bluuebunny/crossref_metadata_2025 huggingface dataset:
IL‐18, but not IL‐15, contributes to the IL‐12‐dependent induction of NK‐cell effector functions by Leishmania infantum in vivo
Authors: Haeberlein Simone , Sebald Heidi , Bogdan Christian , Schleicher Ulrike
Published: March 2010

Activation of NK cells is a hallmark of infections with intracellular pathogens. We previously showed that the protozoan parasite Leishmania infantum triggered a rapid NK‐cell response in mice that required TLR9‐positive myeloid DC and IL‐12, but no IFN‐α/β. Here, we investigated whether IL‐15 or IL‐18 mediate the activity of IL‐12 or function as independent activators of NK cells. In contrast to earlier studies that described IL‐15 as crucial for NK‐cell priming in response to TLR ligands, the expression of IFN‐γ, FasL, perforin and granzyme B by NK cells in L. infantum‐infected mice was completely preserved in the absence of IL‐15, whereas the proliferative capacity of NK cells was lower than in WT mice. IFN‐γ secretion, cytotoxicity and FasL expression of NK cells from infected IL‐18−/− mice were significantly reduced compared with controls, but, unlike IL‐12, IL‐18 was not essential for NK‐cell effector functions. Part of the NK‐cell‐stimulatory effect of IL‐12 was dependent on IL‐18. We conclude that IL‐15 is not functioning as a universal NK‐cell priming signal and that IL‐18 contributes to the NK‐cell response in visceral leishmaniasis. The cytokine requirements for NK‐cell activation appear to differ contingent upon the infectious pathogen.
Enantioselective Arylations Catalyzed by Carbohydrate‐Based Chiral Amino Alcohols
Authors: Wouters Ana Dionéia , Trossini Gustavo H. G. , Stefani Hélio A. , Lüdtke Diogo S.
Published: March 2010

The application of carbohydrate‐derived amino alcohols in the asymmetric arylation of aldehydes by using arylboronic acids as the source of transferable aryl groups is described. The best ligand is derived from the readily available sugar D‐xylose and it mediates the addition of a range of arylboronic acids to various aromatic aldehydes in excellent yields and high enantiomeric excesses.
Recent Developments in the Synthesis of Pyrrolidine‐Containing Iminosugars (Eur. J. Org. Chem. 9/2010)
Authors: Stocker Bridget L. , Dangerfield Emma M. , Win‐Mason Anna L. , Haslett Gregory W. , Timmer Mattie S. M.
Published: March 2010

The cover picture shows a representation of the synthesis of several iminosugars. Iminosugars are sugar mimetics found widely in nature. They have potential in the treatment of a number of diseases, and accordingly, much effort has been spent in developing efficient routes for their syntheses. Recent developments in the synthesis of pyrrolidine‐containing iminosugars are outlines in the Microreview by B. L. Stocker, M. S. M. Timmer et al. on page 1615 ff. The plant in the background is a Ponga (silver fern, cyathea dealbata) endemic to New Zealand. It was chosen to highlight the fact that iminosugars are naturally occurring in many plant species from around the world. The authors thank Sam Win‐Mason for the photograph used for the cover picture.
Impact of EMS outreach: Successful developments in Latin America
Authors: Olivero Ofelia A. , Larramendy Marcelo , Soloneski Sonia , Menck Carlos F.M. , Matta Jaime , Folle Gustavo A. , Zamorano‐Ponce Enrique , Spivak Graciela
Published: March 2010

This collection of articles was inspired by the long‐standing relationship between the Environmental Mutagen Society and Latin American scientists, and by the program for the 39th Environmental Mutagen Society meeting in Puerto Rico in 2008, which included a symposium featuring “South of the border” scientists. This collection, compiled by Graciela Spivak and Ofelia Olivero, both originally from Argentina, highlights scientists who work in or were trained in Latin American countries and in Puerto Rico in a variety of scientific specialties related to DNA repair and cancer susceptibility, genomic organization and stability, genetic diversity, and environmental contaminants. Environ. Mol. Mutagen., 2010. © 2010 Wiley‐Liss, Inc.
Time is of the essence
Authors: Heckmann Lars-Henrik , Baas Jan , Jager Tjalling
Published: March 2010

An organism is a dynamic system, and its life history results from underlying processes in time. The effects of biological and chemical stressors on this system therefore also change temporally. In the present short communication, we emphasize the importance of including time as a factor in stress ecology and ecotoxicology and argue that current standard test protocols may benefit considerably from this, improving data interpretation and thus also risk assessment and risk management. Environ. Toxicol. Chem. 2010;29:1396–1398. © 2010 SETAC
Characterization of the androgen-sensitive MDA-kb2 cell line for assessing complex environmental mixtures
Authors: Blake Lindsey S. , Martinović Dalma , Gray L. Earl , Wilson Vickie S. , Regal Ron R. , Villeneuve Daniel L. , Ankley Gerald T.
Published: March 2010

