bluuebunny/crossref_metadata_2025 huggingface dataset:
Competing Large and Small Angles in a Double End‐On Azido Copper(II) Binuclear Complex: A Combined Experimental and Theoretical Study of Magnetic Interactions
Authors: Jia Qin‐Xiang , Bonnet Marie‐Laure , Gao En‐Qing , Robert Vincent
Published: May 2009

The structure and magnetic properties of double azido‐bridged CuII binuclear complex 1 with the chelating chiral ligand (S,S)‐2,2′‐isopropylidenebis(4‐phenyl‐2‐oxazoline) were analyzed by combining experimental and theoretical techniques. The CuII ions adopt a square pyramidal geometry with different degrees of distortion, whereas the two end‐on azido bridges disposed at the equatorial positions exhibit significantly different Cu–N–Cu angles, 110.6 and 97.3°, which are respectively smaller and larger than the critical 108° value distinguishing the ferromagnetic and antiferromagnetic regimes. The asymmetry in 1 arises from the use of the bulky asymmetric ligand, giving rise to two different magnetic pathways between the CuII ions. The magnetic pathway along the large Cu–N–Cu angle value dominates over the small one, resulting in a net antiferromagnetic behavior with J = –78.6 cm–1. On the basis of wavefunction calculations, we investigate the exchange interactions in synthetic compound 1 and fictitious analogs 2 and 3 holding either two large (i.e., 110.6°) or two small (i.e., 97.3°) Cu–N–Cu angles. The calculated exchange interaction in 1(–104 cm–1) is in relatively good agreement with the experimental value and corresponds precisely to the average between the antiferromagnetic value in 2 (–218 cm–1) and the ferromagnetic one in 3 (21 cm–1). The significant enhancement in the antiferromagnetic contribution accompanying the expansion of one of the Cu–N–Cu bridging angles is undoubtedly the driving force for the observed antiferromagnetic behavior in 1. The control of the local metal environments allowed us to monitor the exchange coupling interactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Enantiomerically Pure Bis(phosphanyl)carbaborane(12) Compounds
Authors: Bauer Sebastian , Tschirschwitz Steffen , Lönnecke Peter , Frank René , Kirchner Barbara , Clarke Matthew L. , Hey‐Hawkins Evamarie
Published: May 2009

Enantiomerically pure (RP,RP)‐ and (RP,SP)‐1,2‐bis[1‐adamantyloxy‐(–)‐menthyloxyphosphanyl]‐closo‐dicarbaborane(12), 1,2‐bis[bis(–)‐menthyloxyphosphanyl]‐closo‐dicarbaborane(12)and 1,2‐bis[bis(4‐tert‐butylphenyloxy)phosphanyl]‐closo‐dicarbaborane(12) were synthesised by the reaction of dilithiated 1,2‐dicarba‐closo‐dodecaborane(12) with two equivalents of the corresponding chlorophosphite. The phosphonites are stable towards epimerisation, oxygen and water. P···P through‐space coupling was observed, and the 3JPP coupling constants were determined by spectral simulation and DFT calculations. Late transition‐metal complexes with molybdenum and rhodium were prepared to study the coordination properties of the bis(phosphanyl)carbaborane(12) compounds. Catalytic properties of various rhodium complexes were investigated in homogeneous catalytic hydroformylation reactions with various olefins. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Drop‐out from treatment for the eating disorders: A problem for clinicians and researchers
Authors: Campbell Mari
Published: May 2009

All professionals who work in the field of eating disorders will have encountered patients who do not make it into or through a course of treatment. This paper considers some of the difficulties that drop‐out poses to clinicians and researchers. It also suggests strategies for addressing these challenges in future research and clinical practice. Copyright © 2009 John Wiley & Sons, Ltd and Eating Disorders Association.
Meta‐analysis on drugs in people with eating disorders
Authors: Calero‐Elvira Ana , Krug Isabel , Davis Kimberley , López Carolina , Fernández‐Aranda Fernando , Treasure Janet
Published: May 2009

Objective

The aim of this study was to examine whether drug use (DU) is higher in people with eating disorders (EDs) compared to a healthy control group and to perform a meta‐analysis on the literature related to DU in people with EDs.

Method

We searched electronic databases (Medline, PsycINFO, Web of Science and CINAHL) and reviewed studies published from 1994 to August, 2007, in English, German or Spanish. A total of 16 papers fulfilled the inclusion criteria and were included.

Results

The general meta‐analysis revealed a negligible albeit significant effect size (0.119, p < .05). Risk was found to be higher in bulimia nervosa (BN, δ = 0.462, p =  < .001), smaller in binge eating disorder (δ = 0.14, p < .05) and non‐significant in anorexia nervosa (AN, δ = −.167, p = .070).

Conclusions

The differential risk observed in patients with BN might be related to differences in temperament or might be the result of reward sensitization. Copyright © 2009 John Wiley & Sons, Ltd and Eating Disorders Association.
Feature extraction and recognition of UHF partial discharge signals in GIS based on dual‐tree complex wavelet transform
Authors: Xie Yanbin , Tang Ju , Zhou Qian
Published: May 2009

