bluuebunny/crossref_metadata_2025 huggingface dataset:
Prozessanalytik als Instrument des Informationsmanagements in der Chemischen und Pharmazeutischen Industrie
Authors: Maiwald M.
Published: March 2010

Die Wettbewerbsfähigkeit der Chemischen und Pharmazeutischen Industrie basiert auf der Sicherung der geforderten Produktqualität bei einer optimalen Nutzung von Anlagen, Rohstoffen und Energie [1]. Eine gute Prozessführung unter Einsatz zuverlässiger Prozessanalytik sichert hier den globalen Wettbewerbsvorteil gegenüber Niedriglohnländern, die mit weniger effizienten Verfahren produzieren. Prozessanalytik trägt zur Erhöhung der Prozess‐ und Anlagensicherheit bei. In Kombination mit geeigneten Informationsmanagementsystemen verbessert dieser Ansatz ständig das Wissen über den Prozess und führt damit zu einer präventiven Sicherstellung der geforderten Qualität.
Softsensorsysteme – Mathematik als Bindeglied zum Prozessgeschehen
Authors: Becker T. , Krause D.
Published: March 2010

Softsensorsysteme sind Gebilde, die aus der Notwendigkeit und dem Bewusstsein heraus entstanden sind, dass für eine Vielzahl von Leitgrößen insbesondere in der chemischen oder biotechnologischen Prozesstechnik keine geeigneten Sensoren zur Prozessbeobachtung und darauf aufbauenden Automatisierung vorliegen. Softwaresensoren bestehen in der Regel aus einer Anordnung von einem oder mehreren Sensoren bzw. Messgrößen in Kombination mit einem mathematischen Modellierungsansatz, mit dessen Hilfe eine Relation der verfügbaren Messgrößen zu den gewünschten Prozessgrößen aufgebaut wird. Die Prozessgrößen müssen laboranalytisch erfassbar sein. In Abhängigkeit von der vorliegenden Prozessinformation werden als Algorithmus chemometrische, linguistische, kognitive oder aber auch modellgestützte Verfahren eingesetzt. Der Beitrag gibt einen Überblick über den Aufbau, das Ineinandergreifen der Bestandteile und die Einsatzmöglichkeiten im Prozess.
Excellent outcomes with adjuvant toremifene or tamoxifen in early stage breast cancer
Authors: Lewis Jaime D. , Chagpar Anees B. , Shaughnessy Elizabeth A. , Nurko Jacob , McMasters Kelly , Edwards Michael J.
Published: March 2010

BACKGROUND:

Fareston (toremifene) and tamoxifen, both selective estrogen receptor modulators, are therapeutically equivalent treatments for metastatic breast cancer. We hypothesized that toremifene as compared with tamoxifen given as adjuvant therapy for early stage breast cancer would result in equivalent survival with an improved side effect profile, therefore, providing superior therapeutic efficacy.

METHODS:

The North American Fareston versus Tamoxifen Adjuvant trial assigned 1813 perimenopausal or postmenopausal women with hormone receptor (HR)‐positive invasive breast cancer to adjuvant treatment with either tamoxifen or toremifene. The primary outcomes evaluated were disease‐free survival (DFS) and overall survival (OS).

RESULTS:

Median follow‐up was 59 months. The baseline characteristics of the 2 treatment groups were well‐balanced. On the basis of intent‐to‐treat, 5‐year actuarial DFS was not significantly different between tamoxifen and toremifene (91.2% [standard error of the mean [SE] 1.2%] vs 91.2% [SE 1.1%], respectively). Similarly, 5‐year actuarial OS was not significantly different between tamoxifen and toremifene (92.7% [SE 1.1%] vs 93.7% [SE 1.0%], respectively). Controlling for patient age, tumor size, and tumor grade, a Cox multivariate survival analysis found no difference between patients randomized to toremifene versus tamoxifen in terms of OS (OR = 0.951; 95% confidence interval [CI], 0.623‐1.451, P = .951) or DFS (OR = 1.037; 95% CI, 0.721‐1.491, P = .846). Adverse events were similar in the 2 groups.

CONCLUSIONS:

Women treated with adjuvant hormonal therapy enjoyed excellent DFS and OS. No significant differences were found between treatment with either tamoxifen or toremifene. Treatment of HR‐positive patients with either tamoxifen or toremifene is appropriate. Cancer 2010. © 2010 American Cancer Society.
Invasive carcinoma of the uterine cervix associated with pregnancy
Authors: Pettersson B. Folke , Andersson Sonia , Hellman Kristina , Hellström Ann‐Cathrin
Published: March 2010

BACKGROUND:

This study is a representation of 90 years of experience with carcinoma of the uterine cervix in pregnancy. The objective was to retrospectively study changes in the distribution of cervical carcinoma (CC) by age, disease stage, histopathology, survival, and the development of second primary cancers.

METHODS:

Altogether, 18,474 women with newly diagnosed CC were examined and treated at the Radiumhemmet between 1914 and 2004, including 9247 women who were of a childbearing age (<50 years) and 219 women who were pregnant.

RESULTS:

The mean patient age declined from 35 years (during 1914‐1943) to 32.2 years (during 1960‐2004). Similarly, the age range changed from ages 23 to 51 years (during 1914‐1943) to ages 21 to 47 years (during 1960‐2004). The relative incidence for all women aged <50 years who were treated for CC dropped considerably from 4.2% (during 1914‐1943) to 1.2% (during 1960‐2004), which translated into a reduction of by approximately 66%. At the time of diagnosis, stage I CC was observed in 75.6% of patients during 1960 to 2004 compared with 24.8% of patients during 1914 to 1943. The 10‐year actuarial survival rate improved significantly during the study period from 27% (1914‐2004) to 79% (1960‐2004). The 10‐year cause‐specific cumulative actuarial survival rate for 41 women who were treated during 1960 to 2004 did not differ statistically from the rate for an age‐matched, stage‐matched, and histopathology‐matched control series from the total cohort of women with CC who were treated at the Radiumhemmet during the same period (log‐rank test; P = .85).

