bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclic 1,2‐Diketones as Core Building Blocks: A Strategy for the Total Synthesis of (−)‐Terpestacin
Authors: Trost Barry M. , Dong Guangbin , Vance Jennifer A.
Published: April 2010

We report a full account of our work towards the total synthesis of (−)‐terpestacin (1), a sesterterpene originally isolated from fungal strain Arthrinium sp. FA1744. Its promising anti‐HIV and anti‐cancer activity, as well as its novel structure, make terpestacin an attractive synthetic target. A strategy based on the unique reactivity of cyclic 1,2‐diketones (diosphenols) was developed and total synthesis of 1 was achieved in 20 steps, in the longest linear sequence, from commercially available 2‐hydroxy‐3‐methyl‐2‐cyclopenten‐1‐one. The key feature of our synthesis is the double usage of a “Pd AAA‐Claisen” protocol (AAA=asymmetric allylic alkylation), first in the early stages to generate the C1 quaternary center and then in the late stages to install the side chain. In addition, a rather unusual ene‐1,2‐dione moiety was synthesized and utilized as an excellent Michael acceptor to attach the C15 substituent. Several possible routes towards the total synthesis have been examined and carefully evaluated. During our exploration many interesting chemoselectivity issues have been addressed, such as a highly selective ring‐closing metathesis and a challenging oxidation of a disubstituted olefin in the presence of three trisubstiuted ones.
Oligomerization of 1,2‐Ethanedithiol: An Expedient Approach to Oligothiaethylenethioglycols
Authors: Berkovich‐Berger Dvora , Lemcoff N. Gabriel , Abramson Sarah , Grabarnik Mikhail , Weinman Sarah , Fuchs Benzion
Published: April 2010

Reactions of ethylenedithioglycol (ETG) with Na2CO3, K2CO3, and Cs2CO3 provided the oligothiaethylenethioglycols (nETG): di‐ (DETG), tri‐ (TrETG), tetra‐ (TETG), and pentathiaethylenethioglycol (PETG), along with higher polymers. The most efficient carbonate was K2CO3 and reactions using DETG and TrETG as starting materials—or their mixtures—were also found to afford similar species. This largely unknown oligomerization process was thoroughly explored and potential pathways were put forward. A convenient conversion of ETG to laboratory quantities of the otherwise scarce and/or expensive DETG, TrETG, TETG, and PETG oligomers, in organic or aqueous media was achieved. Notably, this straightforward reaction takes place without the addition of expensive or toxic metal catalysts and with pure water as the solvent, thereby highlighting its potential as a green chemical reaction. Moreover, the process opens up new approaches to dynamic combinatorial libraries (DCLs) of oligomers and macrocycles with manifolded nETG [(SCH2CH2)nS] bridges.
Stereodivergent Quaternization of 2‐Alkyl‐2‐p‐tolylsulfinylacetonitriles: NMR Spectroscopic Evidence of Planar and Pyramidal Benzylic Carbanions
Authors: García Ruano José Luis , Martín‐Castro Ana M. , Tato Francisco , Torrente Esther , Poveda Ana M.
Published: April 2010

Enantiomerically enriched α,α‐disubstituted phenylacetonitriles have been readily prepared by stereoselective quaternization of 2‐alkyl‐2‐[2‐(p‐tolylsulfinyl)phenyl]acetonitriles with different alkylating electrophiles in the presence of bases. The use of potassium hexamethyldisilazane (KHMDS)/[18]crown‐6 ether and NHMDS with alkyl halides afforded S,SS and R,SS diastereoisomers, respectively, in high enantiomeric purities, thus providing stereodivergent processes for synthesizing both isomers. The dependence of the stereochemical course of the reactions on the experimental conditions (mainly on the counterion) has been rationalized by assuming a planar or pyramidal structure for the benzylic carbanions. This hypothesis has been supported by NMR spectroscopic studies, which permit one to assign a chelated pyramidal structure to the sodium benzylic carbanions and an almost planar naked carbanionic structure to the potassium benzylic carbanions generated in the presence of [18]crown‐6 ether.
Response to the Comment on “The Interplay between Steric and Electronic Effects in SN2 Reactions”
Authors: Fernández Israel , Frenking Gernot , Uggerud Einar
Published: April 2010

Only by allowing full geometry optimization for all energy points along the reaction coordinates does it become possible to perform a meaningful analysis of the variation of the various energy terms during a chemical reaction. Great care should also be taken in the definitions of the energy terms, and only Pauli repulsion should be included in the steric interaction term.
Double CH Activation of Ethane by Metal‐Free SO2.+ Radical Cations
Authors: de Petris Giulia , Cartoni Antonella , Troiani Anna , Barone Vincenzo , Cimino Paola , Angelini Giancarlo , Ursini Ornella
Published: April 2010

