bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of misspecification of random effects distributions in clustered data settings with outcome‐dependent sampling
Authors: Neuhaus John M. , McCulloch Charles E.
Published: July 2011

Genetic epidemiologists often gather outcome‐dependent samples of family data to measure within‐family associations of genetic factors with disease outcomes. Generalized linear mixed models provide effective methods to estimate within‐family associations but typically require parametric specification of the random effects distribution. Although misspecification of the random effects distribution often leads to little bias in estimated regression coefficients in standard, prospective clustered data settings, some recent studies suggest that such misspecification will impact parameter estimates from outcome‐dependent cluster sampling designs. Using analytic results, simulation studies and fits to example data, this study examines the effect of misspecification of random effects distributions on parameter estimates in clustered data settings with outcome‐dependent sampling. We show that the effects are consistent with results from prospective cluster sampling settings. In particular, ascertainment corrected mixed model methods that assume normally distributed random intercepts and conditional likelihood approaches provide accurate estimates of within‐family covariate effects even under a misspecified random effects distribution. The Canadian Journal of Statistics 39: 488–497; 2011 © 2011 Statistical Society of Canada
Spin–Orbit Coupling in Phosphorescent Iridium(III) Complexes
Authors: Smith Arthur R. G. , Burn Paul L. , Powell Ben J.
Published: July 2011

We study the excited states of two iridium(III) complexes with potential applications in organic light‐emitting diodes: fac‐tris(2‐phenylpyridyl)iridium(III) [Ir(ppy)3] and fac‐tris(1‐methyl‐5‐phenyl‐3‐n‐propyl‐[1,2,4]triazolyl)iridium(III) [Ir(ptz)3]. Herein we report calculations of the excited states of these complexes from time‐dependent density functional theory (TDDFT) with the zeroth‐order regular approximation (ZORA). We show that results from the one‐component formulation of ZORA, with spin–orbit coupling included perturbatively, accurately reproduce both the results of the two‐component calculations and previously published experimental absorption spectra of the complexes. We are able to trace the effects of both scalar relativistic correction and spin–orbit coupling on the low‐energy excitations and radiative lifetimes of these complexes. In particular, we show that there is an indirect relativistic stabilisation of the metal‐to‐ligand charge transfer (MLCT) states. This is important because it means that indirect relativistic effects increase the degree to which SOC can hybridise singlet and triplet states and hence plays an important role in determining the optical properties of these complexes. We find that these two compounds are remarkably similar in these respects, despite Ir(ppy)3 and Ir(ptz)3 emitting green and blue light respectively. However, we predict that these two complexes will show marked differences in their magnetic circular dichroism (MCD) spectra.
Joule heating effects on electroosmotic flow in insulator‐based dielectrophoresis
Authors: Sridharan Sriram , Zhu Junjie , Hu Guoqing , Xuan Xiangchun
Published: July 2011

Insulator‐based dielectrophoresis (iDEP) is an emerging technology that has been successfully used to manipulate a variety of particles in microfluidic devices. However, due to the locally amplified electric field around the in‐channel insulator, Joule heating often becomes an unavoidable issue that may disturb the electroosmotic flow and affect the particle motion. This work presents the first experimental study of Joule heating effects on electroosmotic flow in a typical iDEP device, e.g. a constriction microchannel, under DC‐biased AC voltages. A numerical model is also developed to simulate the observed flow pattern by solving the coupled electric, energy, and fluid equations in a simplified two‐dimensional geometry. It is observed that depending on the magnitude of the DC voltage, a pair of counter‐rotating fluid circulations can occur at either the downstream end alone or each end of the channel constriction. Moreover, the pair at the downstream end appears larger in size than that at the upstream end due to DC electroosmotic flow. These fluid circulations, which are reasonably simulated by the numerical model, form as a result of the action of the electric field on Joule heating‐induced fluid inhomogeneities in the constriction region.
Immunoglobulin G and bovine serum albumin streaming dielectrophoresis in a microfluidic device
Authors: Nakano Asuka , Chao Tzu‐Chiao , Camacho‐Alanis Fernanda , Ros Alexandra
Published: July 2011

Dielectrophoresis (DEP) has demonstrated to be a versatile tool to manipulate micro‐ and nanoparticles with applications for positioning, separation and fractionation. Recent developments of DEP have also shown that DEP can be used for the manipulation of biomolecules, such as DNA. Here, we focus on the manipulation of proteins using insulator‐based dielectrophoresis (iDEP). We designed suitable post arrays in a microfluidic channel and use numerical simulations to calculate the electric field distribution as well as concentration of proteins according to a convection–diffusion model for both negative and positive DEP. Experimentally, we find DEP trapping of mainly protein aggregates in phosphate buffer. However, when adding a charged zwitterionic detergent, we observed DEP streamlining of immunoglobulin G (IgG) and bovine serum albumin (BSA). Our experimental observations are in excellent agreement with numerical simulations and indicate positive DEP behavior of IgG and BSA under the employed experimental conditions. Our results demonstrate DEP streaming of proteins in an iDEP device for the first time and indicate the potential of protein DEP for separation and fractionation.
Capillary electrophoretic mobility shift assay for binding of DNA with NFAT3, a transcription factor from H9c2 cardiac myoblast cells
Authors: Park Soo Hyun , Ban Eunmi , Song Eun Joo , Lee Hyunjung , Chung Doo Soo , Yoo Young Sook
Published: July 2011