Ultra‐high‐frequency (UHF) partial discharge (PD) detection is an effective means for evaluation of dielectric condition of gas insulated switchgear (GIS). Time‐resolved data pattern is utilized to recognize insulation defect because of its attractive advantages that there exists some direct relationship between the shape of PD signal and the physics of the defect. Therefore, the main task is feature extraction of time‐resolved data. However, it is hard to extract features in time domain because there is no obvious difference in types of signals. UHF PD signals are non‐stationary, so feature extraction in frequency domain is not suitable as well. Feature extraction in time‐frequency domain based on discrete wavelet transform (DWT) is a solution for this problem, but there is a weak point which hampers the application of this method, that is, lack of shift invariance, which means that small shifts in the input signal can cause major variations in the distribution of energy between DWT coefficients at different scales. In this paper, a new method of feature extraction of UHF PD signal on the basis of dual‐tree complex wavelet transform (CWT) which can reduce shift sensitive is proposed. UHF PD signals are acquired in lab and decomposed by a dual‐tree CWT. Then the feature space is constructed through the energy on all frequency bands and modulus maxima on all scales. At last feature space is inputted into a radial base function (RBF) neural network classifier. The results show the superiority of this method over traditional ones. Copyright © 2009 John Wiley & Sons, Ltd.
Sequential feasible optimal power flow: theoretical basis and numerical implementation
Authors: Jiang Quanyuan , Chiang Hsiao‐Dong
Published: May 2009

Sequential feasible optimal (SFO) power flow is developed for power systems. One distinguished feature of this algorithm is that it can maintain feasibility for both equality and inequality constraints during iterations. SFO consists of two phases: Phase I is used to obtain a feasible point from any infeasible initial point. The feasible point is obtained by solving an active‐set quotient gradient system (AS‐QGS) using pseudo‐transient continuation method. Starting from the feasible point obtained in Phase I, Phase II yields a series of feasible points until it converges to KKT point. At each iteration of Phase II, the movement from one feasible point to another feasible point with a smaller objective value is achieved by two stages: objective improving stage and feasibility enforcing stage. Numerical studies on several testing systems indicate that the proposed feasible approach can be terminated at any iteration and yield a feasible operating point. Moreover, SFO can also be used to help operators to diagnose the divergence cases, identify the unreasonable constraints. Based on the diagnosis results, operator can adjust it to obtain a convergence case. Copyright © 2009 John Wiley & Sons, Ltd.
Increased inferior frontal activation during word generation: A marker of genetic risk for schizophrenia but not bipolar disorder?
Authors: Costafreda Sergi G. , Fu Cynthia H.Y. , Picchioni Marco , Kane Fergus , McDonald Colm , Prata Diana P. , Kalidindi Sridevi , Walshe Muriel , Curtis Vivienne , Bramon Elvira , Kravariti Eugenia , Marshall Nicolette , Toulopoulou Timothea , Barker Gareth J. , David Anthony S. , Brammer Michael J. , Murray Robin M. , McGuire Philip K.
Published: May 2009

During verbal‐fluency tasks, impairments in performance and functional abnormalities in the inferior frontal cortex have been observed in both schizophrenia patients and their unaffected relatives. We sought to examine whether such functional abnormalities are a specific marker of genetic vulnerability to schizophrenia. We studied a sample of 132 subjects, comprising 39 patients with schizophrenia, 10 unaffected monozygotic (MZ) cotwins of schizophrenia probands, 28 patients with bipolar disorder, 7 unaffected MZ cotwins of bipolar disorder probands and 48 healthy controls. Blood oxygen level‐dependent response was measured using functional magnetic resonance imaging during the performance of an overt verbal‐fluency task with two levels of task difficulty, in a cytoarchitectonic region of interest encompassing Brodmann areas 44 and 45 bilaterally. Patients with schizophrenia and the unaffected MZ cotwins of schizophrenia probands showed increased activation in the inferior frontal cortex relative to healthy controls and bipolar patients. Increased engagement of the inferior frontal cortex during verbal‐fluency may thus be a marker of genetic vulnerability to schizophrenia. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Cerebral blood flow changes induced by pedunculopontine nucleus stimulation in patients with advanced Parkinson's disease: A [15O] H2O PET study
Authors: Ballanger Benedicte , Lozano Andres M. , Moro Elena , van Eimeren Thilo , Hamani Clement , Chen Robert , Cilia Roberto , Houle Sylvain , Poon Yu Yan , Lang Anthony E. , Strafella Antonio P.
Published: May 2009

Patients with advanced Parkinson's disease (PD) develop disabling axial symptoms, including gait disturbances, freezing and postural instability poorly responsive to levodopa replacement therapy. The pedunculopontine nucleus (PPN) is involved in locomotion, control of posture, and behavioral states [i.e. wakefulness, rapid eye movement sleep]. Recent reports suggested that PPN modulation with deep brain stimulation (DBS) may be beneficial in the treatment of axial symptoms. However, the mechanisms underlying these effects are still unknown. We used [15O] H2O PET to investigate regional cerebral blood flow in three patients with advanced PD who underwent a new experimental surgical procedure with implantation of unilateral PPN‐DBS. Patients were studied Off‐medication with stimulator Off and On, both at rest and during a self‐paced alternating motor task of the lower limbs. We used SPM2 for imaging data analysis, threshold P < 0.05 corrected at the cluster level. Stimulation induced significant regional cerebral blood flow increment in subcortical regions such as the thalamus (P < 0.006), cerebellum (P < 0.001), and midbrain region (P < 0.001) as well as different cortical areas involving medial sensorimotor cortex extending into caudal supplementary motor area (BA 4/6; P < 0.001). PPN‐DBS in advanced PD resulted in blood flow and presumably neuronal activity changes in subcortical and cortical areas involved in balance and motor control, including the mesencephalic locomotor region (e.g. PPN) and closely interconnected structures within the cerebello‐(rubro)‐thalamo‐cortical circuit. Whether these findings are associated with the DBS‐PPN clinical effect remains to be proven. However, they suggest that PPN modulation may induce functional changes in neural networks associated with the control of lower limb movements. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Detection of synchronous lung tumors in patients presenting with squamous cell carcinoma of the head and neck
Authors: Ghosh Samit K. , Roland Nicholas J. , Kumar Aman , Tandon Sankalap , Lancaster Jeffrey L. , Jackson Shaun R. , Jones Andrew , Lewis Jones Huw , Hanlon Rebecca , Jones Terry M.
Published: May 2009

Background.

