bluuebunny/crossref_metadata_2025 huggingface dataset:
Lung cancer risk in the electroplating industry in Lombardy, Italy, using the Italian occupational cancer monitoring (OCCAM) information system
Authors: Panizza Celestino , Bai Edoardo , Oddone Enrico , Scaburri Alessandra , Massari Stefania , Modonesi Carlo , Contiero Paolo , Marinaccio Alessandro , Crosignani Paolo
Published: September 2011

Background

Occupational Cancer Monitoring (OCCAM) is an Italian organization that monitors occupational cancers, by area and industrial sector, by retrieving cases and employment history from official databases. OCCAM previously estimated a relative risk (RR) of lung cancer of about 1.32 among “metal treatment” workers in Lombardy, northern Italy, potentially exposed to chrome and nickel. In the present study, lung cancer risk was estimated among electroplating workers only.

Methods

Lombardy electroplating companies were identified from descriptions in Social Security files. Lung cancer risk was evaluated from 2001 to 2008 incident cases identified from hospital discharge records.

Results

The RR for lung cancer among electroplating workers was 2.03 (90% CI 1.33–3.10, 18 cases) for men; 3.00 (90% CI 1.38–9.03, 4 cases) for women.

Conclusions

Electroplaters had higher risks than “metal treatment” workers. Although the risks were due to past exposure, case histories and recent acute effects indicate a present carcinogenic hazard in some Lombardy electroplating factories. Am. J. Ind. Med. 55:1–4, 2012. © 2011 Wiley Periodicals, Inc.
Association of GRIN1 and GRIN2A‐D With schizophrenia and genetic interaction with maternal herpes simplex virus‐2 infection affecting disease risk
Authors: Demontis Ditte , Nyegaard Mette , Buttenschøn Henriette N. , Hedemand Anne , Pedersen Carsten B. , Grove Jakob , Flint Tracey J. , Nordentoft Merete , Werge Thomas , Hougaard David M. , Sørensen Karina M. , Yolken Robert H. , Mors Ole , Børglum Anders D. , Mortensen Preben Bo
Published: September 2011

N‐methyl‐D‐aspartate (NMDA) receptors are very important for proper brain development and several lines of evidence support that hypofunction of the NMDA receptors are involved in the pathophysiology of schizophrenia. Gene variation and gene–environmental interactions involving the genes encoding the NMDA receptors are therefore likely to influence the risk of schizophrenia. The aim of this study was to determine (1) whether SNP variation in the genes (GRIN1, GRIN2A, GRIN2B, GRIN2C, and GRIN2D) encoding the NMDA receptor were associated with schizophrenia; (2) whether GRIN gene variation in the offspring interacted with maternal herpes simplex virus‐2 (HSV‐2) seropositivity during pregnancy influencing the risk of schizophrenia later in life. Individuals from three independently collected Danish case control samples were genotyped for 81 tagSNPs (in total 984 individuals diagnosed with schizophrenia and 1,500 control persons) and antibodies against maternal HSV‐2 infection were measured in one of the samples (365 cases and 365 controls). Nine SNPs out of 30 in GRIN2B were significantly associated with schizophrenia. One SNP remained significant after Bonferroni correction (rs1806194, Pnominal = 0.0008). Significant interaction between maternal HSV‐2 seropositivity and GRIN2B genetic variation in the offspring were observed for seven SNPs and two remained significant after Bonferroni correction (rs1805539, Pnominal = 0.0001 and rs1806205, Pnominal = 0.0008). The significant associations and interactions were located at the 3′ region of GRIN2B suggesting that genetic variation in this part of the gene may be involved in the pathophysiology of schizophrenia. © 2011 Wiley Periodicals, Inc.
Development of high predictive soft sensor method and the application to industrial polymer processes
Authors: Kaneko Hiromasa , Funatsu Kimito
Published: September 2011

In industrial plants, soft sensors are widely used to estimate process variables that are difficult to measure online. One of the problems of soft sensors is that their predictive accuracy gradually decreases with changes in the state of the plants. Although regression models are reconstructed with new data to solve this problem, some problems remain in practice. Hence, it is attempted to construct soft sensor models based upon the time difference of an objective variable and that of explanatory variables for reducing the effects of deterioration with age such as the drift and gradual changes in the state of plants. However, the time difference model cannot account for the nonlinearity in process variables. Therefore, to consider the nonlinearity and the effects of changes with age, we have proposed to construct time difference models after modeling nonlinear relationship between and among process variables. Variables obtained by physical models or those calculated by statistical nonlinear regression methods are used to consider the nonlinearity, and then, a time difference model is constructed including these variables. First, we verified the superiority of the proposed methods over traditional ones. Then, we applied these methods to the actual industrial data obtained during an industrial polymer process. The proposed models achieved high predictive accuracy for melt flow rate and density, and the bias of the prediction errors could be eased in both cases by using the proposed methods. We confirmed the usefulness of the proposed methods without reconstruction of soft sensor models. © 2011 Curtin University of Technology and John Wiley & Sons, Ltd.
Optimal investment and reinsurance policies in insurance markets under the effect of inside information
Authors: Baltas I.D. , Frangos N.E. , Yannacopoulos A.N.
Published: September 2011

