bluuebunny/crossref_metadata_2025 huggingface dataset:
Cover Picture: Heavy‐Metal‐Ion Capture, Ion‐Exchange, and Exceptional Acid Stability of the Open‐Framework Chalcogenide (NH4)4In12Se20 (Chem. Eur. J. 1/2007)
Authors: Manos Manolis J. , Malliakas Christos D. , Kanatzidis Mercouri G.
Published: December 2006

Purely inorganic open‐framework compounds (NH4)4In12Se20 (1) and (NH4)2In12Se19 (2) have been synthesized and their ion‐exchange properties are reported by M. Kanatzidis et al. in their Full Paper on page 51ff. The chalcogenide framework has innate reactivity towards soft heavy‐metal ions (Hg2+, Pb2+, Ag+) and its pores are well suited for their capture. The authors show that 1 can effectively and selectively remove such metal ions from water.
Inhibitory Effect of Umbelliferone Aminoalkyl Derivatives on Oxidosqualene Cyclases from S. cerevisiae, T. cruzi, P. carinii, H. sapiens, and A. thaliana: a Structure–Activity Study
Authors: Oliaro‐Bosso Simonetta , Viola Franca , Taramino Silvia , Tagliapietra Silvia , Barge Alessandro , Cravotto Giancarlo , Balliano Gianni
Published: December 2006

Eighteen coumarin derivatives were tested as inhibitors of oxidosqualene cyclases (OSCs) from Saccharomyces cerevisiae, Trypanosoma cruzi, Pneumocystis carinii, Homo sapiens, and Arabidopsis thaliana, all expressed in an OSC‐defective strain of S. cerevisiae.35 All the compounds have an aminoalkyl chain bound to an aromatic nucleus; unconventional synthetic procedures (microwave‐ and ultrasound‐promoted reactions) were successfully used to prepare some of them. The most interesting structure‐dependent difference in inhibitory activities was observed with an N‐oxide group replacement of the tertiary amino group at the end of the side chain. An interesting species specificity also emerged: T. cruzi OSC was the least sensitive enzyme; P. carinii and A. thaliana OSCs were the most sensitive. The remarkable activities of three compounds on the T. cruzi enzyme and of five of them on the P. carinii enzyme suggest the present series as a promising compound family for the development of novel antiparasitic agents.
Development of an ovarian cancer symptom index
Authors: Goff Barbara A. , Mandel Lynn S. , Drescher Charles W. , Urban Nicole , Gough Shirley , Schurman Kristi M. , Patras Joshua , Mahony Barry S. , Andersen M. Robyn
Published: December 2006

BACKGROUND.

Currently, screening for ovarian cancer is not recommended for the general population. Targeting women with specific symptoms for screening has been evaluated only recently, because it was believed that symptoms had limited specificity.

METHODS.

A case‐control study of 149 women with ovarian cancer, including 255 women who were in a screening program and 233 women who were referred for pelvic/abdominal ultrasound, was conducted by inviting women to complete a survey of symptoms. Patients were divided randomly into an exploratory group and a confirmatory group. Symptom types, frequency, severity, and duration were compared between cases and controls. Logistic regression analyses were used to determine which factors independently predicted cancer in the exploratory group and then were used to develop a symptom index, which was tested for sensitivity and specificity in the confirmatory group.

RESULTS.

Symptoms that were associated significantly with ovarian cancer were pelvic/abdominal pain, urinary urgency/frequency, increased abdominal size/bloating, and difficulty eating/feeling full when they were present for <1 year and occurred >12 days per month. In a logistic regression analysis, symptoms that were associated independently with cancer were pelvic/abdominal pain (P < .001), increased abdominal size/bloating (P<.001), and difficulty eating/feeling full (P = .010). A symptom index was considered positive if any of those 6 symptoms occurred >12 times per month but were present for <1 year. In the confirmatory sample, the index had a sensitivity of 56.7 for early‐stage disease and 79.5% for advanced‐stage disease. Specificity was 90% for women age >50 years and 86.7% for women age <50 years.

CONCLUSIONS.

Specific symptoms in conjunction with their frequency and duration were useful in identifying women with ovarian cancer. A symptom index may be useful for identifying women who are at risk. Cancer 2007. © 2006 American Cancer Society.
Antibody constructs in cancer therapy
Authors: Beckman Robert A , Weiner Louis M. , Davis Hugh M.
Published: December 2006

Whereas over 85% of human cancers are solid tumors, of the 8 monoclonal antibodies (mAbs) currently approved for cancer therapy, 25% are directed at solid tumor surface antigens (Ags). This shortfall may be due to barriers to achieving adequate exposure in solid tumors. Advancements in tumor biology, protein engineering, and theoretical modeling of macromolecular transport are currently enabling identification of critical physical properties for antitumor Abs. It is now possible to structurally modify Abs or even replace full Abs with a plethora of Ab constructs. These constructs include Fab and Fab′2fragments, scFvs, multivalent scFvs (e.g., diabodies and tribodies), minibodies (e.g., scFv‐CH3 dimers), bispecific Abs, and camel variable functional heavy chain domains. The purpose of the article is to provide investigators with a conceptual framework for exploiting the recent scientific advancements. The focus is on 2 properties that govern tumor exposure: 1) physical properties that enable penetration of and retention by tumors, and 2) favorable plasma pharmacokinetics. It is demonstrated that manipulating molecular size, charge, valence, and binding affinity can optimize these properties. These manipulations hold the key to promoting tumor exposure and to ultimately creating successful Ab therapies for solid tumors. Cancer 2007. © 2006 American Cancer Society.
Ovarian cancer symptom index
Authors: Black Sherry Salway , Butler Susan Lowell , Goldman Patricia A. , Scroggins Mary Jackson
Published: December 2006

