bluuebunny/crossref_metadata_2025 huggingface dataset:
From Activity Cliffs to Target‐Specific Scoring Models and Pharmacophore Hypotheses
Authors: Seebeck Birte , Wagener Markus , Rarey Matthias
Published: July 2011

The role of activity cliffs in drug discovery projects is certainly two‐edged: on the one hand, they often lead to the failure of QSAR modeling techniques; on the other, they are highly valuable for identifying key aspects of SARs. In the presence of activity cliffs the results of purely ligand‐based QSAR approaches often remain puzzling, and the resulting models have limited predictive power. Herein we present a new approach for the identification of structure‐based activity cliffs (ISAC). It uses the valuable information of activity cliffs in a structure‐based design scenario by analyzing interaction energies of protein–ligand complexes. Using the relative frequency at which a protein atom is involved in activity cliff events, we introduce a novel visualization of hot spots in the active site of a protein. The ISAC approach supports the medicinal chemist in elucidating the key interacting atoms of the binding site and facilitates the development of pharmacophore hypotheses. The hot spot visualization can be applied to small data sets in early project phases as well as in the lead optimization process. Based on the ISAC approach, we developed a method to derive target‐specific scoring functions and pharmacophore constraints, which were validated on independent external data sets in virtual screening experiments. The activity‐cliff‐based approach shows an improved enrichment over the generic empirical scoring function for various protein targets in the validation set.
SNP–SNP interactions between DNA repair genes were associated with breast cancer risk in a Korean population
Authors: Han Wonshik , Kim Kyoung‐Yeon , Yang Song‐Ju , Noh Dong‐Young , Kang Daehee , Kwack KyuBum
Published: July 2011

BACKGROUND:

Single nucleotide polymorphisms (SNPs) in nucleotide excision repair (NER) pathway genes may modulate DNA repair capacity and increase susceptibility to breast cancer (BC). A case‐control study was conducted by evaluating genes involved in DNA repair to identify polymorphisms associated with BC.

METHODS:

The 384 SNPs of 38 candidate genes were genotyped using the Illumina GoldenGate method. Genotypes were determined in a case‐control study that consisted of 346 BC patients and 361 controls. Odds ratios and 95% confidence intervals were computed using logistic regression models. Multiple logistic regression models adjusted for age, family history of BC, and body mass index were used.

RESULTS:

Gene–gene interaction analysis among the DNA repair pathway genes showed significant effects on BC risk. ERCC2 rs50872 (TC genotype) in combination with XPA rs2808668 (TC genotype) and rs1800975 (AG genotype) was strongly associated with an increased risk of BC (P = .0004 and .0002, PBonferroni = .023 and .014, respectively). Moreover, the T‐G (including rs2808668 and rs1800975) haplotype in XPA combined with the ERCC2 T allele in rs50872 carriers was also associated with additive risk effect of BC (odds ratios: 2.58, 2.62, and 3.49, respectively).

CONCLUSION:

Genetic variation in DNA repair genes involved in NER mechanisms increased the risk of BC development. These results suggested that a stronger combined effect of SNPs via gene–gene interaction may help to predict BC risk. Cancer 2012;. © 2011 American Cancer Society.
Novel antagonists of growth hormone‐releasing hormone inhibit growth and vascularization of human experimental ovarian cancers
Authors: Klukovits Anna , Schally Andrew V. , Szalontay Luca , Vidaurre Irving , Papadia Andrea , Zarandi Marta , Varga Jozsef L. , Block Norman L. , Halmos Gabor
Published: July 2011

BACKGROUND:

Antagonists of growth hormone‐releasing hormone (GHRH) inhibit the proliferation of various human cancer cell lines and experimental tumors by mechanisms that include direct action on GHRH receptors in cancer cells.

METHODS:

In this study, the effects of newly synthesized GHRH antagonists, MIA‐313, MIA‐602, MIA‐604, and MIA‐610, were investigated in 2 human ovarian epithelial adenocarcinoma cell lines, OVCAR‐3 and SKOV‐3, in vitro and in vivo. The expression of receptors for GHRH was demonstrated by Western blot analysis and ligand competition methods in the OVCAR‐3 and SKOV‐3 cell lines and in tumors from those cells grown in athymic nude mice. The effects of GHRH antagonists on the secretion of vascular endothelial growth factor (VEGF) by OVCAR‐3 cells and on the vascularization of OVCAR‐3 xenografts also were evaluated.

RESULTS:

Both the pituitary and the splice variant type 1 (SV1) GHRH receptors were detected in the 2 cell lines and in tumor xenografts, and SV1 was expressed at higher levels. Cell viability assays revealed the antiproliferative effect of all GHRH antagonists that were. Maximal tumor growth inhibition was approximately 75% in both models. MIA‐313 and MIA‐602 decreased VEGF secretion of OVCAR‐3 cells, as measured by enzyme‐linked immunosorbent assay, and reduced tumor vascularization in a Matrigel plug assay, but caused no change in the expression of VEGF or VEGF receptor in the terminal ileum of mice with OVCAR‐3 tumors.

CONCLUSIONS:

Results from the current study indicated that a he novel approach based on GHRH antagonists may offer more effective therapeutic alternatives for patients with advanced ovarian cancer and who do not tolerate conventional anti‐VEGF therapy. Cancer 2012;. © 2011 American Cancer Society.
Rates and predictors of colorectal cancer screening by race among motivated men participating in a prostate cancer risk assessment program
Authors: Hall Michael J. , Ruth Karen , Giri Veda N.
Published: July 2011

BACKGROUND:

Screening by fecal occult blood test and lower endoscopy has lowered colorectal cancer (CRC) mortality, but compliance gaps persist. Of concern are possible disparities in uptake of CRC screening between white and African American men. The goal of this study was to assess for disparities in uptake of CRC screening among men participating in a high‐risk prostate cancer clinic. If present, such disparities could support hypotheses for further research examining racial differences in awareness and patient preferences in undergoing CRC screening.