Nuclear factor of activated T‐cells (NFAT) is a transcription factor involved in the development of cardiac and skeletal muscle and the nervous system. NFAT is activated by calcium signal pathway and translocated into the nucleus. The quantification of binding between NFAT and NFAT‐specific DNA gives important information about cardiac hypertrophy. We investigated the binding of NFAT3 in nuclear extracts from H9c2 cells to its specific DNA by capillary electrophoretic mobility shift assay. The binding reaction time required for stable formation of the DNA–NFAT3 complex was 3 h and the separation of the complex and free DNA was achieved within 10 min by CE. The formation of NFAT3–DNA complex was confirmed by the competitive reaction. Comparison of the ratios of complex/free DNA peak area for 1 μM endothelin‐1 (ET‐1)‐treated cells and control cells showed the NFAT3 translocation into the nucleus promoted by ET‐1. The binding constant between NFAT3 and DNA was estimated to be 7.7×109 M−1 at 4°C.
Blue native/SDS‐PAGE combined with iTRAQ analysis reveals advanced glycation end‐product‐induced changes of synaptosome proteins in C57 BL/6 mice
Authors: Xie Chunliang , Liu Nvying , Long Jia , Tang Cheng , Li Jianglin , Huo Linju , Wang Xianchun , Chen Ping , Liang Songping
Published: July 2011

Evidence shows that administration of high‐level D‐galactose induces the production of advanced glycation end‐products (AGEs) that have been implicated in the development of diabetic complications such as neuropathy. The deterioration of learning and memory during neuropathy might be associated with the altered expression of proteins in synapse. To evaluate AGE‐induced protein network alterations in synapse, blue native/SDS‐PAGE and iTRAQ proteomic methods were used to screen for differentially expressed synaptic proteins of cerebral cortex in D‐galactose‐induced C57 BL/6 mice. In total, the expression level of 84 proteins is changed during AGE accumulation. The significantly differentially expressed proteins mainly participate in neurotransmission, energy metabolism and signal transduction pathway, suggesting that energy metabolism is damaged and neurotransmission is attenuated in synapse. The results of in vivo activities of malondialdehyde and superoxide dismutase suggested that AGE accumulation in the brain leads to the generation of reactive oxygen species. Therefore, elucidating the differentially expressed proteins underlying the AGE accumulation will open a new window to the mechanism of learning and memory impairments in neuropathy.
Repetitive exposure to zinc oxide nanoparticles induces dna damage in human nasal mucosa mini organ cultures
Authors: Hackenberg Stephan , Zimmermann Franz‐Zeno , Scherzed Agmal , Friehs Gudrun , Froelich Katrin , Ginzkey Christian , Koehler Christian , Burghartz Marc , Hagen Rudolf , Kleinsasser Norbert
Published: July 2011

Data on the toxicological properties of zinc oxide nanoparticles (ZnO‐NPs) is incomplete. ZnO‐NPs may enter humans via inhalation or ingestion. The aim of the current study was to evaluate ZnO‐NP‐induced genotoxicity in three‐dimensional (3D) mini organ cultures (MOCs) of human nasal mucosa following repeated exposure to ZnO‐NP and regeneration. Nasal MOCs of 10 patients and ZnO‐NPs were cultivated for one week and then characterized by electron microscopy. Nasal MOCs were partially covered by ciliated epithelium after one week of cultivation. ZnO‐NPs were distributed to the cytoplasm and the nucleus. MOCs were exposed once, twice, or three times to 0.1 or 5 μg/ml of ZnO‐NPs for 1 hr per exposure and were then evaluated for cytotoxicity and genotoxicity. MOCs were cultivated for 24 hr after the triple ZnO‐NP exposure to allow for regeneration. ZnO‐NP exposure did not result in significant cytotoxicity or apoptosis, as determined by trypan blue exclusion and caspase‐3 activity, respectively. A significant increase in DNA damage was detected following repetitive exposure compared to single exposure to ZnO‐NPs at 5 μg/ml, but not 0.1 μg/ml ZnO‐NPs. At both concentrations of ZnO‐NP, DNA fragmentation increased after 24 hr of regeneration. In contrast, DNA damage which was induced by the positive control, methyl methanesulfonate, was significantly reduced after 24‐hr regeneration. Thus, our results suggest that repetitive exposure to low concentrations of ZnO‐NPs results in persistent or ongoing DNA damage. Environ. Mol. Mutagen. 2011. © 2011 Wiley‐Liss, Inc.
Equilibrium modeling: A pathway to understanding observed perfluorocarboxylic and perfluorosulfonic acid behavior
Authors: Webster Eva M , Ellis David A
Published: July 2011

Equilibrium distribution models of hydrophobic neutral partitioning of the perfluorinated carboxylic and sulfonic acids were shown, without the need for any physical chemical properties, to successfully predict the sediment–water distribution (DSW) directly from independently measured equilibrium tissue distributions known as the bioconcentration factor (BCF). The constant of proportionality required by the models successfully predicted the correlation between the biotic and abiotic distributions of both sets of chemicals, thus demonstrating the applicability of the assumptions inherent in the models, that is, hydrophobically driven partitioning of the neutral species, and thus the applicability of the models themselves. Colloquially speaking, the models are thus validated as applicable to these chemicals. Subsequent application of the standard equilibrium models showed order of magnitude agreement for 83% of measured BCF values and 88% of measured DSW for the perfluorinated carboxylic acids, confirming the physical chemical properties used. The applicability of the models to perfluorooctane sulfonic acid (PFOSA) was shown by the successful prediction of DSW from BCF. Therefore, the measured DSW and BCF could be used to calculate the octanol–water distribution, DOW, and hence the corresponding pKa:KOW solution set, thus providing independent experimentally based estimates of these properties. For both the perfluorinated carboxylic and sulfonic acids, the existing standard equilibrium models are shown to be applicable. Environ. Toxicol. Chem. 2011;30:2229–2236. © 2011 SETAC
Leukemia stem cells
Authors: Buss Eike C. , Ho Anthony D.
Published: July 2011

