bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic mastocytosis in adults: 2011 update on diagnosis, risk stratification, and management
Authors: Pardanani Animesh
Published: March 2011

Disease overview: Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extracutaneous organs.

Diagnosis: The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V.

Risk stratification: The prognostic relevance of the 2008 World Health Organization (WHO) classification of SM has recently been confirmed. Classification of SM patients into indolent (SM), aggressive SM (ASM), SM associated with a clonal non‐MC lineage disease (SM‐AHNMD), and mast cell leukemia (MCL) subgroups is a useful first step in establishing prognosis.

Risk‐adapted therapy: SM treatment is generally palliative. ISM patients have a normal life expectancy and receive symptom‐directed therapy; infrequently, cytoreductive therapy may be indicated for refractory symptoms. ASM patients have disease‐related organ dysfunction; interferon‐α (±corticosteroids) can control dermatological, hematological, gastrointestinal, skeletal, and mediator‐release symptoms, but is hampered by poor tolerability. Similarly, cladribine has broad therapeutic activity, with particular utility when rapid MC debulking is indicated; the main toxicity is myelosuppression. Imatinib has a therapeutic role in the presence of an imatinib‐sensitive KIT mutation or in KITD816‐unmutated patients. Treatment of SM‐AHNMD is governed primarily by the non‐MC neoplasm; hydroxyurea has modest utility in this setting. Dasatinib's in vitro anti‐ KITD816V activity has not translated into significant therapeutic activity in most SM patients. In contrast, preliminary data suggest that Midostaurin may produce significant decreases in MC burden in some patients. Am. J. Hematol. 86:363–371, 2011. © 2011 Wiley‐Liss, Inc.
Identification of prognostic factors for plerixafor‐based hematopoietic stem cell mobilization
Authors: Basak Grzegorz W. , Jaksic Ozren , Koristek Zdenek , Mikala Gabor , Mayer Jiri , Masszi Tamas , Labar Boris , Wiktor‐Jedrzejczak Wieslaw ,   for the Central and Eastern European Leukemia Group (CELG)
Published: March 2011

The introduction of plerixafor has enabled successful collection of stem cells in the majority of patients with lymphoma or myeloma in whom previous attempts at mobilization have failed. However, a proportion of patients have been shown to be resistant to this mobilization regimen. To identify the factors that impair stem cell mobilization and collection with plerixafor, we reviewed the data for 197 patients who had undergone mobilization with plerixafor and granulocyte‐colony stimulating factor in Central Europe. Predictors of mobilization failure were evaluated using logistic regression analysis. Among the 197 patients mobilized, the target of ≥2.0 × 106 CD34+ cells/kg was collected from 133 (67.5%). Our analysis revealed that previous treatment with lenalidomide, bortezomib, melphalan, radiotherapy, or autologous stem cell transplantation and regimen of plerixafor use in combination with chemotherapy had no significant effect on the efficiency of collection. In contrast, an age ≥65 years (odds ratio 0.331, 95% CI: 0.112–0.977, P < 0.05), a diagnosis of non‐Hodgkin's lymphoma (odds ratio 0.277, 95% CI: 0.124–0.622, P < 0.01), and treatment with ≥ four chemotherapy regimens (odds ratio 0.366, 95% CI: 0.167–0.799, P < 0.05) were associated significantly with failed mobilization. The rate of successful mobilizations was decreased in patients treated with purine analogues (odds ratio 0.323, 95% CI: 0.096–1.094, P = 0.07) but increased in female patients (odds ratio 1.961, CI: 0.943–4.080, P = 0.07). Patients who are characterized by the above negative features could benefit potentially from further improvement in the mobilization strategy. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.
Diagnosis and prevalence of uterine leiomyomata in female chimpanzees (Pan troglodytes)
Authors: Videan E.N. , Satterfield W.C. , Buchl S. , Lammey M.L.
Published: March 2011

Uterine leiomyomata are common, affecting 70–80% of women between 30 and 50 years of age. Leiomyomata have been reported for a variety of primate species, although prevalence rates and treatments have not been widely reported. The prevalence, diagnosis, and treatment of uterine leiomyomata in the Alamogordo Primate Facility and the Keeling Center for Comparative Medicine and Research were examined. Uterine leiomyomata were diagnosed in 28.4% of chimpanzees with an average age at diagnosis of 30.4±8.0 years. Advanced age (>30 years) was related to an increase in leiomyomata and use of hormonal contraception was related to a decrease in leiomyomata. As the captive chimpanzee population ages, the incidence of leiomyomata among female chimpanzees will likely increase. The introduction of progesterone‐based contraception for nonbreeding research and zoological chimpanzees may reduce the development of leiomyomata. Finally, all chimpanzee facilities should institute aggressive screening programs and carefully consider treatment plans. Am. J. Primatol. 73:665–670, 2011. © 2011 Wiley‐Liss, Inc.
J‐Aggregate: von ihrer zufälligen Entdeckung bis zum gezielten supramolekularen Aufbau funktioneller Farbstoffmaterialien
Authors: Würthner Frank , Kaiser Theo E. , Saha‐Möller Chantu R.
Published: March 2011