METHODS:

Baseline data on a racially diverse cohort of men aged 50 to 69 years at increased risk of prostate cancer collected via the Prostate Cancer Risk Assessment Program at Fox Chase Cancer Center were analyzed. Predictors of uptake of CRC screening were assessed using multivariate logistic regression.

RESULTS:

Compared with whites, African American men had statistically significantly lower uptake of fecal occult blood testing (African American 49.0% vs white 60.7%, P = .035), lower endoscopy (African American 44.1% vs white 58.5%, P = .011), and any CRC screening (African American 66.2% vs white 76.3%, P = .053). Predictors of uptake of lower endoscopy among African American men included older age (odds ratio [OR], 3.61; 95% confidence interval [CI], 1.87‐6.97), family history of CRC (OR, 3.47; 95% CI, 1.30‐9.25), and insurance status (OR, 1.90; 95% CI, 1.04‐3.46).

CONCLUSIONS:

Despite awareness of cancer risk and motivation to seek prostate cancer screening through a specialized prostate cancer risk assessment program, evidence supporting compliance gaps with CRC screening among men was found. Tailored messages to younger African American men with and without a family history of CRC are needed. Cancer 2011;. © 2011 American Cancer Society.
Racial and ethnic differences in lymph node examination after colon cancer resection do not completely explain disparities in mortality
Authors: Rhoads Kim F. , Cullen Jennifer , Ngo Justine V. , Wren Sherry M.
Published: July 2011

BACKGROUND:

In 1999, a multidisciplinary panel of experts in colorectal cancer reviewed the relevant medical literature and issued a consensus recommendation for a 12‐lymph node (LN) minimum examination after resection for colon cancer. Some authors have shown racial/ethnic differences in receipt of this evidence‐based care. To date, however, none has investigated the correlation between disparities in LN examination and disparities in outcomes after colon cancer treatment.

METHODS:

This retrospective analysis used California Cancer Registry linked to California Office of Statewide Health Planning and Development discharge data (1996‐2006). Chi‐square analysis, logistic regression, and Cox proportional hazard models predicted disparities in receipt of an adequate examination and the effect of an inadequate exam on mortality and disparities. Patients with stage I and II colon cancers undergoing surgery in California were included; patients with stage III and IV disease were excluded.

RESULTS:

A total of 37,911 records were analyzed. Adequate staging occurred in fewer than half of cases. An inadequate examination (<12 LNs) was associated with higher mortality rates. Hispanics had the lowest odds of receiving an adequate exam; however, blacks, not Hispanics, had the highest risk of mortality compared with whites. This disparity was not completely explained by inadequate LN examination.

CONCLUSIONS:

Inadequate LN exam occurs often and is associated with increased mortality. There are disparities in receipt of the minimum exam, but this only explains a small part of the observed disparity in mortality. Improving the quality of LN examination alone is unlikely to correct colon cancer disparities. Cancer 2011;. © 2011 American Cancer Society.
A nomogram to predict postresection 5‐year overall survival for patients with uterine leiomyosarcoma
Authors: Zivanovic Oliver , Jacks Lindsay M. , Iasonos Alexia , Leitao Mario M. , Soslow Robert A. , Veras Emanuela , Chi Dennis S. , Abu‐Rustum Nadeem R. , Barakat Richard R. , Brennan Murray F. , Hensley Martee L.
Published: July 2011

BACKGROUND:

The clinical course of patients with uterine leiomyosarcoma (LMS) is difficult to predict with the currently available categorical staging systems of the American Joint Committee on Cancer (AJCC) and the International Federation of Gynecology and Obstetrics (FIGO). The objective of the current study was to develop and validate a novel, clinically relevant, individualized prognostic model for patients with uterine LMS.

METHODS:

Patients with uterine LMS who presented at the authors' institution from 1982 to 2008 were analyzed. The nomogram model was chosen based on the clinical evidence and statistical significance of the predictors, including age at diagnosis, tumor size, histologic grade, uterine cervix involvement, extrauterine spread, distant metastases, and mitotic index. Five‐year overall survival (OS) was the predicted endpoint. The concordance probability (CP) was used as a predictive accuracy measure and compared with the CP of current staging systems. The model was internally validated using 200 bootstrap samples to correct for over fitting.

RESULTS:

One hundred eighty‐five of 270 patients were eligible for the nomogram analysis. The median follow‐up was 5.4 years, and the median OS was 3.75 years (95% confidence interval, 3‐6 years). The CP of the newly developed nomogram was 0.67 (95% confidence interval, 0.63‐0.72). This was superior to predictions based on AJCC and FIGO staging. The bootstrap‐validated CP was 0.65 with good calibration accuracy.

CONCLUSIONS:

The authors developed and internally validated a uterine LMS‐specific nomogram to predict 5‐year OS. This novel, individualized prognostic model outperforms traditionally used categorical staging systems and may be useful for patient counseling and for better selection of patients for adjuvant therapy trials. Cancer 2012;. © 2011 American Cancer Society.
Phase 2 Southwest Oncology Group‐directed intergroup trial (S0505) of sorafenib in advanced soft tissue sarcomas
Authors: von Mehren Margaret , Rankin Cathryn , Goldblum John R. , Demetri George D. , Bramwell Vivien , Ryan Christopher W. , Borden Ernest
Published: July 2011

BACKGROUND:

Patients with advanced soft tissue sarcomas (STS) have limited therapeutic options. Sorafenib (BAY 43‐9006) is a multitargeted tyrosine kinase inhibitor of raf, vascular endothelial growth factor receptors 1 (VEGFR1) through 3, platelet‐derived growth factor B, fms‐like tyrosine kinase 3, and c‐kit, and some of these may be relevant in STS.