CONCLUSIONS:

During the study period, the incidence of CC during pregnancy declined, the cases were discovered at earlier stages, and survival improved. Furthermore, there was no increase in second primary cancers, and pregnancy did not appear to influence prognosis. Cancer 2010. © 2010 American Cancer Society.
Do racial or socioeconomic disparities exist in lung cancer treatment?
Authors: Yang Relin , Cheung Michael C. , Byrne Margaret M. , Huang Youjie , Nguyen Dao , Lally Brian E. , Koniaris Leonidas G.
Published: March 2010

BACKGROUND:

Determine the effects of race, socioeconomic status, and treatment on outcomes for patients diagnosed with lung cancer.

METHODS:

The Florida cancer registry and inpatient and ambulatory data were queried for patients diagnosed from 1998‐2002.

RESULTS:

A total 76,086 of lung cancer patients were identified. Overall, 55.6% were male and 44.4% were female. The demographic distribution of patients was 92.7% Caucasian, 6.7% African American, and 5.7% Hispanic. The mean age of diagnosis was 70 years old. African American patients presented at a younger age, with more advanced disease, and were less likely to undergo surgical therapy than their Caucasian counterparts. Median survival time (MST) for the entire cohort was 8.7 months, while MST for African American patients was 7.5 months. Patients who received surgery, chemotherapy, or radiation therapy demonstrated significantly improved outcomes. Stepwise multivariate analysis revealed that African American race was no longer a statistically significant predictor of worse outcomes once corrections were made for demographics and comorbid conditions, suggesting that the originally reported disparities in lung cancer outcomes and race may be in part because of poor pretreatment performance status. In contrast, patients of the lowest socioeconomic status continue to have a slightly worse overall prognosis than their affluent counterparts (hazard ratio = 1.05, P = .001).

CONCLUSIONS:

Lung cancer continues to carry a poor prognosis for all patients. Once comorbidities are corrected for, African American patients carry equivalently poor outcomes. Nonetheless, emphasis must be placed on improving pretreatment performance status among African American patients and efforts for earlier diagnosis among the impoverished patients must be made. Cancer 2010. © 2010 American Cancer Society.
Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma
Authors: Mougiakakos Dimitrios , Johansson C. Christian , Trocme Eric , All‐Ericsson Charlotta , Economou Mario A. , Larsson Olle , Seregard Stefan , Kiessling Rolf
Published: March 2010

BACKGROUND:

Forkhead box P3 (FOXP3)‐positive regulatory T cells (Tregs) are key mediators of peripheral tolerance and suppress efficient antitumor responses. Prostaglandin E2 (PGE2) produced by inducible cyclooxygenase‐2 (COX‐2) can lead to Treg induction. COX‐2 expression has been linked to tumorigenesis and growth in various malignancies. The objective of the current study was to investigate whether Tregs infiltrate uveal melanomas (UMs) and whether their prevalence is linked to COX‐2 expression and the prediction of overall survival (OS).

METHODS:

One hundred patients who underwent enucleation after they were diagnosed with UM were included in the study. Immunohistochemical staining with monoclonal anti‐FOXP3, anti‐CD4, and anti‐COX‐2 antibodies was performed, and immunoreactivity was assessed. Correlations of COX‐2 expression with the presence of Tregs, established clinicopathologic parameters, and OS were evaluated in univariate and multivariate analyses.

RESULTS:

High expression of COX‐2 was predictive of shortened OS. FOXP3‐positive Tregs were detectable in 24% of UMs and were restricted to malignant tissue. The extent of COX‐2 expression was associated significantly with Treg prevalence (P = .004) and Treg intratumoral localization (P = .005). Intratumoral Tregs (but not the prevalence of Tregs) were independent marker for worse OS with a hazard ratio of 5.36 in patients with COX‐2–positive tumors.

CONCLUSIONS:

The current results demonstrated that high COX‐2 expression is associated with OS and Treg prevalence in UM. These findings are in line with the observations that COX‐2/PGE2 induces Tregs and that Tregs may alter antitumor responses, resulting in a negative effect on the clinical disease course. Intratumoral Tregs are an independent prognostic marker for COX‐2–positive UM, and these results put COX‐2 inhibitors and Treg depletion into the spotlight of potential novel treatment modalities for patients with UM. Cancer 2010. © 2010 American Cancer Society.
Central nervous system prophylaxis in adults with acute lymphoblastic leukemia
Authors: Jabbour Elias , Thomas Deborah , Cortes Jorge , Kantarjian Hagop M. , O'Brien Susan
Published: March 2010