In this paper, we study the problem of optimal investment and proportional reinsurance coverage in the presence of inside information. To be more precise, we consider two firms: an insurer and a reinsurer who are both allowed to invest their surplus in a Black–Scholes‐type financial market. The insurer faces a claims process that is modeled by a Brownian motion with drift and has the possibility to reduce the risk involved with this process by purchasing proportional reinsurance coverage. Moreover, the insurer has some extra information at her disposal concerning the future realizations of her claims process, available from the beginning of the trading interval and hidden from the reinsurer, thus introducing in this way inside information aspects to our model. The optimal investment and proportional reinsurance decision for both firms is determined by the solution of suitable expected utility maximization problems, taking into account explicitly their different information sets. The solution of these problems also determines the reinsurance premia via a partial equilibrium approach. Copyright © 2011 John Wiley & Sons, Ltd.
Unraveling the complex relationship between folate and cancer risk
Authors: Mason Joel B.
Published: September 2011

Epidemiologic evidence generally indicates that an abundant intake of foodstuffs rich in folate conveys protection against the development of colorectal cancer and perhaps some other common cancers as well. Preclinical models substantiate that the relationship is a genuinely causal one. However, the issue is rather complex because some observations in animal and human studies demonstrate that an overly abundant intake of folate among those who harbor existing foci of neoplasia might instead produce a paradoxical promotion of tumorigenesis. The pharmaceutical form of the vitamin, folic acid, might affect the process in a manner that is distinct from natural forms of the vitamin, although this remains a speculative concept. We should not allow the complex nature of this relationship to compel us to ignore it, as understanding its true nature will greatly facilitate our ability to construct intelligent, effective, and safe strategies for the prevention of birth defects and cancer.
Folic acid and primary prevention of birth defects
Authors: Taruscio Domenica , Carbone Pietro , Granata Orietta , Baldi Francesca , Mantovani Alberto
Published: September 2011

Birth defects (BDs) are an important public health problem, due to their overall incidence, occurring in 2–3% of live births in European Union. Neural tube defects (NTDs) are among major NTDs, due to their severity and relatively high incidence; in the meanwhile NTDs are also the most effectively preventable BDs to date. In particular, an adequate folic acid (FA) intake reduces both the occurrence and the recurrence of NTDs; FA is the synthetic form of folates, naturally occurring vitamins in a number of foods, especially vegetables. The daily intake of 0.4 mg of FA should be recommended to all women of childbearing age who plan to become pregnant. The Italian Network for Primary Prevention of BDs through FA Promotion has achieved a significant improvement in FA awareness and use in the periconceptional period. Nevertheless, primary prevention of BDs needs to make further progress; the Italian National Centre for Rare Diseases participates in european sureveillance of congenital anomalies (EUROCAT) Joint Action as coordinator of activities on the effectiveness of BDs prevention. Mandatory food fortification with FA has not been introduced in any European country. The health benefits of FA in reducing the risk of NTDs are undisputed; however mechanistic and animal studies suggest a relationship between high FA intakes and increased cancer promotion, while human studies are still inconsistent and inconclusive. A Working Group organized by the European Food Safety Authority pointed out significant uncertainties about fortification safety and the need for more studies; currently, FA intake from fortified foods and supplements should not exceed 1 mg/day in adults. In conclusion, based on up‐to‐date scientific evidence, the Italian Network strategy pivots on periconceptional supplementation integrated with promotion of healthy eating habits, support to health education, enhancing the role of women in managing life choices about their health and pregnancy and increasing the scientific knowledge about BDs primary prevention.
Phosphatidylinositol transfer proteins: Negotiating the regulatory interface between lipid metabolism and lipid signaling in diverse cellular processes
Authors: Ghosh Ratna , Bankaitis Vytas A.
Published: September 2011

Phosphoinositides represent only a small percentage of the total cellular lipid pool. Yet, these molecules play crucial roles in diverse intracellular processes such as signal transduction at membrane‐cytosol interface, regulation of membrane trafficking, cytoskeleton organization, nuclear events, and the permeability and transport functions of the membrane. A central principle in such lipid‐mediated signaling is the appropriate coordination of these events. Such an intricate coordination demands fine spatial and temporal control of lipid metabolism and organization, and consistent mechanisms for specifically coupling these parameters to dedicated physiological processes. In that regard, recent studies have identified Sec14‐like phosphatidylcholine transfer protein (PITPs) as “coincidence detectors,” which spatially and temporally link the diverse aspects of the cellular lipid metabolome with phosphoinositide signaling. The integral role of PITPs in eukaryotic signal transduction design is amply demonstrated by the mammalian diseases associated with the derangements in the function of these proteins, to stress response and developmental regulation in plants, to fungal dimorphism and pathogenicity, to membrane trafficking in yeast, and higher eukaryotes. This review updates the recent advances made in the understanding of how these proteins, specifically PITPs of the Sec14‐protein superfamily, operate at the molecular level and further describes how this knowledge has advanced our perception on the diverse biological functions of PITPs.
Influence of preoperative chemotherapy for advanced thoracic oesophageal squamous cell carcinoma on perioperative complications
Authors: Hirao M , Ando N , Tsujinaka T , Udagawa H , Yano M , Yamana H , Nagai K , Mizusawa J , Nakamura K
Published: September 2011

Background

The Japan Clinical Oncology Group (JCOG) 9907 trial has changed the standard of care for advanced thoracic oesophageal cancer in Japan from postoperative chemotherapy to preoperative chemotherapy. The impact of preoperative chemotherapy on the risk of developing postoperative complications remains controversial. This article reports the safety analysis of JCOG9907, focusing on risk factors for postoperative complications.

Methods

Patients with potentially resectable advanced thoracic oesophageal squamous cell carcinoma were randomized to either postoperative or preoperative chemotherapy followed by transthoracic oesophagectomy with D2–3 lymphadenectomy. Chemotherapy consisted of two cycles of cisplatin and 5-fluorouracil. Clinical baseline data, intraoperative complications, postoperative complications and in-hospital mortality, collected on the case report forms in a predetermined format, were analysed. Univariable and multivariable analyses were used to explore the risk of postoperative complications in relation to treatment group, age, sex, tumour depth, nodal metastasis, stage and location.