METHODS:

The authors tested sorafenib at a dose of 400 mg twice daily in patients with advanced vascular sarcoma (VS), high‐grade liposarcomas, and leiomyosarcomas who had received 0 or 1 previous regimens for advanced disease.

RESULTS:

Fifty‐one patients were accrued to the study, and 37 were evaluable for toxicity and response. There were no unexpected side effects and no confirmed responses. The median progression‐free survival was 3 months, and the median overall survival was 17 months. Six of 8 patients in the VS cohort had prolonged clinical benefit (stable disease or better), resulting in a median progression‐free survival of 5 months compared with 2 to 3 months for the patients who had liposarcoma and leiomyosarcomas.

CONCLUSIONS:

Sorafenib at the dose and schedule studied did not result in any responses in the VS, liposarcoma, or leiomyosarcoma cohort according to Response Evaluation Criteria in Solid Tumors. Cancer 2012;. © 2011 American Cancer Society.
Synergistic inhibitory effect of apomine and lovastatin on osteosarcoma cell growth
Authors: Moriceau Gatien , Roelofs Anke J. , Brion Régis , Redini Françoise , Ebetion Frank H. , Rogers Michael J. , Heymann Dominique
Published: July 2011

BACKGROUND:

Osteosarcoma is the most frequent malignant primary bone tumor that occurs mainly in the young, with an incidence peak observed at age 18 years. Both apomine and lovastatin have antitumor activity in a variety of cancer cell lines. Apomine, a 1,1‐bisphosphonate‐ester, increases the rate of degradation of 3‐hydroxy‐3 methylglutaryl‐coenzyme A (HMG‐CoA) reductase, the rate‐limiting enzyme in the mevalonate pathway, whereas lovastatin competitively inhibits HMG‐CoA reductase enzyme activity, thereby preventing protein prenylation and cholesterol synthesis.

METHODS:

The authors of this report investigated the effect of combined treatment with apomine and lovastatin in vitro on human and murine osteosarcoma cell lines and in vivo using a murine syngeneic model of osteosarcoma. Apomine and lovastatin synergistically decreased viability and induced apoptosis in both murine and human osteosarcoma cell lines.

RESULTS:

Combined apomine and lovastatin strongly decreased HMG‐CoA reductase enzyme levels compared with lovastatin treatment alone. Consequently, the accumulation of unprenylated ras‐related protein 1A induced by lovastatin was enhanced in the presence of apomine. All synergistic effects on cell viability, apoptosis, and protein prenylation were overcome by the addition of mevalonate or geranylgeraniol, 2 mevalonate pathway intermediates downstream from the target enzyme, HMG‐CoA reductase. This confirmed that the mechanism of synergy in osteosarcoma cells is through augmented inhibition of HMG‐CoA reductase. Finally, treatment of POS‐1 osteosarcoma‐bearing mice with a combination of apomine and lovastatin significantly reduced tumor progression in these mice compared with single treatments, which had no effect at the doses used.

CONCLUSIONS:

The results from this study revealed that combination therapy with apomine and lovastatin may be a novel treatment strategy for osteosarcoma. Cancer 2012;. © 2011 American Cancer Society.
Management of malignant colonic polyps: A population‐based analysis of colonoscopic polypectomy versus surgery
Authors: Cooper Gregory S. , Xu Fang , Barnholtz Sloan Jill S. , Koroukian Siran M. , Schluchter Mark D.
Published: July 2011

BACKGROUND:

The management of colon polyps containing invasive carcinoma includes surgical resection or colonoscopic polypectomy. To date, there are very limited population‐based data comparing outcomes with the 2 management approaches.

METHODS:

Using the linked Surveillance Epidemiology and End Results–Medicare database, we identified 2077 patients aged ≥66 years with an initial diagnosis of stage T1N0M0 malignant polyp from 1992‐2005. Patients were categorized as surgical or polypectomy depending on the most invasive treatment. To adjust for potential selection bias in treatment assignment, using multivariate analysis, patients were divided into quintiles of likelihood of polypectomy (propensity scores), and outcomes were compared in each quintile.

RESULTS:

Surgical resection was performed in 1340 (64.5%) patients and polypectomy was performed in 737 (35.5%) patients. Predictors for undergoing polypectomy (P<.001) included older age, greater comorbidity, no history of polyps, diagnosis in 2002 or later, left colon site of cancer, well‐differentiated tumors, and colonoscopy performed in an outpatient setting. Both 1‐year and 5‐year survival were higher in the surgical group (92% and 75%, respectively) than in the polypectomy group (88% and 62%, respectively). The unadjusted hazard ratio was 1.51 (95% confidence interval [CI], 1.31‐1.74). After adjusting for propensity quintile, the hazard ratio was 1.15 (95% CI, 0.98‐1.33). Within each propensity quintile, the risk of death was similar between the 2 groups (interaction test P = .96).

CONCLUSIONS:

In this large, population‐based sample, more than one‐third of patients with malignant polyps were treated with colonoscopic polypectomy. Outcomes were similar to surgical patients with comparable clinical characteristics and could be offered to patients who meet appropriate clinical criteria. Cancer 2012;. © 2011 American Cancer Society.
Rhabdomyosarcoma in adolescents
Authors: Bisogno Gianni , Compostella Alessia , Ferrari Andrea , Pastore Guido , Cecchetto Giovanni , Garaventa Alberto , Indolfi Paolo , De Sio Luigi , Carli Modesto
Published: July 2011

BACKGROUND:

In many types of cancer, the survival rates are reported to be less favorable for adolescents compared with younger children. To investigate whether this is true for adolescents with rhabdomyosarcoma (RMS), the results obtained in patients enrolled in protocols run by the Italian Soft Tissue Sarcoma Committee (STSC) were analyzed.