J‐Aggregate sind von Interesse für organische Materialen, die mithilfe supramolekularer Ansätze konzipiert werden. Ihre Entdeckung in den 1930er Jahren war ein Meilenstein der Farbstoffchemie und ein Startpunkt für die supramolekulare Chemie. Die interessanten optischen Eigenschaften von J‐Aggregaten (besonders ihre sehr schmalen, im Vergleich zu denen des Monomers rotverschobenen Absorptionsbanden und ihre Fähigkeit zur Delokalisierung und zum Transport von Excitonen) sowie das daraus resultierende Anwendungspotenzial motivierten Wissenschaftler, sich mit J‐Aggregaten zu befassen, weshalb bereits zahlreiche Beiträge zu diesem Gebiet veröffentlicht wurden. Dieser Aufsatz gibt einen Überblick über nach supramolekularen Konstruktionsprinzipien hergestellte J‐Aggregate verschiedener Farbstoffklassen (darunter Cyanine, Porphyrine, Phthalocyanine und Perylenbisimide) und diskutiert ihre optischen und photophysikalischen Eigenschaften sowie ihre Anwendungsperspektiven. Damit sollte dieser Übersichtsartikel für die supramolekulare und Photochemie wie auch die Materialwissenschaften von Interesse sein.
Comment on “A Low‐Spin Ruthenium(IV)–Oxo Complex: Does the Spin State Have an Impact on the Reactivity”
Authors: Schröder Detlef , Shaik Sason
Published: March 2011

Slippery spin states: When the metal center in a transition‐metal complex can adopt multiple spin states, the reactivity of the complex may be influenced. In such cases, care must be taken that experimental and computational evidence are interpreted correctly.
A fundamental analysis of continuous flow bioreactor and membrane reactor models with non‐competitive product inhibition. III. Linear inhibition
Authors: Nelson Mark Ian , Lim Wei Xian
Published: March 2011

The steady‐state production of a product produced through the growth of microorganisms in a continuous flow bioreactor is presented. A generalised reactor model is used in which both the classic well‐stirred bioreactor and the idealised membrane bioreactor are considered as special cases. The reaction is assumed to be governed by Monod growth kinetics subject to non‐competitive product inhibition. Inhibition is modelled as a decreasing linear function of the product concentration with a finite cut‐off. This reaction scheme is well documented in the literature, although a stability analysis of the governing equations has not previously been presented.

The steady‐state solutions for the models have been obtained, and the stability has been determined as a function of the residence time. The key dimensionless parameter (γ) that controls the degree of non‐competitive product inhibition is obtained by scaling of the equations, and its effect on the reactor performance is quantified in the limit when product inhibition is ‘small’ and ‘large’. The parameter γ is the reciprocal of a scaled inhibition constant (Pm) that depends upon the substrate and product yield factors and the Monod constant (). © 2011 Curtin University of Technology and John Wiley & Sons, Ltd.
Event correlation analysis for alarm system rationalization
Authors: Noda Masaru , Higuchi Fumitaka , Takai Tsutomu , Nishitani Hirokazu
Published: March 2011

Event correlation analysis is a data‐mining method that detects statistical similarities among discrete occurrences of alarms or operations. By grouping correlated events based on degree of similarity, a policy for reducing alarms and operations can be designed more easily than by analyzing individual alarms and operations. In this study, event correlation analysis was applied to event log data at an Idemitsu Kosan ethylene plant in Japan to reduce the number of alarms and operations, where events are defined by both tag names and types of tag. The obtained results were helpful for identifying unnecessary alarms and operations, such as sequential alarms and routine operations, buried in a lot of noisy plant data. Copyright © 2011 Curtin University of Technology and John Wiley & Sons, Ltd.
A new result on state feedback robust stabilization for discrete‐time fuzzy singularly perturbed systems
Authors: Chen Jinxiang , Yin Yixin , Sun Fuchun
Published: March 2011

This paper presents the novel results for stabilizing uncertain standard discrete‐time fuzzy singularly perturbed systems (SPSs) via a state feedback control law. Two standard discrete‐time fuzzy SPSs are constructed firstly by using the Takagi‐Sugeno (T‐S) fuzzy model. Based on a matrix spectral norm approach, two new ε‐dependent stability conditions are derived, which guarantee the resulting closed‐loop systems are asymptotically stable. The gains of controllers are obtained by solving a set of ε‐dependent linear matrix inequalities (LMIs). In contrast to the existing results, the proposed methods have two advantages: (i) the designed controllers can overcome the external disturbances and parameter uncertainty; and (ii) the upper bound of ε is improved, especially it is not required to be smaller than one. Examples are provided to illustrate the reduced conservatism of our results.

Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Solution structure of an alternate conformation of helix27 fromEscherichia coli16S rRNA
Authors: Spano Meredith Newby , Walter Nils G.
Published: March 2011

Helix (H)27 of 16S ribosomal (r)RNA fromEscherichia coliwas dubbed the “switch helix” when mutagenesis suggested that two alternative base pair registers may have distinct functional roles in the bacterial ribosome. Although more recent genetic analyses suggest that H27 conformational switching is not required for translation, previous solution studies demonstrated that the isolatedE. coliH27 can dynamically convert between the 885 and 888 conformations. Here, we have solved the nuclear magnetic resonance solution structure of a locked 888 conformation. NOE and residual dipolar coupling restraints reveal an architecture that markedly differs from that of the 885 conformation found in crystal structures of the bacterial ribosome. In place of the loop E motif that characterizes the 885 conformer and that the 888 conformer cannot adopt, we find evidence for an asymmetrical A‐rich internal loop stabilized by stacking interactions among the unpaired A's. Comparison of the isolated H27 888 solution structure with the 885 crystal structure within the context of the ribosome suggests a difference in overall length of H27 that presents one plausible reason for the absence of H27 conformational switching within the sterically confining ribosome. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 653–668, 2011.
A chemically synthesized peptoid‐based drag‐tag enhances free‐solution DNA sequencing by capillary electrophoresis
Authors: Haynes Russell D. , Meagher Robert J. , Barron Annelise E.
Published: March 2011