Results

Of 330 patients randomized, 166 were assigned to receive postoperative chemotherapy and 164 preoperative chemotherapy; 162 and 154 patients respectively underwent surgery. The incidence of intraoperative complications, postoperative complications and in-hospital mortality was similarly low in both groups. Multivariable analysis showed that age, sex and tumour location were independently associated with an increase in postoperative complications, but preoperative chemotherapy was not.

Conclusion

Preoperative chemotherapy does not increase the risk of complications or hospital mortality after surgery for advanced thoracic oesophageal cancer. Registration number: NCT00190554 (http://www.clinicaltrials.gov).
Stability of Caffeic Acid Phenethyl Amide (CAPA) in Rat Plasma
Authors: Yang John , Kerwin Sean M. , Bowman Phillip D. , Stavchansky Salomon
Published: September 2011

A validated C18 reverse‐phase HPLC method with UV detection at 320 nm was developed and used for the stability evaluation of caffeic acid phenethyl amide (CAPA) and caffeic acid phenethyl ester (CAPE) in rat plasma. CAPA is the amide derivative of CAPE, a naturally occurring polyphenolic compound that has been found to be active in a variety of biological pathways. CAPA has been shown to protect endothelial cells against hydrogen peroxide‐induced oxidative stress to a similar degree to CAPE. CAPE has been reported to be rapidly hydrolyzed in rat plasma via esterase enzymes. CAPA is expected to display a longer half‐life than CAPE by avoiding hydrolysis via plasma esterases. The stability of CAPA and CAPE in rat plasma was investigated at three temperatures. The half‐lives for CAPA were found to be 41.5, 10 and 0.82 h at 25, 37 and 60 °C, respectively. The half‐lives for CAPE were found to be 1.95, 0.35 and 0.13 h at 4, 25 and 37 °C, respectively. The energy of activation was found to be 22.1 kcal/mol for CAPA and 14.1 kcal/mol for CAPE. A more stable compound could potentially extend the beneficial effects of CAPE. Copyright © 2011 John Wiley & Sons, Ltd.
UPLC‐MS/MS method for bioequivalence study of oral drugs of meldonium
Authors: Pidpruzhnykov Yuriy V. , Sabko Valerii E. , Iurchenko Volodymyr V. , Zupanets Igor A.
Published: September 2011

A rapid and simple method based on ultra‐performance liquid chromatography on a hydrophilic interaction chromatography column with tandem mass‐selective detection (UPLC‐MS/MS) to determine meldonium in human plasma was developed. The calibration curve acquired in the range of 10–6000 ng/mL had quadratic form. Method validation proved the conformity of its properties (selectivity, matrix effect, lower limit of quantification, accuracy, precision and recovery) with the established requirements. The stability tests necessary for bioanalytical studies were performed. For the first time, the method was successfully applied to the bioequivalence studies of generic and brand name oral drugs of meldonium in capsules. Based on data from 24 volunteers, it was determined that the mean pharmacokinetic curves of the drugs are characterized by a double peak profile. Copyright © 2011 John Wiley & Sons, Ltd.
Evidence for Fully Conjugated Double‐Stranded Cycles
Authors: Standera Malte , Häfliger Rolf , Gershoni‐Poranne Renana , Stanger Amnon , Jeschke Gunnar , van Beek Jacco D. , Bertschi Louis , Schlüter A. Dieter
Published: September 2011

A chain of circumstantial evidence for the existence of the first fully conjugated, double‐stranded cycles is presented. The products have the structure of the belt‐region of fullerene C84 (D2) and carry either four hexyl chains or four phenyl groups. The unsubstituted parent cycle is also presented. The chain of evidence is mainly based on mass spectrometric analysis and trapping reactions, the latter being supported by quantum mechanical calculations. It is also of importance that the phenyl‐substituted and unsubstituted products cannot undergo a [1,5] hydrogen shift, the only reasonable side‐reaction that recently could not be excluded for the alkyl‐substituted analogue. It is concluded that the fully aromatic targets truly exist in the gas phase. Whether they can be generated in solution under the applied conditions cannot yet be firmly decided; theoretical evidence speaks against.
Neighboring‐Group Participation by C‐2 Ether Functions in Glycosylations Directed by Nitrile Solvents
Authors: Chao Chin‐Sheng , Lin Ching‐Yu , Mulani Shaheen , Hung Wei‐Cheng , Mong Kwok‐kong Tony
Published: September 2011

Ether‐protecting functions at C‐2 hydroxy groups have been found to play participating roles in glycosylations when the reactions are conducted in nitrile solvent mixtures. The participation mechanism is based on intramolecular interaction between the lone electron pair of the oxygen atom of the C‐2 ether function and the nitrile molecule when they are positioned in a cis configuration. A 1,2‐cis glycosyl oxazolinium intermediate is formed. This participation, in conjunction with the anomeric effect of the glycosyl donor, confers high 1,2‐trans selectivities on glycosylations. Further application of this concept has led to efficient preparations of α‐(1→5)‐arabinan oligomers.
Acetylene‐Expanded Dendralene Segments with Exotopic Phosphaalkene Units
Authors: Geng Xue‐Li , Ott Sascha
Published: September 2011