METHODS:

From 1988 through 2005, 643 patients were registered (567 children ages birth‐14 years and 76 adolescents ages 15‐19 years) and treated in 4 STSC protocols. The number of patients enrolled was compared with the expected number calculated from incidence rates derived from the Italian network of cancer registries.

RESULTS:

Only 27% of the expected number of adolescents with RMS were enrolled in the STSC trials. Compared with children, adolescents were found to have a longer interval from initial symptoms to diagnosis (8 weeks vs 4.6 weeks), more alveolar RMS (47.4% vs 32.6%), lymph node infiltration (39.1% vs 23.3%), and metastases at the time of diagnosis (30.7% vs 17.8%). The 2 age groups received similar treatments. The 5‐year overall survival (OS) rate was 68.9% in children versus 57.2% in adolescents (P = .006), and the progression‐free survival (PFS) rate was 64.3% in children versus 48.1% in adolescents (P = .0237). On multivariate analysis, age, tumor site, lymph node involvement, and metastases were found to be significant prognostic factors for OS and PFS.

CONCLUSIONS:

Survival for adolescents with RMS enrolled in STSC protocols appears to be satisfactory. The higher prevalence of unfavorable tumor characteristics noted among adolescents seems to explain their worse outcome compared with children. However, the limited number of adolescents enrolled in STSC studies is worrisome, and cooperation with oncologists who treat adults needs to be improved. Cancer 2012;. © 2011 American Cancer Society.
Role of BRAFV600E mutation analysis and second cytologic review of fine‐needle aspiration for evaluating thyroid nodule
Authors: Kang Guhyun , Cho Eun Yoon , Shin Jung Hee , Chung Jae‐Hoon , Kim Jong Won , Oh Young Lyun
Published: July 2011

BACKGROUND:

Thyroid fine‐needle aspiration (FNA) is the primary diagnostic tool used for the evaluation of thyroid nodules. Although most aspirates provide diagnostic cytology, some are classified as indeterminate. The aim of this study was to determine whether the second review of FNA cytology can improve the diagnostic values and to assess the role of proto‐oncogene B‐Raf (BRAF) mutation testing in the diagnosis of papillary carcinoma (PC).

METHODS:

Thyroid aspirates from 1060 patients were submitted for cytologic evaluation and BRAFV600E mutation analysis. A second cytologic review was performed by 2 cytopathologists in light of the mutation status.

RESULTS:

Of the 313 patients who received surgery, 200 (63.9%) had been initially diagnosed as malignant by cytology. They were surgically confirmed as PCs, and the BRAFV600E mutation was detected in 82.5% of the cases. Ninety‐five of 102 cases (93.1%) with indeterminate cytology turned out to be malignant, and the mutation was present in 63.3% of PCs. The sensitivity, accuracy, and negative predictive value (NPV) of the second review were better than those of initial cytologic diagnosis (P <.001). The addition of the mutation analysis significantly increased the sensitivity, accuracy, and NPV for detecting PCs compared with those of cytology alone.

CONCLUSIONS:

Qualified cytologic diagnosis increases the effectiveness of FNA, forgoing the need for repeat biopsy or intraoperative frozen section evaluation. Preoperative BRAF mutation testing can supplement the routine cytology in the selection of thyroid nodules for surgery. Cancer (Cancer Cytopathol) 2012. © 2011 American Cancer Society.
Surface‐Plasmon‐Coupled Emission of Rhodamine 110 in a Silica Nanolayer
Authors: Rangełowa‐Jankowska Simeonika , Jankowski Dawid , Grobelna Beata , Gryczyński Ignacy , Gryczyński Zygmunt , Bogdanowicz Robert , Bojarski Piotr
Published: July 2011

The first observation of strong directional surface‐plasmon‐coupled emission (SPCE) of Rhodamine 110 in silica nanofilms deposited on silver nanolayers is reported. The preparation of the material is described in detail. The intensity of SPCE exceeds 10 times that of free space fluorescence and total linear light polarization in the SPCE ring is observed. A new experimental setup and an original data collection method is presented. Our material completely preserves its fluorescence properties for at least eight months.
Thymic but not splenic CD8+ DCs can efficiently cross‐prime T cells in the absence of licensing factors
Authors: Dresch Christiane , Ackermann Mathias , Vogt Bernd , de Andrade Pereira Bruna , Shortman Ken , Fraefel Cornel
Published: July 2011

Cross‐presentation is an important mechanism to elicit both immune defenses and tolerance. Although only a few DC subsets possess the machinery required for cross‐presentation, little is known about differences in cross‐presenting capabilities of DCs belonging to the same subpopulation but localized in different lymphoid organs. In this study, we demonstrate that steady‐state thymic CD8+ DCs can efficiently cross‐prime naïve CD8+ T cells in the absence of costimulation. Surprisingly, cross‐priming by splenic CD8+ DCs was dependent on licensing factors such as GM‐CSF. In the absence of GM‐CSF, antigen–MHC‐class‐I complexes were detected on thymic but not on splenic CD8+ DCs, indicating that the cross‐presentation capacity of the thymic subpopulation was higher. The observed cross‐priming differences between thymic and splenic CD8+ DCs did not correlate with differential antigen capture or costimulatory molecules found on the surface of DCs. Moreover, we did not detect overall impairment of antigen presentation, as peptide‐loaded splenic CD8+ DCs were able to induce CD8+ T‐cell proliferation. The observation that thymic CD8+ DCs are more efficient than splenic CD8+ DCs in T‐cell cross‐priming in the absence of licensing factors indicates that the requirements for efficient antigen presentation differ between these cells.
Bis(2‐methylbenzimidazolyl)amine‐Derived Copper Complexes and Their Antineoplastic Activity
Authors: Rodríguez Solano Laura A. , Aguiñiga Itzen , López Ortiz Manuel , Tiburcio Reynaldo , Luviano Axel , Regla Ignacio , Santiago‐Osorio Edelmiro , Ugalde‐Saldívar Víctor M. , Toscano Rubén A. , Castillo Ivan
Published: July 2011