Synthetic and natural steroidal androgens and estrogens and many other non-steroidal endocrine-active compounds commonly occur as complex mixtures in aquatic environments. It is important to understand the potential interactive effects of these mixtures to properly assess their risk. Estrogen receptor agonists exhibit additivity in mixtures when tested in vivo and in vitro. Little is known, however, concerning possible mixture interactions of androgen receptor agonists. In these studies we used the MDA-kb2 cell line, a human breast cancer cell line with endogenous androgen receptors and a stably transfected luciferase reporter gene construct to quantify the androgenic activity of seven natural and synthetic androgens: 17β-trenbolone, dihydrotestosterone, methyltestosterone, testosterone, trendione, 17α-trenbolone, and androstenedione. We tested combinations of these androgens and compared the observed activity to expected androgenic activity based on a concentration addition model. Our analyses support the hypothesis that androgen receptor agonists cause additive responses in a mixture. Binary mixtures of 17β-trenbolone with 17β-estradiol or triclocarban (an anti-microbial found in the environment) were also tested. 17β-Estradiol induced androgenic activity, but only at concentrations 600-fold greater than those found in the environment. Triclocarban enhanced the activity of 17β-trenbolone. Additionally, three anti-androgens were each paired with three androgens of varying potencies. The relative potencies of the antagonists were a vinclozolin metabolite (M2) > procymidone > prochloraz regardless of the androgen used. The results of our studies demonstrate the potential utility of the androgen-responsive MDA-kb2 cell line for quantifying the activity of mixtures of endocrine-active chemicals in complex wastes such as municipal effluents and feedlot discharges. Environ. Toxicol. Chem. 2010;29:1367–1376. © 2010 SETAC
Uptake and elimination of perfluorinated phosphonic acids in the rat
Authors: D'eon Jessica C. , Mabury Scott A.
Published: March 2010

The mono- and di-substituted perfluorinated phosphonic acids (mono-PFPAs and di-PFPAs) are high production volume fluorinated surfactants. Mono-PFPAs have been observed in Canadian surface waters and wastewater treatment plant (WWTP) effluent. The first observation of the di-PFPAs in the environment is reported here, with the observation of the C6/C6 and C6/C8 di-PFPAs in the National Institute for Standards and Technology (NIST) WWTP sludge standard reference material (SRM) 2781. To characterize the risk associated with human exposure to the mono-PFPAs and di-PFPAs, we determined uptake and elimination parameters in the rat. After oral gavage all of the mono-PFPA and di-PFPA congeners were observed in the blood of the dosed animals. Half-lives after intraperitoneal dosing ranged from 0.96 ± 0.11 to 2.8 ± 0.5 days for the mono-PFPAs and 1.8 ± 0.1 to 9.3 ± 1.5 days for the di-PFPAs. These half-lives are of similar magnitude to those for perfluorooctane sulfonate (PFOS, 8 to 30 days in male rats) and perfluorooctanoate (PFOA, 6 days in male rats and 1 hour in female rats). Both PFOS and PFOA have human half-lives on the order of years, and so the mono-PFPAs and di-PFPAs may also have significant lifetimes in the human body. The analysis of paired whole blood and plasma samples demonstrated that the mono-PFPAs may bind to blood cells underestimating their concentration in plasma and sera samples. The biological fate of the mono-PFPAs and di-PFPAs determined here suggest there is the potential for human exposure and that if exposure does occur, they may be long-lived in the body. Environ. Toxicol. Chem. 2010;29:1319–1329. © 2010 SETAC
Microsphere size effects on embryoid body incorporation and embryonic stem cell differentiation
Authors: Carpenedo Richard L. , Seaman Scott A. , McDevitt Todd C.
Published: March 2010

Differentiation of pluripotent embryonic stem cells (ESCs)in vitrovia multicellular spheroids called embryoid bodies (EBs) is commonly performed to model aspects of early mammalian development and initiate differentiation of cells for regenerative medicine technologies. However, the three‐dimensional nature of EBs poses unique challenges for directed ESC differentiation, including limited diffusion into EBs of morphogenic molecules capable of specifying cell fate. Degradable polymer microspheres incorporated within EBs can present morphogenic molecules to ESCs in a spatiotemporally controlled manner to more efficiently direct differentiation. In this study, the effect of microsphere size on incorporation into EBs and ESC differentiation in response to microsphere‐ mediated morphogen delivery were assessed. PLGA microspheres with mean diameters of 1, 3, or 11 μm were fabricated and mixed with ESCs during EB formation. Smaller microspheres were incorporated more efficiently throughout EBs than larger microspheres, and regardless of size, retained for at least 10 days of differentiation. Retinoic acid release from incorporated microspheres induced EB cavitation in a size‐dependent manner, with smaller microspheres triggering accelerated and more complete cavitation than larger particles. These results demonstrate that engineering the size of microsphere delivery vehicles incorporated within stem cell environments can be used to modulate the course of differentiation. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
Mutations in Keap1 are a potential prognostic factor in resected non‐small cell lung cancer
Authors: Takahashi Tsuyoshi , Sonobe Makoto , Menju Toshi , Nakayama Ei , Mino Nobuya , Iwakiri Shotaro , Nagai Shinjiro , Sato Kiyoshi , Miyahara Ryo , Okubo Kenichi , Hirata Toshiki , Date Hiroshi , Wada Hiromi
Published: March 2010

Background

Mutations in Kelch‐like ECH‐associated protein 1 (Keap1) have been reported to protect tumor cells from chemotherapeutic agents. However, their prognostic significance in nonsmall cell lung cancer (NSCLC) is still unclear. In this study, we examined the effect of Keap1 gene mutations on survival and disease‐free interval using resected primary NSCLC tissue.