We report a capillary‐based DNA sequencing read length of 100 bases in 16 min using end‐labeled free‐solution conjugate electrophoresis (FSCE) with a monodisperse poly‐N‐substituted glycine (polypeptoid) as a synthetic drag‐tag. FSCE enabled rapid separation of single‐stranded (ss) DNA sequencing fragments with single‐base resolution without the need for a viscous DNA separation matrix. Protein‐based drag‐tags previously used for FSCE sequencing, for example, streptavidin, are heterogeneous in molar mass (polydisperse); the resultant band‐broadening can make it difficult to obtain the single‐base resolution necessary for DNA sequencing. In this study, we synthesized and HPLC‐purified a 70mer poly‐N‐(methoxyethyl)glycine (NMEG) drag‐tag with a molar mass of ∼11 kDa. The NMEG monomers that comprise this peptoid drag‐tag are interesting for bioanalytical applications, because the methoxyethyl side chain's chemical structure is reminiscent of the basic monomer unit of polyethylene glycol, a highly biocompatible commercially available polymer, which, however, is not available in monodisperse preparation at an ∼11 kDa molar mass. This is the first report of ssDNA separation and of four‐color, base‐by‐base DNA sequencing by FSCE through the use of a chemically synthesized drag‐tag. These results show that high‐molar mass, chemically synthesized drag‐tags based on the polyNMEG structure, if obtained in monodisperse preparation, would serve as ideal drag‐tags and could help FSCE reach the commercially relevant read lengths of 100 bases or more. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96:702–707, 2011.
Mechanism of kinase inactivation and nonbinding of fratide to GSK3β due to K85M mutation: Molecular dynamics simulation and normal mode analysis
Authors: Lu ShaoYong , Jiang YongJun , Lv Jing , Zou JianWei , Wu TianXing
Published: March 2011

As a serine/threonine protein kinase, glycogen synthase kinase 3β (GSK3β) is an essential component of several cellular processes, including insulin, growth factor, and Wnt signaling. The conserved K85 is important to GSK3β activity and FRATide binding. To elucidate the mechanisms concerning kinase inactivation and nonbinding of FRATide to GSK3β, molecular dynamics (MD) simulation, molecular mechanics generalized Born/surface area (MM_GBSA) calculation, and normal mode analysis (NMA) were performed on both the wild‐type (WT) and the K85M mutation of the GSK3β‐FRATide complex. The results revealed that the periodic open‐closed conformational change of the G loop, together with the compact conformation of the RD pocket, was disturbed in the K85M mutant, in contrast to those in the WT. This in turn caused inhibition of GSK3β. Specifically, the correct folding pattern of GSK3β was disrupted in the K85M mutant, resulting in the loss of two key hydrogen bonds between K214 of FRATide and E290 and K292 of GSK3β, respectively. Furthermore, MM_GBSA calculations indicated that the K85M mutation could lead to a less energy‐favorable GSK3β‐FRATide complex. In addition, NMA demonstrated that the “rocking” of the N‐ and C‐terminal domains of GSK3β, which coordinates the mutual movement of both lobes, inducing the opening and closing of the active site of GSK3β, which may assist the entry of ATP into the ATP binding site and the release of the ADP product. Strikingly, this phenomenon was not clearly observed in the K85M mutation. This study provides a structural basis for the effect of the K85M mutation on the GSK3β‐FRATide complex. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 669–;681, 2011.
Overproduction of human M3 muscarinic acetylcholine receptor: An approach toward structural studies
Authors: Romero‐Fernandez Wilber , Garriga Pere , Borroto‐Escuela Dasiel O.
Published: March 2011

Human M3 muscarinic acetylcholine receptor (M3R), present in both the central and the peripheral nervous system, is involved in several neurodegenerative and autoimmune diseases. Recently, M3R overexpression has been suggested to play a role in certain forms of cancer, showing promise as a new potential pharmacological target. However, the lack of structural information hampered to develop a new potent selective and potent antagonist. We describe here different strategies for overexpressing functional M3R on the perspective of future biophysical studies. To achieve this goal, four tagged M3R genes were engineered and codon optimized. Different heterologous expression systems, including mammalian cells and viral transfection, were employed to overexpress M3R. Although codon optimization resulted in only twofold to threefold increase of M3R expression, we found that epitope tagging of the synthetic M3R, especially with hemagglutinin and Flag epitope tags, could improve M3R expression levels. On the other hand, viral transfection led to a yield of 27 pmol/mg protein that is the highest level reported so far for this receptor subtype in mammalian cells. Taking together several of the strategies used can help increasing M3R expression, not only to start purification efforts but also for secondary structural analysis trial and functional analyses. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Transition‐Metal‐Complexed Cyclic [3]‐ and [4]Pseudorotaxanes Containing Rigid Ring‐and‐Filament Conjugates: Synthesis and Solution Studies
Authors: Voignier Julie , Frey Julien , Kraus Tomáš , Buděšínský Miloš , Cvačka Josef , Heitz Valérie , Sauvage Jean‐Pierre
Published: March 2011