Bis‐TMS protected C,C‐diacetylenic phosphaalkene (A2PA) 1 (Mes*PC(C≡CTMS)2; Mes*=2,4,6‐tBu3Ph) has been used as a building block for the construction of butadiyne‐expanded dendralene fragments in which phosphaalkenes feature as exotopic double bonds. Treatment of 1 with CuCl gives rise to a CuI acetylide that is selectively formed at the acetylene trans to the Mes* group. The cis‐TMS‐acetylene engages in similar chemistry, albeit at higher temperatures and longer reaction times. The differentiation between the two acetylene termini of 1 allows for the controlled synthesis of the title compounds by a variety of different Cu‐ and Pd‐catalyzed oxidative acetylene homo‐ and heterocoupling protocols. Crystallographic characterization of A2PA 1 and dimeric Mes*PC(C≡CR1)C4(R2C≡C)CPMes* (3 b, R1=R2=Ph; 6, R1=R2=TMS), and 10 (R1=R2=C≡CPh) verifies that the stereochemistry across the PC bond is conserved during the coupling reactions, whereas spectroscopic evidence reveals cis/trans isomerization in an iodo‐substituted A2PA intermediate 4 (Mes*PC(C≡CTMS)(C≡CI). UV/Vis spectroscopic and electrochemical studies reveal that efficient π conjugation operates through the entire acetylenic phosphaalkene framework, even in the cross‐conjugated dimeric structures. The P centers contribute considerably to the frontier molecular orbitals of the compounds, thereby leading to smaller HOMO–LUMO gaps than in all‐carbon‐based congeners. Phenyl‐ and/or ethynylphenyl substituents at the A2PA framework influence the HOMO and LUMO to a varying degree depending on their relationship to the Mes* group, thus enabling a fine‐tuning of the frontier molecular orbitals of the compounds.
Discovery of a Pharmacologically Active Antagonist of the Two‐Pore‐Domain Potassium Channel K2P9.1 (TASK‐3)
Authors: Coburn Craig A. , Luo Yunfu , Cui Mingxiang , Wang Jiabing , Soll Richard , Dong Jingchao , Hu Bin , Lyon Michael A. , Santarelli Vincent P. , Kraus Richard L. , Gregan Yun , Wang Yi , Fox Steven V. , Binns Jacquelyn , Doran Scott M. , Reiss Duane R. , Tannenbaum Pamela L. , Gotter Anthony L. , Meinke Peter T. , Renger John J.
Published: September 2011

TWIK‐related acid‐sensitive K+ (K2P9.1, TASK‐3) ion channels have the capacity to regulate the activity of neuronal pathways by influencing the resting membrane potential of neurons on which they are expressed. The central nervous system (CNS) expression of these channels suggests potential roles in neurologic disorders, and it is believed that the development of TASK‐3 antagonists could lead to the therapeutic treatment of a number of neurological conditions. While a therapeutic potential for TASK‐3 channel modulation exists, there are only a few documented examples of potent and selective small‐molecule channel blockers. Herein, we describe the discovery and lead optimization efforts for a novel series of TASK‐3 channel antagonists based on a 5,6,7,8‐tetrahydropyrido[4,3‐d]pyrimidine high‐throughput screening lead from which a subseries of potent and selective inhibitors were identified. One compound was profiled in detail with respect to its physical properties and demonstrated pharmacological target engagement as indicated by its ability to modulate sleep architecture in rodent electroencephalogram (EEG) telemetry models.
Salvage stereotactic radiosurgery for breast cancer brain metastases
Authors: Kelly Paul J. , Lin Nancy U. , Claus Elizabeth B. , Quant Eudocia C. , Weiss Stephanie E. , Alexander Brian M.
Published: September 2011

BACKGROUND:

Salvage stereotactic radiosurgery (SRS) is often considered in breast cancer patients previously treated for brain metastases. The goal of this study was to analyze clinical outcomes and prognostic factors for survival in the salvage setting.

METHODS:

The authors retrospectively examined 79 consecutive breast cancer patients who received salvage SRS (interval of >3 months after initial therapy), 76 of whom (96%) received prior whole‐brain radiation therapy. Overall survival (OS) and central nervous system (CNS) progression‐free survival rates were calculated from the date of SRS using the Kaplan‐Meier method. Prognostic factors were evaluated using the Cox proportional hazards model.

RESULTS:

Median age was 50.5 years. Fifty‐eight percent of this population was estrogen receptor positive, 62% was HER2 positive, and 10% was triple negative. At the time of SRS, 95% had extracranial metastases, with 81% of extracranial metastases at other visceral sites (lung/pleura/liver). Forty‐eight percent had stable extracranial disease. Median interval from initial brain metastases therapy to SRS was 8.4 months. Median CNS progression‐free survival after SRS was 5.7 months (interquartile range [IQR], 3.6‐11 months), and median OS was 9.8 months (IQR, 3.8‐18 months). Eighty‐two percent of evaluable patients received further systemic therapy after SRS. HER2 status (adjusted hazard ratio [HR], 2.4; P = .008) and extracranial disease status (adjusted HR, 2.7; P = .004) were significant prognostic factors for survival on multivariate analysis.

CONCLUSIONS:

In patients with good Karnofsky performance status, salvage SRS for breast cancer brain metastases is a reasonable treatment option, given an associated median survival in excess of 9 months. Furthermore, patients with HER2‐positive tumors at diagnosis or stable extracranial disease at the time of SRS have an improved clinical course, with median survival of >1 year. Cancer 2012. © 2011 American Cancer Society.
Identification of novel immunogenic human leukocyte antigen‐A*2402‐binding epitopes of human papillomavirus type 16 E7 for immunotherapy against human cervical cancer
Authors: Jang Sunphil , Kim Young Tae , Chung Hye Won , Lee Kyoung‐Ryul , Lim Jong‐Baeck , Lee Kyungwon
Published: September 2011

BACKGROUND:

A study was undertaken to identify new immunogenic human leukocyte antigen (HLA)‐A*2402‐restricted epitopes from human papillomavirus (HPV) type 16 E7 protein for immunotherapy against cervical cancer.