Central nervous system (CNS) recurrence continues to be a significant complication in the treatment of adult patients with acute lymphoblastic leukemia (ALL). Preventing CNS recurrence has been a therapeutic challenge and has not been addressed critically in many clinical trials. Adult studies modeled on childhood ALL studies have used multiple treatment modalities, including radiation therapy, systemic therapy, intrathecal therapy, and combinations thereof. Cranial irradiation is effective but is offset by substantial toxicity, including neurologic sequelae. Systemic chemotherapy, especially with cytarabine (AraC) and methotrexate, has demonstrated promise in decreasing CNS recurrence, but therapeutic levels of drugs in the cerebrospinal fluid (CSF) are not maintained. Intrathecal chemotherapy with or without high‐dose systemic therapy is the most common approach to CNS prophylaxis. Liposomal AraC recently has become available and confers prolonged levels of free AraC in the CSF, a critical requirement for CNS prophylactic therapy. This review discusses the various modalities used for CNS prophylaxis in patients with ALL and the emerging trends, with specific emphasis on the outcome in terms of event‐free survival and toxicity. Cancer 2010. © 2010 American Cancer Society.
Evaluation of the prognostic significance of Eosinophilia and Basophilia in a larger cohort of patients with myelodysplastic syndromes
Authors: Wimazal Friedrich , Germing Ulrich , Kundi Michael , Noesslinger Thomas , Blum Sabine , Geissler Philipp , Baumgartner Christian , Pfeilstoecker Michael , Valent Peter , Sperr Wolfgang R.
Published: March 2010

BACKGROUND:

Lineage involvement and maturation arrest are considered to have prognostic significance in patients with myelodysplastic syndromes (MDS). However, although the prognostic value of neutropenia, thrombocytopenia, and monocytosis have been documented, little is known about the impact of eosinophils and basophils.

METHODS:

The authors examined the prognostic significance of eosinophils and basophils in 1008 patients with de novo MDS. Patients were enrolled from 3 centers of the Austrian‐German MDS Working Group and were analyzed retrospectively. Blood eosinophils and basophils were quantified by light microscopy, and their impact on survival and leukemia‐free survival was calculated by using Cox regression.

RESULTS:

Eosinophilia (eosinophils >350/μL) and basophilia (basophils >250/μL) predicted a significantly reduced survival (P < .05) without having a significant impact on leukemia‐free survival. In multivariate analysis, eosinophilia and basophilia were identified as lactate dehydrogenase (LDH)‐independent prognostic variables with International Prognostic Scoring System (IPSS)‐specific impact. Although elevated LDH was identified as a major prognostic determinant in IPSS low‐risk, intermediate‐1 risk, and high‐risk subgroups, the condition “eosinophilia and/or basophilia” was identified as a superior prognostic indicator in the IPSS intermediate‐2 risk subgroup.

CONCLUSIONS:

The evaluation of eosinophils and basophils in patients with MDS was helpful and may complement the spectrum of variables to optimize prognostication in MDS. Cancer 2010. © 2010 American Cancer Society.
Pelvic radiotherapy and the risk of secondary leukemia and multiple myeloma
Authors: Wright Jason D. , St. Clair Caryn M. , Deutsch Israel , Burke William M. , Gorrochurn Prakash , Sun Xuming , Herzog Thomas J.
Published: March 2010

BACKGROUND:

Although several studies had examined secondary malignancies in patients with specific primary tumor types, to the authors' knowledge there are very few data examining the long‐term sequelae of pelvic radiation as a whole. The goal of the current study was to examine the risk of treatment‐associated leukemia and multiple myeloma in patients treated with pelvic radiotherapy.

METHODS:

Patients with invasive tumors of the vulva, cervix, uterus, anus, and rectosigmoid treated from 1973 to 2005 and recorded in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patients were stratified based on receipt of pelvic radiotherapy. The incidence of secondary leukemia (except chronic lymphocytic leukemia) and multiple myeloma were examined. Multivariate Cox proportional hazards models and Kaplan‐Meier curves were constructed to examine the association between pelvic radiation and the development of subsequent hematologic malignancies.

RESULTS:

A total of 199,268 individuals, including 66,896 (34%) who received pelvic radiotherapy and 132,372 (66%) not treated with radiation, were identified. In a Cox proportional hazards model adjusting for other risk factors, post‐treatment leukemia was increased by 72% (hazard ratio [HR], 1.72; 95% confidence interval [95% CI], 1.37‐2.15) in the patients who received pelvic radiotherapy. The risk of secondary leukemia peaked at 5 to 10 years after primary treatment (HR, 1.85; 95% CI, 1.40‐2.44) and remained elevated even 10 to 15 years after initial treatment (HR, 1.50; 95% CI, 1.03‐2.18). There was no significant association between radiation and the development of multiple myeloma (HR, 1.08; 95% CI, 0.81‐1.44).

CONCLUSIONS:

Pelvic radiation was associated with an increased risk of secondary leukemia but did not appear to increase the risk of multiple myeloma. Cancer 2010. © 2010 American Cancer Society.
Malignant solitary fibrous tumor
Authors: Bishop Justin A. , Rekhtman Natasha , Chun Joyce , Wakely Paul E. , Ali Syed Z.
Published: March 2010

BACKGROUND:

Malignant solitary fibrous tumors (SFTs) are extremely uncommon and poorly understood mesenchymal neoplasms. There are only rare published accounts of the cytopathologic features of these tumors, prompting the current study.

DESIGN:

All cases of malignant SFT with preoperative fine‐needle aspirations (FNAs) from 1999 to 2008 were retrieved from the archives of 3 large teaching hospitals. FNA smears and cell block material including immunoperoxidase stains were reviewed, and the cytologic characteristics were described.

RESULTS:

Thirteen cases of malignant SFT were identified in 11 patients. Mean age was 58 years, with a men:women ratio of 1:2.6. The tumors were generally large, with a mean size of 13.4 cm. Cytomorphologic features included mostly hypercellular smears with tissue fragments of monotonous, plump spindled cells with blunt‐ended and indented nuclei and fragile, wispy cytoplasm. Also seen were bare nuclei, occasional mitoses, and rare necrosis. Some cases showed a predominance of epithelioid cells, whereas others displayed a loose myxomatous matrix. There was a general lack of single cells. None of the cases was diagnosed accurately as malignant SFT on FNA, and only 6 cases were called malignant or suspicious for malignancy.