The room‐temperature CH activation of ethane by metal‐free SO2.+ radical cations has been investigated under different pressure regimes by mass spectrometric techniques. The major reaction channel is the conversion of ethane to ethylene accompanied by the formation of H2SO2.+, the radical cation of sulfoxylic acid. The mechanism of the double CH activation, in the absence of the single activation product HSO2+, is elucidated by kinetic studies and quantum chemical calculations. Under near single‐collision conditions the reaction occurs with rate constant k=1.0×10−9 (±30 %) cm3 s−1 molecule−1, efficiency=90 %, kinetic isotope effect kH/kD=1.1, and partial H/D scrambling. The theoretical analysis shows that the interaction of SO2.+ with ethane through an oxygen atom directly leads to the CH activation intermediate. The interaction through sulfur leads to an encounter complex that rapidly converts to the same intermediate. The double CH activation occurs by a reaction path that lies below the reactants and involves intermediates separated by very low energy barriers, which include a complex of the ethyl cation suitable to undergo H/D scrambling. Key issues in the observed reactivity are electron‐transfer processes, in which a crucial role is played by geometrical constraints. The work shows how mechanistic details disclosed by the reactions of metal‐free electrophiles may contribute to the current understanding of the CH activation of ethane.
New Chiral N‐Heterocyclic Carbene Ligands in Palladium‐Catalyzed α‐Arylations of Amides: Conformational Locking through Allylic Strain as a Device for Stereocontrol
Authors: Jia Yi‐Xia , Katayev Dmitry , Bernardinelli Gérald , Seidel Thomas M. , Kündig E. Peter
Published: April 2010

New Enders/Herrmann‐type chiral N‐heterocyclic carbene (NHC) ligands have been developed and applied in asymmetric palladium‐catalyzed intramolecular α‐arylations of amides. The best ligands feature the bulky tert‐butyl group and ortho‐substituted aryl groups at the stereogenic centers. Aryl bromides readily react at room temperature and aryl chlorides at 50 °C. The highly enantiomerically enriched (up to 96 % ee) 3‐alkyl‐3‐aryloxindole products were obtained in generally high yields (>95 %) except in cases of steric congestion. The critical roles both of the bulky alkyl group and of the ortho‐aryl substituent at the stereogenic center of the ligand were revealed in the crystal structure of a [Pd(η3‐allyl)(NHC‐L*)(I)] complex. The ligand aryl location and orientation is fixed by conformational locking that minimizes A1,3‐strain and enables optimal transfer of chiral information.
Supramolecular Tetrad of Subphthalocyanine–Triphenylamine–Zinc Porphyrin Coordinated to Fullerene as an “Antenna‐Reaction‐Center” Mimic: Formation of a Long‐Lived Charge‐Separated State in Nonpolar Solvent
Authors: El‐Khouly Mohamed E. , Ju Dong Kyu , Kay Kwang‐Yol , D'Souza Francis , Fukuzumi Shunichi
Published: April 2010

We report here the formation of a long‐lived charge‐separated state of a self‐assembled donor–acceptor tetrad, formed by axial coordination of a fulleropyrrolidine appended with an imidazole coordinating ligand (C60Im) to the zinc center of a subphthalocyanine–triphenylamine–zinc porphyrin (SubPc–TPA–ZnP), as a charge‐stabilizing antenna reaction center mimic in toluene. The subphthalocyanine and triphenylamine entities, with their high‐energy singlet states, act as an energy‐transferring antenna unit to produce a singlet zinc porphyrin. The formation constant for the self‐assembled tetrad was determined to be 1.0×104 M−1, suggesting a moderately stable complex formation. The geometric and electronic structures of the covalently linked SubPc–TPA–ZnP triad and self‐assembled SubPc–TPA–ZnP:C60Im tetrad were examined by using an ab initio B3LYP/6‐31G method. The majority of the highest occupied frontier molecular orbital was found over the ZnP and TPA entities, whereas the lowest unoccupied molecular orbital was located over the fullerene entity, suggesting the formation of the radical‐ion pair (SubPc–TPA–ZnP.+:C60Im.−). The redox measurements revealed that the energy level of the radical‐ion pair in toluene is located lower than that of the singlet and triplet states of the zinc porphyrin and fullerene entities. The femtosecond transient absorption measurements revealed fast charge separation from the singlet porphyrin to the coordinated C60Im with a lifetime of 1.1 ns. Interestingly, slow charge recombination (1.6×105 s−1) and the long lifetime of the charge‐separated state (6.6 μs) were obtained in toluene by utilizing the nanosecond transient measurements.
Transition States and Origins of 1,4‐Asymmetric Induction in Alkylations of 2,2,6‐Trialkylpiperidine Enamines
Authors: Um Joann M. , Kaka Naeem S. , Hodgson David M. , Houk K. N.
Published: April 2010