Methods

We retrospectively analyzed the tumors from 79 patients with completely resected pathological Stage I–II NSCLC for the presence of Keap1 gene mutations and examined the prognosis of the patients.

Results

Keap1 gene mutations were detected in four patients (5.1%). The postoperative 5‐year survival rate for patients with Keap1 mutations was significantly lower than those without a mutation (25% vs. 76%, P = 0.038). The postoperative 5‐year disease‐free survival rate for patients with a mutant Keap1 tumor was slightly lower than for patients with Keap1 wild‐type tumors (25% vs. 66%, P = 0.057).

Conclusions

Keap1 gene mutations are likely to be associated with a worse prognosis and lower postoperative disease‐free survival rates in pathological Stage I–II NSCLC. J. Surg. Oncol. 2010; 101:500–506. © 2010 Wiley‐Liss, Inc.
Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocelluar carcinoma (HCC)
Authors: Dhanasekaran Renumathy , Kooby David A. , Staley Charles A. , Kauh John S. , Khanna Vinit , Kim Hyun S.
Published: March 2010

Background and Objectives

Chemoembolization with doxorubicin drug eluting beads (DEB) is a novel locoregional treatment modality for unresectable hepatocellular carcinoma (HCC). Initial animal studies and clinical trials suggest that treatment with DEB may provide safer and more effective short‐term outcomes than conventional chemoembolization. Current study explores long‐term survival benefits.

Methods

Consecutive patients who received transcatheter therapy with DEB or conventional chemoembolization as sole therapy between 1998 and 2008 were studied. Statistical analysis was performed using Kaplan–Meier estimator with log‐rank testing, chi‐squared, and independent t‐tests.

Results

Seventy‐one patients were included in this study, 45 (63.4%) received therapy with DEB (group A) and 26 (36.6%) underwent conventional chemoembolization (group B). Median survival from diagnosis of HCC in groups A and B were 610 (351–868) and 284 days (4–563; P = 0.03), respectively. In Okuda stage I, survival in groups A and B were 501 (421–528) and 354 days (148–560, P = 0.02). In Child–Pugh classes A and B, survival in groups A and B were 641 (471–810) and 323 days (161–485, P = 0.002). Median survival in patients with Cancer of Liver Italian Program (CLIP) score ≤3 in groups A and B were 469 (358–581) and 373 days (195–551, P = 0.03). NCI CTCAEv3 Grade 5 clinical toxicity was similar.

Conclusions

In our study, transcatheter therapy with DEB offers a survival advantage over conventional chemoembolization for patients with unresectable HCC. J. Surg. Oncol. 2010; 101:476–480. © 2010 Wiley‐Liss, Inc.
The management of thyroid carcinoma invading the larynx or trachea
Authors: Honings Jimmie , Stephen Antonia E. , Marres Henri A. , Gaissert Henning A.
Published: March 2010

Objectives/Hypothesis:

To describe the controversies in the management of thyroid carcinoma invading the airway.

Study Design:

Contemporary review of literature; level of evidence: 5.

Results:

Invasion of the larynx or trachea by thyroid carcinoma is uncommon and often identified at the time of operation, when the surgeon must decide the extent of resection. Invasion of the airway is associated with loss of tumor differentiation and a reduction in long‐term survival compared to tumors limited to the thyroid gland. Whether or not the invaded airway should be resected remains controversial. Tangential shave excision of tumor is commonly performed, despite a marked risk of local recurrence. Circumferential sleeve resection of the larynx and trachea is safe and lowers the risk of local recurrence. In recurrent disease, laryngotracheal resection provides effective palliation of airway obstruction and hemoptysis.

Conclusions:

Long‐term (>10–20 years) prospective studies are required to compare the outcome after shave excision with segmental airway resection for thyroid carcinoma. Based on the current literature and on our experience, we advocate circumferential tracheal resection in the setting of airway involvement. Laryngoscope, 2010
Correlates of chemosensory malingering
Authors: Doty Richard L. , Crastnopol Benjamin
Published: March 2010

Objectives/Hypothesis:

Smell and taste tests are commonly employed to quantify chemosensory sequelae of head trauma, toxic exposures, and iatrogenesis. Malingering on forced‐choice chemosensory tests can be detected by improbable responding. This study determined whether chemosensory test malingerers differ from nonmalingerers in terms of age, sex, education, and a range of self‐reported behaviors and symptoms, potentially providing information of value for malingering detection.

Study Design:

Case control.

Methods:

Twenty‐two chemosensory malingerers were identified from a large clinical database and matched, randomly, to 66 nonmalingerers on the basis of etiology. Differences in demographics and responses to intake questionnaire items were statistically assessed. Logistic regression was used to identify variables that best predicted malingering behavior.

Results:

Relative to nonmalingerers, malingerers reported significantly fewer allergies, dental problems, cigarettes smoked, surgical operations, nasal sinus problems, and use of medications, and significantly more putative symptom‐related psychological duress, interference with daily activities, weight loss, decreased appetite, and taste loss. Litigation involvement was higher in malingerers than nonmalingerers. Age, sex, education, and length of symptom descriptions did not differentiate malingerers from nonmalingerers.