METHODS:

Synthetic overlapping peptides were screened by measuring the frequency of CD8+ cytotoxic T lymphocytes (CTLs) producing intracellular interferon‐γ (IFN‐γ) using flow cytometry and were validated in SiHa cells with a Cr release cytotoxicity assay. In vivo antitumor effects of peptide‐sensitized peripheral blood mononuclear cells (PBMCs) and isolated CD8+ CTLs were evaluated using BALB/c nude mice with SiHa cell xenotransplants.

RESULTS:

Among 14 overlapping 15‐amino acid peptides, E761‐75(CDSTLRLCVQSTHVD) and E767‐81(LCVQSTHVDIRTLED) induced significantly higher IFN‐γ production (P < .05) and showed higher in vitro cytotoxicity against SiHa cells than did cells sensitized with the negative control. To determine the exact HLA‐A*2402‐restricted epitopes, a total of 25 overlapping 9‐ or 10‐amino acid peptides spanning E761‐75 and E767‐81 were synthesized. E761‐69(CDSTLRLCV) and E767‐76(LCVQSTHVDI) induced significantly greater IFN‐γ production as well as increased in vitro cytotoxicity against SiHa cells compared with those of other peptides and the negative control (P < .01), and the antitumor effects of these peptide‐sensitized PBMCs were induced by CD8+ CTLs. E761‐69‐sensitized and E767‐76‐sensitized PBMCs and isolated CD8+ CTLs showed a much greater suppression of tumor growth in vivo compared with that of control groups treated with PBS (P < .01). The authors also confirmed the synergistic antitumor effect of cisplatin followed by E767‐76‐sensitized PBMCs in vivo.

CONCLUSIONS:

E761‐69 and E767‐76 were identified as novel HPV type 16 E7 epitopes for HLA‐A*2402, which could be used for immunotherapy against cervical cancer. Cancer 2012. © 2011 American Cancer Society.
Clinicopathologic characteristics of carcinomas that develop after a biopsy containing columnar cell lesions
Authors: Boulos Fouad I. , Dupont William D. , Schuyler Peggy A. , Sanders Melinda E. , Page David L. , Fedda Faysal A. , Simpson Jean F.
Published: September 2011

BACKGROUND:

Columnar cell lesions are frequently associated with atypical ductal hyperplasia, lobular neoplasia, and tubular carcinoma, and have been suggested as a precursor lesion for low‐grade carcinomas. However, in long‐term follow‐up studies, columnar cell lesions are associated with only a slight increase in later breast cancer development. If columnar cell lesions are precursor lesions, one would expect subsequent cancers to develop at the same site as the biopsy and to be preferentially of low grade. The goal of this article is to review the clinical and pathologic features of carcinomas that develop after a diagnosis of columnar cell lesion to try to establish whether these lesions are precursors to low‐grade invasive carcinoma.

METHODS:

The authors reviewed biopsies containing columnar cell lesions, using the criteria of Schnitt and Vincent‐Salomon, from 77 women in the Nashville Breast Cohort who developed subsequent breast carcinoma. Clinicopathologic features including laterality, type, and grade of the subsequent cancer were recorded.

RESULTS:

Breast cancer developed a median of 11 years after initial biopsy. The median age at diagnosis was 60 years. The majority of invasive carcinomas were of no special type and of intermediate grade. Moreover, the carcinomas were as likely to occur in the contralateral breast as in the breast that was originally diagnosed with columnar cell lesion, regardless of columnar cell lesion subtype (P = .48).

CONCLUSIONS:

Carcinoma subsequent to columnar cell lesions may occur in either breast and tends to show a similar grade and type distribution as sporadic breast cancer. These findings argue against columnar cell lesions being a true precursor for low‐grade invasive carcinoma. Cancer 2012. © 2011 American Cancer Society.
Disparities in receipt of adjuvant radiation therapy after breast‐conserving surgery among the cancer‐reporting regions of California
Authors: Parise Carol A. , Bauer Katrina R. , Caggiano Vincent
Published: September 2011

BACKGROUND:

Incidence and mortality of breast cancer vary according to demographic factors such as age, race/ethnicity, socioeconomic status (SES), and geographic region. This study assesses the variation of these factors in the use of adjuvant radiation therapy (RT) after breast‐conserving surgery (BCS) among 8 regions of California.

METHODS:

The authors identified 85,574 cases of first primary female invasive breast cancer with complete data diagnosed between January 1, 2000 and December 31, 2007. Logistic regression was used to determine the association between race/ethnicity, age, SES, and receipt of RT after BCS within each of the regions of California. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed.

RESULTS:

Age was a significant predictor of receipt of RT after BCS in all regions. In Los Angeles (LA), lower SES was associated with decreasing odds of RT. Racial disparities were evident only in LA, where black (OR, 0.85; 95% CI, 0.74‐0.97) and Hispanic (OR, 0.86; 95% CI, 0.78‐0.96) women were about 15% less likely to receive RT than white women.