Copper(II) complexes (1–4) of tri‐ or tetradentate bis(2‐methylbenzimidazolyl)amine ligands (L1–L4) have been prepared and characterized by spectroscopic methods in solution, as well as in the solid state by X‐ray crystallography. The ligands act as tridentate donors towards the cupric ions through one central amine and two benzimidazole N atoms in the solid state; a water ligand and a bridging perchlorate group define the distorted octahedral environments of2and3. Complex4has square‐pyramidal coordination geometry, with an additional thioether donor attached to the central N atom in the axial position. Electrospray mass spectrometry characterized the complexes as monomeric in acetonitrile solution. Cyclic voltammetry studies established that amine N benzyl‐containing3has the highest half‐wave redox potential of all of these complexes at –0.08 V (vs. Fc+/Fc) for the Cu2+/Cu+couple. The complexes display dose‐dependent cytotoxicity against one human and four murine cancer cell lines. Complexes3and4have good antiproliferative activity against the human chronic leukemia cell line K562. Moreover, for3the proliferation of all malignant cell lines decreases at concentrations lower than the IC50for healthy bone marrow cells.
Simultaneous Determination of Pb and Cd Traces in Water Samples by Anodic Stripping Voltammetry Using a Modified GC Electrode
Authors: Stankovic Dalibor , Manojlovic Dragan , Roglic Goran , Kostic‐Rajacic Sladjana , Andjelkovic Ivan , Dojcinovic Biljana , Mutic Jelena
Published: July 2011

The determination of Pb and Cd with a Nafion‐modified glassy carbon electrode and Cu‐DPABA complex (Cu‐DPABA–NA/GCE; DPABA is methyl 3,5‐bis{bis‐[(pyridin‐2‐yl)methyl]amino}methyl‐benzoate) as an alternative electrode for anodic stripping voltammetry was described. Pb and Cd were accumulated in acetate buffer pH 4 at a potential of −1.4 V (vs. Ag/AgCl electrode) for 120 s followed by a DPASV scan from −1.2 to −0.2 V. Under optimum conditions the calibration curves were linear in the range of 4.8×10−9–5.0×10−5 and 5.0×10−9–5×10−5 mol L−1 for Pb and Cd, respectively. Detection limits were 1.8×10−9 and 1.2×10−9 mol L−1 for Pb and Cd, respectively. Different parameters and conditions, such as membrane ingredients, accumulation time, potential and pH value were optimized. A study of interfering substances was also performed. A significant increase in current was achieved at the modified electrode in comparison with the bare glassy carbon electrode. The validation of the proposed method was made by Pb and Cd determination in the certified reference material Groundwater CRM 610 (BCR, Community Bureau of Reference, Brussels, Belgium). The electrode was successfully applied for determination of Pb and Cd in river water with a high content of organic contaminants without any pretreatment.
Numerical prediction of turbulent flow structure generated by a synthetic cross‐jet into a turbulent boundary layer
Authors: Javadi Ardalan , El‐Askary Wageeh A.
Published: July 2011

A detailed numerical study using large‐eddy simulation (LES) and unsteady Reynolds‐averaged Navier–Stokes (URANS) was undertaken to investigate physical processes that are engendered in the injection of a circular synthetic (zero‐net mass flux) jet in a zero pressure gradient turbulent boundary layer. A complementary study was carried out and was verified by comparisons with the available experimental data that were obtained at corresponding conditions with the aim of achieving an improved understanding of fluid dynamics of the studied processes. The computations were conducted by OpenFOAM C++, and the physical realism of the incoming turbulent boundary layer was secured by employing random field generation algorithm. The cavity was computed with a sinusoidal transpiration boundary condition on its floor. The results from URANS computation and LES were compared and described qualitatively and quantitatively. There is a particular interest for acquiring the turbulent structures from the present numerical data. The numerical methods can capture vortical structures including a hairpin (primary) vortex and secondary structures. However, the present computations confirmed that URANS and LES are capable of predicting current flow field with a more detailed structure presented by LES data as expected. Copyright © 2011 John Wiley & Sons, Ltd.
Coordination polymers based on building blocks of dimethyltin(IV) Chloride iso‐thiocyanate and dimethyltin(IV) di‐iso‐thiocyanate with pyrazine‐2‐carboxylate and 4, 4′‐bipyridine
Authors: Najafi Ezzatollah , Amini Mostafa M. , Sadeghi Omid , Khavasi Hamid Reza , Ng Seik Weng
Published: July 2011