Conclusions:

Malingerers of chemosensory tests exaggerate symptom severity and underreport factors that might be construed as contributing to their dysfunction, such as smoking behavior, medication use, and general health. This contrasts with the behavior of malingerers of psychiatric symptoms, who typically exaggerate their general health problems. These data suggest that careful review of past medical records should be used to verify patient reports to better detect chemosensory malingering in cases where financial or other external incentives are present. Laryngoscope, 2010
Impulsive‐compulsive spectrum behaviors in pathologically confirmed progressive supranuclear palsy
Authors: O'Sullivan Sean S. , Djamshidian Atbin , Ahmed Zeshan , Evans Andrew H. , Lawrence Andrew D. , Holton Janice L. , Revesz Tamas , Lees Andrew J.
Published: March 2010

There is growing awareness of impulsive‐compulsive spectrum behaviors (ICBs) in patients with Parkinson's disease (PD) treated with dopamine replacement therapy (DRT). These include pathological gambling, hypersexuality, compulsive shopping, binge eating, punding and compulsive use of DRT, or dopamine dysregulation syndrome. In PD, difficulties exist in separating the effects of DRT from the underlying disease process and aberrant dopaminergic systems in determining the aetiology of ICBs. Recent reports of ICBs associated with dopamine agonist use for conditions other than PD may suggest a significant etiological role for these medications, but currently published cases thus far lack pathological confirmation of diagnoses. We present three cases of pathologically confirmed progressive supranuclear palsy who developed ICBs in association with dopamine agonist use. Pathological comparisons between these three cases and other case series of progressive supranuclear palsy are made. © 2010 Movement Disorder Society
Hypothyroidism after 131I‐monoclonal antibody treatment of neuroblastoma
Authors: Bhandari Sonal , Cheung Nai‐Kong V. , Kushner Brian H. , Kramer Kim , Modak Shakeel , Larson Steven M. , Yeh Samuel , Heller Glenn , Sklar Charles A.
Published: March 2010

Background

To determine the prevalence of and risk factors for primary hypothyroidism following treatment with a radiolabeled monoclonal antibody (131I‐3F8) in children with neuroblastoma.

Procedure

In the current study, we assessed thyroid function in 51 neuroblastoma patients who survived for ≥3 months after treatment with 131I‐3F8 (a murine IgG3 monoclonal antibody that reacts with the ganglioside GD2) at 4 mCi/kg/day × 5 days (total 20 mCi/kg). Prior therapy in all subjects included dose‐intensive chemotherapy; 13 subjects also received external beam radiation to the neck. Oral iodide and liothyronine sodium (T3) were administered for protection of the thyroid gland.

Results

Thirty‐two of 51 subjects (63%) developed hormonal evidence of primary hypothyroidism. The median time to hypothyroidism after treatment with 131I‐3F8 was 6.4 months. The probability of developing hypothyroidism was 56% at 2 years following treatment with 131I‐3F8. There was evidence for an association between thyroidal uptake of 131I and development of hypothyroidism (hazard ratio 1.83, 95% confidence interval 0.91–3.30; P = 0.09).

Conclusions

We conclude that hormonal evidence of primary hypothyroidism developed in a majority of subjects treated with 131I‐3F8, despite pretreatment with oral iodide plus liothyronine sodium. Alternative strategies for thyroid gland protection are needed. Pediatr Blood Cancer 2010;55:76–80. © 2010 Wiley‐Liss, Inc.
Viral myocarditis induced by Coxsackievirus B3 in A.BY/SnJ mice: Analysis of changes in the myocardial proteome
Authors: Hammer Elke , Phong Truong Quoc , Steil Leif , Klingel Karin , Salazar Manuela Gesell , Bernhardt Jörg , Kandolf Reinhard , Kroemer Heyo K. , Felix Stephan B. , Völker Uwe
Published: March 2010

Enteroviral myocarditis displays highly diverse clinical phenotypes ranging from mild dyspnoea or chest pain to cardiogenic shock and death. Despite detailed studies of the virus life cycle in vitro and in vivo, the molecular interplay between host and virus in disease progression is largely unresolved. Murine models of Coxsackievirus B3 (CVB3)‐induced myocarditis well mimic the human disease patterns and can thus be explored to study mechanisms leading from acute to chronic myocarditis. Here, we present a 2‐D gel‐based proteomic survey of the changes in the murine cardiac proteome that occurs following infection with CVB3. In total, 136 distinct proteins were affected. Proteins, which are involved in immunity and defense and protein metabolism/modification displayed pronounced changes in intensity not only during acute but also at later stages of CVB3 myocarditis. Proteins involved in maintenance of cell structure and associated proteins were particularly influenced in the acute phase of myocarditis, whereas reduction of levels of metabolic enzymes was observed in chronic myocarditis. Studies about changes in protein intensities were complemented by an analysis of protein phosphorylation that revealed infection‐associated changes in the phosphorylation of myosin binding protein C, atrial and ventricular isoforms of myosin regulatory light chain 2, desmin, and Rab GDP dissociation inhibitor beta‐2.
Synthesis and properties of new aromatic polyisophthalamides with adamantylamide pendent groups
Authors: Espeso Jorge F. , Lozano Ángel E. , de la Campa José G. , García‐Yoldi Íñigo , de Abajo Javier
Published: March 2010