Leukemia stem cells (LSCs) might originate from malignant transformation of normal hematopoietic stem cells (HSCs), or alternatively, of progenitors in which the acquired mutations have re‐installed a dysregulated self‐renewal program. LSCs are on top of a hierarchy and generate leukemia cells with more differentiated characteristics. While most leukemia cells are initially sensitive to chemo‐ and radiotherapy, LSCs are resistant and are considered to be the basis for disease relapse after initial response. Albeit important knowledge on LSC biology has been gained from xenogeneic transplantation models introducing human leukemia cells into immune deficient mouse models, the prospective identification and isolation of human LSC candidates has remained elusive and their prognostic and therapeutic significance controversial. This review focuses on the identification, enrichment and characterization of human LSC derived from patients with acute myeloid leukemia (AML). Experimental data demonstrating the clinical significance of estimating LSC burden and strategies to eliminate LSC will be summarized. For long‐term cure of AML, it is of importance to define LSC candidates and to understand their tumor biology compared to normal HSCs. Such comparative studies might provide novel markers for the identification of LSC and for the development of treatment strategies that might be able to eradicate them.
Synthesis of Conjugated Polymers in Chiral Nematic Liquid Crystal Fields
Authors: Matsushita Satoshi , Akagi Kazuo
Published: July 2011

This review presents the progress made on current research in the synthesis of π‐conjugated polymers in chiral nematic liquid crystal (N*‐LC) fields through either chemical or electrochemical polymerization. The following are noteworthy advances in the field of π‐conjugated polymers. (i) Helical aliphatic conjugated polymers of helical polyacetylene (H‐PA) were synthesized using asymmetric interfacial polymerization in N*‐LC fields. (ii) Helical aromatic conjugated polymers with electroactive properties, such as poly(3,4‐ethylenedioxythiophene) (PEDOT) and polybithiophene (PBT), were synthesized using asymmetric electrochemical polymerization in N*‐LC fields. (iii) Chiral aromatic conjugated copolymers, such as the poly(bithienylene‐phenylene) (PBTP) derivative, were synthesized using the asymmetric Stille polycondensation reaction in N*‐LC fields. Throughout the document, it has been emphasized that by using N*‐LC systems as asymmetric polymerization fields, helix formation is possible for aliphatic and aromatic π‐conjugated polymers without chiroptical substituents on the side chains.
Patients with sclerosteosis and disease carriers: Human models of the effect of sclerostin on bone turnover
Authors: van Lierop Antoon H , Hamdy Neveen AT , Hamersma Herman , van Bezooijen Rutger L , Power Jon , Loveridge Nigel , Papapoulos Socrates E
Published: July 2011

Sclerosteosis is a rare bone sclerosing dysplasia, caused by loss-of-function mutations in the SOST gene, encoding sclerostin, a negative regulator of bone formation. The purpose of this study was to determine how the lack of sclerostin affects bone turnover in patients with sclerosteosis and to assess whether sclerostin synthesis is decreased in carriers of the SOST mutation and, if so, to what extent this would affect their phenotype and bone formation. We measured sclerostin, procollagen type 1 amino-terminal propeptide (P1NP), and cross-linked C-telopeptide (CTX) in serum of 19 patients with sclerosteosis, 26 heterozygous carriers of the C69T SOST mutation, and 77 healthy controls. Chips of compact bone discarded during routine surgery were also examined from 6 patients and 4 controls. Sclerostin was undetectable in serum of patients but was measurable in all carriers (mean 15.5 pg/mL; 95% confidence interval [CI] 13.7 to 17.2 pg/mL), in whom it was significantly lower than in healthy controls (mean 40.0 pg/mL; 95% CI 36.9 to 42.7 pg/mL; p < 0.001). P1NP levels were highest in patients (mean 153.7 ng/mL; 95% CI 100.5 to 206.9 ng/mL; p = 0.01 versus carriers, p = 0.002 versus controls), but carriers also had significantly higher P1NP levels (mean 58.3 ng/mL; 95% CI 47.0 to 69.6 ng/mL) than controls (mean 37.8 ng/mL; 95% CI 34.9 to 42.0 ng/mL; p = 0.006). In patients and carriers, P1NP levels declined with age, reaching a plateau after the age of 20 years. Serum sclerostin and P1NP were negatively correlated in carriers and age- and gender-matched controls (r = 0.40, p = 0.008). Mean CTX levels were well within the normal range and did not differ between patients and disease carriers after adjusting for age (p = 0.22). Our results provide in vivo evidence of increased bone formation caused by the absence or decreased synthesis of sclerostin in humans. They also suggest that inhibition of sclerostin can be titrated because the decreased sclerostin levels in disease carriers did not lead to any of the symptoms or complications of the disease but had a positive effect on bone mass. Further studies are needed to clarify the role of sclerostin on bone resorption. © 2011 American Society for Bone and Mineral Research
Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip bone mineral density induced by weight loss despite decline in bone-active hormones
Authors: Shah Krupa , Armamento-Villareal Reina , Parimi Nehu , Chode Suresh , Sinacore David R , Hilton Tiffany N , Napoli Nicola , Qualls Clifford , Villareal Dennis T
Published: July 2011

