression of pro‐inflammatory biomarkers. Consistent with these results the production of NF‐κB, TNF‐α, and IL‐1β was reduced (18.2–22.4%, 28.0–64.8%, and abolished, respectively) in cell cultures exposed to gliadin digestions inoculated with bifidobacteria. Therefore, bifidobacteria change the gliadin‐derived peptide pattern and, thereby, attenuate their pro‐inflammatory effects on Caco‐2 cells. J. Cell. Biochem. 109: 801–807, 2010. © 2009 Wiley‐Liss, Inc.
Involvement of integrins α3β1 and α5β1 and glycoprotein IIb in megakaryocyte‐induced osteoblast proliferation
Authors: Lemieux Justin M. , Horowitz Mark C. , Kacena Melissa A.
Published: January 2010

As the prevalence of osteoporosis is expected to increase over the next few decades, the development of novel therapeutic strategies to combat this disorder becomes clinically imperative. These efforts draw extensively from an expanding body of knowledge pertaining to the physiologic mechanisms of skeletal homeostasis. To this body of knowledge, we contribute that cells of hematopoietic lineage may play a crucial role in balancing osteoblastic bone formation against osteoclastic resorption. Specifically, our laboratory has previously demonstrated that megakaryocytes (MKs) can induce osteoblast (OB) proliferation in vitro, but do so only when direct cell‐to‐cell contact is permitted. To further investigate the nature of this interaction, we have effectively neutralized several adhesion molecules known to function in the analogous interaction of MKs with another cell type of mesenchymal origin—the fibroblast (FB). Our findings implicate the involvement of fibronectin/RGD‐binding integrins including α3β1 (VLA‐3) and α5β1 (VLA‐5) as well as glycoprotein (gp) IIb (CD41), all of which are known to be expressed on MK membranes. Furthermore, we demonstrate that interleukin (IL)‐3 can enhance MK‐induced OB activation in vitro, as demonstrated in the MK–FB model system. Taken together, these results suggest that although their physiologic and clinical implications are very different, these two models of hematopoietic–mesenchymal cell activation are mechanistically analogous in several ways. J. Cell. Biochem. 109: 927–932, 2010. © 2010 Wiley‐Liss, Inc.
Improved in vivo gene transfer into tumor tissue by stabilization of pseudodendritic oligoethylenimine‐based polyplexes
Authors: Russ Verena , Fröhlich Thomas , Li Yunqiu , Halama Anna , Ogris Manfred , Wagner Ernst
Published: January 2010

Background

HD O is a low molecular weight pseudodendrimer containing oligoethylenimine and degradable hexanediol diacrylate diesters. DNA polyplexes display encouraging gene transfer efficiency in vitro and in vivo but also a limited stability under physiological conditions. This limitation must be overcome for further development into more sophisticated formulations.

Methods

HD O polyplexes were laterally stabilized by crosslinking surface amines via bifunctional crosslinkers, bioreducible dithiobis(succimidyl propionate) (DSP) or the nonreducible analog disuccinimidyl suberate (DSS). Optionally, in a subsequent step, the targeting ligand transferrin (Tf) was attached to DSP‐linked HD O polyplexes via Schiff base formation between HD O amino groups and Tf aldehyde groups, which were introduced into Tf by periodate oxidation of the glycosylation sites.

Results

Crosslinked DNA polyplexes showed an increased stability against exchange reaction by salt or heparin. Disulfide bond containing DSP‐linked polyplexes were susceptible to reducing conditions. These polyplexes displayed the highest gene expression levels in vitro and in vivo (upon intratumoral application in mice), and these were significantly elevated and prolonged over standard or DSS‐stabilized HD O formulations. DSP‐stabilized HD O polyplexes with or without Tf coating were well‐tolerated after intravenous application. High gene expression levels were found in tumor tissue, with negligible gene expression in any other organ.

Conclusions

Lateral stabilization of HD O polyplexes with DSP crosslinker enhanced gene transfer efficacy and was essential for the incorporation of a ligand (Tf) into a stable particle formulation. Copyright © 2010 John Wiley & Sons, Ltd.
Polyethylenimine/small interfering RNA‐mediated knockdown of vascular endothelial growth factor in vivo exerts anti‐tumor effects synergistically with Bevacizumab
Authors: Höbel Sabrina , Koburger Ivette , John Matthias , Czubayko Frank , Hadwiger Philipp , Vornlocher Hans‐Peter , Aigner Achim
Published: January 2010

Background

RNA interference is a powerful method for the knockdown of pathologically relevant genes. The in vivo delivery of siRNAs, preferably through systemic, nonviral administration, poses the major challenge in the therapeutic application of RNAi. Small interfering RNA (siRNA) complexation with polyethylenimines (PEI) may represent a promising strategy for siRNA‐based therapies and, recently, the novel branched PEI F25‐LMW has been introduced in vitro. Vascular endothelial growth factor (VEGF) is frequently overexpressed in tumors and promotes tumor growth, angiogenesis and metastasis and thus represents an attractive target gene in tumor therapy.