By using the “gathering‐and‐threading” effect of copper(I) with rigid ring‐and‐string conjugates, daisy‐chain‐type [3]‐ and [4]pseudorotaxanes could be prepared in high yields. The organic fragment used consisted of a 2,9‐diphenyl‐1,10‐phenanthroline (dpp)‐containing ring attached to a coordinating filament capable of threading through the ring of another molecule by coordination to copper(I). The bidentate chelate introduced in the axis was also a 1,10‐phenanthroline (phen) derivative with two methyl groupsorthoto the nitrogen atoms of the phen unit. The organic component was prepared following a multistep strategy, one of the key steps being the attachment of the ring to the lateral axis. This connection was done by a condensation reaction between anorthodione located at the back of a ring‐incorporated phen and an aromatic aldehyde, which was the end‐function of the thread. An oxazole nucleus was obtained after the condensation, which provided a rigid connection between the ring and the axis. In this way, the coordination axes of the ring‐incorporated bidentate chelate and of the ligand belonging to the lateral filament were approximately orthogonal to one another. The design was such that the tetrameric complex, a [4]pseudorotaxane, seemed to be the most stable species, owing to the mutual geometrical arrangement of the filament and the ring. Various spectroscopic techniques, such as1H NMR spectroscopy, including DOSY, and electrospray ionization mass spectroscopy (ESI‐MS), clearly demonstrated that a mixture of cyclic [3]‐ and [4]pseudorotaxane was obtained; the proportions of both components depended on concentration and temperature. Copper(I) was not the only metal center leading to the formation of cyclic pseudorotaxanes. A similar effect was observed with silver(I) as the templating metal: quantitative formation of threaded species was observed, with a higher proportion of trimer over tetramer than in the copper(I) case. Concentration and temperature effects were investigated for both series of CuI‐ and AgI‐complexed threaded species showing that formation of the trimer was favored upon dilution or heating of the solution.
Microwave‐Assisted Aminocarbonylation of Ynamides by Using Catalytic [Fe3(CO)12] at Low Pressures of Carbon Monoxide
Authors: Pizzetti Marianna , Russo Adele , Petricci Elena
Published: March 2011

The microwave‐assisted aminocarbonylation of ynamides at low pressures of CO is reported. A new class of (E)‐acrylamides that are potentially suitable for several applications has been regioselectively synthesized after microwave irradiation for only 20 min by using eco‐friendly [Fe3(CO)12] as the catalyst precursor and triethylamine as the ligand. This transformation is atom economic as all reactants are used in stoichiometric quantities. Furthermore, the transformation is efficiently applied to the alkoxycarbonylation of alkynes as well. Moreover, running these reactions under microwave irradiation allows the simplification of the reaction conditions with remarkable reductions in time, temperature and gas pressure.
p16/ki‐67 dual‐stain cytology in the triage of ASCUS and LSIL Papanicolaou cytology
Authors: Schmidt Dietmar , Bergeron Christine , Denton Karin J , Ridder Ruediger ,   for the European CINtec Cytology Study Group
Published: March 2011

BACKGROUND:

The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual‐stain protocol, which simultaneously detects p16INK4a and Ki‐67 expression in cervical cytology samples, for identifying high‐grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (ASCUS) or low‐grade squamous intraepithelial lesions (LSIL).

METHODS:

Residual liquid‐based cytology material from 776 retrospectively collected ASCUS/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki‐67 dual staining. The presence of 1 or more double‐immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow‐up.

RESULTS:

Sensitivity of p16/Ki‐67 dual‐stain cytology for biopsy‐confirmed CIN2+ was 92.2% (ASCUS) and 94.2% (LSIL), while specificity rates were 80.6% (ASCUS) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual‐stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing.

CONCLUSIONS:

The results of this study show that p16/Ki‐67 dual‐stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with ASCUS or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single‐stain cytology. However, the specificity of this morphology‐independent interpretation of p16/Ki‐67 dual‐stain cytology testing was further improved compared with the earlier p16 single‐stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
Infrared Spectrum of the Ag+–(Pyridine)2 Ionic Complex: Probing Interactions in Artificial Metal‐Mediated Base Pairing
Authors: Chakraborty Shamik , Dopfer Otto
Published: March 2011

The isolated pyridine–Ag+–pyridine unit (PyAg+Py) is employed as a model system to characterize the recently observed Ag+‐mediated base pairing in DNA oligonucleotides at the molecular level. The structure and infrared (IR) spectrum of the Ag+Py2 cationic complex are investigated in the gas phase by IR multiple‐photon dissociation (IRMPD) spectroscopy and quantum chemical calculations to determine the preferred metal‐ion binding site and other salient properties of the potential‐energy surface. The IRMPD spectrum has been obtained in the 840–1720 cm−1 fingerprint region by coupling the IR free electron laser at the Centre Laser Infrarouge d’Orsay (CLIO) with a Fourier‐transform ion cyclotron resonance (FT‐ICR) mass spectrometer equipped with an electrospray ionization source. The spectroscopic results are interpreted with quantum chemical calculations conducted at the B3LYP/aug‐cc‐pVDZ level. The analysis of the IRMPD spectrum is consistent with a σ complex, in which the Ag+ ion binds to the nitrogen lone pairs of the two Py ligands in a linear configuration. The binding motif of PyAg+Py in the gas phase is the same as that observed in Ag+‐mediated base pairing in solution. Ag+ bonding to the π‐electron system of the aromatic ring is predicted to be a substantially less‐favorable binding motif.
Determination of partitioning of drug molecules using immobilized liposome chromatography and chemometrics methods
Authors: Noorizadeh Hadi , Farmany Abbas
Published: March 2011