Weight loss therapy to improve health in obese older adults is controversial because it causes further bone loss. Therefore, it is recommended that weight loss therapy should include an intervention such as exercise training (ET) to minimize bone loss. The purpose of this study was to determine the independent and combined effects of weight loss and ET on bone metabolism in relation to bone mineral density (BMD) in obese older adults. One-hundred-seven older (age >65 years) obese (body mass index [BMI] ≥30 kg/m2) adults were randomly assigned to a control group, diet group, exercise group, and diet-exercise group for 1 year. Body weight decreased in the diet (−9.6%) and diet-exercise (−9.4%) groups, not in the exercise (−1%) and control (−0.2%) groups (between-group p < 0.001). However, despite comparable weight loss, bone loss at the total hip was relatively less in the diet-exercise group (−1.1%) than in the diet group (−2.6%), whereas BMD increased in the exercise group (1.5%) (between-group p < 0.001). Serum C-terminal telopeptide (CTX) and osteocalcin concentrations increased in the diet group (31% and 24%, respectively), whereas they decreased in the exercise group (−13% and −15%, respectively) (between-group p < 0.001). In contrast, similar to the control group, serum CTX and osteocalcin concentrations did not change in the diet-exercise group. Serum procollagen propeptide concentrations decreased in the exercise group (−15%) compared with the diet group (9%) (p = 0.04). Serum leptin and estradiol concentrations decreased in the diet (−25% and −15%, respectively) and diet-exercise (−38% and −13%, respectively) groups, not in the exercise and control groups (between-group p = 0.001). Multivariate analyses revealed that changes in lean body mass (β = 0.33), serum osteocalcin (β = −0.24), and one-repetition maximum (1-RM) strength (β = 0.23) were independent predictors of changes in hip BMD (all p < 0.05). In conclusion, the addition of ET to weight loss therapy among obese older adults prevents weight loss–induced increase in bone turnover and attenuates weight loss–induced reduction in hip BMD despite weight loss–induced decrease in bone-active hormones. © 2011 American Society for Bone and Mineral Research
Is greater lumbar vertebral BMD associated with more disk degeneration? A study using µCT and discography
Authors: Wang Yue , Boyd Steven K , Battié Michele C , Yasui Yutaka , Videman Tapio
Published: July 2011

It is well documented that osteoarthritis is associated with greater BMD in peripheral extremities. Yet the relationship between vertebral BMD and disk degeneration (DD) remains controversial in the lumbar spine, which may be due largely to the inadequacies of BMD and DD measures. Aiming to clarify the association between vertebral BMD and adjacent DD, we studied 137 cadaveric lumbar vertebrae and 209 corresponding intervertebral disks from the spines of 48 white men aged 21 to 64 years. DD was evaluated using discography. The vertebrae were scanned using a micro–computed tomography (µCT) system to obtain volumetric BMD for the whole vertebra, the vertebral body, the vertebral body excluding osteophytes, and the vertebral body excluding osteophytes and endplates. A random effects model was used to examine the association between the different definitions of vertebral BMD and adjacent DD. No significant association was found between the BMD of the whole vertebra and adjacent DD. However, when the posterior elements were excluded, there was a significant association between greater vertebral body BMD and more severe degeneration in the disk cranial to the vertebra. This association remained after further excluding osteophytes and endplates from the vertebral body BMD measurements. Also, a trend of greater BMD of the vertebral body associated with more adjacent DD was evident. These results clarify the association between vertebral BMD and DD and specifically indicate that it is higher BMD of the vertebral body, not the entire vertebra, that is associated with more severe adjacent DD. This association may be obscured by the posterior elements and is not confounded by osteophytes and endplate sclerosis. © 2011 American Society for Bone and Mineral Research
Mucosal healing of esophageal involvement of Crohn's disease with granulocyte/monocyte adsorption
Authors: Moribata Kosaku , Kato Jun , Iimura Sae , Yoshida Satoshi , Shingaki Naoki , Ueda Kazuki , Deguchi Hisanobu , Inoue Izumi , Maekita Takao , Iguchi Mikitaka , Tamai Hideyuki , Ichinose Masao
Published: July 2011

We report a case of a 16‐year‐old male who suffered from Crohn's disease (CD) with esophageal involvement, showing remarkable improvement with granulocyte/monocyte adsorption (GMA). The patient had been diagnosed as ileocolic CD and was treated with 5‐aminosalicylate. He was admitted to our hospital with symptoms of fever, diarrhea, and odynophagia. Endoscopic examinations revealed that the exacerbation of ileocolic ulcers, and advent of ulcers in esophagus. Because of the patient's refusal to receive corticosteroids, immunomodulators, or biologics, he underwent GMA twice a week. After 10 sessions of GMA, he entered remission with significant decrease in clinical activity. In addition, endoscopic examinations showed remarkable improvement of ileocolic ulcers and disappearance of esophageal lesions. No adverse events were observed. GMA could be effective for manifestations of CD in gastrointestinal tract other than ileum or colon. J. Clin. Apheresis, 2011. © 2011 Wiley‐Liss, Inc.
Outcomes of previously healthy pediatric patients with fulminant sepsis‐induced multisystem organ failure receiving therapeutic plasma exchange
Authors: Qu Lirong , Kiss Joseph E. , Dargo Gina , Carcillo Joseph A.
Published: July 2011