The asymmetric C‐alkylation of chiral enamines derived from terminal epoxides and lithium 2,2,6‐trialkylpiperidides has previously been shown to provide α‐alkylated aldehydes by intermolecular nucleophilic substitution in good levels of asymmetric induction. We now report a computational study of the origins of asymmetric induction in these reactions. Computational modeling with density functional theory (B3LYP/6‐31G(d)) agrees closely with the experimental observations. This stereoselectivity is attributed to a preferential conformation of the enamine and the piperidine ring that places the C‐6 alkyl substituent in an axial position due to A1, 3 strain. Preferential attack occurs away from the axial group, for steric reasons. The effects of changing the C‐6 substituent from methyl to isopropyl were studied, and twist transition states were found to contribute significantly in the latter alkylations.
Counterion Effects on the Columnar Mesophases of Triphenylene‐Substituted [18]Crown‐6 Ethers: Is Flatter Better?
Authors: Kaller Martin , Deck Christopher , Meister Annette , Hause Gerd , Baro Angelika , Laschat Sabine
Published: April 2010

The twisted lateral tetraalkyloxy ortho‐terphenyl units in dibenzo[18]crown‐6 ethers 1 a–f were readily converted into the flat tetraalkyloxytriphenylene systems 2 a–f by oxidative cyclization with FeCl3 in nitromethane. Reactions of the latter with potassium salts gave complexes KX⋅2, which displayed mesomorphic properties. The aromatization increased both the clearing and melting points; the mesophase stabilities, however, were mainly influenced by the respective anions upon complexation with various potassium salts. In contrast, the alkyl chain lengths played only a secondary role. Among the potassium complexes of triphenylene‐substituted crown ethers KX⋅2, only those with the soft anions I− and SCN− displayed mesophases with expanded phase temperature ranges of 93 °C and 132 °C (for KX⋅2 e), respectively, as compared to the corresponding o‐terphenyl‐substituted crown ether complexes KI⋅1 e (ΔT=51 °C) and KSCN⋅1 e (plastic crystal phase). Anions such as Br−, Cl−, and F− decreased the mesophase stability, and PF6− led to complete loss of the mesomorphic properties of KPF6⋅2 although not for KPF6⋅1. For crown ether complexes KX⋅2 (X=F, Cl, Br, I, BF4, and SCN), columnar rectangular mesophases of different symmetries (c2 mm, p2 mg, and p2 gg) were detected. In contrast to findings for the twisted o‐terphenyl crown ether complexes KX⋅1, the complexation of the flat triphenylene crown ethers 2 with KX resulted in the formation of organogels. Characterization of the organogel of KI⋅2 e in CH2Cl2 revealed a network of fibers.
Immunosuppressive Resveratrol Aneuploids from Hopea chinensis
Authors: Ge Hui Ming , Yang Wen Hao , Shen Yan , Jiang Nan , Guo Zhi Kai , Luo Qiong , Xu Qiang , Ma Jing , Tan Ren Xiang
Published: April 2010

Two novel resveratrol aneuploids, hopeachinols A (1) and B (2), as well as a potent immunosuppressive polyphenol diptoindonesin G (3) were characterized from the ethanol extract of Hopea chinensis stem barks. The structure of the polyphenols was accommodated by comprehensive spectroscopic analysis with the absolute stereochemistry determined by the CD approach coupled with theoretical ECD spectra computer‐generated through the Gaussian 03 program. The distinct structure and biological profile of 3 recommended it as a starting molecule for the relevant drug discovery.
Open system approaches in deterministic models of the emergence of homochirality
Authors: Lente Gábor
Published: April 2010