The quantitative structure‐property relationship (QSPR) of drug molecules against the immobilized liposome chromatography partitioning (log Ks) was studied. The genetic algorithm (GA) was employed to select the variables that resulted in the best‐fitted models. After the variables were selected, the linear multivariate regressions (e.g. partial least squares (PLS)) as well as the non‐linear regressions (e.g. the kernel PLS (KPLS) and Levenberg‐Marquardt artificial neural network (L‐M ANN)) were utilized to construct the linear and non‐linear QSPR models. The correlation coefficient cross validation (Q2) and relative error for calibration, prediction and test sets L‐M ANN model are (0.987, 0.971, 0.952) and (3.14, 3.54, 6.61), respectively. The obtained results using L‐M ANN were compared with those of GA‐PLS and GA‐KPLS, exhibiting that the L‐M ANN model demonstrated a better performance than that of the other models. This is the first research on the QSPR of the drug molecules against the log Ks using the GA‐KPLS and L‐M ANN. Copyright © 2011 John Wiley & Sons, Ltd.
Electrospray ionization LC‐MS/MS validated method for the determination of the active metabolite (R‐138727) of prasugrel in human plasma and its application to a bioequivalence study
Authors: Lukram Ojikumar , Zarapkar Mukund , Kumar Jha Chandan , Parmar Shivaji , Tomar Keshav S. , Hande Amit
Published: March 2011

A rapid and sensitive liquid chromatography tandem mass spectrometry method has been developed and validated for the determination of the active metabolite (R‐138727) of prasugrel in human plasma. Because R‐138727 contains a thiol group, it requires stabilization by derivatizing with N‐ethyl maleimide. Commercially available trandolapril was used as the internal standard (IS). The derivatives of R‐138727 and IS were extracted from human plasma using a liquid‐liquid extraction technique. Chromatography was performed on a Hypurity C18, 5 µ (50 mm × 4.6 mm, i.d.) column, with the mobile phase consisting of acetonitrile and 10 mM ammonium formate (pH 3.0, 50:50 V/V), followed by detection using mass spectrometry. No significant endogenous peaks corresponding to R‐138727 or IS were detected in the blank human plasma samples and no significant matrix effect was observed for R‐138727 and IS in the human plasma samples. The mean recovery for R‐138727 ranged from 90.1 to 104.1%, with the lower limit of quantification set at 1 ng/ml. Linearity was established for concentrations in the range of 1.0–500.12 ng/ml, with a coefficient of determination (r2) of 0.9958. The derivatized R‐138727 was stable in human plasma for 3 months at − 20 °C. This method increased the sensitivity and selectivity, resulting in high‐throughput analysis of R‐138727 using trandolapril as the IS in pharmacokinetic and bioequivalence studies, with a chromatographic run time of 3.7 min. Copyright © 2011 John Wiley & Sons, Ltd.
Application of genetic algorithm‐kernel partial least square as a novel non‐linear feature selection method: partitioning of drug molecules
Authors: Noorizadeh H. , Sobhan Ardakani S. , Ahmadi T. , Mortazavi S. S. , Noorizadeh M.
Published: March 2011

Genetic algorithm (GA) and partial least squares (PLS) and kernel PLS (KPLS) techniques were used to investigate the correlation between immobilized liposome chromatography partitioning (log Ks) and descriptors for 65 drug compounds. The models were validated using leave‐group‐out cross validation LGO‐CV. The results indicate that GA‐KPLS can be used as an alternative modelling tool for quantitative structure‐property relationship (QSPR) studies. Copyright © 2011 John Wiley & Sons, Ltd.
Study of photodegradation kinetics of melatonin by multivariate curve resolution (MCR) with estimation of feasible band boundaries
Authors: De Luca Michele , Tauler Romà , Ioele Giuseppina , Ragno Gaetano
Published: March 2011

Multivariate curve resolution—alternating least squares (MCR‐ALS) has been applied to data collected from UV spectrophotometric analysis of melatonin samples exposed to light with varying irradiance power. MCR‐ALS was able to explain the degradation kinetics of this drug, deducing the pure spectra and concentration changes of the different species present throughout the entire process. Possible rotational ambiguities associated with MCR solutions were investigated and their extent was evaluated. The extent of the rotation ambiguity was estimated from the band boundaries of feasible solutions calculated using the MCR‐BANDS procedure. The use of a non‐linear fitting routine allowed improving kinetic information and provided a method of evaluation of the rate constants of the degradation process. The degradation pathway was found to follow a first‐order reaction model, in which melatonin underwent photo‐oxidation of the indole ring to give a formylamine group. Kinetics of the reaction was shown to be dependent on irradiation conditions, with an increase of the rate constants when light power also increased. Copyright © 2011 John Wiley & Sons, Ltd.
Afp::mCherry, a red fluorescent transgenic reporter of the mouse visceral endoderm
Authors: Viotti Manuel , Nowotschin Sonja , Hadjantonakis Anna‐Katerina
Published: March 2011

Section through the intestine of a P3 (postnatal day 3) Afp::mCherry; Afp::GFP double transgenic mouse. Red and green fluorescent reporter‐expressing cells are located in the endoderm layer along villi, but excluded from the crypt stem cell zone. See the article by Viotti at al. in this issue.
Climate and land use controls over terrestrial water use efficiency in monsoon Asia
Authors: Tian Hanqin , Lu Chaoqun , Chen Guangsheng , Xu Xiaofeng , Liu Mingliang , Ren Wei , Tao Bo , Sun Ge , Pan Shufen , Liu Jiyuan
Published: March 2011