CONCLUSIONS:

Racial disparities in the receipt of RT after BCS exist only in LA, where African American and Hispanic women are less likely to receive this form of adjuvant treatment. Lower SES was also associated with a reduced likelihood of receipt of RT in LA. Women age 70 years and older are less likely to receive RT after BCS in all regions of California. Cancer 2012. © 2011 American Cancer Society.
Semi‐implicit numerical modeling of axially symmetric flows in compliant arterial systems
Authors: Casulli Vincenzo , Dumbser Michael , Toro Eleuterio F.
Published: September 2011

Blood flow in arterial systems is described by the three‐dimensional Navier–Stokes equations within a time‐dependent spatial domain that accounts for the viscoelasticity of the arterial walls. These equations are simplified by assuming cylindrical geometry, axially symmetric flow, and hydrostatic equilibrium in the radial direction. In this paper, an efficient semi‐implicit method is formulated in such a fashion that numerical stability is obtained at a minimal computational cost. The resulting computer model is relatively simple, robust, accurate, and extremely efficient. These features are illustrated on nontrivial test cases where the exact analytical solution is known and by an example of a realistic flow through a complex arterial system. Copyright © 2011 John Wiley & Sons, Ltd.
Intrinsic Viscosities of Polyelectrolytes: Determination and Modeling of the Effects of Extra Salt
Authors: Eich Andreas , Wolf Bernhard A.
Published: September 2011

Based on early measurements of J. J. Hermans and co‐workers (D. T. F. Pals, J. J. Hermans, Recl. Trav. Chim. Pays‐Bas 1952, 71, 513–520; D. T. F. Pals, J. J. Hermans, J. Polym. Sci. 1950, 5, 733–734; D. T. F. Pals, J. J. Hermans, J. Polym. Sci. 1948, 3, 897–898), the present contribution demonstrates how primary data should be evaluated in order to obtain reliable intrinsic viscosities. This procedure yields detailed information on the changes of the intrinsic viscosities and of the corresponding viscometric interaction parameters caused by an increasing salinity of water. Both quantities decline from a maximum value in the pure solvent to a minimum value, which is approached in the limit of sufficiently high salt concentrations, and can be modeled quantitatively by means of a Boltzmann sigmoid. Particular attention is paid to the significance of results obtained by means of the method of isoionic dilution, proposed by J. J. Hermans and co‐workers.
Performance analysis of dynamic channel allocation based on the greedy approach for orthogonal frequency‐division multiple access downlink systems
Authors: Oh Eunsung , Woo Choongchae
Published: September 2011

This paper presents a performance analysis of dynamic channel allocation (DCA) based on the greedy approach (GA) for orthogonal frequency‐division multiple access downlink systems over Rayleigh fading channels. The GA‐based DCA achieves its performance improvement using multiuser diversity. We analyze the statistics of the number of allocable users that represents the multiuser diversity order at each allocation process. The derived statistics are then used to analyze the performance of GA‐based DCA. The analysis results show that the number of subcarriers allocated to each user must be equal to achieve the maximum system performance based on outage probability and data throughput. Copyright © 2011 John Wiley & Sons, Ltd.
In vitro metabolism of tiletamine, zolazepam and nonbenzodiazepine sedatives: Identification of target metabolites for equine doping control
Authors: Fenwick Susanna J. , Scarth James P.
Published: September 2011

Within horseracing, the detection of prohibited substance doping often requires urine analysis; hence, it is necessary to understand the metabolism of the drugs in question. Here, the previously unknown equine metabolism of eight sedatives is reported in order to provide information on target metabolites for use in doping control. Phase I metabolite information was provided by incubation with equine liver S9 fraction. In vitro techniques were chosen in order to reduce the ethical and financial issues surrounding the study of so many compounds, none of which are licensed for use in horses in the UK.

Several metabolites of each drug were identified using liquid chromatography‐high resolution mass spectrometric (LC‐HRMS) analysis on an LTQ‐Orbitrap. Further structural information was obtained by tandem mass spectrometry (MS/MS) analysis; allowing postulation of the structure of some of the most abundant in vitro metabolites. The most abundant metabolites of alpidem, etifoxine, indiplon, tiletamine, zaleplon, zolazepam, zolpidem, and zopiclone related to hydroxylation/N‐oxidation, deethylation, demethylation, deethylation, hydroxylation/N‐oxidation, demethylation, hydroxylation/N‐oxidation and hydroxylation/N‐oxidation, respectively. In many cases, further work would be required to fully elucidate the precise positioning of the functional groups involved.

The results of this study provide metabolite information that can be used to enhance equine anti‐doping screening methods. However, the in vitro metabolites identified are at present only a prediction of those that may occur in vivo. In the future, any positive findings of these drugs and/or their metabolites in horse urine samples could help validate these findings and/or refine the choice of target metabolites. Copyright © 2011 John Wiley & Sons, Ltd.
Differential role for CD277 as a co‐regulator of the immune signal in T and NK cells
Authors: Messal Nassima , Mamessier Emilie , Sylvain Aude , Celis‐Gutierrez Javier , Thibult Marie‐Laure , Chetaille Bruno , Firaguay Guylène , Pastor Sonia , Guillaume Yves , Wang Qian , Hirsch Ivan , Nunès Jacques A. , Olive Daniel
Published: September 2011