CONCLUSIONS:

The FNA diagnosis of malignant SFT is extremely difficult and needs histologic material for accurate interpretation. Predominant FNA diagnoses were SFT or spindle cell neoplasm. Malignant SFT must be included in the differential diagnosis of a spindle cell neoplasm of any anatomic site, particularly if it displays features not typical of benign SFT. Immunoperoxidase staining has some utility, mainly in ruling out other neoplasms in the differential diagnosis. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.
The use of immunohistochemistry to distinguish reactive mesothelial cells from malignant mesothelioma in cytologic effusions
Authors: Hasteh Farnaz , Lin Grace Y. , Weidner Noel , Michael Claire W.
Published: March 2010

BACKGROUND:

The distinction of benign from malignant mesothelial proliferations in cytologic specimens can be problematic. In this study, the authors investigated the utility of immunohistochemical (IHC) markers in making this distinction.

METHODS:

Archival paraffin‐embedded cell blocks of pleural and peritoneal fluids from 52 patients with malignant meothelioma (MM) and 64 patients with reactive mesothelial hyperplasia (MH) were retrieved. IHC stains included desmin, epithelial membrane antigen (EMA), glucose‐transport protein 1 (GLUT‐1), Ki67, and p53.

RESULTS:

Desmin was positive in 84% (54 of 64) cases of reactive MH and in 6% (3 of 52) of MM cases (P < .001). EMA was positive in 9% (6 of 64) of benign and 100% (52 of 52) of malignant cases (P < .001). GLUT‐1 was positive in 12% (5 of 43) of benign and 47% (7 of 15) of malignant cases. Ki67 showed strong nuclear positivity in >40% of mesothelial cells in 9% (6 of 64) of benign and 16% (8 of 49) of malignant cases (P = .38). p53 showed strong nuclear positivity in 2% (1 of 46) of benign and 47% (7 of 15) of malignant cases (P < .001). EMA positivity and desmin negativity were found in 2% (1 of 64) of reactive MH cases and 98% (49 of 52) of MM cases (P < .001). EMA negativity and desmin positivity were found in 86% (55 of 64) of reactive MH cases and 0% of MM cases.

CONCLUSIONS:

The combination of positive EMA and negative desmin strongly favors MM; conversely, a combination of negative EMA and positive desmin favors a reactive process. Likewise, strong membranous positivity for GLUT‐1 and/or strong nuclear staining for p53 favors a mesothelioma. Ki67 proliferative index showed no significant difference between reactive MH and MM cases. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.
Tailoring a cognitive behavioural model for unexplained physical symptoms to patient's perspective: a bottom‐up approach
Authors: Zonneveld Lyonne N. L. , Duivenvoorden Hugo J. , Passchier Jan , van 't Spijker Adriaan
Published: March 2010

The prevalence of unexplained physical symptoms (UPS) in primary care is at least 33%. Cognitive behavioural therapy has shown to be effective. Within cognitive behavioural therapy, three models can be distinguished: reattribution model, coping model and consequences model. The consequences model, labelling psychosocial stress in terms of consequences rather than as causes of UPS, has high acceptance among patients and is effective in academic medical care. This acceptance is lost when applied in primary care. To increase acceptance of the consequences model among patients in primary care, we tailor this model to patient's perspective by approaching the model from bottom‐up instead of top‐down. Subsequently, we use this tailored model in an easily accessible group training. We illustrate our approach using two illustrative cases. Copyright © 2010 John Wiley & Sons, Ltd.

Key Practitioner Message:

• The prevalence of unexplained physical symptoms (UPS) in primary care is at least 33%.

• Cognitive behavioural therapy has shown to be most effective for UPS. The most interesting cognitive behavioural model is the consequences model because 81% of the patients with UPS in secondary care accepts a therapy based on this model.

• The consequences model labels psychosocial stress as consequences rather than as causes of UPS and aims to change the consequences in that UPS reduces.

• The acceptance of the consequences model drops in primary care, making a therapy based on this model not feasible for primary care.

• If the acceptance of the consequences model in primary care could be raised by tailoring this model more closely to patients' perspective of their symptoms approaching the model innovatively from bottom‐up, then the opportunity of a positive outcome for patients in primary care could be improved.

Trial registration:

Nederlands Trial Register, NTR1609

http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1609
Photoelectron Generation by Photosystem II Core Complexes Tethered to Gold Surfaces
Authors: Vittadello Michele , Gorbunov Maxim Y. , Mastrogiovanni Daniel T. , Wielunski Leszek S. , Garfunkel Eric L. , Guerrero Fernando , Kirilovsky Diana , Sugiura Miwa , Rutherford A. William , Safari Ahmad , Falkowski Paul G.
Published: March 2010

By using a nondestructive, ultrasensitive, fluorescence kinetic technique, we measure in situ the photochemical energy conversion efficiency and electron transfer kinetics on the acceptor side of histidine‐tagged photosystem II core complexes tethered to gold surfaces. Atomic force microscopy images coupled with Rutherford backscattering spectroscopy measurements further allow us to assess the quality, number of layers, and surface density of the reaction center films. Based on these measurements, we calculate that the theoretical photoelectronic current density available for an ideal monolayer of core complexes is 43 μA cm−2 at a photon flux density of 2000 μmol quanta m−2 s−1 between 365 and 750 nm. While this current density is approximately two orders of magnitude lower than the best organic photovoltaic cells (for an equivalent area), it provides an indication for future improvement strategies. The efficiency could be improved by increasing the optical cross section, by tuning the electron transfer physics between the core complexes and the metal surface, and by developing a multilayer structure, thereby making biomimetic photoelectron devices for hydrogen generation and chemical sensing more viable.
Sodium oxybate in the treatment of binge eating disorder: An open‐label, prospective study
Authors: McElroy Susan L. , Guerdjikova Anna I. , Winstanley Erin L. , O'Melia Anne M. , Mori Nicole , Keck Paul E. , Hudson James I.
Published: March 2010

Objective:

To assess preliminarily the effectiveness of sodium oxybate in binge eating disorder.