Much concern has been raised regarding how and to what extent climate change and intensive human activities have altered water use efficiency (WUE, amount of carbon uptake per unit of water use) in monsoon Asia. By using a process‐based ecosystem model [dynamic land ecosystem model (DLEM)], we examined effects of climate change, land use/cover change, and land management practices (i.e. irrigation and nitrogen fertilization) on WUE in terrestrial ecosystems of monsoon Asia during 1948–2000. Our simulations indicated that due to climate variability/change, WUE in the entire area decreased by 3·6% during the study period, with the largest decrease of 6·8% in the 1990s. Grassland was the most sensitive biome to a drying climate, with a decrease of 16·2% in WUE in the 1990s. Land conversion from natural vegetation to croplands, accounting for 79% of the total converted land areas, led to a decrease in WUE, with the largest decrease of 42% while forest was converted to cropland. In contrast, WUE increased by more than 50% while cropland was converted to natural vegetation. Simulated results also showed that intensive land management practices could alleviate the decrease in WUE induced by climate change and land conversion. Changes in WUE showed substantial spatial variation, varying from the largest decrease of over 50% in northwestern China and some areas of Mongolia to the largest increase of over 30% in western, southern China, and large areas of India. To adapt to climate change and sustain terrestrial ecosystem production, more attention ought to be paid to enhance water use efficiency through land use and management practices, especially in the drying areas. Copyright © 2011 John Wiley & Sons, Ltd.
Organization of complexity in water limited ecohydrology
Authors: Jenerette G. Darrel , Barron‐Gafford Greg A. , Guswa Andrew J. , McDonnell Jeffrey J. , Villegas Juan Camilo
Published: March 2011

Water limited ecohydrological systems (WLES), with their broad extent, large stores of global terrestrial carbon, potential for large instantaneous fluxes of carbon and water, sensitivity to environmental changes, and likely global expansion, are particularly important ecohydrological systems. Strong nonlinear responses to environmental variability characterize WLES, and the resulting complexity of system dynamics has challenged research focussed on general understanding and site specific predictions. To address this challenge our synthesis brings together current views of complexity from ecological and hydrological sciences to look towards a framework for understanding ecohydrological systems (in particular WLES) as complex adaptive systems (CAS). This synthesis suggests that WLES have many properties similar to CAS. In addition to exhibiting feedbacks, thresholds, and hysteresis, the functioning of WLES is strongly affected by self‐organization of both vertical and horizontal structure across multiple scales. As a CAS, key variables for understanding WLES dynamics are related to their potential for adaptation, resistance to variability, and resilience to state changes. Several essential components of CAS, including potential for adaptation and rapid changes between states, pose challenges for modelling and generating predictions of WLES. Model evaluation and predictable quantities may need to focus more directly on temporal or spatial variance in contrast to mean state values for success at understanding system‐level characteristics. How coupled climate and vegetation changes will alter available soil, surface and groundwater supplies, and overall biogeochemistry will reflect how self‐organizational ecohydrological processes differentially partition precipitation and overall net metabolic functioning. Copyright © 2011 John Wiley & Sons, Ltd.
Forest ecohydrological processes in a changing environment
Authors: Wei Xiaohua , Sun Ge , Vose James M. , Otsuki Kyoichi , Zhang Zhiqiang , Smetterm Keith
Published: March 2011

The papers in this issue are a selection of the presentations made at the second International Conference on Forests and Water in a Changing Environment. This special issue ‘Forest Ecohydrological Processes in a Changing Environment’ covers the topics regarding the effects of forest, land use and climate changes on ecohydrological processes across forest stand, watershed and regional spatial scales. Copyright © 2011 John Wiley & Sons, Ltd.
Two‐Step versus One‐Step Spin Transitions in Iron(II) 1D Chain Compounds
Authors: Bauer Wolfgang , Scherer Wolfgang , Altmannshofer Sandra , Weber Birgit
Published: March 2011

Eleven iron(II) 1D coordination polymers with the general formula [FeLeq(Lax)]·solvent were synthesised and characterised, where Leq = (E,E)‐{diethyl 2,2′‐[1,2‐phenylenebis(iminomethylidyne)]bis(3‐oxobutanato) (2‐)‐N,N′,O3,O3′} (L1) and {[3,3′]‐[1,2‐phenylenebis(iminomethylidyne)]bis(2,4‐pentane‐dionato)(2‐)‐N,N′,O2,O2′} (L2); Lax = 4,4′‐bipyridine (bipy), 1,2‐bis(4‐pyridyl)ethane (bpea) and 1,3‐bis(4‐pyridyl)propane (bppa) and solvent = MeOH, EtOH and toluene (Tol). [FeL1(bpea)]·MeOH (3·MeOH) shows an abrupt one‐step spin crossover with thermal hysteresis(27 K) and [FeL2(bppa)]·MeOH (2·MeOH), [FeL2(bpea)] (4), [FeL2(bpea)]·0.25MeOH (4·0.25MeOH) and [FeL1(bipy)]·MeOH (5·MeOH) show a two‐step spin transition with an IP at γHS ≈ 0.5 (IP is intermediate plateau and γHS is high‐spin mol fraction) and up to 50 K wide hysteresis loops (5·MeOH). [FeL1(bppa)] (1), [FeL2(bppa)]·EtOH (2·EtOH) and [FeL1(bpea)]·1.5Tol (3·1.5Tol) show an abrupt incomplete spin transition that stops at γHS ≈ 0.5; for [FeL1(bppa)]·0.25MeOH (1·0.25MeOH) and [FeL1(bpea)] (3), the spin transition is gradual and incomplete. The X‐ray crystal structures of six complexes were determined (1, 2·MeOH, 3·MeOH, 3·1.5Tol, 4·0.25MeOH and 5·MeOH). In the case of 4·0.25MeOH, the crystal structures for the HS and LS states were dertermined; for compounds 1, 2·MeOH and 3·1.5Tol, the crystal structure of the HS and the IP state was investigated. For all complexes, the iron(II) centre is located in a distorted octahedral coordination sphere. Each axially coordinated ligand “connects” two iron(II) centres, which results in the formation of extended 1D chains with varying structures from linear (bipy) over steplike (bpea) to zigzag (bppa). Analysis of the intermolecular interactions reveals that the hysteresis width depends on both the stiffness of the axial ligand and the number of intermolecular contacts, while zigzag chains support stepwise spin transitions.
Synthesis, Swelling, and Exfoliation of Microporous Lamellar Titanosilicate AM‐4
Authors: Casado Clara , Ambroj Diego , Mayoral Álvaro , Vispe Eugenio , Téllez Carlos , Coronas Joaquín
Published: March 2011