The ovarian cancer survivor community has long espoused using symptoms to help identify the presence of disease while awaiting the development and validation of an effective diagnostic panel or screening tool. Currently, awareness of these symptoms is the best hope for early detection.
Unimolecular Reactivity of Uracil–Cu2+ Complexes in the Gas Phase
Authors: Lamsabhi Al Mokhtar , Alcamí Manuel , Mó Otilia , Yáñez Manuel , Tortajada Jeanine , Salpin Jean‐Yves
Published: December 2006

The gas‐phase interaction of copper(II) ions with uracil are studied by means of mass spectrometry and B3LYP/6‐311+G(2df,2p)//B3LYP/6‐31G(d) calculations. Positive‐ion electrospray spectra show that the reaction of uracil with copper(II) gives rise to singly charged species, whereby the [Cu(uracilH)]+ complex is the most intense ion in the spectra at low concentration. Mass spectrometry/mass spectrometry (MS/MS) experiments show that the loss of HNCO and NCO are the dominant fragmentation processes, accompanied by a minor loss of CO. A systematic study of the spectra obtained with different labeled species, namely, 2‐13C‐ (m/z 175), 2‐13C,1,3‐15N2‐ (m/z 177) and 3‐15N‐uracil (m/z 175), concludes unambiguously that both the loss of HNCO and NCO involve exclusively C2 and N3, whereas only C4 is involved in the loss of CO. Suitable mechanisms for these fragmentation processes are proposed through a theoretical survey of the corresponding potential energy surface. In these mechanisms, π complexes, which lie high in energy with respect to the global minimum, play a significant role in the loss of NCO; this explains why both products, HNCO and NCO involve the same atoms of the ring.
A transmission line model for metallic carbon nanotube interconnects
Authors: Maffucci A. , Miano G. , Villone F.
Published: December 2006

A transmission line (TL) model describing the propagation of electric signals along metallic single wall carbon nanotube (CNT) interconnects is derived in a simple and self‐consistent way within the framework of the classical electrodynamics. The conduction electrons of metallic CNTs are modelled as an infinitesimally thin cylindrical layer of a compressible charged fluid with friction, moving in a uniform neutralizing background. The dynamic of the electron fluid is studied by means of the linearized hydrodynamic equations with the pressure assumed to be that of a degenerate spin‐½ ideal Fermi gas. Transport effects due to the electron inertia, quantum fluid pressure and electron scattering with the ion lattice significantly influence the propagation features of the TL. The simplicity and robustness of the fluid model make the derivation of the TL equations more straightforward than other derivations recently proposed in the literature and provide simple and clear definitions of the per unit length (p.u.l.) TL parameters. In particular, this approach has provided a new circuit model that can be used effectively in the analysis of networks composed of CNT transmission lines and lumped elements. The differences and similarities between the proposed model and those given in the literature are highlighted. Copyright © 2006 John Wiley & Sons, Ltd.
On the inclusion of geographic information systems (GIS) in global navigation satellite systems (GNSS)
Authors: Sadoun Balqies , Al‐Bayari Omar
Published: December 2006

The latest innovation of the global navigation satellite systems (GNSS) technologies plays an important role in improving the quality and safety of modern life. Most of the applications evolved from the integration between GNSS, geographical information systems (GIS) and wireless communications and networking (WCN) systems. The wide spread applications that are using these technologies include: the automatic vehicle location (AVL), tracking systems, navigation systems, pedestrian navigation systems, intelligent transportation systems, precise positioning, and emergency callers, among others. The location‐based services (LBS) are possible only by the combination of GNSS, GIS and WCN. The growing need for commercial LBS has forced cellular‐phone and network manufacturers to concentrate on positioning solutions, which are even more precise than the regulatory mandates for positioning of emergency callers and other user services and applications. In this paper, we will present a literature review of the GNSS, the three satellite systems GPS, GLONASS and Galileo, which are aimed to support GNSS services, and a comparison between them and their role in creating a GIS. Copyright © 2006 John Wiley & Sons, Ltd.
Linear and Rectangular Trinuclear Phthalocyanines
Authors: Makarov Sergey G. , Suvorova Olga N. , Litwinski Christian , Ermilov Eugeny A. , Röder Beate , Tsaryova Olga , Dülcks Thomas , Wöhrle Dieter
Published: December 2006

Isomeric linear and rectangular trinuclear metal‐free andzinc(II) phthalocyanine complexes connected by common annulated benzene rings have been synthesized by the mixed cyclotetramerization of a 1,2,4,5‐tetracyanobenzene derivative and 4,5‐bis(2,6‐dimethylphenoxy)phthalonitrile. Their electronic‐absorption and fluorescence spectra have been studied in comparison with the corresponding mono‐ and dinuclear phthalocyanines. For the zinc complexes, the molecular orbitals and electronic spectra have been calculated semi‐empirically. The trinuclear phthalocyanines exhibit absorptions up to 940 nm with extinction coefficients up to about 700000 M–1 cm–1, which shows the extension of the π‐electron system.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Paramagnetic (Alkene)Rh and (Alkene)Ir Complexes: Metal or Ligand Radicals?
Authors: de Bruin Bas , Hetterscheid Dennis G. H.
Published: December 2006