Screening for synchronous pulmonary tumors in patients presenting with squamous cell carcinoma of the head and neck (SCCHN) is important, because detection may alter subsequent management.

Methods.

We conducted a retrospective review, comparing effectiveness of pulmonary screening using thoracic CT or chest X‐ray, in 1882 patients presenting with SCCHN.

Results.

The overall rate of synchronous pulmonary tumors was 4.3%. The number needed to scan, ie, the number of thoracic CTs required to detect 1 pulmonary tumor, is reported for recurrent primary tumors, primary disease load (T and N classification), and individual primary sites. The incidence of pulmonary metastases is related to locoregional disease load while the incidence of bronchogenic carcinoma is sporadic.

Conclusion.

Although it is possible to propose a pragmatic screening protocol for pulmonary metastases, this is not possible for bronchogenic carcinomas. Therefore, we recommend that thoracic CT is used in all cases to screen for coexistent pulmonary pathology. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Squamous cell carcinoma of the nasal vestibule 1993–2002: A nationwide retrospective study from DAHANCA
Authors: Agger Andreas , von Buchwald Christian , Madsen Anders Rørbæk , Yde Jesper , Lesnikova Iana , Christensen Charlotte Birk , Foghsgaard Søren , Christensen Thomas Broe , Hansen Hanne Sand , Larsen Susanne , Bentzen Jens , Andersen Elo , Andersen Lisbeth , Grau Cai
Published: May 2009

Background.

A retrospective nationwide study of cancer of the nasal vestibule was conducted to evaluate classification systems and prognostic factors for treatment outcome.

Methods.

Patients treated between 1993 and 2002 at head and neck oncology centers in Denmark were included.

Results.

The 5‐year results were locoregional control 67%, overall survival 50%, cancer‐specific survival 74%. Cancer‐specific survival according to Wang classification was 83%, 63%, and 39% for T1, T2, T3, respectively (p < .000). Regarding T1 tumors, 5‐year locoregional control for surgery, surgery + radiotherapy (RT), or RT was 94%, 87%, or 61%, respectively (p < .000). Fifty‐four Gray in 18 fractions was found comparable with 66 Gy in 33 fractions regarding T1 tumors.

Conclusion.

This national survey is the largest series of nasal vestibule cancer ever published. Wang classification is more prognostic and easier to use than the Union Internationale Contre le Cancer 2002. Surgery or hypofractionated RT can be used for T1 lesions, whereas larger lesions should be treated with combined approach. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Surgical anatomy of the external branch of the superior laryngeal nerve in Chinese adults and its clinical applications
Authors: Chuang Fu‐Jie , Chen Jui‐Yu , Shyu Jia‐Fwu , Su Cheng‐Hsi , Shyr Yi‐Ming , Wu Chew‐Wun , Lui Wing‐Yui , Lee Chen‐Shen , Chen Tien‐Hua
Published: May 2009

Background.

The purpose of this study was to determine the anatomic features of the external branch of the superior laryngeal nerve (EBSLN) in Chinese adults.

Methods.

We analyzed the anatomic distribution of the 86 EBSLNs in 43 cadavers.

Results.

The incidences of the EBSLN in the thyroid area were 94.2% and 91.3% on the right and left sides, respectively. In accord with the Cernea classification, type 1 was 16.2%, type2a was 39.5%, and type 2 was 38.3%. There were no significant differences between the right and the left side. The high‐risk position of the EBSLN was 77.8%.

Conclusions.

The inferior cornu of the thyroid cartilage was a reliable landmark in identifying the external branch of superior laryngeal nerve. Racial variations between the white and the Chinese should be taken into consideration for an explanation of the differences. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Papillary microcarcinoma in comparison with larger papillary thyroid carcinoma in BRAFV600E mutation, clinicopathological features, and immunohistochemical findings
Authors: Park Young Joo , Kim Young A. , Lee You Jin , Kim Soon Hui , Park So Yeon , Kim Kyung Won , Chung June Key , Youn Yeo Kyu , Kim Kwang Hyun , Park Do Joon , Cho Bo Youn
Published: May 2009

Background.

Papillary thyroid microcarcinoma (PMC; ≤1 cm) is thought to take a benign course during the lifetime. However, recent studies showed high recurrence rates for PMC.

Methods.

We analyzed the clinicopathological features, long‐term prognosis, and some molecular characteristics including BRAFV600E mutation by retrospectively reviewing the records of 1150 patients with papillary thyroid carcinoma (PTC), 278 with PMC, and 868 with PTC >1 cm.

Results.

The prevalence of extrathyroidal invasion (52.2%) and initial nodal metastasis (34.9%) in patients with PMC was surprisingly high and almost as high as that for patients with PTC (72.4% and 51.8%, respectively). The rate of recurrent or persistent disease did not differ between patients with PMC and PTC (recurrent or persistent disease, 6.1% vs 14.1%; 53.4‐ vs 84.2‐month follow‐up; n = 98 vs 647; corrected p = .112). The frequency of BRAFV600E mutation was similar in patients with PMC and PTC (65.6% vs 67.2%). Immunohistochemical staining showed no different expression pattern according to the tumor size.

Conclusion.

