bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Route to 1‐Substituted 3‐(Dialkylamino)‐9‐oxo‐9H‐indeno[2,1‐c]pyridine‐4‐carbonitriles
Authors: Landmesser Thomas , Linden Anthony , Hansen Hans‐Jürgen
Published: February 2008

Heptalenecarbaldehydes 1/1′ as well as aromatic aldehydes react with 3‐(dicyanomethylidene)‐indan‐1‐one in boiling EtOH and in the presence of secondary amines to yield 3‐(dialkylamino)‐1,2‐dihydro‐9‐oxo‐9H‐indeno[2,1‐c]pyridine‐4‐carbonitriles (Schemes 2 and 4, and Fig. 1). The 1,2‐dihydro forms can be dehydrogenated easily with KMnO4 in acetone at 0° (Scheme 3) or chloranil (=2,3,5,6‐tetrachlorocyclohexa‐2,5‐diene‐1,4‐dione) in a ‘one‐pot’ reaction in dioxane at ambient temperature (Table 1). The structures of the indeno[2,1‐c]pyridine‐4‐carbonitriles 5′ and 6a have been verified by X‐ray crystal‐structure analyses (Fig. 2 and 4). The inherent merocyanine system of the dihydro forms results in a broad absorption band in the range of 515–530 nm in their UV/VIS spectra (Table 2 and Fig. 3). The dehydrogenated compounds 5, 5′, and 7a–7f exhibit their longest‐wavelength absorption maximum at ca. 380 nm (Table 2). In contrast to 5 and 5′, 7a–7f in solution exhibit a blue‐green fluorescence with emission bands at around 460 and 480 nm (Table 4 and Fig. 5).
Total Synthesis of the Alkaloid (±)‐Aspidophytine Based on Carbonyl Ylide Cycloaddition Chemistry
Authors: Mejía‐Oneto José M. , Padwa Albert
Published: February 2008

The RhII‐catalyzed cycloaddition cascade of an indolyl‐substituted α‐diazo imide was used for the total synthesis of the complex pentacyclic alkaloid (±)‐aspidophytine. Treatment of the resulting dipolar cycloadduct with BF3⋅OEt2 induces a domino fragmentation cascade. The reaction proceeds by an initial cleavage of the oxabicyclic ring and formation of a transient N‐acyl iminium ion which reacts further with the adjacent tert‐butyl ester and sets the required lactone ring present in aspidophytine. A three‐step sequence was then used to remove both the ester and OH groups. Subsequent functional group manipulations allowed for the high‐yielding conversion to (±)‐aspidophytine.
Three New Pteridines, Hirudinoidines A – C, from Hirudo nipponicaWhitman
Authors: Li You‐Bin , Huang Wei‐Hua , Xiang Yu
Published: February 2008

Three new pteridines, hirudinoidines A – C (1–3, resp.), with novel structural features were isolated from Hirudo nipponica Whitman, and their structures were elucidated on the basis of extensive spectroscopic analyses and by comparison of their spectral data with those of related metabolites. The configuration of 1 was unequivocally confirmed by single‐crystal X‐ray diffraction (Fig. 2).
Pyrrolizidine Alkaloids and Bisabolane Sesquiterpenes from the Roots of Ligularia cymbulifera
Authors: Liu Chun‐Mei , Wang He‐Xiang , Wei Shi‐Lei , Gao Kun
Published: February 2008

The new pyrrolizidine alkaloid glycoside 1, and the three new highly oxygenated bisabolane sesquiterpenes 4–6, together with the two known pyrrolizidine alkaloids 2 and 3, were isolated from the roots of Ligularia cymbulifera (W. W. Smith) Hand.‐Mazz. Their structures were established on the basis of spectroscopic analysis, especially 1D‐ and 2D‐NMR data. The cytotoxic activities of compounds 1, 2, and 4–6 were evaluated against hepatoma (BEL‐7402), human leukemia (HL‐60), human ovarian carcinoma (HO‐8910), and nasopharyngeal carcinoma (KB) cell lines (Tables 1–3). Compound 6 showed weak cell‐growth inhibition of BEL‐7402 cell.
Pteridines. Part CXIX.
Authors: Pfleiderer Wolfgang
Published: February 2008

A variety of pyrimidine precursors 12–25 were converted into a series of new 7‐hydroxylumazines (=7‐hydroxypteridine‐2,4(1H,3H)‐diones) 26–35 which functioned as starting materials for the transformation into the corresponding 7‐chlorolumazines 36–45. Subsequent reaction with hydrazine led to the 7‐hydrazinolumazines 46–55 which gave on nitrosation the 7‐azidolumazines 1 and 56–64. These compounds were subjected to short heating in xylene whereby 1 and 56–61 showed a new pteridine–purine interconversion in forming a new type of 1,3‐disubstituted or 3‐substituted xanthin‐8‐amine‐derived nitrilium ylides (2,3,6,7‐tetrahydro‐N‐methylidyne‐2,6‐dioxo‐1H‐purin‐8‐aminium ylides) 11 and 65–70. The presence of an additional 6‐alkyl substituent in the 7‐azidolumazines 63 and 64 or of an unsubstituted N(3) position in 62 caused further rearrangement to xanthine‐9‐carbonitriles 71–73. Prolonged heating of 7‐azido‐1,3‐dimethyllumazine (1) also afforded theophylline‐9‐carbonitrile (=1,2,3,6‐tetrahydro‐1,3‐dimethyl‐2,6‐dioxo‐9H‐purine‐9‐carbonitrile; 5). The nitrilium ylide function was established by NMR and UV spectra as well as by elemental analyses. Confirmation of the nitrilium ylide structures was suggested by the result of the heating of 1,3‐dimethyl‐N‐methylidynexanthin‐8‐aminium ylide 11 in EtOH or of 1 in pentan‐1‐ol leading to 8‐aminotheophylline (=8‐amino‐3,7‐dihydro‐1,3‐dimethyl‐1H‐purin‐2,6‐dione; 74).
Hydrological response to timber harvest in northern Idaho: implications for channel scour and persistence of salmonids
Authors: Tonina Daniele , Luce Charles H. , Rieman Bruce , Buffington John M. , Goodwin Peter , Clayton Stephen R. , Alì Shawkat Md. , Barry Jeffrey J. , Berenbrock Charles
Published: February 2008