In this review a detailed overview is given of the (electronic) structure and reactivity of open‐shell (paramagnetic) alkene rhodium and iridium complexes Mx(alkene) (M = Rh, Ir; x = 0, +II). In most cases these species are highly reactive, but some notable exceptions of stable species for which not much reactivity has been described are also included (section 2). Understanding the electronic structure of the reactive nitrogen‐ligand‐based [MII(por)(alkene)] and [MII(alkene)(N‐ligand)]2+ species (section 3) is complicated by a substantial spin distribution over the metal and the alkene ligand. This dual‐mode metallo‐radical and ligand radical behavior is reflected by their high and diverse reactivity. Metallo‐radical character is demonstrated by a variety of metal‐to‐radical coupling reactions with a series of other radicals, as well as metal‐based allylic hydrogen atom abstractions from MII(α‐alkene) species. On the other hand, (donor induced) ligand radical character is crucial in a variety of M–C and C–C radical coupling reactions, C–O bond formation by oxygenation of MII(alkene) species and alkene “insertions” into (por)M–H bonds. The review concludes with some speculations about possible roles of paramagnetic M(olefin) (M = Rh, Ir) species in catalytic olefin oxygenation and carbene transfer reactions.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Experimental study of the formation of high‐resistivity zones at the gel/buffer interface in CE
Authors: Khozikov Vyacheslav , Kosobokova Olga , Citver Gregory , Tyshko George , Gavrilov Dmitri N. , Gudkov George , Gorfinkel Vera
Published: December 2006

A novel, nondamaging method for experimental characterization of the formation and propagation of high‐resistivity zones in CE, based on the measurement of time‐dependent Joule heating on the outer capillary surface is proposed. The method detects propagation of resistive regions in capillaries in real time and allows the estimation of their velocity and resistance. The presented experimental data are in agreement with the results of the computer simulation as well as with previous data on the subject. The proposed method is useful for the development of new polymers as well as for the refinement and optimization of new CE protocols.
Screening of acetylcholinesterase inhibitors in natural extracts by CE with electrophoretically mediated microanalysis technique
Authors: Tang Zhong‐mei , Wang Zhao‐yan , Kang Jing‐wu
Published: December 2006

An electrophoretically mediated microanalysis (EMMA) method for screening acetylcholinesterase (AChE) inhibitors in natural extracts is described. In this method, solutions of AChE and the mixture of the substrate and the natural extract were successively injected into the capillary, and mixed electrophoretically by applying a voltage for a short time. Afterwards the voltage was reapplied to separate the product from the unreacted substrate and the natural extract. The measured peak area of the product at UV 230 nm represents the enzyme activity. Since the extract is mixed with the substrate, there is no need to separate the components before testing the inhibition. The inhibitory activity of the natural extract as a whole can be easily found if the peak area of the product is reduced. This makes the present method suitable for screening inhibitors in complex mixtures, such as natural extracts. Compared to the commonly used spectrometric method for screening of AChE inhibitors, the major advantage of the present method is the elimination of Ellman reagent, which is essential for the spectrometric method. This not only simplifies the experimental procedure but also minimizes false‐positive results. Moreover, it is an obvious advantage of combining the separation power with the on‐column enzyme assay for further investigating which compound(s) is/are responsible for the inhibition. The method was validated using a commercially available AChE inhibitor tacrine and a small chemical library containing four AChE inhibitors and 32 natural extracts. Inhibitors in natural extracts were identified with the present method.
CE detector based on light‐emitting diodes
Authors: Xiao Dan , Zhao Shulin , Yuan Hongyan , Yang Xiupei
Published: December 2006

CE detectors based on light‐emitting diodes (LEDs) as light sources are receiving considerable attention due to their exceptionally high stability, high intensity, low cost, and a variety of wavelengths in the UV and visible spectrum. This article is a comprehensive review on CE methods using LED‐based detectors with absorbance and fluorescence detection, and several applications on the determination of riboflavin, bacteria, drug, and amino acids in biological samples are described.
Clinical and socio‐demographic characteristics of university students referred to an eating disorders service
Authors: Arcelus Jon , Button Eric
Published: December 2006

This study describes the socio‐demographic characteristics and eating disorders symptomatology of university students assessed by a specialised NHS eating disorders service in the UK over a 4‐year period. Information was gathered on past treatment history, source of referral, details of university and course of study, whether the patient was still open to the service or discharged, and if the patient had dropped out of contact from services. The study also describes the diagnosis of the assessed patients as well as the results of the Eating Disorders Inventory (EDI), Rosenberg Self‐Esteem Scale (RSES) and Revised Symptom Check List 90 (SCL‐90‐R) questionnaires. The study shows that the university students attending an eating disorder service often suffer from severe conditions, which are generally well‐established before they start their university studies. The study discuses the implication of those results in service delivery and future service development. Copyright © 2006 John Wiley & Sons, Ltd and Eating Disorders Association.
Boundary element simulation of DC stray currents in oil industry due to cathodic protection interference
Authors: Metwally I. A. , Al‐Mandhari H. M. , Nadir Z. , Gastli A.
Published: December 2006

This paper presents a 3D theoretical simulation and analysis of DC stray current corrosion (SCC) in oil fields that could contribute to oil leak and finally oil deferment of electric submersible pump (ESP) systems. Application of the boundary element analysis system (BEASY) allowed cathodic protection (CP) interference to be assessed in terms of the normal current density, which is directly proportional to the corrosion rate, rather than using the qualitative approach of measuring the potential shift of the soil. Different real structures consisting of pipelines and/or well casings with different arrangements and interference conditions are simulated. The results reveal that the application of impressed current cathodic protection (ICCP) systems creates DC SCC on other nearby unprotected structures. This is an inherent potential problem with the application of such systems which dominates with decreasing soil conductivity, and/or increasing the anode current density and its proximity to the protected structures. On the contrary, SCC can be reduced by using multi‐groundbed anodes. Copyright © 2006 John Wiley & Sons, Ltd.
GFP chimeric models exhibited a biphasic pattern of mesenchymal cell invasion in tendon healing
Authors: Kajikawa Yoshiteru , Morihara Toru , Watanabe Nobuyoshi , Sakamoto Hirotaka , Matsuda Ken‐ichi , Kobayashi Masashi , Oshima Yasushi , Yoshida Atsuhiko , Kawata Mitsuhiro , Kubo Toshikazu
Published: December 2006