The human butyrophilin (BTN) 3 or CD277 molecules belong to the B7 family members and are expressed in various immune cells such as T and NK cells. Here, we show that CD277 triggering considerably enhances TCR‐induced cytokine production and cell proliferation, even when another co‐stimulatory molecule, CD28, is engaged. These CD277‐induced additive functional effects are in accordance with the detection of early T‐cell activation events such as TCR‐induced cell signaling being increased upon CD277 engagement. However, we found that CD277 triggering is not involved in CD16‐ or NKp46‐induced NK cell activation. BTN3/CD277 comprises three structurally related members, BTN3A1, BTN3A2 and BTN3A3. CD277 antibodies recognize all isoforms and we describe a differential expression of BTN3 isoforms between T and NK cells that could explain differential CD277 functions between T and NK cells. Our results show that, while T cells express all BTN3/CD277 transcripts, NK cells express mostly BTN3A2, which lacks the B30.2 intracellular domain. Furthermore, NKp30‐induced cytokine production is decreased by the specific engagement of BTN3A2, but not by BTN3A1 triggering. Thus, we provide new insights into the CD277 co‐stimulatory pathway that may differentially participate in the regulation of various cell‐mediated immune responses.
Putting the Anion into the Cage – Fluoride Inclusion in the Smallest Trisimidazolium Macrotricycle
Authors: Amendola Valeria , Boiocchi Massimo , Fabbrizzi Luigi , Fusco Nadia
Published: September 2011

The trisbenzimidazolium cyclophane receptor 23+ incorporates the F– anion in MeCN solution, which was inferred by spectrophotometric and 1H NMR titration experiments, with an association constant log K > 7. On the basis of geometric considerations, it is assumed that F– lies in the middle of the triangle 3C, whose vertices are the carbon atoms of the three imidazolium C–H fragments, and profits from three C–H···F H‐bonds. No other anion is encapsulated by 23+ for reasons of size. The parent trisbenzimidazolium tripodal receptor 43+ does not exert size exclusion selectivity and forms 1:1 complexes not only with F–, but also with other mono‐ (Br–) and polyatomic anions (NO3–). X‐ray diffraction studies on [4···Br]2+ and [4···NO3]2+ complexes indicated that, due to the steric restraints of the tripodal receptor, the anion is not positioned in the middle of the 3C triangle but stays below it, profiting from H‐bonds. Cage effects are observed in the higher thermodynamic stability of the [2···F]2+ complex with respect to [4···F]2+ and in its resistance to excess F–. In fact, on addition of excess fluoride, the tripodal [4···F]2+ complex decomposes with deprotonation of a C–H fragment and formation of the very stable HF2– complex.
A Combined Vinylogous Mannich/Diels–Alder Approach for the Stereoselective Synthesis of Highly Functionalized Hexahydroindoles
Authors: Ruff Bettina M. , Zhong Sabilla , Nieger Martin , Sickert Marcel , Schneider Christoph , Bräse Stefan
Published: September 2011

A versatile strategy for the formation of hydroindole derivatives is reported. The molecules synthesized are highly functionalized and bear up to six stereogenic centers. We were able to develop a stereoselective route starting from nonchiral commercially available materials. Key steps in the formation of the bicyclic products are an organocatalytic vinylogous Mukaiyama–Mannich and a Diels–Alder reaction. The former uses a 1,1′‐bi‐2‐napthol (BINOL)‐based chiral Brønsted acid catalyst to build the first stereogenic center. The [4+2] cycloaddition proceeds highly diastereoselectively and furnishes one main stereoisomer, which represents the scaffold of the mycotoxins Rostratin B–D. Other transformations include iodolactonization, a Curtius rearrangement, additions, oxidations, and reductions.
Modeling and kinetic parameter estimation of alcohol dehydrogenase‐catalyzed hexanol oxidation in a microreactor
Authors: Tušek Ana , Šalić Anita , Kurtanjek Želimir , Zelić Bruno
Published: September 2011

A mathematical model for hexanol oxidation catalyzed by NAD+‐dependent alcohol dehydrogenase from baker's yeast in a microreactor was developed and compared with the model when the reaction takes place in a macroscopic reactor. The enzyme kinetics was modeled as a pseudo‐homogeneous process with the double substrate Michaelis–Menten rate expression. In comparison with the kinetic parameters estimated in the cuvette, a 30‐fold higher maximum reaction rate and a relatively small change in the saturation constants are observed for the kinetic parameters estimated in the continuously operated tubular microreactor (Vm1=197.275 U/mg, Kmhexanol=9.420 mmol/L, and Km1NAD+=0.187 mmol/L). Kinetic measurements performed in the microreactor, estimated from the initial reaction rate experiments at the residence time of 36 s, showed no product inhibition, which could be explained by hydrodynamic effects and the continuous removal of inhibiting products. The Fourier amplitude sensitivity test method was applied for global kinetic parameter analysis, which shows a significant increase in the sensitivity of Km1NAD+ in the microreactor. Independent experiments performed in the microreactor were used to validate and to verify the developed mathematical model.
Circular conditional autoregressive modeling of vector fields
Authors: Modlin Danny , Fuentes Montserrat , Reich Brian
Published: September 2011

As hurricanes approach landfall, there are several hazards for which coastal populations must be prepared. Damaging winds, torrential rains, and tornadoes play havoc with both the coast and inland areas; but, the biggest seaside menace to life and property is the storm surge. Wind fields are used as the primary forcing for the numerical forecasts of the coastal ocean response to hurricane force winds, such as the height of the storm surge and the degree of coastal flooding. Unfortunately, developments in deterministic modeling of these forcings have been hindered by computational expenses. In this paper, we present a multivariate spatial model for vector fields, that we apply to hurricane winds. We parameterize the wind vector at each site in polar coordinates and specify a circular conditional autoregressive model for the vector direction, and a spatial CAR model for speed. We apply our framework for vector fields to hurricane surface wind fields for Hurricane Floyd of 1999 and compare our circular conditional autoregressive model to prior methods that decompose wind speed and direction into its N‐S and W‐E cardinal components. Copyright © 2011 John Wiley & Sons, Ltd.
It is time for changes in the analysis of whole effluent toxicity data
Authors: Diamond Jerry , Denton Debra , Anderson Brian , Phillips Bryn
Published: September 2011