Method:

This was an open‐label, prospective, 16‐week, flexible dose study of sodium oxybate in binge eating disorder. The primary outcome was binge eating episode frequency.

Results:

Twelve individuals received sodium oxybate, 10 completed at least one postbaseline evaluation, and five completed the study. Mean dose at endpoint was 7.1 (2.0) g/day. Sodium oxybate was associated with significant reductions in frequency of binge days and binge episodes, as well as measures of clinical severity, eating pathology, obsessive‐compulsive symptoms, food cravings, body mass index, and body weight. Nine participants had remission of binge eating and five lost ≥5% of their baseline weight; all five of the latter participants had remission of binge eating.

Discussion:

In this open‐label trial, sodium oxybate was effective in binge eating disorder, but associated with high a discontinuation rate. © 2010 by Wiley Periodicals, Inc. (Int J Eat Disord 2011; 44:262–268)
Mixed‐Anion and Mixed‐Cation Borohydride KZn(BH4)Cl2: Synthesis, Structure and Thermal Decomposition
Authors: Ravnsbæk Dorthe B. , Sørensen Lise H. , Filinchuk Yaroslav , Reed Daniel , Book David , Jakobsen Hans J. , Besenbacher Flemming , Skibsted Jørgen , Jensen Torben R.
Published: March 2010

KZn(BH4)Cl2, synthesized for the first time, contains a heteroleptic complex anion [Zn(BH4)Cl2]–, extending the structural diversity of metal borohydrides. In‐situ synchrotron powder diffraction, NMR and Raman spectroscopy were used to characterize KZn(BH4)Cl2 and to evaluate the mechanism for its thermal decomposition. The title compound decomposes at a significantly lower temperature than KBH4 and may be used for inspiration for the design of novel hydrogen storage materials. Combining different ligands in modified metal borohydrides is proposed as a way to adjust stability with respect to hydrogen desorption.
C3v (Trimethyl) p‐(Benzyloxy)calix[6]arene: A Versatile Platform for the Synthesis of Functionalized C3v Calix[6]arenes
Authors: Huc Vincent , Guérineau Vincent
Published: March 2010

Partial methylation of p‐(benzyloxy)calix[6]arene leads to the corresponding trimethylated C3v derivative. This compound was used for the synthesis of new functional calixarenes. The presence of the p‐(benzyloxy) substituent allows this new C3v derivative to be directly oxidized to the tris(quinone). These new C3v derivatives open the way to new supramolecular receptors, bearing easily derivatized hydroxy groups at the upper rim position.
CE‐TOF MS analysis of complex protein hydrolyzates from genetically modified soybeans – A tool for foodomics
Authors: Simó Carolina , Domínguez‐Vega Elena , Marina Maria Luisa , García María Concepción , Dinelli Giovanni , Cifuentes Alejandro
Published: March 2010

A CE‐TOF MS proteomic approach was applied for the analysis of hydrolyzates from complex soybean protein mixtures. After CE‐TOF MS method development, the new approach provided the simultaneous analysis of more than 150 peptides from the soybean protein fraction soluble in ACN‐water (80/20 v/v). The method is fast (about 30 min of analysis per sample) and is characterized by a relatively low running cost. The approach was used to study the substantial equivalence between a genetically modified variety of soybean compared with its traditional counterpart. No significant differences were found between the two studied soybeans based on the protein fraction studied. The capacity of the CE‐TOF MS method to analyze complex mixtures of peptides in short times opens interesting possibilities in the growing Foodomics area.
Sensitivity improvement of CE/ESI/MS analysis of gangliosides using a liquid‐junction/low‐flow interface
Authors: Hsueh Yun‐Hung , Huang Ju‐Li , Tseng Mei‐Chun , Her Guor‐Rong
Published: March 2010

Methodology is presented which greatly improves the sensitivity of ganglioside analysis by CE/MS without compromising separation efficiency. In this method, non‐volatile additives were removed, where possible, to reduce ion suppression. Specifically, α‐CD, used to break up ganglioside micelle formation, was replaced with isopropyl alcohol. To reduce ion suppression from sodium ions, ammonium borate was substituted for sodium borate in the preparation of borate buffer. Because borate anions were found to be essential for CE separation, a liquid‐junction/low‐flow interface was employed to restrict borate anions from entering the ESI ion source. With proper control over the EOF in the connecting capillary, borate anions were controlled to migrate away from the ESI ion source. With these modifications, the sensitivity of CE/MS analysis of gangliosides was improved significantly.
CEC‐ESI ion trap MS of multiple drugs of abuse
Authors: Aturki Zeineb , D'Orazio Giovanni , Rocco Anna , Bortolotti Federica , Gottardo Rossella , Tagliaro Franco , Fanali Salvatore
Published: March 2010