The reaction of 4,4′‐bipy with dimethyltin(IV) chloride iso‐thiocyanate affords the one‐dimensional (1D) coordination polymer, [Me2Sn(NCS)Cl·(4,4′‐bipy)]n (1), whereas reaction of dimethyltin(IV) dichloride with sodium pyrazine‐2‐carboxylate in the presence of potassium iso‐thiocyanate affords the two‐dimensional (2D) coordination polymer, {[Me2Sn(C4H3N2COO)2]2 [Me2Sn(NCS)2]}n (2). Both coordination polymers were characterized by elemental analysis and infrared spectroscopy in addition to 1H and 13C NMR spectroscopy of the soluble coordination polymer (1). A single‐crystal structure determination showed that the asymmetric unit in 1 contains Me2Sn(NCS)Cl and 4,4′‐bipy moieties and a 1D infinite rigid chain structure forms through bridging of the 4,4′‐bipy ligand between tin atoms and the geometry around the tin atom is a distorted octahedral. Coordination polymer 2 contains two distinct tin atom geometrics in which one tin atom is seven coordinate, and the other is six coordinate. The two tin atom environments are best described as a pentagonal bipyramidal in the former and distorted octahedral in the latter where the carboxylate groups bridge the two tin atoms and construct a 2D‐coordination polymer. The 119Sn NMR spectroscopy indicates the octahedral geometry of 1 retains in solution. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:699–706, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/.20736
Synthesis and use of borane and platinum(II) complexes of 3‐diphenylphosphino‐1‐ phenylphospholane (LuPhos)
Authors: Pietrusiewicz K. Michał , Flis Anna , Ujj Viktória , Körtvélyesi Tamás , Drahos László , Pongrácz Péter , Kollár László , Keglevich György
Published: July 2011

3‐Diphenylphosphinoyl‐1‐phenylphospholane 1‐oxide (2) obtained by the Michael addition of diphenylphosphine oxide to the double‐bond of 1‐phenyl‐2‐phospholene 1‐oxide (1) was subjected to double deoxygenation to afford the corresponding bisphosphine (3, LuPhos) that was converted to bis(phosphine borane) 4 and to cis chelate platinum(II) complex 6. A mixed phosphine oxide–phosphine borane 5 was also prepared. Stereostructures of the bidentate P‐ligand 3 and the ring platinum(II) complex (6) were evaluated by quantum chemical calculations. Complex 6 used as a catalyst showed modest activity, but unusual regioselectivity in the hydroformylation of styrene and its 4‐substituted analogues. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:730–736, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20741
The synthesis and tuberculostatic activity of benzenesulfonohydrazide derivatives
Authors: Wisterowicz Krystyna , Gobis Katarzyna , Foks Henryk , Augustynowicz‐Kopeć Ewa
Published: July 2011

The series of novel N′‐aminocarbonothioyl‐benzenesulfonohydrazides were synthesized in a reaction of benzenesulphonyl chlorides with various aminocarbothiohydrazides. The structures were confirmed by IR and NMR spectra as well as elemental analysis. All of the obtained compounds were screened in vitro for their tuberculostatic activity. Preliminary results indicated that some target compounds exhibited promising results, especially toward Mycobacterium tuberculosis (Mtb) resistant strain 210. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:99–104, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20743
HDAC inhibition promotes cardiogenesis and the survival of embryonic stem cells through proteasome‐dependent pathway
Authors: Chen Hong P. , DeNicola Megan , Qin Xin , Zhao Yu , Zhang Ling , Long Xi L. , Zhuang Shougang , Liu Paul Y. , Zhao Ting C.
Published: July 2011

Histone deacetylase (HDAC) inhibition plays a crucial role in mediating cardiogenesis and myocardial protection, whereas HDAC degradation has recently attracted attention in mediating the biological function of HDACs. However, it remains unknown whether HDAC inhibition modulates cardiogenesis and embryonic stem cell (ESC) survival through the proteasome pathway. Using the well‐established mouse ESC culture, we demonstrated that HDAC inhibitors, both trichostatin A (TSA,50 nmol/L) and sodium butyrate (NaB, 200 µmol/L) that causes the pronounced reduction of HDAC4 activity, decreased cell death and increased viability of ESCs in response to oxidant stress. HDAC inhibition reduced the cleaved caspases 3, 6, 9, PARP, and TUNEL positive ESCs, which were abrogated with MG132 (0.5 µmol/L), a specific proteasome inhibitor. Furthermore, HDAC inhibition stimulates the growth of embryoid bodies (EB), which are associated with a faster spontaneous rhythmic contraction. HDAC inhibition increases the up‐regulation of GATA4, MEF2C, Nkx2.5, cardiac actin, and α‐SMA mRNA and protein levels that were abrogated by MG132. TSA and NaB resulted in a significant increase in cardiac lineage commitments that were blocked by the proteasome inhibition. Notably, HDAC inhibitors led to noticeable HDAC4 degradation, which was effectively prevented by MG132. Luciferase assay demonstrates an activation of MEF2 cardiac transcriptional factor by HDAC inhibition, which was repressed by MG132, revealing that the degradation of HDAC4 allows for the activation of MEF2. Taken together, our study is the first to demonstrate that HDAC inhibition through proteasome pathway forms a novel signaling to determine the cardiac lineage commitment and elicits the survival pathway. J. Cell. Biochem. 112: 3246–3255, 2011. © 2011 Wiley Periodicals, Inc.
Transgenic expression of an altered angiotensin type I AT1 receptor resulting in marked modulation of vascular type I collagen
Authors: Yu Jun , Taylor Linda , Rich Celeste , Toselli Paul , Stone Philip , Green Daniel , Warburton Rod , Hill Nicholas , Goldstein Ronald , Polgar Peter
Published: July 2011