A new diacid monomer containing a pendent adamantyl ring was reacted with various aromatic diamines to prepare novel aromatic polyisophthalamides (PIPAs). The polymers were obtained in high yield and high molecular weight by the Yamazaki‐Higashi phosphorylation method of polycondensation. Inherent viscosities ranged from 0.40 to 0.82 dL/g, which corresponds to weight‐average and number‐average molecular weights (GPC) in the range 21,000–63,000 g/mol and 9000–31,000 g/mol, respectively. The polymers were essentially amorphous and soluble in a variety of polar aprotic solvents, and they afforded transparent, creasable films by the solution‐casting method. The great size of the polyhedral adamantyl moiety brought about a significant restriction of segmental mobility, which translated into a strong increase of Tg, so that very high glass transition temperatures were observed, in the range 335–370 °C (DSC), which are 70–90 °C above the glass transition temperatures of homologous PIPAs without pendent groups. Thus, it can be stated that these adamantyl containing polyamides are among the soluble aromatic PIPAs with highest Tg ever described. Conversely, the initial decomposition temperature, as measured by thermogravimetric analysis, was about 400 °C, which is lower by 40–70° than that of unsubstituted counterparts. Polymer films exhibited good mechanical properties, with tensile strengths over 65 MPa and tensile moduli between 2.0 and 2.6 GPa. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1743–1751, 2010
Facile, efficient functionalization of polyethylene via regioselective copolymerization of ethylene with cyclic dienes
Authors: Hong Miao , Pan Li , Ye Wei‐Ping , Song Dong‐Po , Li Yue‐Sheng
Published: March 2010

The copolymerizations of ethylene with cyclic dienes [dicyclopentadiene (DCPD) and 2,5‐norbornadiene (NBD)] using bis(β‐enaminoketonato)titanium complexes [PhN = C(R2)CHC(R1)O]2TiCl2 (1a: R1 = CF3, R2 = CH3; 1b: R1 = t‐Bu, R2 = CF3; 1c: R1 = Ph, R2 = CF3) have been investigated. In the presence of modified methylaluminoxane, these complexes exhibited high catalytic activities in the copolymerization of ethylene with DCPD or NBD, affording high molecular weight copolymers with unimodal molecular weight distributions. 1H and 13C‐NMR spectra reveal ethylene/DCPD copolymerizations by catalysts 1a–c proceeds through the enchainment of norbornene ring. Catalysts 1a and 1c showed a tendency to afford alternating copolymers. More noticeably, catalysts 1b and 1c bearing bulky substituents on the ligands promote ethylene/NBD copolymerization without crosslinking, affording the copolymer containing intracyclic double bonds. The NBD incorporation as high as 27.2 mol % has been achieved by catalyst 1c. Moreover, the microstructures of the copolymers were further confirmed by the measurement of reactivity ratios and dyad monomer sequences as well as mean sequence lengths. The intracyclic double bonds of ethylene/DCPD or ethylene/NBD copolymers can be fully converted into polar groups such as epoxy, amine, silane, and hydroxyl groups under mild conditions. Convenient synthesis of hydroxylated polyethylene can be provided for the first time through the ring opening reaction of epoxide. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1764–1772, 2010
Optical anisotropy of A‐ and M‐plane InN grown on free‐standing GaN substrates
Authors: Schley P. , Räthel J. , Sakalauskas E. , Gobsch G. , Wieneke M. , Bläsing J. , Krost A. , Koblmüller G. , Speck J. S. , Goldhahn R.
Published: March 2010

Wurtzite A‐ and M‐plane InN films were grown by molecular beam epitaxy (MBE) on free‐standing GaN substrates. Spectroscopic ellipsometry (SE) in the photon energy range from 0.56 up to 15 eV was applied in order to determine the ordinary and extraordinary complex dielectric function (DF) of InN. A distinct optical anisotropy was found over the whole energy range. The extraordinary absorption edge in comparison to the ordinary one is shifted to higher energies confirming previous studies. The investigations in the upper vacuum‐ultraviolet (VUV) spectral range (9.5–15 eV) yielded transition energies for four critical points (CPs) of the band structure (BS) which have not been observed so far.
The role of InGaN interlayers on the microstructure of InN epilayers grown via metal organic vapour phase epitaxy
Authors: Kadir Abdul , Ganguli Tapas , Gokhale M. R. , Shah A. P. , Bhattacharya Arnab
Published: March 2010

A detailed study on the influence of an InGaN interlayer between the GaN buffer and InN epilayer on the microstructural properties of the InN layer is reported. Using high‐resolution X‐ray diffraction measurements the mosaicity of MOVPE grown InN epilayers deposited directly on c‐plane sapphire, on GaN buffer layers, and on different InGaN interlayers have been compared. Generally the angle of tilt and hence the screw dislocation density in the InN epilayers can be controlled by growth conditions, while the angle of twist, corresponding to the edge dislocation density is usually weakly dependent on growth conditions. However, for a given layer thickness the edge dislocation density can be significantly reduced by the insertion of an InGaN interlayer.
Electron ionization and electrospray ionization mass spectrometric study of a series of isomeric N‐chloro(or bromo)benzyl‐substituted (E)‐2′(3′‐ or 4′)‐hydroxy‐4‐stilbazole halides
Authors: Prukała Dorota , Prukała Wiesław , Sikorski Marek
Published: March 2010