AM‐4 is a layered porous titanosilicate built from TiO6 and SiO4 polyhedra. An improved synthesis of AM‐4 crystalsenabling control of particle size by secondary growth and reducing synthesis time is presented. A new material, UZAR‐S2, has been obtained by exfoliation of the smaller AM‐4. The exfoliation consists of proton exchange with acetic acid, intercalation with nonylamine, and final activation by washing with HCl/water/ethanol. Besides XRD, TEM, N2 adsorption, FTIR, and UV/Vis characterization highlighting the delaminated character of UZAR‐S2, CO2 adsorption was also measured.
A Convenient Road to 1‐Chloropentacycloundecanes – A Joint Experimental and Computational Investigation
Authors: Sharapa Dmitry I. , Gayday Alexander V. , Mitlenko Alena G. , Levandovskiy Igor A. , Shubina Tatyana E.
Published: March 2011

An efficient synthetic strategy to obtain 1‐chloro‐Cs‐trishomocubane and 1‐chloro‐D3‐trishomocubane is described. 1‐Chloro‐Cs‐trishomocubane is synthesized by a regioselective Diels–Alder reaction, and B3PW91/6‐31G(d,p) calculations offer a plausible explanation of the reaction mechanism. Surprisingly, 1‐chloro‐Cs‐trishomocubane does not undergo an acid‐catalyzed rearrangement to form 1‐chloro‐D3‐trishomocubane and was obtained by chlorosulfation of Cookson's diketone. A possible mechanism of the reaction involving the formation of Cs‐ and D3‐trishomocubane nonclassical cations was proposed on the basis of a mechanistic [B3PW91/6‐31G(d,p) and MP2/cc‐pVDZ] study.
Titanium(IV) Chloride‐Mediated Carbocyclization of 1,6‐Enynes: Selective Synthesis of 3‐Azabicyclo[3.1.0]hexanes and Functionalized Allenes by Controlling the Reaction Temperature
Authors: Zhang Zhen , Shi Min
Published: March 2011

1,6‐Enynes can be transformed into 3‐azabicyclo[3.1.0]hexanes and functionalized allenes in moderate to good yields along with moderate to high diastereoselectivities by controlling the reaction temperature in the presence of titanium(IV) chloride. A plausible mechanism is proposed.
Source distribution modelling for end‐member mixing in hydrology
Authors: Brewer M. J. , Tetzlaff D. , Malcolm I. A. , Soulsby C.
Published: March 2011

End‐member mixing is a method in hydrology for attempting to define the runoff sources in river catchments. It involves estimation of the relative proportions of water from different sources, commonly producing a time series. Given regular measurements of a chemical tracer on the target water body and, in addition, corresponding measurements for samples of known sources, it is possible to perform end‐member mixing using Bayesian models taking (essentially) a random effects approach in a hierarchical framework, including covariates if appropriate. This paper considers the case where there are no separate data available for the source components, and develops a model for source distributions via nonlinear regression on the tracer/flow relationship and nonparametric density estimation. We allow these source component distributions to vary from year to year and apply the model to a data set from two streams in central Scotland, comprised of weekly or fortnightly readings over seventeen years. We conclude there is evidence of a change in source distribution over time; that corresponding to low flow conditions exhibits a gradual increase in alkalinity for both of two streams studied, whereas for high flow conditions alkalinity appeared to be rising for only one stream. Copyright © 2011 John Wiley & Sons, Ltd.
Growth by extension, and reworking, of a south‐western Kalahari linear dune
Authors: Telfer Matt W.
Published: March 2011

Optically stimulated luminescence (OSL) dating studies of linear (longitudinal) dunes have been used extensively to elucidate late Quaternary environments and climates in arid or formerly arid regions, yet understanding of the development of such dunes is incomplete. In particular, conflicting opinions have been presented regarding the propensity of linear dunes to migrate laterally, the degree to which they rework their own sediment during accumulation and whether they form primarily by extension, as opposed to lateral sand movement from adjacent interdunes. This study focuses on this last point, although the importance of the other controversies is discussed in context. A simple linear dune in the south‐western Kalahari, which has a prominent termination on a pan (playa) surface, provides an opportunity to directly test hypotheses of dune extension. Chronostratigraphy along a ~600 m transect along the crest of the dune, constrained by 42 OSL ages, reveals that the dune grew by extension on occasions in the late Pleistocene and early Holocene, but has also been subject to reworking along its length, which has continued until recent times. Dune development by extensional growth is suggested to operate under environmental conditions more conducive to net accumulation, whereas reworking is largely independent of conditions throughout the last ~18 ka, and may represent seasonal fluctuations in the position of the dune crest. The relative significance of these two modes of development is suggested to be a key control on the efficacy of linear dunes as archives of environmental and climatic change. Copyright © 2011 John Wiley & Sons, Ltd.
Price–Dividend Ratios and Stock Price Predictability
Authors: Wu Jyh‐Lin , Hu Yu‐Hau
Published: March 2011