This article describes a method for the separation and determination of nine drugs of abuse in human urine, including amphetamines, cocaine, codeine, heroin and morphine. This method was based on SPE on a strong cation exchange cartridge followed by CEC‐MS. The CEC experiments were performed in fused silica capillaries (100 μm×30 cm) packed with a 3 μm cyano derivatized silica stationary phase. A laboratory‐made liquid junction interface was used for CEC‐MS coupling. The outlet capillary column was connected with an emitter tip that was positioned in front of the MS orifice. A stable electrospray was produced at nanoliter per minute flow rates applying a hydrostatic pressure (few kPa) to the interface. The coupling of packed CEC columns with mass spectrometer as detector, using a liquid junction interface, provided several advantages such as better sensitivity, low dead volume and independent control of the conditions used for CEC separation and ESI analysis. For this purpose, preliminary experiments were carried out in CEC‐UV to optimize the proper mobile phase for CEC analysis. Good separation efficiency was achieved for almost all compounds, using a mixture containing ACN and 25 mM ammonium formate buffer at pH 3 (30:70, v/v), as mobile phase and applying a voltage of 12 kV. ESI ion‐trap MS detection was performed in the positive ionization mode. A spray liquid, composed by methanol–water (80:20, v/v) and 1% formic acid, was delivered at a nano‐flow rate of ∼200 nL/min. Under optimized CEC‐ESI‐MS conditions, separation of the investigated drugs was performed within 13 min. CEC‐MS and CEC‐MS2 spectra were obtained by providing the unambiguous confirmation of these drugs in urine samples. Method precision was determined with RSDs values ≤3.3% for retention times and ≤16.3% for peak areas in both intra‐day and day‐to‐day experiments. LODs were established between 0.78 and 3.12 ng/mL for all compounds. Linearity was satisfactory in the concentration range of interest for all compounds (r2≥0.995). The developed CEC‐MS method was then applied to the analysis of drugs of abuse in spiked urine samples, obtaining recovery data in the range 80–95%.
Complexation of metals by phytosiderophores revealed by CE‐ESI‐MS and CE‐ICP‐MS
Authors: Dell'mour Madeleine , Koellensperger Gunda , Quirino Joselito P. , Haddad Paul R. , Stanetty Christian , Oburger Eva , Puschenreiter Markus , Hann Stephan
Published: March 2010

CE‐ESI‐MS and CE‐ICP‐MS were implemented for studying three phytosiderophores (mugineic acid, epi‐mugineic acid and deoxymugineic acid) and their metal complexes. Free ligands and ferric complexes were analyzed using the first methodology, while six free metals (Co(II), Cu(II), Fe(III), Mn(II), Ni(II) and Zn(II)) together with the corresponding complexes were investigated by the latter technique. CE separation was realized at a voltage of +25 kV employing a BGE containing 20 mM ammonium bicarbonate at pH 7.2. Both techniques revealed limits of detection in the high nM to low μM range. Standard additions to hydroponic samples of H. distichon, cv. Bodega (spring barley) showed regression coefficients for the metal–ligand complexes ranging from 0.984 to 0.999. Additionally, results of a competitivity study allowed the determination of relative metal–phytosiderophore complex stability constants of deoxymugineic/mugineic acid.
Influence of the BGE composition on analyte response in CD‐mediated NACE‐MS
Authors: Servais Anne‐Catherine , Fillet Marianne , Mol Roelof , Rousseau Anne , Crommen Jacques , Somsen Govert W. , de Jong Gerhardus J.
Published: March 2010

The influence of the BGE composition, including the addition of a single‐isomer sulfated β‐CD derivative, on the ionization performance of the model compound carvedilol in NACE‐ESI‐MS was studied using an alternative infusion method. This approach employs voltage‐induced infusion of the BGE containing the analyte, and takes into account the effects of variations in EOF and effective analyte mobility on the ESI‐MS intensity. First, the optimal composition of the sheath liquid for CE‐MS in terms of signal abundance and stability was determined. The BGE ammonium formate, acetate, and camphorsulfonate were found to have similar effects on analyte ionization. Addition of single‐isomer sulfated β‐CD derivatives (available as sodium salt) to the BGE revealed that the anionic CD derivatives did not give rise to the same ionization suppression effect. This result can be attributed to differences in the dissociation state of these sodium salts. Finally, it is shown that information about chiral selectivity can also be obtained with the applied infusion method.
Mutagenic repair of DNA interstrand crosslinks
Authors: Shen Xi , Li Lei
Published: March 2010

Formation of DNA interstrand crosslinks (ICLs) in chromosomal DNA imposes acute obstruction of all essential DNA functions. For over 70 years bifunctional alkylators, also known as DNA crosslinkers, have been an important class of cancer chemotherapeutic regimens. The mechanisms of ICL repair remains largely elusive. Here, we review a eukaryotic mutagenic ICL repair pathway discovered by work from several laboratories. This repair pathway, alternatively termed recombination‐independent ICL repair, involves the incision activities of the nucleotide excision repair (NER) mechanism and lesion bypass polymerase(s). Repair of the ICL is initiated by dual incisions flanking the ICL on one strand of the double helix; the resulting gap is filled in by lesion bypass polymerases. The remaining lesion is subsequently removed by a second round of NER reaction. The mutagenic repair of ICL likely interacts with other cellular mechanisms such as the Fanconi anemia pathway and recombinational repair of ICLs. These aspects will also be discussed. Environ. Mol. Mutagen., 2010. © 2010 Wiley‐Liss, Inc.
Influence of soil type and organic matter content on the bioavailability, accumulation, and toxicity of α-cypermethrin in the springtail Folsomia candida
Authors: Styrishave Bjarne , Hartnik Thomas , Christensen Peter , Andersen Ole , Jensen John
Published: March 2010