The electron ionization (EI) mass spectra and electrospray ionization (ESI) mass spectra of a series of isomeric N‐chlorobenzyl‐ and N‐bromobenzyl‐substituted (E)‐2′(3′ or 4′)‐hydroxy‐4‐stilbazole chlorides and bromides (1–12) were recorded. The fragmentation pathways of all of the compounds and the characteristic fragment ions formed by EI‐MS were studied by means of B/E and B2/E constant linked‐scanning techniques. The formation of ions originating from preionization reactions, characteristic of quaternary halides under EI‐MS conditions, such as the elimination of chloro‐ or bromobenzyl halides, dehydrohalogenation or substitution reactions, is explained. As soft ionization methods cause no such degradation reactions, the ESI‐MS spectra of the studied compounds were also obtained for comparison. We thus demonstrated the applicability of EI‐MS even in cases when preionization takes place, as long as such secondary processes are properly accounted for. Copyright © 2010 John Wiley & Sons, Ltd.
Electrospray ionization mass spectrometric analysis of newly synthesized α,β‐unsaturated γ‐lactones fused to sugars
Authors: Madeira Paulo J. Amorim , Rosa Ana Margarida , Xavier Nuno M. , Rauter Amélia P. , Florêncio M. Helena
Published: March 2010

Knowledge of the fragmentation mechanisms of lactones and their behaviour under electrospray ionization (ESI) conditions can be extended to larger and more complex natural products that contain an α,β‐unsaturated γ‐lactone moiety in their structure. Moreover, little is known about the gas‐phase behaviour of α,β‐unsaturated γ‐lactones linked or fused to sugars. Therefore, five α,β‐unsaturated γ‐lactones (butenolides) fused to a pyranose ring, recently synthesized compounds with potential relevance regarding their biological properties, were investigated using ESI‐MS and ESI‐MS/MS in both positive and negative ion modes. Their fragmentation mechanisms and product ion structures were compared. It was observed that two isomers could be unambiguously distinguished in the negative ion mode by the fragmentation pathways of their deprotonated molecules as well as in the positive ion mode by the fragmentation pathways of either the protonated or the sodiated molecule.

Fragmentation mechanisms are proposed taking into account the MS/MS data and semi‐empirical calculations using the PM6 Hamiltonean. The semi‐empirical calculations were also very useful in determining the most probable protonation and cationization sites. Copyright © 2010 John Wiley & Sons, Ltd.
The application of multiplexed, multi‐dimensional ultra‐high‐performance liquid chromatography/tandem mass spectrometry to the high‐throughput screening of lysosomal storage disorders in newborn dried bloodspots
Authors: Kasper David C. , Herman Joseph , De Jesus Victor R. , Mechtler Thomas P. , Metz Thomas F. , Shushan Bori
Published: March 2010

Lysozomal storage disorders are just beginning to be routinely screened using enzyme activity assays involving dried blood spots and tandem mass spectrometry (MS/MS). This paper discusses some of the analytical challenges associated with published assays including complex sample preparation and potential interference from excess residual substrate. Solutions to these challenges are presented in the form of on‐line two‐dimensional chromatography to eliminate off‐line liquid‐liquid extraction (LLE) and solid‐phase extraction (SPE), the use of ultra‐high‐performance liquid chromatography (UHPLC) to separate excess substrate from all other analytes and multiplexed sample introduction for higher throughput required of a population screening assay. High sensitivity, specificity and throughput were demonstrated using this novel method. Copyright © 2010 John Wiley & Sons, Ltd.
In situ lipid dip‐pen nanolithography under water
Authors: Lenhert Steven , Mirkin Chad A. , Fuchs Harald
Published: March 2010

Lipids form the structural and functional basis of biological membranes, and methods for studying their self‐organization in well‐defined nano‐ and micro‐scale model systems can provide insights into biology. Using lipids as an ink for dip‐pen nanolithography (lipid DPN) permits the rapid nanostructuring of multicomponent model lipid membrane systems, but this technique has so far been limited to air. Here we demonstrate that lipid DPN can be carried out under water with single tips or parallel arrays. Using the same tip for deposition and imaging in aqueous solution permits imaging of self‐spreading lipid bilayer spots in situ and quantification of the nanoscale spreading kinetics in real time by means of lateral‐force microscopy. Furthermore, using fluorophore‐labeled phospholipids, we directly observed, by confocal laser scanning microscopy, a two‐phase (oil in water) meniscus formed around the contact point between the DPN tip and surface, gaining insights into the mechanisms of the ink transport. The methods described here provide a new tool and environment for high‐resolution studies of lipid nanodynamics and molecular printing processes in general. SCANNING 32: 15–23, 2010. © 2010 Wiley Periodicals, Inc.
Adding local components to global functions for continuous covariates in multivariable regression modeling
Authors: Binder H. , Sauerbrei W.
Published: March 2010

When global techniques, based on fractional polynomials (FPs), are employed for modeling potentially nonlinear effects of several continuous covariates on a response, accessible model equations are obtained. However, local features might be missed. Therefore, a procedure is introduced, which systematically checks model fits, obtained by the multivariable fractional polynomial (MFP) approach, for overlooked local features. Statistically significant local polynomials are then parsimoniously added. This approach, called MFP + L, is seen to result in an effective control of the Type I error with respect to the addition of local components in a small simulation study with univariate and multivariable settings. Prediction performance is compared with that of a penalized regression spline technique. In a setting unfavorable for FPs, the latter outperforms the MFP approach, if there is much information in the data. However, the addition of local features reduces this performance difference. There is only a small detrimental effect in settings where the MFP approach performs better. In an application example with children's respiratory health data, fits from the spline‐based approach indicate many local features, but MFP + L adds only few significant features, which seem to have good support in the data. The proposed approach may be expected to be superior in settings with local features, but retains the good properties of the MFP approach in a large number of settings where global functions are sufficient. Copyright © 2010 John Wiley & Sons, Ltd.
A weighted Cox model for modelling time‐dependent exposures in the analysis of case–control studies
Authors: Leffondre Karen , Wynant Willy , Cao Zhirong , Abrahamowicz Michal , Heinze Georg , Siemiatycki Jack
Published: March 2010