Three different general strategies are proposed for kinetic models of the emergence of homochirality in open systems: flow‐through reactors, photochemical energy input, and chemical energy input from a sacrificial reagent. Using a simple, second‐order chiral autocatalytic core model, it is shown that all these scenarios lead to similar mathematical description despite the fundamentally different chemical background and practically complete homochirality is reached in all of these cases. It is also argued that the photochemical energy input scenario might not be compatible with a sunlight‐driven natural process. Chirality, 2010. © 2010 Wiley‐Liss, Inc.
ESI‐MS investigation of solvent effects on the chiral recognition capacity of tartar emetic towards neutral side‐chain amino acids
Authors: Wijeratne Aruna B. , Yang Samuel H. , Gracia Jose , Armstrong Daniel W. , Schug Kevin A.
Published: April 2010

The effect of solvent systems on previously‐reported ESI‐MS based proton‐assisted enantioselective molecular recognition phenomena of tartar emetic, L‐antimony(III)‐tartrate, was evaluated. This was achieved by carrying out a series of competitive binding experiments using chiral selectors, bis(sodium) D‐ and ‐L‐antimony(III)‐tartrates with chiral selectands, neutral side‐chain amino acid enantiomeric isotopomers of alanine (Ala), valine (Val), leucine (Leu) and phenylalanine (Phe), in three different solvent systems, ACN/H2O (75/25 v/v), H2O (100%) and H2O/MeOH (25/75 v/v). Observations from these experiments suggest that the effect of solvent systems on previously reported proton‐assisted chiral recognition capacity of D,L‐antimony(III)‐tartrates is small, but not negligible. It was observed that an ACN/H2O (75/25 v/v) solvent system facilitates and enhances the chiral discrimination capacity of protonated {[D,L‐Sb2‐tar2][H]}− ionic species. Further, amino acid enantiomers showed a general trend of increasing selectivity order, Val ≤ Ala < Leu ≈ Phe towards the protonated {[D,L‐Sb2‐tar2][H]}− ionic species which was independent of the solvent system employed. The lack of enantioselective binding for {[D,L‐Sb2‐tar2]}2− ionic species was consistently recorded in respective mass spectra from all performed experiments, which suggests that ESI‐friendly solvent systems have no effect and do not influence this phenomenon. Chirality, 2011. © 2010 Wiley‐Liss, Inc.
The product operator formalism: A physical and graphical interpretation
Authors: Goldenberg David P.
Published: April 2010

The product‐operator formalism is the most commonly used tool for describing and designing multidimensional NMR experiments. Despite its relative simplicity and sound theoretical underpinnings, however, students and practitioners often find it difficult to relate the mathematical manipulations to a physical picture. In an effort to address this pedagogical challenge, the present article begins with a quantum‐mechanical treatment of pure populations of scalar‐coupled spin pairs, rather than the equilibrium population of spin pairs in different quantum states, which is the usual starting point for treatments based on the density matrix and product operators. In the context of pure populations, the product operators are shown to represent quantum correlations between the nuclei in individual molecules, and a new variation on the classical vector diagram is introduced to represent these correlations. The treatment is extended to mixed populations that begin at thermal equilibrium, and the density matrix is introduced as an efficient means of carrying out quantum calculations for a mixed population. Finally, it is shown that the operators for observable magnetization and correlations can be used as a basis set for the density matrix, providing the formal justification for the widely used rules of the product‐operator treatment. Throughout the discussion, the vector diagrams are used to help maintain a connection between the mathematics and the sometimes subtle physical principles. An electronic supplement created with the Mathematica computer program is used to provide additional mathematical details and the means to carry out further calculations. © 2010 Wiley Periodicals, Inc. Concepts Magn Reson Part A 36A: 1–23, 2010.
Compliance with quality assurance measures in patients treated for early oral tongue cancer
Authors: Hessel Amy C. , Moreno Mauricio A. , Hanna Ehab Y. , Roberts Dianna B. , Lewin Jan S. , El‐Naggar Adel K. , Rosenthal David I. , Weber Randal S.
Published: April 2010

BACKGROUND:

The objective of this study was to identify measurable parameters that provide quality data for assessing how well cancer care adheres to accepted treatment guidelines and is delivered to any given patient with oral tongue cancer.

METHODS:

A retrospective chart review included 116 patients treated for T1‐T2/N0‐N1 squamous cell carcinoma (SCC) of the oral tongue between 1998 and 2003. A set of quality measures considered critical for outcome included: 1) accurate TNM staging at presentation, 2) documentation of margin status, 3) appropriate referral for adjuvant radiation therapy, and 4) neck dissection for depth of invasion >4 mm. In addition, 26 clinical endpoints involving pretreatment assessment, staging, treatment, surveillance, and symptom control were analyzed.