The influence of organic matter (OM) content on α-cypermethrin porewater concentrations and springtail Folsomia candida accumulation was investigated in two soils with different levels of organic matter, a forest soil with a total organic carbon (TOC) content of 5.0% (OM = 11.5%) and an agricultural soil with a TOC content of 1.3% (OM = 4.0%). Also, the effects of α-cypermethrin concentrations in soil and pore water and the influence of soil aging on springtail reproduction were investigated. Springtail reproduction was severely affected by increasing α-cypermethrin in soil with 1.3% TOC; the median effective concentration value (EC50) was estimated to 23.4 mg/kg (dry wt). Reproduction was only marginally affected in the soil with 5.0% TOC, and no EC50 value could be estimated. However, when expressing α-cypermethrin accumulation as a function of soil α-cypermethrin concentrations, no difference was found between the two soil types, and no additional α-cypermethrin uptake was observed at soil concentrations above approximately 200 mg/kg (dry wt). By using solid-phase microextraction (SPME), it could be demonstrated that α-cypermethrin porewater concentrations were higher in the soil with low organic matter (LOM) content than in the soil with high organic matter (HOM) content. Furthermore, a clear relationship was found between α-cypermethrin concentrations in springtails and porewater. Soil aging was not found to exert any effect on α-cypermethrin toxicity toward springtails. The study indicates that the springtail's accumulation of α-cypermethrin and reproduction is governed by α-cypermethrin porewater concentrations rather than the total α-cypermethrin concentration in soil. Environ. Toxicol. Chem. 2010;29:1084–1090. © 2010 SETAC
Radioactive uranium measurement in vivo using a handheld interfaced analyzer
Authors: Ly Suw Young , Lee Jin-Hui , Jung Dong Ho
Published: March 2010

A trace uranium (U) detection method was developed with a handheld voltammetric analyzer that was the size of a mobile phone, with working sensors made of simple graphite pencil electrode (PE). The optimum stripping voltammetric conditions were sought, and the following results were obtained: 0.0 to 0.08 ng/L working ranges and a statistically relative standard deviation of 1.78% (RSD; n = 15) at a 10.0 µg/L U spike. The experiment accumulation time used was only 150 s. Under this condition, the diagnostic detection limit approached 0.007 ng/L. The method was applied to soil of a natural rock in a radioactive mineralogy site. Earthworms that resided at this site were assayed. The method was found to be applicable in biological diagnosis or in real-time in vivo survey. Environ. Toxicol. Chem. 2010;29:1025–1030. © 2010 SETAC
Effects of 17 β-estradiol exposure on Xenopus laevis gonadal histopathology
Authors: Wolf Jeffrey C. , Lutz Ilka , Kloas Werner , Springer Timothy A. , Holden Larry R. , Krueger Henry O. , Hosmer Alan J.
Published: March 2010

The natural estrogen 17 β-estradiol (E2) is a potential environmental contaminant commonly employed as a positive control substance in bioassays involving estrogenic effects. The aquatic anuran Xenopus laevis is a frequent subject of reproductive endocrine disruptor research; however, histopathological investigations have tended to be less than comprehensive. Consequently, a study was designed to characterize gross and microscopic changes in the gonads of X. laevis as a result of E2 exposure. Additional goals of this study, which consisted of three separate experiments, included the standardization of diagnostic terminology and criteria, the validation of statistical methodology, and the establishment of a half maximal effective concentration (EC50) for E2 as defined by an approximately 50% conversion of presumptive genotypic males to phenotypic females. In the first experiment, frogs were exposed to nominal concentrations of 0, 0.2, 1.5, or 6.0 µg/L E2. From these experimental results and those of a subsequent range finding trial, the EC50 for E2 was determined to be approximately 0.2 µg/L. This E2 concentration was utilized in the other two experiments, which were performed at different facilities to confirm the reproducibility of results. Experiments were conducted according to Good Laboratory Practice guidelines, and the histopathologic evaluations were peer reviewed by an independent pathologist. Among the three trials, the histopathological findings that were strongly associated with E2-exposure (p < 0.001 to 0.0001) included an increase in the proportion of phenotypic females, mixed sex, dilated testis tubules, dividing gonocytes in the testis, and dilated ovarian cavities in phenotypic ovaries. A comparison of the gross and microscopic evaluations suggested that some morphologic changes in the gonads may potentially be missed if studies rely entirely on macroscopic assessment. Environ. Toxicol. Chem. 2010;29:1091–1105. © 2010 SETAC
Assessment criteria for using the sea-urchin embryo test with sediment elutriates as a tool to classify the ecotoxicological status of marine water bodies
Authors: Durán Iria , Beiras Ricardo
Published: March 2010

A large, multiyear data set was generated by pooling the sediment elutriate (SET) results collected during previous studies conducted in the Galician Rias (northwest Iberian Peninsula) that met the acceptability criteria in the controls, to ensure optimum quality of data (n = 162). Two subsets of equal to reference and lower than reference sites were identified by comparing the Percentage Net Response (PNR) value from each sampling site with nontoxic, cruise-specific, reference sites by using the t test with the unequal variance assumption. Ecotoxicological Assessment Criteria (EAC0, EAC1, EAC2, and EAC3) were then derived from those two subsets to classify the SET results into five categories of ecotoxicological status: high, good, moderate, poor, and bad, in line with the European legislation. The 50th and 5th percentiles of the PNR distribution of the equal to reference sites subset were EAC0 = 0.879 and EAC1 = 0.694. An EAC2 = 0.508 was obtained from the 50th percentile of the lower than reference sites subset. Because the PNR values of the entire database showed a distribution that can be adjusted to two normal populations, the EAC3 = 0.240 PNR was calculated as the intersection between the first and second normal distributions identified. Power analysis proved that the limit between acceptable and unacceptable status (EAC1) corresponded to a detectable PNR difference to control with a confidence level >99% and a power of 95%. Environ. Toxicol. Chem. 2010;29:1192–1198. © 2010 SETAC
Effects of frozen soil and snow cover on cold‐season soil water dynamics in Tokachi, Japan
Authors: Iwata Yukiyoshi , Hirota Tomoyoshi , Hayashi Masaki , Suzuki Shinji , Hasegawa Shuichi
Published: March 2010