Many exposures investigated in epidemiological case–control studies may vary over time. The effects of these exposures are usually estimated using logistic regression, which does not directly account for changes in covariate values over time within individuals. By contrast, the Cox model with time‐dependent covariates directly accounts for these changes over time. However, the over‐sampling of cases in case–control studies, relative to controls, requires manipulating the risk sets in the Cox partial likelihood. A previous study showed that simple inclusion or exclusion of future cases in each risk set induces an under‐ or over‐estimation bias in the regression parameters, respectively. We investigate the performance of a weighted Cox model that weights subjects according to age‐conditional probabilities of developing the disease of interest in the source population. In a simulation study, the lifetime experience of a source population is first generated and a case–control study is then simulated within each population. Different characteristics of exposure are generated, including time‐varying intensity. The results show that the estimates from the weighted Cox model are much less biased than the Cox models that simply include or exclude future cases, and are superior to logistic regression estimates in terms of bias and mean‐squared error. An application to frequency‐matched population‐based case–control data on lung cancer illustrates similar differences in the estimated effects of different smoking variables. The investigated weighted Cox model is a potential alternative method to analyse matched or unmatched population‐based case–control studies with time‐dependent exposures. Copyright © 2010 John Wiley & Sons, Ltd.
Threshold regression for survival data with time‐varying covariates
Authors: Lee Mei‐Ling Ting , Whitmore G. A. , Rosner Bernard A.
Published: March 2010

Time‐to‐event data with time‐varying covariates pose an interesting challenge for statistical modeling and inference, especially where the data require a regression structure but are not consistent with the proportional hazard assumption. Threshold regression (TR) is a relatively new methodology based on the concept that degradation or deterioration of a subject's health follows a stochastic process and failure occurs when the process first reaches a failure state or threshold (a first‐hitting‐time). Survival data with time‐varying covariates consist of sequential observations on the level of degradation and/or on covariates of the subject, prior to the occurrence of the failure event. Encounters with this type of data structure abound in practical settings for survival analysis and there is a pressing need for simple regression methods to handle the longitudinal aspect of the data. Using a Markov property to decompose a longitudinal record into a series of single records is one strategy for dealing with this type of data. This study looks at the theoretical conditions for which this Markov approach is valid. The approach is called threshold regression with Markov decomposition or Markov TR for short. A number of important special cases, such as data with unevenly spaced time points and competing risks as stopping modes, are discussed. We show that a proportional hazards regression model with time‐varying covariates is consistent with the Markov TR model. The Markov TR procedure is illustrated by a case application to a study of lung cancer risk. The procedure is also shown to be consistent with the use of an alternative time scale. Finally, we present the connection of the procedure to the concept of a collapsible survival model. Copyright © 2010 John Wiley & Sons, Ltd.
Bayesian methods for meta‐analysis of causal relationships estimated using genetic instrumental variables
Authors: Burgess Stephen , Thompson Simon G. ,   CRP CHD Genetics Collaboration
Published: March 2010

Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta‐analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C‐reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes. Copyright © 2010 John Wiley & Sons, Ltd.
High‐Concentration Solvent Exfoliation of Graphene
Authors: Khan Umar , O'Neill Arlene , Lotya Mustafa , De Sukanta , Coleman Jonathan N.
Published: March 2010

A method is demonstrated to prepare graphene dispersions at high concentrations, up to 1.2 mg mL−1, with yields of up to 4 wt% monolayers. This process relies on low‐power sonication for long times, up to 460 h. Transmission electron microscopy shows the sonication to reduce the flake size, with flake dimensions scaling ast−1/2. However, the mean flake length remains above 1 µm for all sonication times studied. Raman spectroscopy shows defects are introduced by the sonication process. However, detailed analysis suggests that predominately edge, rather than basal‐plane, defects are introduced. These dispersions are used to prepare high‐quality free‐standing graphene films. The dispersions can be heavily diluted by water without sedimentation or aggregation. This method facilitates graphene processing for a range of applications.
Shape‐Dependent Cytotoxicity and Proinflammatory Response of Poly(3,4‐ethylenedioxythiophene) Nanomaterials
Authors: Oh Wan‐Kyu , Kim Sojin , Yoon Hyeonseok , Jang Jyongsik
Published: March 2010