RESULTS:

Patients comprised 73 men and 43 women (median age, 57 years). Forty‐one (35.3%) patients presented with stage I disease, 61 (52.6%) with stage II, and 14 (12.1%) with stage III. The overall 5‐year survival rate for all patients was 68.6%. There was a 90.5% compliance with TNM staging at presentation, 99.1% for documentation of margin status, 98.2% for adequate referral to radiation therapy, and 88.7% for appropriate neck dissection based on depth of invasion. Compliance with clinical endpoints was variable and ranged from 100% for endpoints related to radiation therapy to <40% for endpoints related to speech pathology and rehabilitation.

CONCLUSIONS:

Overall compliance with documenting the 4 parameters designated as quality measures for treatment of oral tongue SCC was acceptable, thus demonstrating that it is possible to use these data for measuring effective cancer care. Cancer 2010. © 2010 American Cancer Society.
A population‐based study of follow‐up care for Hodgkin lymphoma survivors
Authors: Hodgson David C. , Grunfeld Eva , Gunraj Nadia , Del Giudice Lisa
Published: April 2010

BACKGROUND:

The majority of Hodgkin lymphoma (HL) patients are cured, and post‐treatment visits are a major component of their management. Little is known about the quality of follow‐up care received by these survivors.

METHODS:

All patients who were diagnosed with HL in Ontario from 1992 through 2000 were identified from a population‐based cancer registry. Individual‐level linkage with physician claims was used to examine the follow‐up care received by 2071 1‐year survivors for up to 15 years after their HL diagnosis. Physician visits, imaging studies, and the use of routine and HL‐specific cancer screening tests were evaluated.

RESULTS:

Most patients had visits with both a primary care provider and an oncologist in Years 2 through 5 after their HL diagnosis. In Year 5 after HL diagnosis, 31.8% of patients had at least 1 computed tomography (CT) scan, and 62.9% had a chest x‐ray. There were 5352 CT scans performed in Years 2 through 5, and 125 patients subsequently received chemotherapy within 6 months of a CT. Among the survivors who met age criteria for routine screening, 62.5% had no evidence of colorectal cancer screening during Years 2 through 15, 32.3% had no evidence of breast cancer screening, and 19.9% had no evidence of cervical cancer screening. Among young women potentially at high risk of breast cancer because of radiation therapy, 87.1% had not received the recommended breast cancer screening.

CONCLUSIONS:

Radiologic surveillance of HL survivors rarely led to salvage therapy. Despite frequent physician contact, many survivors did not receive established cancer screening interventions, and the recommended early initiation of breast cancer screening among young women at high risk was not widely used. Cancer 2010. © 2010 American Cancer Society.
Is it useful to detect lymphovascular invasion in lymph node‐positive patients with primary operable breast cancer?
Authors: Ragage Florence , Debled Marc , MacGrogan Gaëtan , Brouste Véronique , Desrousseaux Marie , Soubeyran Isabelle , Tunon de Lara Christine , Mauriac Louis , de Mascarel Isabelle
Published: April 2010

BACKGROUND:

Lymphovascular invasion (LVI) is a widely recognized prognostic factor in lymph node‐negative breast cancers. However, there are only limited and controversial data about its prognostic significance in lymph node‐positive patients.

METHODS:

Among 931 patients operated on and monitored at the authors' institution for an invasive breast carcinoma between 1989 and 1992, all 374 lymph node‐positive breast cancers entered the study (median follow‐up, 126 months).

RESULTS:

LVI was present in 46% of tumors and was associated with age ≤40 years (P = .02), high histological grade (P = .01), and negative estrogen receptor status (P = .032), but not with tumor size, number of involved lymph nodes, or HER‐2/neu status. LVI was an independent prognostic factor for distant metastases (P = .002). Furthermore, in HER‐2/neu–negative/hormone receptor‐positive (n = 287) tumors, the number of independent prognostic factors (LVI, age, histological grade, number of involved lymph nodes, and tumor size) was associated with a 5‐years metastasis‐free survival ranging from 100% if no factors (n = 25) to 89% ± 2% if 1 or 2 factors (n = 186) and 67% ± 6 if 3, 4, or 5 factors (n = 76) were present (P < .001).