The healing of an injured musculoskeletal system requires an influx of mesenchymal cells that can differentiate into osteoblasts, fibroblasts, chondroblasts, and skeletal myoblasts. However, whether these mesenchymal cells arise from the circulation (bone marrow) or the injured tissues themselves has been controversial. To reveal the spatiotemporal characteristics of the reparative mesenchymal cells, we investigated the healing process after patellar tendon injury using two types of green fluorescent protein (GFP) chimeric rats; one expressing GFP in the circulating cells, and the other expressing it in the patellar tendon. We analyzed the behavior of GFP‐positive cells after experimental tendon injury in both chimeric rats to clarify the origin of reparative cells. At 24 h after the injury, the wound contained circulation‐derived cells but not tendon‐derived cells. Tendon‐derived cells first appeared in the wounded area at 3 days after the injury, and had significantly increased in number with time and had maintained a high level of proliferative activity until 7 days after the injury, whereas the circulation‐derived cells had decreased in number and had been replaced by the tendon‐derived cells. These findings suggest that circulation‐derived and tendon‐derived cells contribute to the healing of tendons in different periods as part of a biphasic process. J. Cell. Physiol. 210: 684–691, 2007. © 2006 Wiley‐Liss, Inc.
Chemotactic peptide fMetLeuPhe induces translocation of the TRPV2 channel in macrophages
Authors: Nagasawa Masahiro , Nakagawa Yuko , Tanaka Shigeyasu , Kojima Itaru
Published: December 2006

The present study was conducted to characterize the regulation and function of TRPV2 in macrophages. Among six members of the TRPV family channels, only the expression of TRPV2 was detected in macrophages. We then determined localization of TRPV2 using TtT/M87 macrophages transfected with TRPV2‐EGFP. In serum‐free condition, most of the TRPV2 signal was located in the cytoplasm and colocalized with the endoplasmic reticulum marker. Treatment with serum induced translocation of some of the TRPV2‐EGFP to the plasma membrane. Serum‐induced translocation was blocked by transfection of short‐form TRPV2 (s‐TRPV2) lacking a pore‐forming region and the sixth transmembrane domain. Addition of a chemotactic peptide formyl Met‐Leu‐Phe (fMLP) also induced translocation of TRPV2‐EGFP to the plasma membrane. The fMLP‐induced translocation was blocked by an inhibitor of PI 3‐kinase, LY294002, and pertussis toxin. Whole‐cell patch clamp analysis showed a Cs+ current in the TtT/M87 cell, which was blocked by an addition of ruthenium red and transfection of either s‐TRPV2 or siRNA for TRPV2. fMLP increased the Cs+ current. fMLP induced a rapid and sustained elevation of cytoplasmic Ca2+ ([Ca2+]C), the sustained phase of which was abolished by removal of extracellular calcium. The sustained elevation of [Ca2+]C was also blocked by ruthenium red, and transfection of either s‐TRPV2 or siRNA. Finally, fMLP‐induced migration of macrophage was blocked by ruthenium red or transfection of s‐TRPV2. These results suggest that fMLP induces translocation of TRPV2 from intracellular compartment to the plasma membrane, and this translocation is critical for fMLP‐induced calcium entry. J. Cell. Physiol. 210: 692–702, 2007. © 2006 Wiley‐Liss, Inc.
Effect of hepatocyte growth factor on methionine adenosyltransferase genes and growth is cell density‐dependent in HepG2 cells
Authors: Yang Heping , Magilnick Nathaniel , Noureddin Mazen , Mato José M. , Lu Shelly C.
Published: December 2006

Hepatocyte growth factor (HGF) is a potent hepatocyte mitogen but its effect in liver cancer is conflicting. Methionine adenosyltransferase (MAT) is an essential enzyme encoded by two genes (MAT1A and MAT2A), while a third gene (MAT2β) encodes for a subunit that regulates the MAT2A‐encoded isoenzyme. MAT1A is silenced while MAT2A and MAT2β are induced in hepatocellular carcinoma (HCC). The current work examined expression of HGF/c‐met in HCC and whether HGF regulates MAT genes and growth in HepG2 cells. We found the mRNA levels of HGF and c‐met are markedly increased in HCC. To study the influence of cell density, HepG2 cells were plated under high‐density (HD) or low‐density (LD) and treated with HGF (10 ng/ml). Cell density had a dramatic effect on MAT1A expression, being nearly undetectable at LD to a ninefold induction under HD. Cell density also determined the effect of HGF. At HD, HGF increased the mRNA levels of p21 and p27, while lowering the levels of MAT genes, cyclin A, and c‐met. At LD, HGF increased the mRNA levels of cyclin A, MAT2A, MAT2β, and c‐met. Consistently, HGF inhibits growth under HD but stimulates growth under LD. HGF induced sustained high ERK activation under HD as compared to LD. In summary, HGF induces genes favoring growth and is mitogenic when HepG2 cells are plated under LD; however, the opposite occurs under HD. This involves cell density‐dependent differences in HGF‐induced ERK activation. This may explain why HGF is mitogenic only when there is loss of cell‐cell contact in vivo. J. Cell. Physiol. 210: 766–773, 2007. © 2006 Wiley‐Liss, Inc.
Thrombospondin‐1 inhibits VEGF levels in the ovary directly by binding and internalization via the low density lipoprotein receptor‐related protein‐1 (LRP‐1)
Authors: Greenaway James , Lawler Jack , Moorehead Roger , Bornstein Paul , LaMarre Jonathan , Petrik Jim
Published: December 2006