Poly(3,4‐ethylenedioxythiophene) (PEDT) is recognized as one of the most promising conducting polymers for future applications in the fields of electronics, optics, energy storage/conversion, and biomedical science. The toxicity of PEDT could be considered to affect the potential for its widespread application. Herein, the cytotoxicity and proinflammatory response of PEDT nanomaterials of three different shapes toward human lung fibroblast (IMR90) and mouse alveolar macrophage (J774A.1) cells are investigated. The shape‐dependent toxicity of the PEDT nanomaterials is evaluated by examining cell morphological change, cytotoxicity, apoptosis/necrosis, oxidative stress, and immune response. The cytotoxicity and apoptosis of the nanomaterials increase with their decreasing aspect ratio in both cell lines. The formation of reactive oxygen species in cells treated with PEDT nanomaterials is dependent on the shape and concentration of the nanomaterial. Proinflammatory cytokines, such as interleukin‐1, interleukin‐6, and tumor necrosis factor α from macrophages, are induced by PEDT nanomaterial‐treated cells.
Produktion, Eigenschaften und Tragverhalten von thermisch gebogenen Floatgläsern für das Bauwesen – Erstprüfung und werkseigene Produktionskontrolle im Rahmen des Zulassungsverfahrens
Authors: Ensslen Frank , Schneider Jens , Schula Sebastian
Published: March 2010

Gebogene Gläser werden zunehmend in der Architektur eingesetzt. Da im Bauwesen bislang keine Produktnormen für gebogene Gläser existieren, ist es notwendig, Qualitätskriterien für die Herstellung und das Inverkehrbringen über eine allgemeine bauaufsichtliche Zulassung oder über eine Zustimmung im Einzelfall zu regeln. Der vorliegende Beitrag gibt einen Überblick über das Herstellverfahren, die mechanischen Eigenschaften und das Tragverhalten thermisch gebogener Floatgläser. Besonders werden die Inhalte für die Erstprüfung und werkseigene Produktionskontrolle im Rahmen des Zulassungsverfahrens vorgestellt.

Production, properties and structural behaviour of bent glasses – Initial testing and production control within the scope of the approval procedure. The market of bent architectural glass is continuously increasing. Due to a lack of product standards in construction engineering, quality standards for manufacturing and handling have to be checked by a general technical approval or individually for each case and project. This article gives an overview about the production, mechanical properties and the structural behavior of bent glasses. The initial testing and production control is specified.
Hybride Glasträger als Fassadenelemente
Authors: Weller Bernhard , Meier Anja , Weimar Thorsten , Menkenhagen Jochen , Koschecknick Kai
Published: March 2010

Glasträger ermöglichen ein erhöhtes Maß an Transparenz in Fassadenkonstruktionen. Die Anwendung erfordert allerdings stets die umfassende Betrachtung der spezifischen Eigenschaften von Glas, wie beispielsweise die Sprödigkeit und die fehlende Resttragfähigkeit. Auch bei Glasträgern aus Verbund‐Sicherheitsglas, die einige Eigenschaften verbessern, ist der Verlust der Tragfähigkeit nach einem Bruch aller Einzelscheiben nicht auszuschließen. Zur Vermeidung des Bruches werden daher bei der Bemessung erhöhte Sicherheitsfaktoren eingesetzt. Die hier vorgestellten hybriden Glasträger zeigen eine Lösung, die Resttragfähigkeit von Glasträgern mittels geklebter Stahlelemente zu erhöhen. Es werden die durchgeführten Vierpunkt‐Biegeversuche zur Bestimmung der Tragfähigkeit und Resttragfähigkeit an Stahl‐Glas‐Trägern mit unterschiedlichen Querschnittsgeometrien erläutert. Anschließend erfolgt die Beschreibung der numerischen Berechnungen und deren Verifizierung basierend auf den experimentellen Untersuchungen.

Glass Beams as Structural Members in Facades. Glass as a structural member enables a higher degree of transparency in facades. However, the application always requires a comprehensive consideration of the specific properties of glass, such as the brittleness and lack of residual bearing capacity. Even with laminated glass beams, which improve several properties, the loss of load‐bearing capacity after breakage of each individual pane can not be excluded. Increased safety factors are used in the design to avoid the breakage. The hybrid beams presented show a solution to increase the residual bearing capacity of glass beams using bonded steel elements. The conducted four‐point bending tests are discussed for the purpose of the determining of the structural strength and post‐breakage behaviour of the beams with different cross‐sectional geometries. Subsequently, the description of the numeric simulations and their verification based on the experimental investigations is illustrated.
Erfahrungen mit Netzwerkbogenbrücken im Eisenbahnbrückenbau
Authors: Gauthier Peter , Krontal Ludolf
Published: March 2010

In den vergangenen zwei Jahren wurden bei der DB AG mehrere Eisenbahnüberführungen als Netzwerkbogenbrücken errichtet. Die Bauweise zeichnet sich vor allem durch eine effektive, wirtschaftliche und ästhetische Tragkonstruktion aus. An den Bauwerksentwurf, die Ausführungsplanung und die Bauausführung sind aufgrund des komplexen Tragverhaltens und der schwierigeren Geometrie hohe Anforderungen zu stellen. Die Erfahrungen bei der Planung und dem Bau der Netzwerkbogenbrücken im Eisenbahnbrückenbau werden im nachfolgenden Aufsatz aufgeführt und anhand von Beispielen erläutert.

Experiences with Network arches for railway bridges. In the past two years several railroad bridges were established as Network arch bridges by DB AG. The construction method is characterized for the bridge construction particularly by an effective, an economical and aesthetically a carrying construction. Considering complex carrying behavior and more difficult geometry high demands on basic design, detailed design and construction works are to be made. The experiences when planning and building of the network arch bridges in the railway bridge construction are specified in the following article and described on the basis of examples.