CONCLUSIONS:

LVI is an independent prognostic factor in lymph node‐positive breast cancer and merits further prospective investigations as a decision tool in the adjuvant chemotherapy setting. Cancer 2010. © 2010 American Cancer Society.
Nuclear factor κB transcription factors are coexpressed and convey a poor outcome in ovarian cancer
Authors: Annunziata Christina M. , Stavnes Helene Tuft , Kleinberg Lilach , Berner Aasmund , Hernandez Lidia F. , Birrer Michael J. , Steinberg Seth M. , Davidson Ben , Kohn Elise C.
Published: April 2010

BACKGROUND:

Recent work has suggested a role for nuclear factor κB (NF‐κB) in the propagation of ovarian cancer cell lines, but the significance and mechanism of NF‐κB in ovarian cancer is unknown. The authors hypothesized that the NF‐κB pathway is over activated in aggressive ovarian cancers.

METHODS:

The levels of 3 NF‐κB transcription factors, the activating inhibitors of NF‐κB (IκB) kinases, and the NF‐κB target matrix metalloproteinase 9 (MMP9) were assessed by immunohistochemistry in specimens of ovarian cancer that were obtained at diagnosis from a cohort of 33 patients who subsequently received combined paclitaxel, cisplatin, and cyclophosphamide. Associations were made between NF‐κB pathway proteins and outcome. The validation of coexpression was performed at the gene level in 2 independently collected cohorts of 185 and 153 ovarian cancers.

RESULTS:

The presence of NF‐κB proteins in newly diagnosed advanced ovarian cancers was established, and a potential association with overall survival was identified. Transcription factors p65 and v‐rel reticuloendotheliosis viral oncogene homolog B (RelB) were coexpressed with IκB kinase α, 1 component of a key trimolecular regulatory complex. Coexpression of the NF‐κB machinery suggested activity of NF‐κB signaling in these ovarian tumors. A significant association of p50 with poor overall survival was observed (P= .02). MMP9 expression had the opposite association, in which patients who had tumors without MMP9 staining had the poorest prognosis (P= .01), and this association held true at the gene expression level in an independently collected cohort of 185 ovarian cancers.

CONCLUSIONS:

The deregulation of NF‐κB activity may influence outcome in women who receive standard therapy for advanced ovarian cancer. Modification of the NF‐κB pathway may present an opportunity to improve outcome in the subset of women who have pathway activity. Cancer 2010. © 2010 American Cancer Society.
Value of cytology in the intraoperative assessment of ovarian tumors
Authors: Stewart Colin J. R. , Brennan Barbara A , Koay Eleanor , Naran Anup , Ruba Sukeerat
Published: April 2010

BACKGROUND:

Intraoperative pathological assessment is frequently requested in patients with suspected ovarian neoplasia so that optimal surgical management can be performed. In this study the accuracy of intraoperative cytology has been assessed and the results compared with frozen section diagnosis.

METHODS:

The study comprised 402 ovarian tumors that were submitted for intraoperative assessment in which both cytology preparations, usually scrape smears, and conventional frozen sections were examined. Each technique was evaluated independently, although the diagnosis transmitted to the surgeon was based upon the combination of the clinical, macroscopic, histological, and cytological information. The results were compared with the final pathological diagnosis in each case and cases with discordant diagnoses were reviewed.

RESULTS:

There were 226 benign lesions, 35 borderline epithelial neoplasms, and 141 malignant tumors according to the final pathological diagnosis. All benign lesions were accurately categorized using both frozen section and cytology. Thirty (86%) of the borderline tumors and 137 (97%) of the malignant tumors were accurately identified on frozen section, whereas the corresponding results for cytology were 23 (66%) and 131 (93%), respectively. There were no false‐positive diagnoses with either technique and the overall accuracy was 97.8%. Cytological evaluation provided better morphologic detail, permitted wider tumor sampling, and directed appropriate ancillary investigations in some cases.

CONCLUSIONS:

Overall, frozen section was more accurate than smear preparations in this series. However, cytology has a complementary role in the intraoperative assessment of ovarian neoplasia and provides a more specific diagnosis in some cases. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.
Dissociative Recombination of Molecular Ions. By Mats Larsson and Ann E. Orel.
Authors: Guberman Steven L.
Published: April 2010

Cambridge University Press 2008, 390 pp., hardcover $ 150.00.— ISBN 978‐0‐521‐82819‐2
Understanding Properties of Cofactors in Proteins: Redox Potentials of Synthetic Cytochromes b
Authors: Gámiz‐Hernández Ana P. , Kieseritzky Gernot , Galstyan Artur S. , Demir‐Kavuk Ozgur , Knapp Ernst‐Walter
Published: April 2010