VEGF is a potent pro‐angiogenic factor whose effects are opposed by a host of anti‐angiogenic proteins, including thrombospondin‐1 (TSP‐1). We have previously shown that VEGF has important extravascular roles in the ovary and that VEGF and TSP‐1 are inversely expressed throughout the ovarian cycle. To date, however, a causal interaction between TSP‐1 and VEGF has not been identified. Here, we show that TSP‐1 has a direct inhibitory effect on VEGF by binding the growth factor and internalizing it via LRP‐1. Mice lacking TSP‐1 are subfertile and exhibited ovarian hypervascularization and altered ovarian morphology. Treatment of ovarian cells with TSP‐1 decreased VEGF levels and rendered the cells more susceptible to TNFα‐induced apoptosis. Knockdown of TSP‐1, through RNA interference, resulted in overexpression of VEGF and reduced cytokine‐induced apoptosis. In conclusion, we demonstrate a direct inhibitory effect of TSP‐1 on VEGF in the ovary. TSP‐1's regulation of VEGF appears to be an important mediator of ovarian angiogenesis and follicle development. J. Cell. Physiol. 210: 807–818, 2007. © 2006 Wiley‐Liss, Inc.
Calculating expected lung deposition of aerosolized administration of AAV vector in human clinical studies
Authors: Leung Kitty , Louca Emily , Munson Keith , Dutzar Benjamin , Anklesaria Pervin , Coates Allan L.
Published: December 2006

Background

Cystic fibrosis is an autosomal recessive disease affecting approximately 1 in 2500 live births. Introducing the cDNA that codes for normal cystic fibrosis transmembrane conductance regulator (CFTR) to the small airways of the lung could result in restoring the CFTR function. A number of vectors for lung gene therapy have been tried and adeno‐associated virus (AAV) vectors offer promise. The vector is delivered to the lung using a breath‐actuated jet nebulizer. The purpose of this project was to determine the aerosolized AAV (tgAAVCF) particle size distribution (PSD) in order to calculate target doses for lung delivery.

Methods

A tgAAVCF solution was nebulized using the Pari LC Plus (n = 3), and the PSD was determined by coupling laser diffraction and inertial impaction (NGI) techniques. The NGI allowed for quantification of the tgAAVCF at each stage of impaction, ensuring that rAAV‐CFTR vector is present and not empty particles. Applying the results to mathematical algorithms allowed for the calculation of expected pulmonary deposition.

Results

The mass median diameter (MMD) for the tgAAVCF was 2.78 ± 0.43 µm. If the system works ideally and the patient only receives aerosol on inspiration, the patient would receive 47 ± 0% of the initial dose placed in the nebulizer, with 72 ± 0.73% of this being deposited beyond the vocal cords.

Conclusions

This technology for categorizing the pulmonary delivery system for lung gene therapy vectors can be adapted for advanced aerosol delivery systems or other vectors. Copyright © 2006 John Wiley & Sons, Ltd.
Specific adeno‐associated virus serotypes facilitate efficient gene transfer into human and non‐human primate mesenchymal stromal cells
Authors: Chng Keefe , Larsen Stephen R. , Zhou Shangzhen , Wright J. Fraser , Martiniello‐Wilks Rosetta , Rasko John E. J.
Published: December 2006

Mesenchymal stromal cells (MSCs) show great promise for ex vivo gene and cell‐mediated therapies. The immunophenotype and in vitro differentiation capacity of primary baboon MSCs was demonstrated to be near‐identical to that observed in human MSCs. To optimize gene transfer efficiency, we compared the efficiency of serotypes 1, 2, 3, 4, 5, 6, and 8 of adeno‐associated virus (AAV) vectors for their ability to mediate transduction of human and baboon MSCs. AAV serotype 2 vectors were the most efficient in transducing MSCs from humans and baboons. As a reference, human Ad293 cells were transduced with these seven AAV serotypes, and were found to have the highest transduction levels followed by baboon MSCs, and then human MSCs. The order of increasing transduction efficiency for the serotypes tested was similar for human and baboon MSCs, but was different for human Ad293 cells. The transduction efficiency of MSCs isolated from different individuals was comparable within the same species. We also demonstrated that baboon MSCs transduced with AAV serotype 2 vectors retain their potential to differentiate into adipocytes in vitro, and can incorporate into injured muscle tissue of NODSCID mice in vivo. We detected β‐galactosidase reporter gene expression in host muscle tissue for up to 9 weeks in this study, indicating engraftment of transduced baboon MSCs and sustained transgene expression in vivo. Copyright © 2006 John Wiley & Sons, Ltd.
Breast MRI lesion classification: Improved performance of human readers with a backpropagation neural network computer‐aided diagnosis (CAD) system
Authors: Meinel Lina Arbash , Stolpen Alan H. , Berbaum Kevin S. , Fajardo Laurie L. , Reinhardt Joseph M.
Published: December 2006

Purpose

To develop and test a computer‐aided diagnosis (CAD) system to improve the performance of radiologists in classifying lesions on breast MRI (BMRI).

Materials and Methods

A CAD system was developed that uses a semiautomated segmentation method. After segmentation, 42 features based on lesion shape, texture, and enhancement kinetics were computed, and the 13 best features were selected and used as inputs to a backpropagation neural network (BNN). The BNN was trained and tested using the leave‐one‐out method on 80 BMRI lesions (37 benign, 43 malignant). Lesion histopathology was used as the reference standard. Five human readers classified the 80 lesions first without and then with CAD assistance. The performance of the computer classifier and the human readers was assessed using receiver operating characteristic curves; the performance of the human readers was also evaluated using multireader multicase (MRMC) analysis.