These results suggest that PMC is not an occult cancer and it can act like larger PTC. Therefore, PMC should not be underestimated in practice. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
IP3 mobilization and diffusion determine the timing window of Ca2+ release by synaptic stimulation and a spike in rat CA1 pyramidal cells
Authors: Manita Satoshi , Ross William N.
Published: May 2009

Synaptically activated calcium release from internal stores in CA1 pyramidal neurons is generated via metabotropic glutamate receptors by mobilizing IP3. Ca2+ release spreads as a large amplitude wave in a restricted region of the apical dendrites of these cells. These Ca2+ waves have been shown to induce certain forms of synaptic potentiation and have been hypothesized to affect other forms of plasticity. Pairing a single backpropagating action potential (bAP) with repetitive synaptic stimulation evokes Ca2+ release when synaptic stimulation alone is subthreshold for generating release. We examined the timing window for this synergistic effect under conditions favoring Ca2+ release. The window, measured from the end of the train, lasted 250–500 ms depending on the duration of stimulation tetanus. The window appears to correspond to the time when both IP3 concentration and [Ca2+]i are elevated at the site of the IP3 receptor. Detailed analysis of the mechanisms determining the duration of the window, including experiments using different forms of caged IP3 instead of synaptic stimulation, suggest that the most significant processes are the time for IP3 to diffuse away from the site of generation and the time course of IP3 production initiated by activation of mGluRs. IP3 breakdown, desensitization of the IP3 receptor, and the kinetics of IP3 unbinding from the receptor may affect the duration of the window but are less significant. The timing window is short but does not appear to be short enough to suggest that this form of coincidence detection contributes to conventional spike timing‐dependent synaptic plasticity in these cells. © 2009 Wiley‐Liss, Inc.
Modulatory metaplasticity induced by pregnenolone sulfate in the rat hippocampus: A leftward shift in LTP/LTD‐frequency curve
Authors: Chen Ling , Cai Weiyan , Chen Lei , Zhou Rong , Furuya Kishio , Sokabe Masahiro
Published: May 2009

We recently have found that an acute application of the neurosteroid pregnenolone sulfate (PREGS) at 50 μM to rat hippocampal slices induces a long‐lasting potentiation (LLPPREGS) via a sustained ERK2/CREB activation at perforant‐path/granule‐cell synapses in the dentate gyrus. This study is a follow up to investigate whether the expression of LLPPREGSinfluences subsequent frequency‐dependent synaptic plasticity. Conditioning electric stimuli (CS) at 0.1–200 Hz were given to the perforant‐path of rat hippocampal slices expressing LLPPREGSto induce long‐term potentiation (LTP) and long‐term depression (LTD). The largest LTP was induced at about 20 Hz‐CS, which is normally a subthreshold frequency, and the largest LTD at 0.5 Hz‐CS, resulting in a leftward‐shift of the LTP/LTD‐frequency curve. Furthermore, the level of LTP at 100 Hz‐CS was significantly attenuated to give band‐pass filter characteristics of LTP induction with a center frequency of about 20 Hz. The LTP induced by 20 Hz‐CS (termed 20 Hz‐LTP) was found to be postsynaptic origin and dependent on L‐type voltage‐gated calcium channel (L‐VGCC) but not onN‐methyl‐D‐aspartate receptor (NMDAr). Moreover, the induction of 20 Hz‐LTP required a sustained activation of ERK2 that had been triggered by PREGS. In conclusion, the transient elevation of PREGS is suggested to induce a modulatory metaplasticity through a sustained activation of ERK2 in an L‐VGCC dependent manner. © 2009 Wiley‐Liss, Inc.
An Efficient Synthesis of Novel Hexahydropyrido[2,3‐d]pyrimidine Derivatives from (Arylmethylidene)pyruvic Acids (=(3E)‐4‐Aryl‐2‐oxobut‐3‐enoic Acids) in Aqueous Media
Authors: Balalaie Saeed , Abdolmohammadi Shahrzad , Soleimanifard Bita
Published: May 2009

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A series of new hexahydropyrido[2,3‐d]pyrimidine derivatives 3 were synthesized by the cyclocondensation reaction of (arylmethylidene)pyruvic acids (=(3E)‐4‐aryl‐2‐oxobut‐3‐enoic acids) 1 and 6‐aminouracils (=6‐aminopyrimidine‐2,4(1H,3H)‐diones) 2 in H2O under reflux conditions (Scheme 1, Table). This novel protocol has the advantages of facility, of easy workup, of high yields, and of an environmentally benign procedure. The structures of compounds 3a–3f were corroborated spectroscopically (IR, 1H‐ and 13C‐NMR, and EI‐MS). A plausible mechanism for the reaction is proposed (Scheme 2).
One‐Pot Three‐Component Synthesis of 2‐(Alkylimino)‐7‐oxo‐1‐oxa‐6‐azaspiro[4.4]nona‐3,8‐diene‐3,4‐dicarboxylates
Authors: Adib Mehdi , Moghimi Setareh , Sayahi Mohammad Hosein , Bijanzadeh Hamid Reza
Published: May 2009

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The reactive zwitterionic 1 : 1 intermediate 6 generated in situ from the reaction between an isocyanide 2 and a dialkyl acetylenedicarboxylate (=dialkyl but‐2‐ynedioate) 3 was trapped by an N‐arylmaleimide or ‐phthalimide 4 to produce a highly functionalized 1‐oxa‐6‐azaspiro[4.4]nona‐3,8‐diene‐3,4‐dicarboxylate 5 in excellent yield (Scheme and Table).
Synthesis of Novel Gemini Dicationic Acidic Ionic Liquids and Their Catalytic Performances in the Beckmann Rearrangement
Authors: Liu Xiaofei , Xiao Linfei , Wu Hugjiltu , Chen Jing , Xia Chungu
Published: May 2009