Haehnel et al. synthesized 399 different artificial cytochrome b (aCb) models.1 They consist of a template‐assisted four‐helix bundle with one embedded heme group. Their redox potentials were measured and cover the range from −148 to −89 mV. No crystal structures of these aCb are available. Therefore, we use the chemical composition and general structural principles to generate atomic coordinates of 31 of these aCb mutants, which are chosen to cover the whole interval of redox potentials. We start by modeling the coordinates of one aCb from scratch. Its structure remains stable after energy minimization and during molecular dynamics simulation over 2 ns. Based on this structure, coordinates of the other 30 aCb mutants are modeled. The calculated redox potentials for these 31 aCb agree within 10 mV with the experimental values in terms of root mean square deviation. Analysis of the dependence of heme redox potential on protein environment shows that the shifts in redox potentials relative to the model systems in water are due to the low‐dielectric medium of the protein and the protonation states of the heme propionic acid groups, which are influenced by the surrounding amino acids. Alternatively, we perform a blind prediction of the same redox potentials using an empirical approach based on a linear scoring function and reach a similar accuracy. Both methods are useful to understand and predict heme redox potentials. Based on the modeled structure we can understand the detailed structural differences between aCb mutants that give rise to shifts in heme redox potential. On the other hand, one can explore the correlation between sequence variations and aCb redox potentials more directly and on much larger scale using the empirical prediction scheme, which—thanks to its simplicity— is much faster.
Water Adsorption on Platinum Dioxide and Dioxygen Complex: Matrix Isolation Infrared Spectroscopic and Theoretical Study of Three PtO2–H2O Complexes
Authors: Gong Yu , Zhou Mingfei
Published: April 2010

The interactions of water molecule with platinum dioxygen complex and dioxide molecule are investigated by means of matrix isolation infrared spectroscopy and density functional calculations. The platinum atoms reacted with dioxygen to form the previously reported Pt(O2) complex. The Pt(O2) complex reacted with water molecule to give the Pt(O2)–H2O complex, which was characterized to involve hydrogen bonding between one O atom of Pt(O2) and one H atom of H2O (structure A). Upon visible light irradiation, the hydrogen bonded Pt(O2)⋅⋅⋅HOH complex rearranged to another Pt(O2)–H2O isomer (structure B), which involves (O2)Pt⋅⋅⋅OH2 interaction. The Pt(O2)–H2O complex in structure B can be isomerized to the weakly bound platinum dioxide‐water complex (structure C) under UV irradiation.
The notion of computation is fundamental to an autonomous neuroscience
Authors: Neske Garrett
Published: April 2010

The increasing sophistication of the tools and results of cellular and molecular neuroscience would appear to suggest that explanatory force in neuroscience is defined by reduction to molecular biology. This view, however, is mistaken in that it loses sight of the goal of neuroscience proper: the characterization of the information content of biophysical variables and the transformation of these variables that lead to behaviors. Neuroscience is thus distinguished from applied molecular and cellular biology by the notion of computation. In this commentary, I will show how the notion of computation in neuroscience differs from that of other fields that investigate complex systems and argue that computation at various levels of neural organization is the paramount goal of neuroscientific explanation and not the so‐called reduction of “mind to molecules.” © 2009 Wiley Periodicals, Inc. Complexity, 16,10–19, 2010
Reducing ICI effect in OFDM system using low‐complexity Kalman filter based on comb‐type pilots arrangement
Authors: Mousa Allam , Mahmoud Hala
Published: April 2010

In OFDM systems, time‐varying channels destroy orthogonality between subcarriers causing Inter‐Carrier Interference. To reduce this effect, a Kalman filter, as a benchmark, is used for channel estimation, based on comb‐type pilot arrangements of the OFDM system. An advantage of comb‐type pilot arrangements in channel estimation is the ability to track the variation of the channel caused by Doppler frequency. Kalman method has been proposed to estimate the channel frequency response (CFR) at the pilot locations, then CFR, at data subchannels, is obtained by means of interpolation between estimates at pilot locations. The low‐complexity Kalman method is introduced to reduce the complexity of the system while achieving the same BER/SNR. Different types of interpolations have been also compared such as Low‐pass, Spline‐cubic and Linear interpolation methods. The BER/SNR performance of BPSK modulation schemes are considered for time varying Rayleigh fading channels. Our results has shown that the low‐complexity Kalman estimation, used with the pilot arrangement and a suitable interpolation method, gives almost the same performance as that of the Kalman method specially for low SNR values and hence the effect of Doppler shift effect is controlled. Copyright © 2010 John Wiley & Sons, Ltd.
On the identification and analysis of Skype traffic
Authors: Molnár Sándor , Perényi Marcell
Published: April 2010

Skype applies strong encryption to provide secure communication inside the whole Skype network. It also uses several techniques to conceal the traffic and the protocol. As a consequence, traditional port‐based or payload‐based identification of Skype traffic cannot be applied. In this paper, after an overview of the Skype P2P system, network entities and operation, we introduce novel algorithms to detect several types of communications (including voice calls primarily) that the Skype client initiates toward dedicated servers of the Skype network and other peers.