Results

The performance of the human readers significantly improved when aided by the CAD system (P< 0.05). MRMC analysis showed that human reader performance with and without CAD system assistance can be generalized to the population of cases (P< 0.001).

Conclusion

A CAD system based on lesion morphology and enhancement kinetics can improve the performance of human readers in classifying lesions on breast MRI. J. Magn. Reson. Imaging 2007. © 2006 Wiley‐Liss, Inc.
Diagnostic accuracy of high‐resolution MRI using a microscopy coil for patients with presumed DCIS following mammography screening
Authors: Zhu Jingzhi , Kurihara Yasuyuki , Kanemaki Yoshihide , Ogata Haruki , Fukuda Mamoru , Nakajima Yasuo , Maeda Ichiro
Published: December 2006

Purpose

To prospectively evaluate the accuracy of high‐resolution (HR)‐MRI as a secondary examination in women with abnormal calcifications detected on mammography.

Materials and Methods

We used a 4.7‐cm microscopy coil to acquire HR‐MRI signal data. We examined 52 women with breast lesions preoperatively using HR‐MRI and vacuum‐assisted core needle biopsy. The lesions were suspicious of malignancy, classified as category 3–5 on mammography (Breast Imaging Reporting and Data System [BI‐RADS]), and without a palpable mass. All visualized suspicious lesions were correlated with histological findings. We compared the HR‐MRI and pathological findings and calculated the sensitivity, specificity, and accuracy.

Results

We compared the breast HR‐MRI results with the gold standard of pathological results for studies of malignancy (DCIS and invasive cancer), and found a sensitivity of 88.5%, specificity of 92.3%, and accuracy of 90.4%. The positive predictive value (PPV) was 92%, and the negative predictive value (NPV) was 88.9%. When breast MRI was compared with pathological results for studies that diagnosed DCIS only, the results revealed a sensitivity of 88.6%, specificity of 88.2%, accuracy of 88.5%, PPV of 93.9%, and NPV of 78.9%.

Conclusion

HR‐MRI using a microscopy coil is a useful, reliable, safe, and minimally invasive procedure that is a good choice for secondary assessment of abnormal calcification in the breast. J. Magn. Reson. Imaging 2007. © 2006 Wiley‐Liss, Inc.
Magnetic resonance voiding cystourethrography for vesicoureteral reflux
Authors: Takazakura Ryutaro , Johnin Kazuyoshi , Furukawa Akira , Nitta Norihisa , Takahashi Masashi , Okada Yusaku , Murata Kiyoshi
Published: December 2006

Purpose

To assess the feasibility of magnetic resonance voiding cystourethrography (MRVCUG) using MR fluoroscopy for evaluation of vesicoureteral reflux (VUR), and its use as a noninvasive alternative to standard VCUG.

Materials and Methods

A total of 22 MR studies of 16 patients (five months to 41 years old) with primary VUR diagnosed by standard VCUG were evaluated. Six patients underwent MR studies and standard VCUG pre‐ and postoperatively. MR fluoroscopy was executed with a non‐enhanced heavily T2‐weighted single‐shot fast spin‐echo (FSE) sequence. The MR findings were correlated with those obtained by the gold standard, standard VCUG.

Results

Of the 44 kidney‐ureter units, 20 were refluxing on MRVCUG and 21 were refluxing on standard VCUG. There were one false‐positive and two false‐negative units. MRVCUG was 90% sensitive with a specificity of 96% for detecting VURs that were calculated based on kidney‐ureter units. Two false‐negative units were found in mild cases (grade I and II). For the units of grade III, IV, and V (high‐grade reflux), MRVCUG detected all of the refluxing renal collecting systems.

Conclusion

MRVCUG can demonstrate high‐grade reflux without ionizing radiation or catheterization. J. Magn. Reson. Imaging 2007. © 2006 Wiley‐Liss, Inc.
Sensitivity comparison of multiple vs. single inversion time pulsed arterial spin labeling fMRI
Authors: van Osch Matthias J.P. , Hendrikse Jeroen , van der Grond Jeroen
Published: December 2006

Purpose

To study the sensitivity for detection of activation for multiple vs. single inversion time (TI) pulsed arterial spin labeling (PASL).

Materials and Methods

The number of activated voxels and the mean t‐statistic over activated voxels was measured by means of multiple and single TI PASL sequences in five volunteers during visual stimulation by means of an alternating checkerboard. Acquisition was performed by means of the transfer insensitive labeling technique (TILT) and TURBO‐TILT.

Results

It was found that the sensitivity for the detection of activation was lower for an individual TI out of a multiple TI sequence than for the corresponding single TI acquisition of equal duration. After averaging over all TIs between and including 600 and 1400 msec, the number of activated voxels and mean t‐statistic were no longer statistically lower for the multiple TI sequence than for the single TI experiment.

Conclusion

Multiple TI PASL can be used for functional MRI (fMRI) studies, when performing the detection of activated brain regions on data that is averaged over all TIs between 600 and 1400 msec. Subsequently the multi‐TI data can be used to quantify cerebral blood flow (CBF) changes upon activation. Additionally, we have shown that single TI PASL fMRI overestimates the CBF changes upon activation due to transit time changes. J. Magn. Reson. Imaging 2007. © 2006 Wiley‐Liss, Inc.
MRI of the lung: Value of different turbo spin‐echo, single‐shot turbo spin‐echo, and 3D gradient‐echo pulse sequences for the detection of pulmonary metastases
Authors: Bruegel Melanie , Gaa Jochen , Woertler Klaus , Ganter Carl , Waldt Simone , Hillerer Claudia , Rummeny Ernst J.
Published: December 2006

Purpose

To compare the value of different MRI sequences of the lung for the detection of pulmonary metastases.