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A series of novel gemini dicationic acidic ionic liquids (GDAILs), compounds 1–3 carrying two SO3H groups at the cation moieties and having anions of the type CF3SO$\rm{ _3^ - }$, were synthesized in good yields (Scheme 1). Some physicochemical properties of 1–3 were determined; due to their unique structures, these novel GDAILs showed noticeable hydrophilic properties and strong acidities (Table 1). Beckmann rearrangements of oximes catalyzed by 1, 2, or 3/zinc chloride (GDAIL/ZnCl2) were investigated (Scheme 2); the corresponding amides were formed in up to 99% yield in the presence of 5 mol‐% of GDAIL/ZnCl2 catalyst under optimized conditions (Tables 2 and 3). The peculiar solubilities of 1–3 made the separation of the catalysts from the products very facile, and the catalytic system could be recycled and reused for three times.
Copper‐ and Phosphine‐Free Sonogashira Coupling Reaction Catalyzed by Polyurea‐Encapsulated Palladi­um(II)
Authors: Kuang Yun‐Yan , Chen Fen‐Er
Published: May 2009

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A polyurea‐encapsulated palladium catalyst (Pd EnCatTM 30) was first applied to Sonogashira cross‐coupling reactions in the absence of a copper salt co‐catalyst and under phosphine‐free conditions. This polymer‐anchored homogeneous palladium catalyst efficiently catalyzed the Sonogashira reaction of various iodoarenes with terminal alkynes in H2O/MeCN, and good yields were obtained at 40° after 3–7 h in the presence of piperidine. Moreover, this catalyst maintains its efficiency through three recycle runs.
New Derivatives of Ascomycin with Modifications in the Amino Acid Region – Synthesis and Biological Activities, and X‐Ray Crystal Structure of 5,6‐Dehydroascomycin
Authors: Bulusu Murty A. R. C. , Waldstätten Peter , Tricotet Thomas , Rochais Christophe , Steck Andrea , Bacher Markus , Schulz Gerhard , Meingassner Josef G. , Hiestand Peter , Zenke Gerhard , Schuler Walter , Wagner Trixie
Published: May 2009

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The immunomodulatory macrolide ascomycin (1a) inhibits T‐cell activation via binding to macrophilin‐12 and inhibition of the phosphatase calcineurin. Its structural analogs pimecrolimus and tacrolimus have recently become available as the first novel topical treatments of atopic dermatitis since the introduction of topical corticosteroids in the 1950s. This stimulated the search for novel derivatives with an improved biological profile. Though several derivatives of 1a are known, only a few derivatives with modifications on the amino acid moiety are available because of the chemical inaccessibility of this region. To this end, we present here a new approach using a photochemical reaction as the key step. Thus, irradiation of ascomycin (1a) led to mixtures of the methoxy products 2a and 8, the cleavage product 4a, the but‐1‐enyl derivative 7, and the oxazolidinone 9 depending on the solvent. The selectivity of the reaction was improved to furnish 2a or 9 in preparatively useful yields. The mechanism and scope of the reaction were investigated. Starting from 2a, several analogs featuring novel modifications on the amino acid moiety, which are not easily accessible through routine methods, were synthesized in a few steps. Further, using the photoreaction key intermediates with potential for broader modifications on the amino acid moiety were synthesized, and their utility was exemplified by the synthesis of vinylpipecolic acid and vinylproline analogs. An interesting photochemical cleavage of the amide bond in the derivatives of ascomycin (1a) is presented. The structural and conformational features of the new analogs together with the X‐ray crystal structure of 5,6‐dehydroascomycin (6a) are presented, and their biological activities are discussed. Of all the derivatives, 6a showed the best activities in in vitro and in vivo models of allergic contact dermatitis whilst showing a lower risk of immunosuppression.
The association study of three FYN polymorphisms with prophylactic lithium response in bipolar patients
Authors: Szczepankiewicz Aleksandra , Skibinska Maria , Suwalska Aleksandra , Hauser Joanna , Rybakowski Janusz K.
Published: May 2009

FYN belongs to the protein kinase family that phosphorylates NMDA receptor subunits, participating in the regulation of ion transmission and BDNF/TrkB signal transduction pathway. Lithium inhibits glutamatergic transmission via NMDA receptors, exerting neuroprotective effect against excitotoxicity. The aim of this study was to find possible association of three polymorphisms of FYN gene with prophylactic lithium response in the group of bipolar patients.

We analyzed 101 bipolar patients treated with lithium carbonate for 5–27 years (mean 15 years). Twenty‐four patients were identified as excellent lithium responders (ER), 51 patients as partial responders (PRs), and 26 patients were non‐responders. Genotypes of the three analyzed polymorphisms were established by PCR‐RFLP. Statistical analysis was done with Statistica.

No significant differences in genotype distribution and allele frequencies were observed between T/G and A/G FYN polymorphisms and lithium response. We observed a trend toward association of TT genotype and T allele of T/C polymorphism with worse lithium response.