Background: Fulminant sepsis‐induced multisystem organ failure (MSOF) in pediatric patients carries substantial morbidity and mortality. Therapeutic plasma exchange (TPE) has been reported to be beneficial in sepsis‐induced MSOF. We evaluated the outcomes of previously healthy children with fulminant sepsis‐induced MSOF receiving TPE. Materials and Methods: Previously healthy pediatric ICU patients who underwent TPE for MSOF due to fulminant bacterial sepsis were retrospectively reviewed. Eleven patients (three females and eight males) with age ranging 8 months to 14 years were identified (eight meningococcemia and three other infections). All patients received daily TPE with fresh frozen plasma (FFP) as replacement fluid. Organ failure index (OFI—maximum score = 6) was assessed daily for 7 days. Results: A median of 4 TPE (1–14) were performed. Improvements in organ function and platelet count occurred in most patients with 2–4 TPE treatments. All 10 patients who were alive had reduced OFI to 2 by day 7 of initial TPE and were all fully recovered (survival rate = 10/11, 91%). The only death occurred in a patient who died the same day after his first TPE treatment, which was initiated 24 h after development of MSOF. The 10 survivors underwent early initiation of TPE (median 5.3 h) after the onset of MSOF. Conclusions: > TPE may contribute to a better outcome in previously healthy pediatric patients with fulminant sepsis‐induced MSOF, especially if instituted early in the course of multiorgan failure. J. Clin. Apheresis, 2011. © 2011 Wiley‐Liss, Inc.
Urinary κ and λ immunoglobulin light chains in normoalbuminuric type 2 diabetes mellitus patients
Authors: Hassan S.B. , Hanna M.O.F.
Published: July 2011

Background and Aim: Kidney disease is one of the major chronic microvascular complications of diabetes. Tubular involvement may precede glomerular involvement and the appearance of microalbuminuria. The aim of the study was to evaluate quantitatively immunoglobulin light chains (IgLCs), kappa and lambda excretion in the urine of patients with type 2 diabetes mellitus with normoalbuminuria and with microalbuminuria compared to control group. Results: Urinary IgLCs levels of the control group were significantly lower than diabetic patients with normoalbuminuria and diabetic patients with albuminuria. IgLCs were significantly associated with the duration of disease and negatively with estimated glomerular filtration rate. Conclusion: Type 2 diabetic patients can have significantly raised concentrations of urinary IgLCs before microalbuminuria or renal disease occurs. Further investigations are recommended to assess LC evaluation in the early management of diabetic renal disease. J. Clin. Lab. Anal. 25:229–232, 2011. © 2011 Wiley‐Liss, Inc.
TGF‐β1 serum concentration as a complementary diagnostic biomarker of lung cancer: establishment of a cut‐point value
Authors: González‐Santiago Ana E. , Mendoza‐Topete Luz A. , Sánchez‐Llamas Francisco , Troyo‐Sanromán Rogelio , Gurrola‐Díaz Carmen M.
Published: July 2011

Lung cancer is a malignant disease with increasing mortality rates. Cytokines play a role in normal cell growth regulation and differentiation and are also implicated in malignant disease. Among these cytokines, Transforming Growth Factor β type 1 (TGF‐β1) acts as a tumor promoter in malignant cells. Several clinical studies have found high levels of TGF‐β1 in various cancer types. The aim of this study was to establish a TGF‐β1 cut‐off point as a complementary diagnostic tool in lung cancer detection. Therefore, 72 clinically well‐characterized individuals were studied, 41 lung cancer patients and 31 healthy subjects. Serum TGF‐β1 concentration was measured by an enzyme‐linked immunosorbent assay (ELISA). We compared statistically the serum TGF‐β1 concentration between both groups with analysis of variance, linear regression and receiver operating curve analysis. We observed that lung cancer patients produced higher TGF‐β1 levels than healthy individuals (37,225±9,436 vs. 28,416±9,324 pg/ml, P<0.001). The cut‐point diagnostic value was 30,500 pg/ml with 80.5% sensitivity, 64.5% specificity and odds ratio: 7.5, 95% CI: 2.6–21.8. Conclusions: We found significantly higher TGF‐β1 levels in lung cancer patients than in healthy individuals. We propose the measurement of serum TGF‐β1 levels as a complementary diagnostic test in lung cancer detection. J. Clin. Lab. Anal. 25:238–243, 2011. © 2011 Wiley‐Liss, Inc.
Clinical significance of simultaneous determination of serum tryptophan and tyrosine in patients with lung cancer
Authors: Ren Ya‐Ping , Tang Ai‐Guo , Zhou Qian‐Xuan , Xiang Zhong‐Yuan
Published: July 2011

Background: To explore the clinical significance of serum tyrosine (Tyr) and tryptophan (Trp) in patients with lung cancer, we used a simple and efficient method of high‐performance liquid chromatography with fluorescence detection (HPLC‐FD) that simultaneously measured serum Trp and Tyr contents. Methods: The concentrations of Tyr and Trp were measured simultaneously by HPLC‐FD in the sera of 80 patients with lung cancer and 120 healthy controls. Results: Trp concentrations were significantly lower in patients with lung cancer than in healthy controls (39.26±5.44 vs. 49.93±5.43 µmol/l, respectively; P<0.01), whereas in Tyr concentrations there were no differences with healthy controls (65.38±7.94 vs.66.40±8.55 µmol/l, respectively; P>0.05). In addition, patients in the adenocarcinoma group had significantly lower Trp and Tyr concentrations than those in squamous cell carcinoma group. There was no difference between the early stage and advanced stage of lung cancer. Conclusions: Determination of serum Trp and Tyr concentrations can be employed to assist the diagnosis of the histotypes of lung cancer and tumor stage. Tyr and Trp as indexes on the lung cancer diagnostic sensitivity, specificity were 54.9, 62.9% and 82.4, 92.1%, Trp is an important and special index for lung cancer diagnosis of which the specificity of diagnosis of lung cancer is more than 92%. J. Clin. Lab. Anal. 25:246–250, 2011. © 2011 Wiley‐Liss, Inc.
Ischemia‐modified albumin as a biochemical marker in children with neuroblastoma and soft tissue sarcomas
Authors: Stachowicz‐Stencel Teresa , Synakiewicz Anna , Owczarzak Anna , Sliwińska Aleksandra , Aleksandrowicz‐Wrona Ewa , Lysiak‐Szydowska Wiesawa , Balcerska Anna
Published: July 2011