Materials and Methods

A total of 28 patients with 225 pulmonary metastases confirmed at multidetector‐row computed tomography (MDCT) underwent MRI of the lung, including breathhold T2‐weighted single‐shot turbo spin‐echo (half‐Fourier single‐shot turbo spin‐echo [HASTE] and inversion recovery [IR]‐HASTE) and conventional turbo spin‐echo (TSE and short‐tau inversion recovery [STIR]) sequences, a respiratory‐ and pulse‐triggered black‐blood STIR sequence (triggered STIR), and breathhold pre‐ and postcontrast volumetric interpolated 3D gradient‐echo (VIBE) sequences. MR images were reviewed by three independent observers and results were correlated with MDCT, which served as standard of reference. Lesion‐to‐lung contrast‐to‐noise ratios (CNRs) and image artifacts were also assessed.

Results

CNRs were highest on TSE images (P < 0.001). Mean sensitivities for lesion detection with triggered STIR, TSE, and STIR were 72.0%, 69.0%, and 63.4%, respectively. With HASTE, IR‐HASTE, and pre‐ and postcontrast VIBE, significantly lower sensitivities were obtained (P < 0.05), although artifacts due to physiological motion were less distinct with these sequences compared to TSE and STIR (P < 0.05).

Conclusion

Conventional TSE sequences are more sensitive in depicting pulmonary metastases than single‐shot TSE or 3D gradient‐echo sequences. Respiratory and pulse triggering can improve lesion detection, but increases acquisition time substantially. J. Magn. Reson. Imaging 2007. © 2006 Wiley‐Liss, Inc.
Detection and validated quantification of nine herbal phenalkylamines and methcathinone in human blood plasma by LC‐MS/MS with electrospray ionization
Authors: Beyer Jochen , Peters Frank T. , Kraemer Thomas , Maurer Hans H.
Published: December 2006

The herbal stimulants Ephedra species, Catha edulis (khat), and Lophophora williamsii (peyote) have been abused for a long time. In recent years, the herbal drug market has grown owing to publicity on the Internet. Some ingredients of these plants are also ingredients of cold remedies. The aim of the presented study is to develop a multianalyte procedure for detection and validated quantification of the phenalkylamines ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedrine, methylpseudoephedrine, cathinone, mescaline, synephrine (oxedrine), and methcathinone in plasma. After mixed‐mode solid‐phase extraction of 1 ml of plasma, the analytes were separated using a strong cation exchange separation column and gradient elution. They were detected using a Q‐Trap LC‐ESI‐MS/MS system (MRM mode). Calibration curves were used for quantification using norephedrine‐d3, ephedrine‐d3, and mescaline‐d9 as internal standards. The method was validated according to international guidelines. The assay was selective for the tested compounds. It was linear from 10 to 1000 ng/ml for all analytes. The recoveries were generally higher than 70%. Accuracy ranged from − 0.8 to 20.0%, repeatability from 2.5 to 12.3%, and intermediate precision from 4.6 to 20.0%. The lower limit of quantification was 10 ng/ml for all analytes. No instability was observed after repeated freezing and thawing or in processed samples. The applicability of the assay was tested by analysis of authentic plasma samples after ingestion of different cold medications containing ephedrine or pseudoephedrine, and after ingestion of an aqueous extract of Herba Ephedra. After ingestion of the cold medications, only the corresponding single alkaloids were detected in human plasma, whereas after ingestion of the herb extract, all six ephedrines contained in the plant were detected. The presented LC‐MS/MS assay was found applicable for sensitive detection and accurate and precise quantification of all studied analytes in plasma. Copyright © 2006 John Wiley & Sons, Ltd.
Leaving group effects on the selectivity of the gas‐phase fragmentation reactions of side chain fixed‐charge‐containing peptide ions
Authors: Roberts Kade D. , Reid Gavin E.
Published: December 2006

The effect of trialkylsulfonium versus quaternaryalkylammonium ions on the multistage gas‐phase fragmentation reactions of side chain, fixed‐charge, cysteine‐containing peptides has been examined in a quadrupole linear ion trap. These tandem mass spectrometry experiments reveal that selective loss of dialkylsulfide from fixed‐charge sulfonium ion derivatives is the dominant fragmentation pathway regardless of the degree of proton mobility, indicating that it is the most energetically favored fragmentation pathway. In contrast, the loss of trimethylamine from the side chain of fixed‐charge ammonium‐ion‐containing cysteine derivatives appears to be less energetically favored, and as a result extensive charge‐remote fragmentation is observed under low proton mobility conditions, while under conditions of high proton mobility, amide bond fragmentation reactions dominate. These findings are supported by molecular orbital calculations at the B3LYP/6‐31 + G(d, p) level of theory, which showed that the neutral loss of dimethylsulfide is both thermodynamically and kinetically preferred over the loss of trimethylamine. Copyright © 2006 John Wiley & Sons, Ltd.
Regeneration of nigrostriatal dopaminergic axons by degradation of chondroitin sulfate is accompanied by elimination of the fibrotic scar and glia limitans in the lesion site
Authors: Li Hong‐Peng , Homma Akiko , Sango Kazunori , Kawamura Koki , Raisman Geoffrey , Kawano Hitoshi
Published: December 2006