The whole effluent toxicity (WET) program in the United States, Canada, and other countries typically requires multi concentration testing of effluents. While multiconcentration testing of chemicals is desirable for regulatory and scientific reasons, we believe this requirement is not as efficient for evaluating effluent compliance in a WET program. The key regulatory question of concern is whether an effluent is toxic or not, which is best answered statistically using a hypothesis approach, not a point estimate approach. However, the traditional hypothesis approach currently recommended does not reward high within-test precision. This report describes the need for 3 specific changes in the analysis of WET compliance data that we believe would yield a more robust WET regulatory program: (1) restate the null hypothesis so that test power is associated with demonstrating that the effluent is not toxic, (2) use USEPA's Test of Significant Toxicity (based on the noninferiority approach) to identify unacceptable toxicity as well as acceptable effects with a high probability, and (3) evaluate only the test control and the critical concentration of concern (e.g., instream waste concentration). We demonstrate that instituting these 3 changes would provide: Positive incentives for permittees to produce high-quality WET data, a transparent analysis approach in which the permittee could have greater control over regulatory decisions based on test results, and potentially a less expensive testing program because fewer effluent concentrations need to be examined within a test. As a result, WET test frequency could be increased for the same cost as current testing programs while providing greater representativeness of effluent quality. Integr Environ Assess Manag 2012; 8: 351–358. © 2011 SETAC
Elevated progesterone receptor membrane component 1/sigma‐2 receptor levels in lung tumors and plasma from lung cancer patients
Authors: Mir Shakeel U.R. , Ahmed Ikhlas S.A. , Arnold Susanne , Craven Rolf J.
Published: September 2011

Cancer is one of the leading causes of death, and there is an urgent need for new biomarkers and therapeutic targets. The progesterone receptor membrane component 1 (Pgrmc1) protein is upregulated in multiple types of cancer, and Pgrmc1 is required for tumor cell proliferation, motility and tumor formation in vivo. Furthermore, a small molecule inhibitor of Pgrmc1 suppressed the growth of lung, breast and cervical cancer cell lines. Recently, Pgrmc1 was identified as the sigma‐2 receptor, a putative type of opioid receptor, and sigma‐2 receptors are induced in cancers. However, Pgrmc1 shares no homology with known opioid or hormone receptors but is related to cytochrome b5, and Pgrmc1 binds to heme and has reducing activity. In this study, we have analyzed Pgrmc1 levels in clinical tumor samples from squamous cell lung cancers (SCLC) and lung adenocarcinomas compared to corresponding nonmalignant tissue. Pgrmc1 levels increased significantly (p ≤ 0.05) in 12/15 SCLC samples and was elevated in poorly differentiated tumors. Pgrmc1 was highly expressed in SCLC cell lines, and SCLC cell survival was inhibited by siRNA knockdown of Pgrmc1 or the Pgrmc1 inhibitor AG‐205. In adenocarcinomas, 6/15 tumors significantly had elevated Pgrmc1 levels, which correlated with patient survival. Pgrmc1 localizes to secretory vesicles in cancer cells, and Pgrmc1 was secreted by lung cancer cells. Furthermore, Pgrmc1 was significantly elevated in the plasma of lung cancer patients compared to noncancer patients. Together, the results demonstrate that Pgrmc1 is a potential tumor and serum biomarker, as well as a therapeutic target, for lung cancer.
Achiral Organic, Inorganic, and Metal Crystals as Auxiliaries for Asymmetric Transformations
Authors: Weissbuch Isabelle , Leiserowitz Leslie , Lahav Meir
Published: September 2011

The use of achiral crystalline architectures as intermediate auxiliaries for the performance of “absolute” asymmetric transformations is reviewed. Such architectures are delineated, in some cases, by pairs of homochiral surfaces of opposite handedness. This phenomenon is more common among organic crystals that frequently appear in triclinic, monoclinic, orthorhombic, or tetragonal space groups. Consequently, the chiral surfaces of such crystals have been shown to display enantiomeric recognition for molecules of the environment, a process that has been instrumental in the conversion of achiral host crystals into enantiomorphous solid‐solutions, for a successful performance of “absolute” asymmetric transformations and for the control of crystal polymorphism. Mixed crystals of reduced symmetry display properties such as second harmonic generation or pyroelectricity. On the other hand, achiral faces delineate metals, which crystallize in cubic space‐groups of high symmetry. However, by slicing such crystals in particular directions, they might express homochiral high Miller index faces that contain homochiral kink sites, which have been successfully exploited in electrochemical separations of sugars and for the resolution of enantiomers by enantioselective desorption. Representative examples of each class of materials are described.
AN INTERACTIVE WATER INDICATOR ASSESSMENT TOOL TO SUPPORT LAND USE PLANNING
Authors: Hellegers P. J. G. J , Jansen H. C. , Bastiaanssen W. G. M.
Published: September 2011

This paper presents an interactive web‐based rapid assessment tool that generates key water related indicators to support decision making by stakeholders in land use planning. The tool is built on a consistent science based method that combines remote sensing with hydrological and socioeconomic analyses. It generates transparent, impartial, and verifiable information regarding the impact of land use changes on water productivity, water consumption, water availability, and employment. The usefulness of the tool was demonstrated in the Inkomati River Basin in Southern Africa, where the tool was used to assess the impact of converting land use on the water resources to prioritize areas for conversion and to track required changes in land use to comply with tripartite water allocation agreements. This contributed to confidence building and to strengthening the process of conscientious land use planning, which is an extension of conventional work in this field. Copyright © 2011 John Wiley & Sons, Ltd.