The angiotensin II (AngII) type I receptor (AT1) was modified by replacing its third intracellular loop and C‐terminal tail with the corresponding regions from the bradykinin B2 receptor. Transgenic mice were produced that overexpress this mutated receptor (AB3T). Considerably less collagen content in the intact aorta and in primary aortic smooth muscle cells (aSMCs) cultures was observed in the transgenic mice. On the other hand, elastin content remained unchanged as measured by Western blot, and insoluble amino acid quantitation. The contraction of isolated aortas also remained unaltered. The aSMCs derived from the transgenic mice showed a reduction in AngII responsive type I collagen production. In aSMCs from transgenic mice, the cascade of Akt to the mammalian target rapamycin (mTOR) to p70 S6 kinase (p70S6K) was not AngII activated, while in the aSMCs from wild‐type (WT) mice the cascade was AngII activated. Angiotensin activation of Smad2 and Stat3 was also reduced in the AB3T aSMCs. However, no change in the effect of transforming growth factor β (TGFβ) on type I collagen production was observed. Also, the activation of ERK and JNK and G‐protein linked signaling remained unaltered in response to AngII. Akt and PI3K activation inhibitors blocked AngII‐stimulated type I collagen expression in WT aSMCs, whereas ERK inhibitor had no such effect. Our results point to an Akt/mTOR/p70S6K regulation of collagen production by AngII with participation of Smad2 and Stat3 cascades in this process. J. Cell. Physiol. 227: 2013–2021, 2012. © 2011 Wiley Periodicals, Inc.
Green microalga Chlorella vulgaris as a potential feedstock for biodiesel
Authors: Mallick Nirupama , Mandal Shovon , Singh Amit Kumar , Bishai Moumita , Dash Archana
Published: July 2011

BACKGROUND: A major bottleneck in microalgal biodiesel production is lipid content, which is often low in microalgal species. The present study examines Chlorella vulgaris as a potential feedstock for biodiesel by identifying and evaluating the relationships between the critical variables that enhance the lipid yield, and characterizes the biodiesel produced for various properties.

RESULTS: Factors affecting lipid accumulation in a green microalga, Chlorella vulgaris were examined. Multifactor optimization raised the lipid pool to 55% dry cell weight against 9% control. When C. vulgaris cells pre‐grown in glucose (0.7%)‐supplemented medium were transferred to the optimized condition at the second stage, the lipid yield was boosted to 1974 mg L−1, a value almost 20‐fold higher than for the control. The transesterified C. vulgaris oil showed the presence of ∼82% saturated fatty acids, with palmitate and stearate as major components, thus highlighting the oxidative stability of C. vulgaris biodiesel. The fuel properties (density, viscosity, acid value, iodine value, calorific value, cetane index, ash and water contents) are comparable with the international (ASTM and EN) and Indian (IS) biodiesel standards.

CONCLUSION: C. vulgaris biomass with 55% lipid content and adequate fuel properties is potentially a renewable feedstock for biodiesel. Copyright © 2011 Society of Chemical Industry
Comparison of diffusion‐weighted MRI and MR volumetry in the evaluation of early treatment outcomes after preoperative chemoradiotherapy for locally advanced rectal cancer
Authors: Kim Young Chul , Lim Joon Seok , Keum Ki Chang , Kim Kyung Ah , Myoung Sungmin , Shin Sang Joon , Kim Myeong‐Jin , Kim Nam Kyu , Suh Jinsuk , Kim Ki Whang
Published: July 2011

Purpose:

To compare diffusion‐weighted imaging (DWI) and magnetic resonance (MR) volumetry for predicting treatment outcomes of locally advanced rectal cancers with preoperative chemoradiotherapy (CRT).

Materials and Methods:

This prospective study was approved by our Institutional Review Board. Thirty‐four patients underwent three MR examinations: pre‐CRT (before CRT), early CRT (2 weeks after CRT initiation), and post‐CRT (before surgery). The tumor apparent diffusion coefficient (ADC), ADC increase rate, and volume reduction rate were compared between responders and nonresponders using three reference standards: downstaging, modified Response Evaluation Criteria in Solid Tumors (mRECIST), and tumor regression grade (TRG). For DWI and volumetry, differences between responders and nonresponders were assessed by receiver operating characteristic analysis.

Results:

The median early tumor volume reduction rate of responders, subgrouped by downstaging and mRECIST (47.97% and 53.97%, respectively), was significantly higher than that of nonresponders (20.94% and 20.36%; P = 0.0024 and 0.0001, respectively), but there were no significant differences in pre‐CRT ADC and early ADC increase rate using all references. When using the downstaging and mRECIST, the diagnostic performance of early tumor volume reduction rate (Az = 0.81 and 0.94, respectively) was higher than that of pre‐CRT ADC (Az = 0.55 and 0.62; P = 0.033 and 0.007) and early ADC increase rate (Az = 0.58 and 0.64; P = 0.055 and 0.01) for predicting the treatment outcome. For TRG, there were no significant differences between DWI and volumetry.

Conclusion:

Early tumor volume reduction rate at the second week after CRT initiation may be a better indicator than DWI based on the mean ADC measurements for predicting CRT treatment outcome. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
Optimized high‐resolution contrast‐enhanced hepatobiliary imaging at 3 tesla: A cross‐over comparison of gadobenate dimeglumine and gadoxetic acid
Authors: Frydrychowicz Alex , Nagle Scott K. , D'Souza Sharon L. , Vigen Karl K. , Reeder Scott B.
Published: July 2011

Purpose:

To evaluate the signal to noise ratio (SNR) and contrast to noise ratio (CNR) performance of 0.05 mmol/kg gadoxetic acid and 0.1 mmol/kg gadobenate dimeglumine for dynamic and hepatobiliary phase imaging. In addition, flip angles (FA) that maximize relative contrast‐to‐noise performance for hepatobiliary phase imaging were determined.

Materials and Methods:

A cross‐over study in 10 volunteers was performed using each agent. Imaging was performed at 3 Tesla (T) with a 32‐channel phased‐array coil using breathheld 3D spoiled gradient echo sequences for SNR and CNR analysis, and for FA optimization of hepatobiliary phase imaging.