A long‐standing puzzle to financial economists is the difficulty of outperforming the benchmark random walk model in out‐of‐sample contests. Using data from the USA over the period of 1872–2007, this paper re‐examines the out‐of‐sample predictability of real stock prices based on price–dividend (PD) ratios. The current research focuses on the significance of the time‐varying mean and nonlinear dynamics of PD ratios in the empirical analysis. Empirical results support the proposed nonlinear model of the PD ratio and the stationarity of the trend‐adjusted PD ratio. Furthermore, this paper rejects the non‐predictability hypothesis of stock prices statistically based on in‐ and out‐of‐sample tests and economically based on the criteria of expected real return per unit of risk. Copyright © 2011 John Wiley & Sons, Ltd.
Mortgagees and receivers exercising powers of sale – An English and Australian comparative analysis
Authors: Werner Carl
Published: March 2011

For many years, the English and Australian courts have been at odds in their respective treatment of the obligations imposed on mortgagees and receivers when exercising powers of sale. Indeed, a Full Court of the Federal Court of Australia has recently confirmed that the more onerous test under English law, as enunciated in Cuckmere Brick,1 does not reflect the current general law in Australia.2 This paper examines the current state of the law in England and Australia and argues that the widely held belief that mortgagees and receivers in Australia are under a lesser duty than their English counterparts is largely misconceived. Copyright © 2011 John Wiley & Sons, Ltd.
The tissue response to photopolymerized PEG‐p(HPMAm‐lactate)‐based hydrogels
Authors: Censi Roberta , van Putten Sander , Vermonden Tina , di Martino Piera , van Nostrum Cornelus F. , Harmsen Martin C. , Bank Ruud A. , Hennink Wim E.
Published: March 2011

Hydrogels are three‐dimensional networks of crosslinked hydrophilic polymers widely used for protein delivery and tissue engineering. To be eligible for in vivo applications, the hydrogels should not evoke an adverse tissue response. In this study the angiogenic and inflammatory responses in vivo after implantation of photopolymerized thermosensitive poly(hydroxypropyl methacrylamide lactate)‐poly(ethyl copolymer hydrogels are investigated. Hydrogels consisting of polymers with different crosslink densities were subcutaneously implanted in Balb/c mice and histological evaluation of the tissue response was performed. The implants showed an acute and localized inflammatory reaction upon implantation, mainly characterized by a strong infiltration of granulocytes. The acute inflammatory reaction was followed by a milder chronic inflammation which was characterized by infiltration of macrophages and persistent but decreasing levels of granulocytes. The number of macrophages and blood vessels was associated with the biodegradation and resorption of the biomaterial and increased in time as the degradation of the materials progressed. The observed degradation rates in vivo correlated well with previously observed in vitro degradation rates, which suggests that hydrolysis is the main mechanism governing the degradation. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Salicylic acid‐derived poly(anhydride‐ester) electrospun fibers designed for regenerating the peripheral nervous system
Authors: Griffin Jeremy , Delgado‐Rivera Roberto , Meiners Sally , Uhrich Kathryn E.
Published: March 2011

Continuous biomaterial advances and the regenerating potential of the adult human peripheral nervous system offer great promise for restoring full function to innervated tissue following traumatic injury via synthetic nerve guidance conduits (NGCs). To most effectively facilitate nerve regeneration, a tissue engineering scaffold within a conduit must be similar to the linear microenvironment of the healthy nerve. To mimic the native nerve structure, aligned poly(lactic‐co‐glycolic acid)/bioactive polyanhydride fibrous substrates were fabricated through optimized electrospinning parameters with diameters of 600 ± 200 nm. Scanning electron microscopy images show fibers with a high degree of alignment. Schwann cells and dissociated rat dorsal root ganglia demonstrated elongated and healthy proliferation in a direction parallel to orientated electrospun fibers with significantly longer Schwann cell process length and neurite outgrowth when compared to randomly orientated fibers. Results suggest that an aligned polyanhydride fiber mat holds tremendous promise as a supplement scaffold for the interior of a degradable polymer NGC. Bioactive salicylic acid‐based polyanhydride fibers are not limited to nerve regeneration and offer exciting promise for a wide variety of biomedical applications. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Clinical device‐related article evaluation of morphology and functions of a foldable capsular vitreous body in the rabbit eye
Authors: Chen Jiajia , Gao Qianying , Liu Yaqin , Ge Jian , Cao Xianwu , Luo Yan , Huang Danping , Zhou Gege , Lin Shaofen , Lin Jianxian , To Chi Ho , Siu Andrew W.
Published: March 2011

We previously proposed a new strategy to replace a vitreous body with a novel foldable capsular vitreous body (FCVB). In this study, the FCVB was designed to mimic natural vitreous morphology, and evaluate its physiological functions compared with traditional silicone oil substitutes, in an established rabbit model of proliferative vitreoretinopathy. We found that FCVB was a very good replacement for closely mimicking the morphology and restoring the physiological functions, such as the support, refraction, and cellular barriers, of the rabbit vitreous body. The study has provided us with a novel research and therapy strategy that could effectively mimic the morphology and physiological function of the rabbit vitreous body. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.