The potential for forest harvest to increase snowmelt rates in maritime snow climates is well recognized. However, questions still exist about the magnitude of peak flow increases in basins larger than 10 km2 and the geomorphic and biological consequences of these changes. In this study, we used observations from two nearly adjacent small basins (13 and 30 km2) in the Coeur d'Alene River basin, one with recent, relatively extensive, timber harvest, and the other with little disturbance in the last 50 years to explore changes in peak flows due to timber harvest and their potential effects on fish. Peak discharge was computed for a specific rain‐on‐snow event using a series of physical models that linked predicted values of snowmelt input to a runoff‐routing model. Predictions indicate that timber harvest caused a 25% increase in the peak flow of the modelled event and increased the frequency of events of this magnitude from a 9‐year recurrence interval to a 3·6‐year event. These changes in hydrologic regime, with larger discharges at shorter recurrence intervals, are predicted to increase the depth and frequency of streambed scour, causing up to 15% added mortality of bull trout (Salvelinus confluentus) embryos. Mortality from increased scour, although not catastrophic, may have contributed to the extirpation of this species from the Coeur d'Alene basin, given the widespread timber harvest that occurred in this region. Copyright © 2008 John Wiley & Sons, Ltd.
Chemical respiratory allergy and occupational asthma: what are the key areas of uncertainty?
Authors: Isola Daniel , Kimber Ian , Sarlo Katherine , Lalko Jon , Sipes I. Glenn
Published: February 2008

There is increasing concern about the association of respiratory disease with indoor air quality and environmental atmospheric pollution. Associated with this is the fact that in many countries there has been a significant increase in the prevalence of asthma. Against this background there is a need to address the toxicological, occupational and public health problems associated with the ability of some chemicals to cause allergic sensitization of the respiratory tract and occupational asthma.

By definition allergic sensitization of the respiratory tract to chemicals is dependent upon the stimulation of an adaptive immune response that leads to development of respiratory allergy and/or asthma. Although IgE antibody is associated typically with respiratory sensitization to protein allergens, there is less certainty about the role played by antibodies of this type in chemical respiratory allergy and occupational asthma. There are currently no validated or widely accepted methods/models for the identification and characterization of chemicals that have the potential to induce allergic sensitization of the respiratory tract.

These and other areas of uncertainty were debated during the course of and following a two day Workshop. The primary purpose of the Workshop was to consider the important clinical and toxicological issues associated with chemical respiratory allergy, and to identify key questions that need to be answered if real progress is to be made. Copyright © 2008 John Wiley & Sons, Ltd.
Viper metalloproteinase (Agkistrodon halys pallas) with antimicrobial activity against multi‐drug resistant human pathogens
Authors: Samy Ramar Perumal , Gopalakrishnakone Ponnampalam , Chow Vincent T.K. , Ho Bow
Published: February 2008

Metalloproteinases are abundant enzymes in crotalidae and viperidae snake venoms. Snake venom metalloproteinases (SVMPs) comprise a family of zinc‐dependent enzymes, which display many different biological activities. A 23.1 kDa protein was isolated from Agkistrodon halys (pallas, Chinese viper) snake venom. The toxin is a single chain polypeptide with a molecular weight of 23146.61 and an N‐terminal sequence (MIQVLLVTICLAVFPYQGSSIILES) relatively similar to that of other metalloprotein‐like proteases isolated from the snake venoms of the Viperidae family. The antibacterial effect of Agkistrodon halys metalloproteinase (AHM) on Burkholderia pseudomallei (strains TES and KHW), Escherichia coli, Enterobacter aerogenes, Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa (Gram‐negative bacteria) and Staphylococcus aureus (Gram‐positive bacterium) was studied at a concentration 120 µM. Interestingly, we found that the metalloproteinase exhibited antibacterial properties and was more active against S. aureus, P. vulgaris, P. mirabilis and multi‐drug resistant B. pseudomallei (strain KHW) bacteria. AHM variants with high bacteriostatic activity (MIC 1.875–60 µM) also tended to be less cytotoxic against U‐937 human monocytic cells up to 1 mM concentrations. These results suggest that this metalloprotein exerts its antimicrobial effect by altering membrane packing and inhibiting mechanosensitive targets. J. Cell. Physiol. 216: 54–68, 2008. © 2008 Wiley‐Liss, Inc.
TNF‐α represses connexin43 expression in hacat keratinocytes via activation of JNK signaling
Authors: Tacheau Chalotte , Laboureau Julien , Mauviel Alain , Verrecchia Franck
Published: February 2008