Results:

Gadobenate dimeglumine (0.1 mmol/kg) had superior SNR performance during the dynamic phase, statistically significant for portal vein and hepatic vein in the portal venous and venous phase (for all, P < 0.05) despite twice the approved dose of gadoxetic acid (0.05 mmol/kg), while gadoxetic acid had superior SNR performance during the hepatobiliary phase. Optimal FAs for hepatobiliary phase imaging using gadoxetic acid and gadobenate dimeglumine were 25–30° and 20–30° for relative contrast liver versus muscle (surrogate for nonhepatocellular tissues), and 45° and 20° (relative contrast liver versus biliary structures), respectively.

Conclusion:

Gadobenate dimeglumine may be preferable for applications that require dynamic phase imaging only, while gadoxetic acid may be preferable when the hepatobiliary phase is clinically important. Hepatobiliary phase imaging with both agents benefits from flip angle optimization. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
Effects of static magnetic fields on cognition, vital signs, and sensory perception: A meta‐analysis
Authors: Heinrich Angela , Szostek Anne , Nees Frauke , Meyer Patric , Semmler Wolfhard , Flor Herta
Published: July 2011

To evaluate whether cognitive processes, sensory perception, and vital signs might be influenced by static magnetic fields in magnetic resonance imaging (MRI), which could pose a risk for health personnel and patients, we conducted a meta‐analysis of studies that examined effects of static magnetic fields. Studies covering the time from 1992 to 2007 were selected. Cohen's d effects sizes were used and combined in different categories of neuropsychology (reaction time, visual processing, eye‐hand coordination, and working memory). Additionally, effects of static magnetic fields on sensory perception and vital signs were analyzed. In the category “neuropsychology,” only effects on the visual system were homogeneous, showing a statistically significant impairment as a result of exposure to static magnetic fields (d = −0.415). Vital signs were not affected and effects on sensory perceptions included an increase of dizziness and vertigo, primarily caused by movement during static magnetic field gradient exposures. The number of studies dealing with this topic is very small and the experimental set‐up of some of the analyzed studies makes it difficult to accurately determine the effects of static magnetic fields by themselves, excluding nonspecific factors. The implications of these results for MRI lead to suggestions for improvement in research designs. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
How to obtain a reliable structural characterization of polished graphitized carbons by Raman microspectroscopy
Authors: Ammar M. R. , Rouzaud J.‐N.
Published: July 2011

A series of graphitized carbon materials, produced by the pyrolysis of an anthracene‐based coke at temperatures ranging from 1600 to 2900 °C, were studied by Raman microspectroscopy to assess the applicability of this technique to the particular case of polished carbon materials. The polishing process was shown to change significantly the first‐order Raman spectra (D band intensity increase) and therefore to induce unacceptable errors in the characterization of the intrinsic structure of these materials. The deconvolution of Raman spectra, related to the unpolished graphitized carbons at varying temperatures, highlighted a linear relationship between the intensity ratio ID/IG and the G band width. Thus, as the latter appears to be insensitive to the polishing, we highly recommend using it for a reliable assessment of the intrinsic structural disorder of polished carbon materials. Copyright © 2011 John Wiley & Sons, Ltd.
Pharmaceutical polymorphs quantified with transmission Raman spectroscopy
Authors: McGoverin Cushla M. , Hargreaves Michael D. , Matousek Pavel , Gordon Keith C.
Published: July 2011

The quantification of polymorphs in dosage forms is important in the pharmaceutical industry. Conventional Raman spectroscopy of solid‐state pharmaceuticals may be used for this, but it has some limitations such as sub‐sampling and fluorescence. These problems can be mitigated through the use of transmission Raman spectroscopy (TRS). The efficacy of TRS measurements for the prediction of polymorph content was evaluated using a ranitidine hydrochloride test system. Four groups of ranitidine hydrochloride‐based samples were prepared: three containing form I and II ranitidine hydrochloride and microcrystalline cellulose (spanning the ranges 0–10%, 90–100% and 0–100% form I fraction of total ranitidine hydrochloride), and a fourth group comprising form I ranitidine hydrochloride (0–10%) spiked commercial formulation. Transmission and conventional Raman spectroscopic measurements were recorded from both capsules and tablets of the four sample groups. Prediction models for polymorph and total ranitidine hydrochloride content were more accurate for the tablet than for the capsule systems. TRS was found to be superior to conventional backscattering Raman spectroscopy in the prediction of polymorph and total ranitidine hydrochloride content. The prediction model calculated for form I content across the 0–100% range was appropriate for process control [ratio of prediction to deviation (RPD) equal to 14.62 and 7.42 for tablets and capsules, respectively]. The 10% range calibrations for both form I and total ranitidine hydrochloride content were sufficient for screening (RPDs greater than 2.6). TRS is an effective tool for polymorph process control within the pharmaceutical industry. Copyright © 2011 John Wiley & Sons, Ltd.
Text Mining for Drugs and Chemical Compounds: Methods, Tools and Applications
Authors: Vazquez Miguel , Krallinger Martin , Leitner Florian , Valencia Alfonso
Published: July 2011

Providing prior knowledge about biological properties of chemicals, such as kinetic values, protein targets, or toxic effects, can facilitate many aspects of drug development. Chemical information is rapidly accumulating in all sorts of free text documents like patents, industry reports, or scientific articles, which has motivated the development of specifically tailored text mining applications. Despite the potential gains, chemical text mining still faces significant challenges. One of the most salient is the recognition of chemical entities mentioned in text. To help practitioners contribute to this area, a good portion of this review is devoted to this issue, and presents the basic concepts and principles underlying the main strategies. The technical details are introduced and accompanied by relevant bibliographic references. Other tasks discussed are retrieving relevant articles, identifying relationships between chemicals and other entities, or determining the chemical structures of chemicals mentioned in text. This review also introduces a number of published applications that can be used to build pipelines in topics like drug side effects, toxicity, and protein‐disease‐compound network analysis. We conclude the review with an outlook on how we expect the field to evolve, discussing its possibilities and its current limitations.