Chondroitin sulfate increases around a lesion site after central nervous system injury and is believed to be an impediment to axonal regeneration, because administration of chondroitinase ABC, a chondroitin sulfate‐degrading enzyme, promotes axonal regeneration of central neurons. To examine the physiological role of chondroitin sulfate up‐regulation after injury, the nigrostriatal dopaminergic axons were unilaterally transected in mice, and chondroitinase ABC was then injected into the lesion site. In mice transected only, tyrosine hydroxylase‐immunoreactive axons did not extend across the lesion at 1 or 2 weeks after the transection. Immunoreactivities of chondroitin sulfate side chains and core protein of NG2 proteoglycan increased in and around the lesion site, and a fibrotic scar containing type IV collagen deposits developed in the lesion center. In contrast, in mice transected and treated with chondroitinase ABC, numerous tyrosine hydroxylase‐immunoreactive axons were regenerated across the lesion at 1 and 2 weeks after the transection. In these animals, chondroitin sulfate immunoreactivity remarkably decreased, and immunoreactivity of 2B6 antibody, which recognizes the stub of degraded chondroitin sulfate side chains, was enhanced. Furthermore, the formation of a fibrotic scar and a glia limitans that surrounds the former was completely prevented, although type IV collagen immunoreactivity remained in newly formed blood capillaries around the lesion site. We discuss the question of whether the chondroitin sulfate is acting as a direct inhibitor of axonal regeneration or whether the observed changes are due to a prevention of the fibrotic scar formation and a rearrangement of astrocytic membranes. © 2006 Wiley‐Liss, Inc.
Late human cytomegalovirus (HCMV) proteins inhibit differentiation of human neural precursor cells into astrocytes
Authors: Odeberg Jenny , Wolmer Nina , Falci Scott , Westgren Magnus , Sundtröm Erik , Seiger Åke , Söderberg‐Nauclér Cecilia
Published: December 2006

Human cytomegalovirus (HCMV) is the most common cause of congenital infections in developed countries, with an incidence varying between 0.5–2.2%. Such infection may be the consequence of either a primary infection or reactivation of a latent infection in the mother and the outcome may vary from asymptomatic to severe brain disorders. Moreover, infants that are asymptomatic at the time of birth may still develop neurologic sequelae at a later age. Our hypothesis is that infection of stem cells of the central nervous system by HCMV alters the proliferation, differentiation or migration of these cells, and thereby gives rise to the brain abnormalities observed. We show that infection of human neural precursor cells (NPCs) with the laboratory strain Towne or the clinical isolate TB40 of HCMV suppresses the differentiation of these cells into astrocytes even at an multiplicity of infection (MOI) as low as 0.1 (by 33% and 67%, respectively). This inhibition required active viral replication and the expression of late HCMV proteins. Infection as late as 24 hr after the onset of differentiation, but not after 72 hr, also prevented the maturation of infected cultures. Furthermore, in cultures infected with TB40 (at an MOI of 1), approximately 54% of the cells were apoptotic and cell proliferation was significantly attenuated. Clearly, HCMV can reduce the capacity of NPCs to differentiate into astrocytes and this effect may provide part of the explanation for the abnormalities in brain development associated with congenital HCMV infection. © 2006 Wiley‐Liss, Inc.
Job control and occupational health: the moderating role of national R&D activity
Authors: Daniels Kevin , Tregaskis Olga , Seaton Jonathan S.
Published: December 2006

Workers (n = 17 275) from 14 European Union (EU) member states provided data on job control, job dissatisfaction, perceived risk of occupational stress, and absence. For each state, level of research and development (R&D) activity was assessed. Associations between individual levels of control and occupational health were stronger where national R&D activity was higher. The moderation occurred for individuals' levels of control in relation to job dissatisfaction, perceived risk of occupational stress, and absence. The findings with job dissatisfaction and absence were replicated in a sample of workers from 10 Eastern European former Communist countries (n = 7926). Copyright © 2007 John Wiley & Sons, Ltd.
Comparative Raman spectroscopic analysis of orientation in fibers and regenerated films of Bombyx mori silk fibroin
Authors: Preghenella Michele , Pezzotti Giuseppe , Migliaresi Claudio
Published: December 2006

This study is focused on the Raman spectroscopic analysis of degummed silk fibroin (SF) fibers and regenerated Bombyx mori silk fibroin films: a correlation was found between some spectral features related to the methylene deformation modes and the molecular orientation of the samples.

Polarized Raman spectra on SF fibers were used to obtain the orientation distribution function of carbonyl groups along the protein backbone. The variation of the intensity ratio of 1400/1450 cm−1 for the peaks attributed to the wagging and bending deformation modes of CH2 groups with respect to the angular orientation of the fiber was measured and quantitatively correlated with the orientation distribution function of the carbonyl groups.

Unpolarized Raman spectra were measured for regenerated silk fibroin films and lyophilized solutions. The variation of the intensity ratio of 1415/1455 cm−1, which is related to the deformation modes of CH2 groups in SF regenerated materials, was qualitatively related to the microstructural orientation of the samples observed by scanning electron microscopy (SEM), and to the presence of Silk I phase as suggested by the analysis of samples obtained in different casting conditions and also by the measurements on mechanically deformed films.

The results obtained showed the utility of the spectroscopic intensity ratio of 1400/1450 cm−1 for the rapid assessment of molecular orientation in silk fibers, which could be useful for quality and process control of regenerated silk‐based textiles. Moreover, the qualitative dependence of the intensity ratio of 1415/1455 cm−1 was found to be sensitive to both the microstructural orientation and Silk I content of regenerated silk fibroin films, suggesting a possible correlation of this Raman marker of the Silk I phase with the degree of molecular order brought about by this polymorph. Copyright © 2006 John Wiley & Sons, Ltd.