We used both pharmacological and gene knockout approaches to elucidate the specific roles played by the Jun‐N‐terminal kinase (JNK) and NFκB pathways downstream of TNF‐α in the context of connexin43 (Cx43) gene expression. We demonstrate that TNF‐α reduces the expression of Cx43 in HaCat cell lines at the protein and mRNA levels, and transcriptionally. We also demonstrate that TNF‐α decreases gap junctional intercellular communication (GJIC) between HaCat cells. Using pharmacological inhibitors of the NFκB signaling pathway, we determined that the NFκB signaling cascade is not implicated in TNF‐α effect on Cx43 expression and in the subsequent decrease of GJIC. Conversely, in NFκB essential modulator (NEMO−) fibroblasts, lack of NFκB activation did not influence both the effect of TNF‐α on Cx43 expression and on GJIC. In contrast, pharmacologic inhibition of JNK abolishes TNF‐α‐driven repression of Cx43 gene expression and GJIC between HaCat cells. Using JNK‐JNK (JNK−/−) fibroblasts, we demonstrate that similar regulatory mechanisms take place in fibroblasts. Together, these results identify JNK and not NFκB, as a critical mediator of TNF‐α repressory effect on Cx43 gene expression. J. Cell. Physiol. 216: 438–444, 2008. © 2008 Wiley‐Liss, Inc.
In vivo MR imaging of hippocampal lesions in multiple sclerosis
Authors: Roosendaal Stefan D. , Moraal Bastiaan , Vrenken Hugo , Castelijns Jonas A. , Pouwels Petra J.W. , Barkhof Frederik , Geurts Jeroen J.G.
Published: February 2008

Purpose

To investigate whether a recently improved version of the three‐dimensional double inversion‐recovery (3D‐DIR) technique enables the in vivo detection of hippocampal lesions in multiple sclerosis (MS).

Materials and Methods

Magnetic resonance images of 16 patients and nine healthy control subjects were acquired at 1.5T. Lesions were scored on 3D‐DIR images and were anatomically classified as white matter (WM), cortical, or hippocampal lesions. Associations between hippocampal, cortical, and WM lesion numbers were evaluated. Also, hippocampal lesions were retrospectively assessed on 3D‐T2 and hippocampal and brain volumes were measured.

Results

No hippocampal lesions were detected in control subjects. By contrast, 14 out of 16 MS patients had at least one hippocampal lesion. The mean number (±SD) of hippocampal lesions detected with 3D‐DIR was 2.6 ± 1.8 in MS patients; only 56% of these lesions could be observed on 3D‐T2.

Conclusion

Hippocampal lesions can be visualized in vivo with 3D‐DIR and occur frequently in MS. The ability to visualize hippocampal lesions in vivo is of fundamental importance to future studies focusing on the role of gray matter (GM) damage in cognitive deficits, which are common in MS. J. Magn. Reson. Imaging 2008. © 2008 Wiley‐Liss, Inc.
A fast navigator‐gated 3D sequence for delayed enhancement MRI of the myocardium: Comparison with breathhold 2D imaging
Authors: Nguyen Thanh D. , Spincemaille Pascal , Weinsaft Jonathan W. , Ho Bernard Y. , Cham Matthew D. , Prince Martin R. , Wang Yi
Published: February 2008

Purpose

To develop a rapid navigator‐gated three‐dimensional (3DNAV) delayed‐enhancement MRI (DE‐MRI) sequence for myocardial viability assessment, and to evaluate its performance with breathhold two‐dimensional (2DBH) DE‐MRI sequence as the reference standard.

Materials and Methods

2DBH DE‐MRI was initiated 10 minutes after contrast administration and followed by 3DNAV DE‐MRI in 23 patients at 1.5 T. Comparison was performed using three qualitative criteria (image quality score, diagnostic outcome, relative diagnostic confidence score) in all patients, and three quantitative criteria (infarct volume, infarct signal‐to‐noise ratio [SNRinf], and infarct‐viable myocardium contrast‐to‐noise ratio [CNRinf‐myo]) in patients with hyperenhanced myocardium.

Results

Compared to 2DBH DE‐MRI, 3DNAV DE‐MRI provided slightly better image quality, the same final diagnostic outcomes, and better relative diagnostic confidence score with 79% SNRinf improvement (P = 0.002) and 90% CNRinf‐myo improvement (P = 0.004) in 39% less scan time (414 ± 118 seconds for 2DBH and 251 ± 93 seconds for 3DNAV). The measured infarct volumes demonstrated excellent correlation (18.9 ± 19.0 mL for 2DBH DE‐MRI vs. 17.6 ± 19.0 mL for 3DNAV DE‐MRI, r2 = 0.998, P < 0.001, N = 7) and narrow limits of agreement (–1.3 ± 1.8 mL).

Conclusion

3DNAV DE‐MRI provides improved image quality and similar infarct detection in less scan time compared to the standard 2DBH DE‐MRI. J. Magn. Reson. Imaging 2008. © 2008 Wiley‐Liss, Inc.
Time‐resolved contrast‐enhanced MR angiography of intracranial lesions
Authors: Zou Zhitong , Ma Lin , Cheng Liuquan , Cai Youquan , Meng Xianghui
Published: February 2008

Purpose

To determine if contrast‐enhanced (CE) MRI of intracranial lesions benefits from time‐resolved MR angiography (MRA) during contrast agent injection.

Materials and Methods

For 126 patients with suspected intracranial lesions undergoing routine CE MRI at 3.0T (N = 88) or 1.5T (N = 38), time‐resolved CE MRA (three‐dimensional [3D] time‐resolved imaging of contrast kinetics [TRICKS]) was performed during injection of the routine gadolinium (Gd) dose of 0.1 mmol/kg. Time to peak (TTP) enhancement of lesions as well as time to internal carotid artery (ICA), middle cerebral artery (MCA), superior sagittal sinus (SSS), and jugular vein enhancement were measured. Source and maximum intensity projection (MIP) images were reviewed to delineate the spatial relationship of lesions and the vasculature.