In this study, the levels of ischemia‐modified albumin (IMA) in pediatric oncology patients with soft tissue sarcomas (STSs) and neuroblastoma (NB) were analyzed. To date, there have been no studies concerning IMA in these groups of patients. Ninety‐nine children with STSs and NB were analyzed from 2006 to 2009, and 30 healthy children were also enrolled in the study. IMA levels were measured throughout treatment in all patients. The levels of IMA in all cancer patients (mean 116.8±39.3 U/ml), in patients with STSs (mean 119.8±27.5 U/ml), and in patients with NB (mean 114.6±36.6 U/ml) were significantly higher than in the control patients (mean 87.3±38.3 U/ml; P=0.0013, 0.0066, and 0.0164, respectively). IMA levels increased before and during the treatment compared with levels in the controls. The determination of IMA levels in pediatric oncology patients with poor prognoses from STSs and NB may play an important role in predicting response to therapy and overall outcome. J. Clin. Lab. Anal. 25:255–258, 2011. © 2011 Wiley‐Liss, Inc.
Evolving methods for single nucleotide polymorphism detection: Factor V Leiden mutation detection
Authors: Oh Herin , Smith Cassandra L.
Published: July 2011

Background: The many techniques used to diagnose the Factor V Leiden (FVL) mutation, the most common hereditary hypercoagulation disorder in Eurasians, and the most frequently requested genetic test reflect the evolving strategies in protein and DNA diagnosis. Methods: Here, molecular methods to diagnose the FVL mutation are discussed. Results: Protein‐based detection assays include the conventional functional activated protein C resistance coagulation test and the recently reported antibody‐mediated sensor detection; and DNA‐based assays include approaches that use electrophoretic fractionation e.g., restriction fragment length polymorphism, denaturing gradient gel electrophoresis, and single‐stranded conformational PCR analysis, DNA hybridization (e.g., microarrays), DNA polymerase‐based assays, e.g., extension reactions, fluorescence polarization template‐directed dye‐terminator incorporation, PCR assays (e.g., amplification‐refractory mutation system, melting curve analysis using real‐time quantitative PCR, and helicase‐dependent amplification), DNA sequencing (e.g., direct sequencing, pyrosequencing), cleavase‐based Invader assay and ligase‐based assays (e.g., oligonucleotide ligation assay and ligase‐mediated rolling circle amplification). Conclusion: The method chosen by a laboratory to diagnose FVL not only depends on the available technical expertise and equipment, but also the type, variety, and extent of other genetic disorders being diagnosed. J. Clin. Lab. Anal. 25:259–288, 2011. © 2011 Wiley‐Liss, Inc.
Correlation of Chlamydia and Chlamydophila spp. IgG and IgM antibodies by microimmunofluorescence with antigen detection methods
Authors: She Rosemary C. , Welch Ryan , Wilson Andrew R. , Davis David , Litwin Christine M.
Published: July 2011

Correlation of serologic titers for Chlamydia trachomatis with other tests has been based on direct fluorescence antibody (DFA) testing and culture, but not on nucleic acid‐based tests that are used for screening. We retrospectively reviewed the specificity of antibodies against C. trachomatis, Chlamydia psittaci, and Chlamydophila pneumoniae by microimmunofluorescence (MIF) when compared with DFA, culture, nucleic acid probe, and transcription‐mediated amplification. Over a 6‐year period, 226 cases had both MIF and one of these other methods performed for comparison. Agreement between C. trachomatis antigen or nucleic acid detection and MIF results was 87% (197/226). C. trachomatis serology had a negative predictive value of 98%, and 10.6% of cases were positive by serology and negative by antigen testing. Of the 13 patients who had a positive C. trachomatis antigen or nucleic acid test result, 9 had IgG and/or IgM titers highest against C. trachomatis, 3 had IgG titers highest against C. pneumoniae, and 1 had undetectable titers for the three chlamydial species. Twenty‐five patients had positive IgG and/or IgM titers to C. trachomatis but negative antigen test results. Serologic testing can increase the sensitivity of detecting C. trachomatis infections. J. Clin. Lab. Anal. 25:305–308, 2011. © 2011 Wiley‐Liss, Inc.
Design and synthesis of some novel quinoline derivatives as anticancer and radiosensitizing agents targeting VEGFR tyrosine kinase
Authors: Ghorab Mostafa M. , Ragab Fatma A. , Heiba Helmy I. , Ghorab Walid M.
Published: July 2011

Quinoline derivatives posses many types of biological activities and have been reported to show significant anticancer activity. There is a variety of mechanisms for the anticancer activity and the most distinguished mechanism is the inhibition of vascular epithelial growth factor receptor tyrosine kinase (VEGFRTK). Novel quinoline derivatives 6, 7a, 7b, 7c, 8, 9, 10, 11, 12 and pyrimido[4,5‐b]quinoline derivatives 16, 17, 18, 19, 20 are reported herein. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7) in which VEGFR is highly expressed. Compounds 6 and 7 with IC50 values of 8.5 μM and 21.9 μM were the most active compounds and exhibited cytotoxic activities higher than that of the reference drug doxorubicin (IC50= 32.02 μM). The most active compounds 6 and 7 were further evaluated for their ability to enhance the cell killing effect of γ‐radiation. J. Heterocyclic Chem., (2011).
A 1900‐year paleohurricane record from Wassaw Island, Georgia, USA
Authors: Kiage Lawrence M , Deocampo Daniel , Mccloskey Terrence A. , Bianchette Thomas A. , Hursey Melissa
Published: July 2011