Methods

In subcutaneous tumor xenograft mouse models, we established the therapeutic efficacy and safety of PEI F25‐LMW/siRNA‐mediated knockdown of VEGF. In biodistribution and siRNA quantification studies, we optimized administration strategies and, employing chemically modified siRNAs, compared the anti‐tumorigenic efficacies of: (i) PEI/siRNA‐mediated VEGF targeting; (ii) treatment with the monoclonal anti‐VEGF antibody Bevacizumab (Avastin®); and (iii) a combination of both.

Results

Efficient siRNA delivery is observed upon systemic administration, with the biodistribution being dependent on the mode of injection. Toxicity studies reveal no hepatotoxicity, proinflammatory cytokine induction or other side‐effects of PEI F25‐LMW/siRNA complexes or polyethylenimine, and tumor analyses show efficient VEGF knockdown upon siRNA delivery, leading to reduced tumor cell proliferation and angiogenesis. The determination of anti‐tumor effects reveals that, in pancreas carcinoma xenografts, single treatment with PEI/siRNA complexes or Bevacizumab is already highly efficacious, whereas, in prostate carcinoma, synergistic effects of both treatments are observed.

Conclusions

PEI F25‐LMW/siRNA complexes, which can be stored frozen as opposed to many other carriers, represent an efficient, safe and promising avenue in anti‐tumor therapy, and PEI/siRNA‐mediated, therapeutic VEGF knockdown exerts anti‐tumor effects. Copyright © 2010 John Wiley & Sons, Ltd.
Investigation of interaction of benzoquinones and naphthoquinones with substituted hydrazides
Authors: Hassan Alaa A. , Ibrahim Yusria R. , Shawky Ahmed M.
Published: January 2010

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Nucleophilic attack by substituted hydrazides on C‐2, C‐3 of 2,3,5,6‐tetrachloro‐1,4‐benzoquinone and 2,3‐dichloro‐1,4‐naphthoquinone initiates the formation of benzo[e][1,3,4]oxadiazine and benzo‐ as well as naphthoxadiazepine derivatives. On the other hand, substituted hydrazides attack 1,4‐naphthoquinone‐2,3‐dicarbonitrile to form benzo[f]indazole‐4,9‐dione derivatives. A rationale for the conversions observed is presented. J. Heterocyclic Chem., 2010.
Synthesis of 2‐arylquinolin‐4(1H)‐ones and their transformation to N‐alkylated and O‐alkylated derivatives
Authors: Mphahlele Malose J.
Published: January 2010

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2‐Aryl‐4‐quinolones are versatile synthetic intermediates and several articles continue to appear in literature describing their synthesis, chemical transformation, structural properties, and biological activities. Their versatility as synthetic intermediates is a consequence of 4‐quinolone moiety, which contains several reactive centers (positions 1, 3, and 4) for possible functionalization and can also enable different degree of unsaturation. In this review, we describe methods developed to‐date for the synthesis of 2‐arylquinolin‐4(1H)‐ones and their N‐alkylated and O‐alkylated derivatives. J. Heterocyclic Chem., 2010.
One pot synthesis of [1,3]‐oxazine and [1,3]‐thiazine derivatives under thermal and microwave conditions
Authors: Tumtin S. , Phucho I. T. , Nongpiur A. , Nongrum R. , Vishwakarma J. N. , Myrboh B. , Nongkhlaw R. L.
Published: January 2010

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A simple and efficient synthesis of substituted benzo [1,3] oxazine and benzo [1,3] thiazine derivatives under conventional heating, as well as microwave irradiation is reported. The compounds were obtained by the reaction of electron rich phenols, formaldehyde, and aromatic amines in methanol. Reactions which take 12–16 hr under conventional heating were successfully completed within a few minutes under microwave irradiation (solventless) with moderate to excellent yields. J. Heterocyclic Chem., 2010.
The development of an ecofriendly procedure for alkaline metal (II) sulfate promoted synthesis of N,N′‐dimethyl substituted (unsubstituted)‐4‐aryl‐3,4‐dihydropyrimidones (thiones) and corresponding bis‐analogues in aqueous medium: Evaluation by green chemistry metrics
Authors: Mukhopadhyay Chhanda , Datta Arup
Published: January 2010