Results

In 61 patients (48%), additional important findings were detected on time‐resolved MRA that were not seen on the routine CE protocol, including aneurysms (N = 6), arteriovenous malformations (N = 7), ICA stenoses (N = 2), vascular anomalies (N = 18), and relationships between lesions and vessels (N = 28). In addition, tumor TTP correlated with glioma grade (r = 0.87) and discriminated epithelial from nonepithelial meningiomas (P = 2.6 × 10–5). MRA added eight minutes to the total exam time.

Conclusion

Time‐resolved MRA performed during contrast agent injection adds information to the routine brain CE MRI examination of intracranial lesions with only a small time penalty and no additional risk to the patient. J. Magn. Reson. Imaging 2008. © 2008 Wiley‐Liss, Inc.
Whole‐brain functional magnetic resonance imaging mapping of acute nociceptive responses induced by formalin in rats using atlas registration‐based event‐related analysis
Authors: Shih Yen‐Yu I. , Chen You‐Yin , Chen Chiao‐Chi V. , Chen Jyh‐Cheng , Chang Chen , Jaw Fu‐Shan
Published: February 2008

Nociceptive neuronal activation in subcortical regions has not been well investigated in functional magnetic resonance imaging (fMRI) studies. The present report aimed to use the blood oxygenation level‐dependent (BOLD) fMRI technique to map nociceptive responses in both subcortical and cortical regions by employing a refined data processing method, the atlas registration‐based event‐related (ARBER) analysis technique. During fMRI acquisition, 5% formalin (50 μl) was injected into the left hindpaw to induce nociception. ARBER was then used to normalize the data among rats, and images were analyzed using automatic selection of the atlas‐based region of interest. It was found that formalin‐induced nociceptive processing increased BOLD signals in both cortical and subcortical regions. The cortical activation was distributed over the cingulate, motor, somatosensory, insular, and visual cortices, and the subcortical activation involved the caudate putamen, hippocampus, periaqueductal gray, superior colliculus, thalamus, and hypothalamus. With the aid of ARBER, the present study revealed a detailed activation pattern that possibly indicated the recruitment of various parts of the nociceptive system. The results also demonstrated the utilization of ARBER in establishing an fMRI‐based whole‐brain nociceptive map. The formalin induced nociceptive images may serve as a template of central nociceptive responses, which can facilitate the future use of fMRI in evaluation of new drugs and preclinical therapies for pain. © 2008 Wiley‐Liss, Inc.
A call for longitudinal research in positive organizational behavior
Authors: Avey James B. , Luthans Fred , Mhatre Ketan H.
Published: February 2008

After defining and providing the current status of psychological capital (PsyCap), we address the need to better understand its stability (i.e., state vs. trait). Specifically, we issue a call for longitudinal research. The balance of this “incubator” article examines the relevance, potential obstacles, and advantages of this design in meeting PsyCap's future research needs. Copyright © 2008 John Wiley & Sons, Ltd.
Gene expression analysis of major lineage‐defining factors in human bone marrow cells: Effect of aging, gender, and age‐related disorders
Authors: Jiang Ying , Mishima Hajime , Sakai Shinsuke , Liu Yin‐kun , Ohyabu Yoshimi , Uemura Toshimasa
Published: February 2008

Adult bone marrow cells (BMCs) include two populations:;mesenchymal stem cells (MSCs), which can differentiate into bone, cartilage, and fat; and hematopoietic stem cells (HSCs), which produce all mature blood lineage. To study the effect of aging, gender, and age‐related disorders on lineage differentiation, we performed quantitative RT‐PCR to examine mRNA expression of the major factors defining BMC lineage, cbfa1 for osteoblasts, ppar‐gamma for adipocytes, sox9 for chondrocytes, and rankl for osteoclasts, in bone marrow from 80 healthy subjects and patients (14–79 years old) with two age‐related disorders: osteoarthritis (OA) and rheumatoid arthritis (RA). Two apoptosis‐related genes, bcl‐2 and drak1, were studied. RANKL and PPAR‐Gamma levels exhibited a clear positive correlation with age in female patients, but not in males, with a slight age‐related decline in CBFa1 transcripts. DRAK1 expression showed an age‐associated ascending trend with significantly greater transcripts of RANKL and DRAK1 in females (p < 0.01). Compared with age‐matched controls, RA patients exhibited increased RANKL, PPAR‐Gamma, and DRAK1 mRNA levels (p < 0.05), and OA showed the higher RANKL and PPAR‐Gamma transcripts (p < 0.05). Furthermore, SOX9 and DRAK1 expressions in the RA group were higher than in the OA group (p < 0.05). Our data indicate that aging and age‐related disorders affect gene expressions differently, suggesting that in aging, the lineage of bone marrow cells was modified with prominent changes in decreased bone marrow osteoblastogenesis, increased adipogenesis and osteoclastogenesis, while in age‐related disorders, marrow adipogenesis and the activity or number of osteoclasts may play an important role in the pathogenesis of arthritic bone loss. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:910–917, 2008
Separation of nonionic compounds by electrokinetic chromatography using an inorganic layered compound as a pseudostationary phase
Authors: Koike Ryo , Kitagawa Fumihiko , Otsuka Koji
Published: February 2008

The use of an inorganic layered compound as a pseudostationary phase (PSP) in EKC was investigated. A synthetic smectite, which is the most typical swellable clay mineral, with an average diameter of 130 nm was selected as the PSP. The retention characteristics of the smectite and on‐line sample concentration by sweeping were examined for the analysis of polyoxyethylene mono phenyl ethers (PPEs) with different degrees of ethoxylation. The retention factor was increased with increase in the number of ethylene oxide groups and a good separation of the PPE homologs was achieved by smectite–EKC. The RSD of the migration time, plate number, and peak area were 0.60, 8.3, and 2.7% (n = 5), respectively. The developed method can be applied to the analysis of PPEs in commercially available consumer products without any sample pretreatments. In addition, ca. 100‐fold sensitivity enhancements for the PPEs with high retention factors were obtained by sweeping.
Micellar electrokinetic chromatography on microchips
Authors: Kitagawa Fumihiko , Otsuka Koji
Published: February 2008