Despite the potential impact of winter soil water movements in cold regions, relatively few field studies have investigated cold‐season hydrological processes that occur before spring‐onset of snowmelt infiltration. The contribution of soil water fluxes in winter to the annual water balance was evaluated over 5 years of field observations at an agricultural field in Tokachi, Hokkaido, Japan. In two of the winters, soil frost reached a maximum depth of 0·2 m (‘frozen’ winters), whereas soil frost was mostly absent during the remaining three winters (‘unfrozen’ winters). Significant infiltration of winter snowmelt water, to a depth exceeding 1·0 m, occurred during both frozen and unfrozen winters. Such infiltration ranged between 126 and 255 mm, representing 28–51% of total annual soil water fluxes. During frozen winters, a substantial quantity of water (ca 40 mm) was drawn from deeper layers into the 0–0·2 m topsoil layer when this froze. Under such conditions, the progression and regression of the freezing front, regulated by the thickness of snow cover, controlled the quantity of soil water flux below the frozen layer. During unfrozen winters, 13–62 mm of water infiltrated to a depth of 0·2 m, before the spring snowmelt. These results indicate the importance of correctly evaluating winter soil water movement in cold regions. Copyright © 2010 John Wiley & Sons, Ltd.
BRAF mutation‐selective inhibition of thyroid cancer cells by the novel MEK inhibitor RDEA119 and genetic‐potentiated synergism with the mTOR inhibitor temsirolimus
Authors: Liu Dingxie , Xing Joanna , Trink Barry , Xing Mingzhao
Published: March 2010

We examined the therapeutic potential of a novel MEK inhibitor, RDEA119, and its synergism with the mTOR inhibitor, temsirolimus, in thyroid cancer cell lines. RDEA119 potently inhibited the proliferation of the 4 cell lines that harbored BRAF mutation but had no or modest effects on the other 4 cells that harbored wild‐type BRAF (IC50 of 0.034–0.217 μM vs. 1.413–34.120 μM). This inhibitory effect of RDEA119 in selected cell lines OCUT1 (BRAF V600E+, PIK3CA H1047R+) and SW1376 (BRAF V600E+) was enhanced by combination with the mTOR inhibitor, temsirolimus. The PTEN‐deficient cell FTC133 was highly sensitive to temsirolimus but insensitive to RDEA119, and simultaneous treatment with the latter enhanced the sensitivity of the cell to the former. The KAT18 (wild‐type) cell was not sensitive to either drug alone but became sensitive to the combination of the 2 drugs. The drug synergy was confirmed by combination index and isobologram analyses. RDEA119 and temsirolimus also showed synergistic effects on autophagic death of OCUT1 and KAT18 cells selectively tested. Dramatic synergistic effects of the 2 drugs were also seen on the growth of FTC133 xenograft tumors in nude mice. Overall, the effects of the 2 drugs on cell proliferation or autophagic death, either alone or in combination, were more pronounced in cells that harbored genetic alterations in the MAP kinase and PI3K/Akt pathways. Thus, these results demonstrated the important therapeutic potential of the novel MEK inhibitor RDEA119 and its synergism with temsirolimus in thyroid cancer.
Possible association between polymorphisms of human vascular endothelial growth factor A gene and susceptibility to glioma in a Chinese population
Authors: Li Rui , Zhao Yao , Fan Weiwei , Chen Hongyan , Chen Yuanyuan , Liu Yanhong , Chen Gong , Zhou Keke , Huang Fengping , Mao Ying , Zhou Liangfu , Lu Daru , Shugart Yin Yao
Published: March 2010

Vascular endothelial growth factor A (VEGFA), one of the most predominant mediators of pathologic angiogenesis, plays a critical role in glioma carcinogenesis and development via promoting tumor growth. We hypothesized that VEGFA polymorphisms may influence glioma risk. We recently genotyped 9 VEGFA single‐nucleotide polymorphisms (SNPs) in 766 glioma patients and 824 cancer‐free controls selected from a Chinese population. We evaluated the glioma risk conferred by individual SNPs, haplotypes as well as cumulative SNP effect. In the single‐locus analysis, we found that rs2010963 (G+405C, G‐634C) [odds ratio (OR) = 1.29; 95% confidence interval (CI) = 1.04–1.58; GC/CC vs. GG] and rs3025030 (OR = 2.21; 95% CI = 1.18–4.14; CC vs. GG/GC) were associated with increased risk for glioma, and rs3024994 (OR = 0.66; 95% CI = 0.47–0.94; CT/TT vs. CC) was associated with reduced glioma risk, albeit insignificant after Bonferroni correction for multiple comparisons. The haplotype‐based analysis revealed that AGG in block 1 and ATT, ACT in block 2 were associated with 20–40% reductions in glioma risk. The inverse association of haplotype AGG containing rs2010963G remained significant after correction for multiple testing (p = 0.002, pcorrected = 0.022). The aforementioned 3 SNPs revealed a significant cumulative risk effect; the increased risk for glioma was 1.38‐fold for each additional adverse genotype he or she carries (ptrend = 8.4 × 10−5). Our findings suggested that VEGFA variants may be involved in glioma risk. Larger studies with ethnically diverse populations are warranted to confirm the results reported in this investigation.