We present here the first paleotempestology record from Wassaw Island on the Georgia Bight, located in the south Atlantic coast of the United States. In the historical period, the Georgia Bight has experienced less frequent hits by hurricanes than other locations along the US Gulf and Atlantic coasts. The 1900‐year record inferred from the overwash sand layers from a back‐barrier marsh on Wassaw Island suggests that the island was directly struck by major storms on nine occasions during this interval. The Wassaw Island record shows alternating regimes, with periods of increased activity from >2000 a BP until ∼1100 a BP, and ∼100 a BP until the present, sandwiching a quiet period from ∼1100 to 250 a BP. Storm deposits from the most recent active period are perhaps amalgamated, indicating that site‐specific conditions may result in event undercounting and suggests that the relative thickness of sand layers in the sedimentary record is not always indicative of hurricane strength. Copyright © 2011 John Wiley & Sons, Ltd.
Monolithic media for applications in affinity chromatography
Authors: Sproß Jens , Sinz Andrea
Published: July 2011

Affinity chromatography presents a highly versatile analytical tool, which relies on exploiting highly specific interactions between molecules and their ligands. This review covers the most recent literature on the application of monoliths as stationary phases for various affinity‐based chromatographic applications. Different affinity approaches as well as separations using molecularly imprinted monoliths are discussed. Hybrid stationary phases created by embedding of particles or nanoparticles into a monolithic stationary phase are also considered in this review article. The ease of preparation of monoliths and the multitude of functionalization techniques, which have matured during the past years, make monoliths interesting for an increasing number of biochemical and medical applications.
Transparent polyimide nanocomposite films: Thermo‐optical properties, morphology, and gas permeability
Authors: Min Ungki , Kim Jeong‐Cheol , Chang Jin‐Hae
Published: July 2011

Poly(amic acid) (PAA) hybrids with organically modified montmorillonite (Cloisite 30B) were synthesized from N,N′‐dimethylacetamide (DMAc) solution. These hybrids were heated at various temperatures, yielding 64‐ to 68‐μm thick films of polyimide (PI)/Cloisite 30B hybrids with various clay contents (0–1.5 wt%). The intercalation of PI chains among the organoclay particles was examined using wide‐angle X‐ray diffraction (XRD) and electron microscopy (TEM) techniques. The thermo‐optical properties were measured by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and ultraviolet‐visible (UV–vis) spectrometry. The optimum thermal and oxygen barrier properties were observed for the hybrids containing 1.0 wt% Cloisite 30B; these properties were degraded gradually by further increases in the clay content. The presence of only 1.0 wt% Cloisite 30B in a PI hybrid film was found to result in an 83% reduction in the rate of O2 permeability with respect to that of the pure PI film. The PI hybrid films were found to exhibit excellent optical transparency and to be almost colorless. However, the transparency of the hybrid films decreased slightly with increasing organoclay content. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers
Heritability in the Era of Molecular Genetics: Some Thoughts for Understanding Genetic Influences on Behavioural Traits
Authors: Johnson Wendy , Penke Lars , Spinath Frank M.
Published: July 2011

Genetic influences on behavioural traits are ubiquitous. When behaviourism was the dominant paradigm in psychology, demonstrations of heritability of behavioural and psychological constructs provided important evidence of its limitations. Now that genetic influences on behavioural traits are generally accepted, we need to recognise the limitations of heritability as an indicator of both the aetiology and likelihood of discovering molecular genetic associations with behavioural traits. We review those limitations and conclude that quantitative genetics and genetically informative research designs are still critical to understanding the roles of gene–environment interplay in developmental processes, though not necessarily in the ways commonly discussed. Copyright © 2011 John Wiley & Sons, Ltd.
Characterization of well‐defined poly(ethylene glycol) hydrogels prepared by thiol‐ene chemistry
Authors: Yang Ting , Long Hui , Malkoch Michael , Kristofer Gamstedt E. , Berglund Lars , Hult Anders
Published: July 2011

Considering the large number of applications for hydrogels, a better understanding of the relation between molecular structure and mechanical properties for well‐defined hydrogel is essential. A new library has been compiled of poly(ethylene glycol) polymers (PEG) of different length end functionalized with diallyl, dithiol, and dimethacrylate, and crosslinked with complementary trifunctional crosslinkers. In this study, the hydrogels were initially analyzed by FT‐Raman and NMR to study the conversion ratio of the functional groups. The effects of solvent type, solid content concentration, curing time and length of the PEG chains on the final leaching, swelling and tensile properties of the hydrogels were studied. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
RAFT kinetics revisited: Revival of the RAFT debate
Authors: Junker Tanja
Published: July 2011