This review highlights the methodological and instrumental developments in microchip micellar EKC (MCMEKC) from 1995. The combination of higher separation efficiencies in micellar EKC (MEKC) with high‐speed separation in microchip electrophoresis (MCE) should provide high‐throughput and high‐performance analytical systems. The chip‐based separation technique has received considerable attention due to its integration ability without any connector. This advantage allows the development of a multidimensional separation system. Several types of 2‐D separation microchips are described in the review. Since complicated channel configurations can easily be fabricated on planar substrates, various sample manipulations can be carried out prior to MCMEKC separations. For example, mixing for on‐chip reactions, on‐line sample preconcentration, on‐chip assay, etc., have been integrated on MEKC microchips. The application of on‐line sample preconcentration to MCMEKC can provide not only sensitivity enhancement but also the elucidation of the preconcentration mechanism due to the visualization ability of MCE. The characteristics of these sample manipulations on MEKC microchips are presented in this review. The scope of applications in MCMEKC covers mainly biogenic compounds such as amino acids, peptides, proteins, biogenic amines, DNA, and oestrogens. This review provides a comprehensive table listing the applications in MCMEKC in relation to detection methods.
Positivity and time behavior of a linear reaction–diffusion system, non‐local in space and time
Authors: Khrabustovskyi Andrii , Stephan Holger
Published: February 2008

We consider a general linear reaction–diffusion system in three dimensions and time, containing diffusion (local interaction), jumps (nonlocal interaction) and memory effects. We prove a maximum principle and positivity of the solution and investigate its asymptotic behavior. Moreover, we give an explicit expression of the limit of the solution for large times. In order to obtain these results, we use the following method: We construct a Riemannian manifold with complicated microstructure depending on a small parameter. We study the asymptotic behavior of the solution to a simple diffusion equation on this manifold as the small parameter tends to zero. It turns out that the homogenized system coincides with the original reaction–diffusion system. Using this and the facts that the diffusion equation on manifolds satisfies the maximum principle and its solution converges to a easily calculated constant, we can obtain analogous properties for the original system. Copyright © 2008 John Wiley & Sons, Ltd.
PAMAM dendrimer‐based contrast agents for MR imaging of Her‐2/neu receptors by a three‐step pretargeting approach
Authors: Zhu Wenlian , Okollie Baasil , Bhujwalla Zaver M. , Artemov Dmitri
Published: February 2008

Pretargeting of receptors is a useful approach in molecular imaging and therapy to reduce background noise or toxicity and enhance selectivity. In this study a three‐step pretargeting approach that includes a biotinylated antibody, avidin/streptavidin, and a biotinylated imaging agent is described. A PAMAM dendrimer generation 4 (G4D)‐based MRI T1 agent biotin‐G4D‐DTPA‐Gd (bG4D‐Gd) and its sister compound with remaining free surface amine groups blocked by succinic anhydride to reduce positive charges (bG4D‐Gd‐SA) were synthesized. Limited selective enhancement in MRI was observed in a Her‐2/neu mouse tumor xenograft by this three‐step pretargeting approach that includes biotinylated trastuzumab, avidin and bG4D‐Gd, or bG4D‐Gd‐SA. However, these dendrimer‐based MRI agents with molecular weight around 29 kD reached and remained in the tumor through the enhanced permeability and retention effect. Prolonged and extensive accumulation of both bG4D‐Gd and b‐G4‐Gd‐SA in the kidneys was also observed. Magn Reson Med, 2008. © 2008 Wiley‐Liss, Inc.
MT effects and T1 quantification in single‐slice spoiled gradient echo imaging
Authors: Ou Xiawei , Gochberg Daniel Frank
Published: February 2008

We investigated magnetization transfer (MT) effects on the steady‐state MR signal for a sample subjected to a series of identical on‐resonance RF pulses, such as would be experienced while imaging a single slice using a spoiled gradient echo sequence. The MT coupling terms for a two‐pool system were added to the Bloch equations and we derived the resulting steady‐state signal equation and compared this result to the conventional signal equation without MT effects. The steady‐state signal is increased by a few percent of the equilibrium magnetization because of MT. One consequence of this MT effect is inaccuracy in T1 values determined via conventional steady‐state gradient echo methods. (Theory predicts greater than 10% errors in T1 for white matter when using short TR.) A second consequence is the ability to quantify the relaxation and MT parameters by fitting the gradient echo steady state signal to the signal equation appropriately modified to include MT effects. The theory was tested in samples of MnCl2, cross‐linked bovine serum albumin (BSA), and cross‐linked BSA + MnCl2. Magn Reson Med, 2008. © 2008 Wiley‐Liss, Inc.
Effect of Gd‐DTPA induCED susceptibility on single‐point dixon fat/water separation
Authors: Hoory Tamar , Ramsay Elizabeth , Plewes Donald B.
Published: February 2008