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Different alkaline metal (II) sulfates were used as catalysts for the N,N′‐dimethyl substituted as well as unsubstituted 4‐aryl‐3,4‐dihydropyrimidones (thiones) and their corresponding bis‐analogues in aqueous medium. Among the various salts, MgSO4·7H2O (Epsom salt) proved to be the best catalyst giving the desired products in good to excellent yields. This catalyst enables the construction of a series of compound libraries particularly for N,N′‐dimethyl substituted DHPM's whose synthesis is very rare in the literature. The reaction on a wide variety substrates was evaluated by the application of green chemistry metrics and a very good correlation was obtained. J. Heterocyclic Chem., 2010.
A simple, mild, and efficient procedure for high‐yield synthesis of benzimidazoles using coppertriflate as catalyst
Authors: Chari M. Adharvana , Sadanandam P. , Shobha D. , Mukkanti K.
Published: January 2010

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Copper triflate has been found to be an efficient catalyst for the synthesis of benzimidazoles from o‐phenylenediamine and aldehydes at reflux temperature under acetonitrile solvent. This new method consistently has the advantage of excellent yields (74–95%) at reflux temperature. J. Heterocyclic Chem., 2010.
Monitoring dehydration kinetics using simultaneous thermal and spectral methods
Authors: Beard Mark A. , Ghita Oana R. , McCabe James , Evans Kenneth E.
Published: January 2010

The dehydration kinetics of theophylline monohydrate is a two‐stage process. The first stage involves loosening of the crystal water followed by a second stage in which the water evaporates from the sample. During differential scanning calorimetry (DSC) measurements, the kinetics of the two stages can be dramatically altered because of the sample environment and DSC pan type. In‐depth understanding of how the sample environment alters the dehydration process and the kinetics involved requires more than DSC experiments alone. This paper describes the use of a novel, simultaneous thermal and spectral technique to monitor the dehydration kinetics of theophylline monohydrate. The analysis of the results obtained on the combined DSC‐near‐infrared and DSC‐Raman equipment clearly detects the two stages of the dehydration process and the polymorphic structural changes that take place. The combined technique provides a powerful method to monitor the dehydration of hydrous systems. Copyright © 2010 John Wiley & Sons, Ltd.
A Raman spectroscopic and TEM study on the structural evolution of Na2Ti3O7 during the transition to Na2Ti6O13
Authors: Liu Hongwei , Yang Dongjiang , Zheng Zhanfeng , Ke Xuebin , Waclawik Eric , Zhu Huaiyong , Frost Ray L.
Published: January 2010

The synthesis of sodium hexatitanate from sodium trititanate was characterized by Raman spectroscopy, X‐ray diffraction (XRD) and high‐resolution transmission electron microscopy (HRTEM). The structural evolution from trititanate to hexatitanate was studied using Raman spectra, XRD and HRTEM techniques. It was found that the Raman bands at 279 cm−1 corresponding to very long TiO bonds and at 883 cm−1 corresponding to the very short TiO bonds decrease in intensity and finally disappear during the transition from sodium trititanate to sodium hexatitanate. The band at 922 cm−1 corresponding to an intermediate‐length TiO bond was observed to become stronger with the increase in temperature, indicating that there is no terminal oxygen atom in the crystal structure of Na2Ti6O13 and that all the oxygen atoms become linearly coordinated by two titanium atoms. Furthermore, the TiO6 octahedron in Na2Ti6O13 are more regular because the very long (2.2 Å) or very short (1.7 Å) TiO bonds disappear. It is revealed that the phase transition from trititanate to hexatitanate is a step‐by‐step slipping process of the TiO6 octahedral slabs with the loss of sodium cations, and a new phase with formula Na1.5H0.5Ti3O7 has been discovered as an intermediate phase to interlink Na2Ti3O7 and Na2Ti6O13. Copyright © 2010 John Wiley & Sons, Ltd.
Raman spectra and simulation of cis‐ and trans‐cyclooctene for conformational analysis compared to inelastic neutron scattering
Authors: Kulterer Martin R. , Hudson Bruce S.
Published: January 2010

Simulated and measured Raman spectra are used to determine the molecular conformation of trans‐cyclooctene. This is the first reported Raman spectrum of this highly strained species. A crown structure results in a computed Raman spectrum, which is in good agreement with the experiment; a chair structure does not. Comparison is made with the case of cis‐cyclooctene. The computed structure and limitations of the method of conformational analysis are discussed. In particular, the relative merits of Raman spectroscopy in comparison with infrared and inelastic neutron scattering (INS) are evaluated using computed spectra for all three methods and comparison of the observed INS for cis‐cyclooctene with that computed for two conformations. It is concluded that the combination of computed and observed Raman spectra provides a useful method for conformational analysis for cases of this type. Copyright © 2010 John Wiley & Sons, Ltd.