The results of the study demonstrated only marginal association between FYN polymorphisms and prophylactic lithium response in bipolar patients. The results are discussed in light of our previous studies on FYN gene in bipolar illness and BDNF gene in lithium response. Copyright © 2009 John Wiley & Sons, Ltd.
Simulation of Populus euphratica root uptake of groundwater in an arid woodland of the Ejina Basin, China
Authors: Zhu Yonghua , Ren Liliang , Skaggs Todd H. , Lü Haishen , Yu Zhongbo , Wu Yanqing , Fang Xiuqin
Published: May 2009

The Ejina Basin is an extremely arid subwatershed in Northwest China. The predominant natural tree species in the area, Populus euphratica, depends on groundwater for sustenance. In recent decades, groundwater overdraft and increased water diversions from the Heihe River caused water table elevations to decline, such that large areas of P. euphratica have withered, creating a highly visible symbol of ecological change and desertification in the Ejina Basin. Ecological restoration efforts aimed at saving existing woodlands and cultivating new stands of P. euphratica are underway. To provide a better scientific basis for ecological restoration plans, it is necessary to understand the effect of water table elevation on P. euphratica water uptake. In this work, we used the HYDRUS‐1D software package to study groundwater movement into the root zone and the uptake of groundwater in a 10‐year‐old P. euphratica woodland. Additionally, we examined the changes in uptake that would occur for different water table elevations. The model calibration was confirmed by comparing predicted soil moisture contents during the P. euphratica growing season with field measured values. The results indicate that in 2000, with an average water table depth of 2·64 m, P. euphratica at the study site obtained about 53% of its water from groundwater during the middle part of the growing season (day of year 160–290). Simulations made with constant water table depths found that increasing the water table depth from 2 to 3 metres resulted in a 74% reduction in transpiration. Many factors can influence the optimal water table depth at a given site. An advantage of the modelling approach is that these factors can be systematically varied, creating a site‐specific impact assessment of water management options that may alter water table depths, thus aiding ecological restoration efforts. Copyright © 2009 John Wiley & Sons, Ltd.
Sphingosine kinase 2 deficient tumor xenografts show impaired growth and fail to polarize macrophages towards an anti‐inflammatory phenotype
Authors: Weigert Andreas , Schiffmann Susanne , Sekar Divya , Ley Stephanie , Menrad Heidi , Werno Christian , Grosch Sabine , Geisslinger Gerd , Brüne Bernhard
Published: May 2009

A challenging task of the immune system is to fight cancer cells. However, a variety of human cancers educate immune cells to become tumor supportive. This is exemplified for tumor‐associated macrophages (TAMs), which are polarized towards an anti‐inflammatory and cancer promoting phenotype. Mechanistic explanations, how cancer cells influence the macrophage phenotype are urgently needed to address potential anti‐cancer strategies along this line. One potential immune modulating compound, sphingosine‐1‐phosphate (S1P), was recently highlighted in both tumor growth and immune modulation. Using a xenograft model in nude mice, we demonstrate a supportive role of sphingosine kinase 2 (SphK2), one of the S1P‐producing enzymes for tumor progression. The growth of SphK2‐deficient MCF‐7 breast tumor xenografts was markedly delayed when compared with controls. Infiltration of macrophages in SphK2‐deficient and control tumors was comparable. However, TAMs from SphK2‐deficient tumors displayed a pronounced anti‐tumor phenotype, showing an increased expression of pro‐inflammatory markers/mediators such as NO, TNF‐α, IL‐12 and MHCII and a low expression of anti‐inflammatory IL‐10 and CD206. These data suggest a role for S1P, generated by SphK2, in early tumor development by affecting macrophage polarization. © 2009 UICC
Insulin‐like growth factor 1 receptor expression in wild‐type GISTs: A potential novel therapeutic target
Authors: Pantaleo Maria A. , Astolfi Annalisa , Di Battista Monica , Heinrich Michael C. , Paterini Paola , Scotlandi Katia , Santini Donatella , Catena Fausto , Manara Maria C. , Nannini Margherita , Maleddu Alessandra , Saponara Maristella , Lolli Cristian , Formica Serena , Biasco Guido
Published: May 2009

Aberrations of the Insulin‐like Growth Factor (IGF) system have been found in association with a variety of cancer types. The potential role of IGF1R has been postulated in a small subset of GISTs, but until now the implications of its aberrations have not been defined. The aim of the study was to examine the IGF1R status in patients with gastric GIST in regard to KIT and PDGFRA genotype. Fresh resection specimens were collected from 8 primary tumours [2 wild‐type (WT) and 6 mutant cases]. IGF1R was studied as gene expression profiling with Affymetrix GeneChip HG‐U133Plus 2.0 arrays and as genomic copy number with SNP array analysis Affymetrix Genome Wide Human SNP 6.0 arrays, and at protein level with western blotting (WB) and immunohistochemistry (IHC). The unsupervised analysis of gene expression profiling of our patients merged with a data set from gastric GISTs identified 2 patients out of 8 with different expression of IGF1R. The data were confirmed by WB and IHC. In particular, IGF1R was upregulated in 2 young patients (<30‐years old), who had both WT disease and metastases at diagnosis. The SNP array analysis showed that none of the tumours had IGF1R amplification. GISTs are characterized by abnormalities of the KIT and PDGFRA receptors that affect prognosis and response to tyrosine kinase inhibitors. Both young adult with WT GIST had the over‐expression of IGF1R at mRNA and protein level. These results further confirm the hypothesis that IGF1R may be a potential therapeutic target in GISTs lacking KIT and PDGFRA mutations. © 2009 UICC
No mutations of FGFR3 in normal urothelium in the vicinity of urothelial carcinoma of the bladder harbouring activating FGFR3 mutations in patients with bladder cancer
Authors: Otto Wolfgang , Denzinger Stefan , Bertz Simone , Gaumann Andreas , Wild Peter J. , Hartmann Arndt , Stoehr Robert
Published: May 2009

Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene causing constitutive oncogenic protein activation have been shown to be frequent in papillary noninvasive bladder tumours and are associated with a low risk of progression and a favourable outcome. FGFR3 alterations have also been found in benign urothelial papilloma and flat urothelial hyperplasia suggesting FGFR3 alterations as an early event in bladder tumorigenesis. To date there is no data available on FGFR3 mutations in normal urothelium from patients with bladder cancer. We therefore analysed 64 samples of histopathological unsuspicious normal urothelium from 38 patients with FGFR3 mutated bladder tumours and 15 samples of urothelium from patients (n = 15) without any urothelial malignancy as a control group. Urothelial cells were microdissected from formalin‐fixed, paraffin‐embedded material. After DNA isolation whole genome amplification was done by I‐PEP‐PCR. FGFR3 mutations were detected using SNaPshot analysis. All samples could successfully be investigated. FGFR3 analyses did not reveal any mutation in the urothelium from neither the control group nor the bladder cancer group. All urothelial samples showed a wildtype sequence for FGFR3. These data suggest that mutations in the FGFR3 gene are not the earliest genetic alterations in bladder carcinogenesis and are associated with a hyperproliferative (hyperplastic) phenotype in the urothelium. Chromosomal alterations like deletions on chromosome 9q or aberrant promoter hypermethylation could play more important roles in early urothelial transformation than mutational FGFR3 activation. © 2009 UICC
Elevated level of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine in leukocytes of BRCA1 mutation carriers compared to healthy controls
Authors: Dziaman Tomasz , Huzarski Tomasz , Gackowski Daniel , Rozalski Rafal , Siomek Agnieszka , Szpila Anna , Guz Jolanta , Lubinski Jan , Olinski Ryszard
Published: May 2009

Carriers of BRCA1 mutation face highly increased risk of breast and ovarian cancer and some studies with cell culture suggest that the encoded protein may be involved in oxidatively damaged DNA repair. However, no studies concerning a possible link between oxidatively damaged DNA and BRCA1 deficiency have been conducted with the mutations carriers. Therefore, to assess an involvement of BRCA in oxidative damage to DNA in the present study a broad spectrum of parameters reflecting oxidative stress/DNA damage were analyzed in 3 subject groups; (i) carriers of BRCA1 mutations without symptoms of the disease; (ii) patients with breast or ovarian cancer with the mutations and (iii) the group of healthy subjects recruited from among close relatives of the group of carriers without symptoms of the disease. We found that the endogenous levels of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodG) in leukocytes DNA and excretion rates of urinary 8‐oxodG were significantly higher in the cancer patients than in the healthy carriers. Similarly, to the cancer patient group, 8‐oxodG level in leukocytes DNA is significantly higher in the carriers group in comparison with control group. That the control group comprised close relatives of the carriers gives further credit to our finding. Since we did not observe substantial differences in the analyzed markers of oxidative stress between the controls and the carriers, the observed increase in the level may be a result of a deficiency in the repair of 8‐oxodG. © 2009 UICC
Prostaglandin E2promotes cell proliferationviaprotein kinase C/extracellular signal regulated kinase pathway‐dependent induction of c‐Myc expression in human esophageal squamous cell carcinoma cells
Authors: Yu Le , Wu William Ka Kei , Li Zhi Jie , Li Hai Tao , Wu Ya Chun , Cho Chi Hin
Published: May 2009

Overexpression of cyclooxygenase‐2 (COX‐2) and elevation of its derivative prostaglandin E2(PGE2) are implicated in human esophageal squamous cell carcinoma. The expression of c‐Myc, an oncogenic transcription factor, is also upregulated in this malignant disease. This study sought to elucidate whether a functional connection exists between COX‐2/PGE2and c‐Myc in esophageal squamous cell carcinoma. Results showed that PGE2substantially increased the proliferation of cultured esophageal squamous cell carcinoma cells. In this regard, PGE2substantially increased the mRNA and protein expression of c‐Myc and its association with the binding partner Max. Knockdown of c‐Myc by RNA interference also significantly attenuated PGE2‐induced cell proliferation. Further, mechanistic study revealed that PGE2increased the protein stability and nuclear accumulation of c‐Mycviaphosphorylation on serine 62 in an extracellular signal regulated kinase (ERK)‐dependent manner. To this end, ERK activation by PGE2was completely abolished by protein kinase C (PKC) inhibitors. Moreover, the effect of PGE2on c‐Myc expression was mimicked by EP2 receptor agonist. In addition, knockdown of EP2 receptor by EP2 siRNA attenuated PGE2‐induced c‐Myc expression. Collectively, our findings suggest that PGE2upregulates c‐Mycviathe EP2/PKC/ERK pathway. This study sheds new light on the carcinogenic mechanism of PGE2in esophageal squamous cell carcinoma. © 2009 UICC
Regulatory role of Sirt1 on the gene expression of fatty acid‐binding protein 3 in cultured porcine adipocytes
Authors: Shan Ti Z. , Ren Yang , Wu Ting , Liu Chen X. , Wang Yi Z.
Published: May 2009

To investigate whether Sirt1 could modulate fatty acid‐binding protein 3 (FABP3), we treated porcine adipocytes either with the Sirt1 inhibitor nicotinamide (NAM), with the Sirt1 activator resveratrol (RES), or by knockdown of Sirt1 by Sirt1‐siRNA. NAM or knockdown with Sirt1‐siRNA significantly inhibited Sirt1 mRNA expression, while increasing FABP3 mRNA levels. RES or RES + Sirt1‐siRNA treatments further proved that Sirt1 negatively regulated FABP3 gene expression in adipocytes. We also found a similar Sirt1 regulation pattern for PPARγ to that of FABP3 in adipocytes. Furthermore, NAM/RES + PPARγ‐siRNA treatments showed that Sirt1 may regulate the FABP3 gene expression partly through the PPARγ‐mediated signals. In summary, Sirt1 regulates the expression of FABP3 gene in adipocytes, and PPARγ apparently plays an important role in this process. J. Cell. Biochem. 107: 984–991, 2009. © 2009 Wiley‐Liss, Inc.
Runx and ThPOK: A balancing act to regulate thymocyte lineage commitment
Authors: Egawa Takeshi
Published: May 2009