A single‐point Dixon (SPD) fat/water separation method is proposed for breast dynamic contrast‐enhanced MRI (DCE‐MRI) in which field inhomogeneities and phase offsets measured prior to the injection of gadopentate dimeglumine (Gd‐DTPA) are used to correct the postinjection images. A breast phantom study was conducted to demonstrate this technique, in which varying excess concentrations of Gd‐DTPA (0–3 mM) were introduced into a 25‐cm3 breast lesion. The presence of excess Gd‐DTPA in the lesion was found to create magnetic field perturbations of up to 0.35 μT per mM excess Gd‐DTPA around the lesion. However, these perturbations had a negligible effect on the quality of the fat/water separation for Gd‐DTPA concentrations in the range of, and exceeding, those observed in breast tumors following a standard 0.1 mmole/kg injection. Therefore, we conclude that the preinjection phase data is adequate for the correction of the postinjection images in breast exams. Magn Reson Med, 2008. © 2008 Wiley‐Liss, Inc.
A note on the mesh independence of convergence bounds for additive Schwarz preconditioned GMRES
Authors: Du Xiuhong , Szyld Daniel B.
Published: February 2008

Additive Schwarz preconditioners, when including a coarse grid correction, are said to be optimal for certain discretized partial differential equations, in the sense that bounds on the convergence of iterative methods are independent of the mesh sizeh. Cai and Zou (Numer. Linear Algebra Appl.2002;9:379–397) showed with a one‐dimensional example that in the absence of a coarse grid correction the usual GMRES bound has a factor of the order of$1/\sqrt {h}$. In this paper we consider the same example and show that for that example the behavior of the method is not well represented by the above‐mentioned bound: We use ana posterioribound for GMRES from (SIAM Rev. 2005;47:247–272) and show that for that example a relevant factor is bounded by a constant. Furthermore, for a sequence of meshes, the convergence curves for that one‐dimensional example, and for several two‐dimensional model problems, are very close to each other; thus, the number of preconditioned GMRES iterations needed for convergence for a prescribed tolerance remains almost constant. Copyright © 2008 John Wiley & Sons, Ltd.
Condensed‐phase flame retardation in nylon 6‐layered silicate nanocomposites: Films, fibers, and fabrics
Authors: Shanmuganathan Kadhiravan , Deodhar Sarang , Dembsey Nicholas A. , Fan Qinguo , Patra Prabir K.
Published: February 2008

Flame‐retardant properties of nylon 6/organically modified montmorillonite (OMMT) thin films, fibers, and fabrics were investigated to determine the efficacy of condensed‐phase flame‐retardant mechanism in relation to montmorillonite concentration, sample geometry, and flame test conditions. Horizontal flame spread conducted on thin films revealed no significant difference in burning behavior between nylon 6 and nanocomposites with 5 wt% OMMT. However, with a higher concentration level of 8–10 wt% OMMT, the films burned without any dripping. The flame spread rate was reduced by 30–40% as compared with nylon 6 films. Cone calorimeter study on nanocomposite films showed that the peak heat release rate of nylon 6 was reduced by 65–67% with 8–10 wt% OMMT. Undrawn nanocomposite monofilaments with 10 wt% OMMT burned slowly and steadily in Bunsen flame without dripping. In cone calorimeter, nanocomposite fabrics with 8 wt% OMMT showed reduced heat release rate and mass loss rate compared to nylon 6 fabrics with increase in fabric tightness factor. The mass loss rate was about 40–60% less when compared with nylon 6 fabrics. The fabric char structure remained intact after burning. This demonstrated the interdependence of fabric tightness factor, OMMT concentration, and source of heat flux in forming a protective char and affecting the flammability of fabrics. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
Yield stress and rheological characterization of the low shear zone of an epoxy molding compound for encapsulation of semiconductor devices
Authors: Yoshii Masaki
Published: February 2008

In encapsulation molding of IC packages, the melt flow inside the cavity is generally controlled in a low shear to prevent wire sweep, and other molding defects. Therefore, it is important to evaluate the rheological properties of epoxy molding compounds (EMC) in a low shear zone including determining the yield stress. In this study, a newly specialized Parallel‐Plate Plastometer for EMCs was built up. Using this plastometer, the yield stress and its temperature dependence were clarified, and the rheological properties in the low shear zone were evaluated. As a result, the rheological properties in a low shear zone of 0.1–10 s−1 were characterized using the Herschel–Bulkley viscosity model which introduced the yield stress, the Castro–Macosko equation as a dependency model of cure, and the WLF equation as a dependency model for temperature. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
Lexical studies of Filipino person descriptors: adding personality‐relevant social and physical attributes
Authors: Imperio Shellah Myra , Church A. Timothy , Katigbak Marcia S. , Reyes Jose Alberto S.
Published: February 2008

Lexical studies have focused on traits. In the Filipino language, we investigated whether additional dimensions can be identified when personality‐relevant terms for social roles, statuses and effects, plus physical attributes, are included. Filipino students (N = 496) rated themselves on 268 such terms, plus 253 markers of trait and evaluative dimensions. We identified 10 dimensions of social and physical attributes—Prominence, Uselessness, Attractiveness, Respectability, Uniqueness, Destructiveness, Presentableness, Strength, Dangerousness and Charisma. Most of these dimensions did not correspond in a one‐to‐one manner to Filipino or alternative trait models (Big Five, HEXACO, ML7). However, considerable redundancy was observed between the social and physical attribute dimensions and trait and evaluative dimensions. Thus, social and physical attributes communicate information about personality traits, and vice versa. Copyright © 2008 John Wiley & Sons, Ltd.
Proteomic analysis of S‐nitrosylated proteins in Arabidopsis thaliana undergoing hypersensitive response
Authors: Romero‐Puertas Maria C. , Campostrini Natascia , Mattè Alessandro , Righetti Pier Giorgio , Perazzolli Michele , Zolla Lello , Roepstorff Peter , Delledonne Massimo
Published: February 2008