Recently, two electron spin resonance (ESR)‐based methods for the determination of addition and fragmentation rate coefficients in dithiobenzoate‐mediated reversible addition fragmentation transfer (RAFT) polymerization were introduced, one being based on a spin‐trapping method and the other on single‐laser pulse initiation in conjunction with ESR detection at microsecond time resolution. For the RAFT‐intermediate radical fragmentation rate, coefficient data differing by six orders of magnitude were obtained, which cannot be explained by the usual model dependencies, that is the so‐called cross‐termination versus stable intermediate model. Even under consideration of fast cross‐termination in both cases, the large difference persists. Both the experimental designs are thus critically reviewed to identify potential error sources and to explain the vast difference in the individual results. Both techniques appear to be robust and only small interferences could be identified. Finally, recommendations for the refinement of the individual techniques are given to achieve a consistent kinetic picture of the underpinning reaction equilibria. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Control of stereospecificity in the radical polymerization of N‐methyl‐N‐(2‐pyridyl)acrylamide by conformational switching of the monomer with protonation
Authors: Hirano Tomohiro , Morikami Akihiro , Ute Koichi
Published: July 2011

Radical polymerization of N‐methyl‐N‐(2‐pyridyl)acrylamide (MPyAAm) was carried out in dichloromethane at low temperatures in the presence of trifluoroacetic acid (TFA). The m dyad contents of the polymers obtained at 0 °C increased linearly from 37 to 60% with an increase in the [TFA]0/[MPyAAm]0 ratio from 1 to 5. Nuclear magnetic resonance (NMR) analysis of MPyAAm–TFA mixtures in dichloromethane‐d2 revealed that the favorable conformation in terms of the pyridyl group to the carbonyl group in MPyAAm switched from s‐trans to s‐cis by protonation. The results suggest that controlling the conformation of MPyAAm resulted in control of the stereospecificity in radical polymerization of the monomer. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Synthesis of a novel macroinimer based on thiophene and poly(ε‐caprolactone) and its use in electrochromic device application
Authors: Kucuk Asuman Celik , Yilmaz Faruk , Can Hatice , Durmaz Hakan , Kosemen Arif , Muftuoglu Ali Ekrem
Published: July 2011

Synthesis of a novel macroinimer comprising poly(ε‐caprolactone) (PCL) and thiophene (Th) and its use in electrochromic device (ECD) application have been reported. First, a novel Th monomer (5) with miktofuntional initiator groups (primary hydroxyl and tertiary bromide at the third position of the thiophene ring) was synthesized in a four‐step reaction sequence. Density functional theory‐predicted bond lengths, angles, and vibrations of 5 were in good agreement with available experimental vibrational spectra. Subsequently, ring‐opening polymerization of ε‐caprolactone (ε‐CL) was carried out in bulk using 5 as the initiator and tin(II) 2‐ethylhexanoate (Sn(Oct)2) as the catalyst at 115 °C, which led to α‐thiophene end‐capped PCL macroinimer (PCL‐Th). Furthermore, PCL‐Th macroinimer was used in electrochemical copolymerization with pyrrole (Py) and Th. PCL‐Th/PTh copolymer film synthesized on indium tin oxide‐coated glass slide showed electrochromic behavior. Optical analyses of the PCL‐Th/PTh copolymer film indicated that the copolymer film was suitable to be used as an anodically coloring material for ECD applications. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Nanostructured organic–inorganic hybrid films prepared by the sol–gel method from self‐assemblies of PS‐b‐paptes‐b‐PS triblock copolymers
Authors: Gamys CÉ Guinto , Beyou Emmanuel , Bourgeat‐Lami Elodie , Alcouffe Pierre , David Laurent
Published: July 2011

ABA‐based triblock copolymers of styrene as block ends and gelable 3‐acryloxypropyltriethoxysilane (APTES) as the middle block were successfully prepared through nitroxide‐mediated polymerization (NMP). The copolymers were bulk self‐assembled into films and the degree of phase separation between the two blocks was evaluated by differential scanning calorimetry (DSC). Their morphology was examined through small angle X‐ray scattering (SAXS) and transmission electron microscopy (TEM), whereas the mechanical properties of the corresponding cross‐linked self‐assembled nanostructures were characterized by dynamic mechanical analysis (DMA). Acidic treatment of the triblock copolymers favored the hydrolysis and condensation reactions of the APTES‐rich nanophase, and induced a mechanical reinforcement evidenced by the increase of storage modulus values and the shift of the glass transition temperature to higher temperatures due to confinement effects. In addition, the lamellar structure of the hybrid films was retained after the removal of the organic part by calcination. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Synthesis of polybenzoxazine/clay nanocomposites by in situ thermal ring‐opening polymerization using intercalated monomer
Authors: Demir Kubra Dogan , Tasdelen Mehmet Atilla , Uyar Tamer , Kawaguchi Asei William , Sudo Atsushi , Endo Takeshi , Yagci Yusuf
Published: July 2011

A new class of polybenzoxazine/montmorillonite (PBz/MMT) nanocomposites has been prepared by the in situ polymerization of the typical fluid benzoxazine monomer, 3‐pentyl‐5‐ol‐3,4‐dihydro‐1,3‐benzoxazine, with intercalated benzoxazine MMT clay. A pyridine‐substituted benzoxazine was first synthesized and quaternized by 11‐bromo‐1‐undecanol and then used for ion exchange reaction with sodium ions in MMT to obtain intercalated benzoxazine clay. Finally, this organomodified clay was dispersed in the fluid benzoxazine monomers at different loading degrees to conduct the in situ thermal ring‐opening polymerization. Polymerization through the interlayer galleries of the clay led to the PBz/MMT nanocomposite formation. The morphologies of the nanocomposites were investigated by both X‐ray diffraction and transmission electron microscopic techniques, which suggested the partially exfoliated/intercalated structures in the PBz matrix. Results of thermogravimetric analysis confirmed that the thermal stability and char yield of PBz nanocomposites increased with the increase of clay content. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011