CD4‐positive helper T cells and CD8‐positive cytotoxic T cells comprise the majority of T lymphocytes present in secondary lymphoid organs and are essential for acquired immunity. These two populations are derived from common precursors in the thymus and selected through interaction between their clonal T‐cell receptors and major histocompatibility complex molecules. Although intensely studied as a model system for binary cell fate decisions, the mechanisms underlying the helper versus cytotoxic lineage choice in the thymus has been elusive. In the past few years, it has been demonstrated that the Runx family of transcription factors, particularly Runx3, is essential for the generation of cytotoxic lineage T cells, whereas the ThPOK zinc finger transcription factor that plays a crucial role in the differentiation of the helper lineage. Recent works have implied that a cross‐regulation between Runx and ThPOK contributes to appropriate thymocyte lineage commitment. In this article, recent findings on the transcription factor networks governing thymocyte lineage decisions are discussed, focusing on the two factors, and provide insights into mechanisms of lineage‐specific gene regulation in the process of T‐cell commitments. J. Cell. Biochem. 107: 1037–1045, 2009. © 2009 Wiley‐Liss, Inc.
Role of hypoxia in the hallmarks of human cancer
Authors: Ruan Kai , Song Gang , Ouyang Gaoliang
Published: May 2009

Hypoxia has been recognized as one of the fundamentally important features of solid tumors and plays a critical role in various cellular and physiologic events, including cell proliferation, survival, angiogenesis, immunosurveillance, metabolism, as well as tumor invasion and metastasis. These responses to hypoxia are at least partially orchestrated by activation of the hypoxia‐inducible factors (HIFs). HIF‐1 is a key regulator of the response of mammalian cells to oxygen deprivation and plays critical roles in the adaptation of tumor cells to a hypoxic microenvironment. Hypoxia and overexpression of HIF‐1 have been associated with radiation therapy and chemotherapy resistance, an increased risk of invasion and metastasis, and a poor clinical prognosis of solid tumors. The discovery of HIF‐1 signaling has led to a rapidly increasing understanding of the complex mechanisms involved in tumor hypoxia and has helped greatly in screening novel anticancer agents. In this review, we will first introduce the cellular responses to hypoxia and HIF‐1 signaling pathway in hypoxia, and then summarize the multifaceted role of hypoxia in the hallmarks of human cancers. J. Cell. Biochem. 107: 1053–1062, 2009. © 2009 Wiley‐Liss, Inc.
A stationary‐wave model of enzyme catalysis
Authors: Canepa Carlo
Published: May 2009

An expression for the external force driving a system of two coupled oscillators in the condensed phase was derived in the frame of the Debye theory of solids. The time dependence and amplitude of the force is determined by the size of the cell embedding the coupled oscillators and its Debye temperature (θD). The dynamics of the driven system of oscillators were followed in the two regimes of (a) low θD and cell diameter, as a model of liquid water, and (b) large θD and cell diameter, as a model of the core of a protein. The response in potential energy of the reference oscillator was computed for all possible values of the internal parameters of the system under investigation. For protein cores, the region in the parameter space of high maximum potential energy of the reference oscillator is considerably extended with respect to the corresponding simulation for water. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Hydrated germanium (II): Irregular structural and dynamical properties revealed by a quantum mechanical charge field molecular dynamics study
Authors: Azam S. Sikander , Lim Len Herald V. , Hofer Thomas S. , Randolf Bernhard R. , Rode Bernd M.
Published: May 2009

Structural and dynamical properties of Ge (II) in aqueous solution have been investigated using the novel ab initio quantum mechanical charge field (QMCF) molecular dynamics (MD) formalism. The first and second hydration shells were treated by ab initio quantum mechanics at restricted Hartree–Fock (RHF) level using the cc‐pVDZ‐PP basis set for Ge (II) and Dunning double‐ζ plus polarization basis sets for O and H. Besides ligand exchange processes and mean ligand residence times to observe dynamics, tilt‐ and theta‐angle distributions along with an advanced structural parameter, namely radial and angular distribution functions (RAD) for different regions were also evaluated. The combined radial and angular distribution depicted through surface plot and contour map is presented to provide a detailed insight into the density distribution of water molecules around the Ge2+ ion. A strongly distorted hydration structure with two trigonal pyramidal substructures within the first hydration shell is observed, which demonstrates the lone‐pair influence and provides a new basis for the interpretation of the catalytic and pharmacological properties of germanium coordination compounds. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Non‐Born–Oppenheimer dynamics calculations using the coherent switching with decay of mixing method
Authors: Li Bin , Chu Tian‐Shu , Han Ke‐Li
Published: May 2009

A theoretical investigation of the nonadiabatic processes that are involved in the full three‐dimensional D+H2, H+D2, D++H2, and H++D2 reaction systems has been performed using the method of coherence switching with decay of mixing (CSDM) developed by Truhlar and coworkers. The electronic density matrix for each trajectory is fully coherent in the CSDM method, and a switching algorithm different to the original “decay of mixing” method is used to determine the pure state toward which the decoherent force drives the system. By solving the equations for the evolution of the electronic state populations along the semiclassical trajectory, the ensemble can present effective physical insight into nonadiabatic dynamics. The calculations for the D+H2 and H+D2 systems is based on the double many body expansion potential energy surface. The potential energy surface constructed by Kamisaka et al. is employed in the calculation of D++H2 and H++D2 reactions. The cross sections and the reaction probabilities for the total angular momentum J = 0 are calculated for all of these systems. The calculated results from the CSDM method are in good agreement with exact quantum mechanical calculations and experimental measurements. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010