Nitric oxide (NO) has a fundamental role in the plant hypersensitive disease resistance response (HR), and S‐nitrosylation is emerging as an important mechanism for the transduction of its bioactivity. A key step toward elucidating the mechanisms by which NO functions during the HR is the identification of the proteins that are subjected to this PTM. By using a proteomic approach involving 2‐DE and MS we characterized, for the first time, changes in S‐nitrosylated proteins in Arabidopsis thaliana undergoing HR. The 16 S‐nitrosylated proteins identified are mostly enzymes serving intermediary metabolism, signaling and antioxidant defense. The study of the effects of S‐nitrosylation on the activity of the identified proteins and its role during the execution of the disease resistance response will help to understand S‐nitrosylation function and significance in plants.
Application of proteomics technology for analyzing the interactions between host cells and intracellular infectious agents
Authors: Coiras Mayte , Camafeita Emilio , López‐Huertas María Rosa , Calvo Enrique , López Juan Antonio , Alcamí José
Published: February 2008

Host–pathogen interactions involve protein expression changes within both the host and the pathogen. An understanding of the nature of these interactions provides insight into metabolic processes and critical regulatory events of the host cell as well as into the mechanisms of pathogenesis by infectious microorganisms. Pathogen exposure induces changes in host proteins at many functional levels including cell signaling pathways, protein degradation, cytokines and growth factor production, phagocytosis, apoptosis, and cytoskeletal rearrangement. Since proteins are responsible for the cell biological functions, pathogens have evolved to manipulate the host cell proteome to achieve optimal replication. Intracellular pathogens can also change their proteome to adapt to the host cell and escape from immune surveillance, or can incorporate cellular proteins to invade other cells. Given that the interactions of intracellular infectious agents with host cells are mainly at the protein level, proteomics is the most suitable tool for investigating these interactions. Proteomics is the systematic analysis of proteins, particularly their interactions, modifications, localization and functions, that permits the study of the association between pathogens with their host cells as well as complex interactions such as the host–vector–pathogen interplay. A review on the most relevant proteomic applications used in the study of host–pathogen interactions is presented.
Comparative LC‐MS: A landscape of peaks and valleys
Authors: America Antoine H. P. , Cordewener Jan H. G.
Published: February 2008

Quantitative proteomics approaches using stable isotopes are well‐known and used in many labs nowadays. More recently, high resolution quantitative approaches are reported that rely on LC‐MS quantitation of peptide concentrations by comparing peak intensities between multiple runs obtained by continuous detection in MS mode. Characteristic of these comparative LC‐MS procedures is that they do not rely on the use of stable isotopes; therefore the procedure is often referred to as label‐free LC‐MS. In order to compare at comprehensive scale peak intensity data in multiple LC‐MS datasets, dedicated software is required for detection, matching and alignment of peaks. The high accuracy in quantitative determination of peptide abundancies provides an impressive level of detail. This approach also requires an experimental set‐up where quantitative aspects of protein extraction and reproducible separation conditions need to be well controlled. In this paper we will provide insight in the critical parameters that affect the quality of the results and list an overview of the most recent software packages that are available for this procedure.
Alignment of LC‐MS images, with applications to biomarker discovery and protein identification
Authors: Vandenbogaert Mathias , Li‐Thiao‐Té Sébastien , Kaltenbach Hans‐Michael , Zhang Runxuan , Aittokallio Tero , Schwikowski Benno
Published: February 2008

LC‐MS‐based approaches have gained considerable interest for the analysis of complex peptide or protein mixtures, due to their potential for full automation and high sampling rates. Advances in resolution and accuracy of modern mass spectrometers allow new analytical LC‐MS‐based applications, such as biomarker discovery and cross‐sample protein identification. Many of these applications compare multiple LC‐MS experiments, each of which can be represented as a 2‐D image. In this article, we survey current approaches to LC‐MS image alignment. LC‐MS image alignment corrects for experimental variations in the chromatography and represents a computational key technology for the comparison of LC‐MS experiments. It is a required processing step for its two major applications: biomarker discovery and protein identification. Along with descriptions of the computational analysis approaches, we discuss their relative merits and potential pitfalls.
UV‐induced crosslinking of ring opening metathesis block copolymer micelles
Authors: Sandholzer Martina , Bichler Sabine , Stelzer Franz , Slugovc Christian
Published: February 2008

Statistical and amphiphilic block copolymers bearing cinnamoyl groups were prepared by ring opening metathesis polymerization (ROMP). The UV‐induced [2 + 2] cycloaddition reaction of polymer bound cinnamic acid groups was studied in polymer thin films as well as in block copolymer micelles. In both cases, exposure to UV‐light for 10 min led to a crosslinking conversion of about 60%, as determined by FT‐IR spectroscopy and UV–vis absorption measurements. Time based IR‐spectroscopy revealed a maximum conversion of 78% reached after an irradiation time of about 16 min. For micelles obtained from polymers bearing 5 mol % or more cinnamoyl groups, the crosslinking reaction proceeded smoothly, yielding in crosslinked particles which were stable in a non‐selective solvent (CHCl3). Diameters determined by dynamic light scattering in the selective solvent (MeOH) were similar for both, non‐crosslinked and crosslinked micelles, whereas diameters of crosslinked micelles in the non‐selective solvent (CHCl3) were significantly larger compared to MeOH samples. This strategy of direct self assembly of block‐copolymers in a selective solvent followed by “clean” crosslinking, without the need for additional crosslinking reagents or crosslinking initiators, provides a straight forward approach toward ROMP‐based polymeric nano‐particles. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2402–2413, 2008
Quantitative IR characterization of urea groups in waterborne polyurethanes
Authors: Shi Ying , Zhan Xiaoli , Luo Zhenhuan , Zhang Qinghua , Chen Fengqiu
Published: February 2008

The purpose of this study is to propose a correlation between IR spectra and the urea fraction of waterborne polyurethanes (PUs) to investigate the side reaction, that is, isocyanate–water reaction, during polymerization. This method is based on the decomposition of the spectrum in amide I range, that is, 1600–1800 cm−1, where the bands of interest overlap. Several individual bands present in this region were resolved by employing Fourier self‐deconvolution (FSD) and Gaussian curve‐fitting techniques, and the intensity ratio of urethane's CO to urea's CO was determined. To realize some quantitative measurements, a calibration curve was established with some polyurethane‐urea samples, characterized by 1H NMR, which were used as standards. The concentration ratios of urethane groups to urea groups were determined from 1H NMR. A good correlation was evidenced between IR and 1H NMR measurements. Moreover, waterborne PUs were prepared by miniemulsion polymerization of IPDI with diols. From quantitative IR analysis, it was shown that a vinylic monomer, as a solvent of polyaddition, restrained the isocyanate–water reaction, and this side reaction was influenced by the hydrophilicity of the vinylic monomers. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2433–2444, 2008
Solvent‐free and nonisocyanate melt transurethane reaction for aliphatic polyurethanes and mechanistic aspects
Authors: Deepa P. , Jayakannan M.
Published: February 2008

A novel melt transurethane polycondensation route for polyurethanes under solvent‐free and nonisocyanate condition was developed for soluble and thermally stable aliphatic or aromatic polyurethanes. The new transurethane process was investigated for A + B, A‐A + B, and A‐A + B‐B (A‐urethane and B‐hydroxyl) ‐type condensation reactions, and also monomers bearing primary and secondary urethane or hydroxyl functionalities. The transurethane process was confirmed by 1H and 13C NMR, and molecular weight of the polymers were obtained as Mn = 10–15 × 103 and Mw = 15–45 × 103 g/mol. The mechanistic aspects of the melt transurethane process and role of the catalyst were investigated using model reactions, 1H NMR, and MALDI‐TOF‐MS. The model reactions indicated the occurrence of 97% reaction in the presence of catalyst, whereas its absence gave only less than 2% of the product. The polymer samples were subjected for end‐group analysis using MALDI‐TOF‐MS, which confirms the Ti‐catalyst mediated nonisocyanate pathway in the melt transurethane process. Almost all the polyurethanes were stable up to 280 °C, and the Tg of the polyurethanes can be easily fine‐tuned from −30 to 120 °C by using appropriate diols in the melt transurethane process. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2445–2458, 2008
Numeric simulation of permafrost degradation in the eastern Tibetan Plateau
Authors: Li Dongqing , Chen Jin , Meng Qingzhou , Liu Dengke , Fang Jianhong , Liu Jiankun
Published: February 2008

Rates of permafrost degradation at both the permafrost table and the base of permafrost were simulated using a prescribed rate of increase in mean annual air temperatures of 0.04°C/a for a site in continuous permafrost near Changshitou Mountain, eastern Tibetan Plateau. The results indicate that over 110 years, the permafrost table descends from a depth of 1.20 m to 1.48 m, and that the base of permafrost rises from the initial value of 55.0 m to 15.2 m. The predicted rate of basal permafrost degradation in low moisture content bedrock reaches a peak of 0.58 m/a after 60 years, assuming a constant thermal gradient at the base of 0.018°C/m. The permafrost is persistent due to the ice‐rich nature of the near‐surface soil layers. Copyright © 2008 John Wiley & Sons, Ltd.
Partially circumventing peripheral tolerance for oncogene‐specific prostate cancer immunotherapy
Authors: Neeley Yilin C. , Arredouani Mohamed S. , Hollenbeck Brent , Eng Marvin H. , Rubin Mark A. , Sanda Martin G.
Published: February 2008

BACKGROUND

Failure of cancer immunotherapy is essentially due to immunological tolerance to tumor‐associated antigens (TAAs), as these antigens are also expressed in healthy tissues.

METHODS

Here, we used transgenic adenocarcinoma of mouse prostate (TRAMP) mice, which develop lethal prostate cancer due to prostate‐specific expression of SV40 T antigen (Tag), to evaluate effects of prostatic transformation on oncogene TAA‐specific tolerance and to test the possibility of breaking such tolerance using a modified recombinant vaccinia virus.

RESULTS

We showed that Tag expression in TRAMP mice is uniquely extra‐thymic, and levels of prostatic Tag expression positively correlate with malignant transformation of the prostate. Yet, young tumor‐free TRAMP mice were tolerant to Tag antigen. We therefore attempted overcoming such peripheral oncogene‐specific T cell tolerance through immunization with a vaccinia construct encoding Tag immunogenic epitopes. This vaccination modality showed that oncogene‐specific tolerance was successfully overcome by effective in vivo priming of Tag‐specific cytotoxic T cells (CTLs). However, this was restricted to young TRAMP mice. Tag‐specific CTL from “tumor naïve” young TRAMP mice showed significant anti‐tumor efficacy in vivo by eliminating established heterotopic prostate tumors and prolonging survival in SCID mice harboring Tag‐expressing tumors. In contrast, older TRAMP mice with established prostate tumors exhibited oncogene‐specific tolerance as evidenced by failure to generate Tag‐specific CTL following Tag‐specific immunization.

CONCLUSIONS

Peripheral tolerance can be overcome for effective anti‐tumor therapy following oncogene‐specific immunization. However, this ability to elicit oncogene‐specific CTL is impeded in the tumor‐bearing host, in the context of increased oncogene expression associated with tumor progression. Prostate 68: 715–727, 2008. © 2008 Wiley‐Liss, Inc.