The common point in these algorithms is that all of them are based on packet headers only and the extracted flow level information. We do not need information from packet payloads. The identification methods allow us to discover logged on Skype users and their voice calls. The whole identification process is scripted in Transact‐SQL; it can thus be executed automatically on a prerecorded (offline) data set. We present identification results, analysis and comparison of data sets captured in mobile and fixed networks. We also present the validation of the algorithms in both network types. Copyright © 2010 John Wiley & Sons, Ltd.
Anomalous development of brain structure and function in spina bifida myelomeningocele
Authors: Juranek Jenifer , Salman Michael S.
Published: April 2010

Spina bifida myelomeningocele (SBM) is a specific type of neural tube defect whereby the open neural tube at the level of the spinal cord alters brain development during early stages of gestation. Some structural anomalies are virtually unique to individuals with SBM, including a complex pattern of cerebellar dysplasia known as the Chiari II malformation. Other structural anomalies are not necessarily unique to SBM, including altered development of the corpus callosum and posterior fossa. Within SBM, tremendous heterogeneity is reflected in the degree to which brain structures are atypical in qualitative appearance and quantitative measures of morphometry. Hallmark structural features of SBM include overall reductions in posterior fossa and cerebellum size and volume. Studies of the corpus callosum have shown complex patterns of agenesis or hypoplasia along its rostral‐caudal axis, with rostrum and splenium regions particularly susceptible to agenesis. Studies of cortical regions have demonstrated complex patterns of thickening, thinning, and gyrification. Diffusion tensor imaging studies have reported compromised integrity of some specific white matter pathways. Given equally complex ocular motor, motor, and cognitive phenotypes consisting of relative strengths and weaknesses that seem to align with altered structural development, studies of SBM provide new insights to our current understanding of brain structure–function associations. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:23–30.
Psychosocial and family functioning in spina bifida
Authors: Holmbeck Grayson N. , Devine Katie A.
Published: April 2010

A developmentally oriented bio‐neuropsychosocial model is introduced to explain the variation in family functioning and psychosocial adjustment in youth and young adults with spina bifida (SB). Research on the family functioning and psychosocial adjustment of individuals with SB is reviewed. The findings of past research on families of youth with SB support a resilience–disruption view of family functioning. That is, the presence of a child with SB disrupts normative family functioning but many families adapt to such disruption and exhibit considerable resilience in the face of adversity. Parents of youth with SB, and particularly those from lower socio‐economic status (SES) homes, are at‐risk for psychosocial difficulties. Individuals with SB are at‐risk for developing internalizing symptoms, attention problems, educational difficulties, social maladjustment, and delays in the development of independent functioning. Emerging adults are often delayed in achieving milestones related to this stage of development (e.g., vocational and educational achievements). Methodologically sound, longitudinal, and theory‐driven studies of family and psychosocial functioning are needed, as are randomized family‐based intervention trials, to promote adaptive functioning and better psychosocial outcomes in families of individuals with SB. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:40–46.
Epidemiologic and genetic aspects of spina bifida and other neural tube defects
Authors: Au Kit Sing , Ashley‐Koch Allison , Northrup Hope
Published: April 2010

The worldwide incidence of neural tube defects (NTDs) ranges from 1.0 to 10.0 per 1,000 births with almost equal frequencies between two major categories: anencephaly and spina bifida (SB). Epidemiological studies have provided valuable insight for (a) researchers to identify nongenetic and genetic factors contributing to etiology, (b) public health officials to design and implement policies to prevent NTD pregnancies, and (c) individuals to take precautions to reduce the chance of having an NTD‐affected pregnancy. Despite extensive research, our knowledge of the genetic etiology of human NTDs is limited. Although more than 200 small animal models with NTDs exist, most of these models do not replicate the human disease phenotype. Over a hundred candidate genes have been examined for risk association to human SB. The candidate genes studied include those important in folic acid metabolism, glucose metabolism, retinoid metabolism, and apoptosis. Many genes that regulate transcription in early embryogenesis and maintain planar cell polarity have also been tested as candidates. Additionally, genes identified through mouse models of NTDs have been explored as candidates. We do not know how many genes in the human genome may confer risk for NTDs in human. Less than 20% of the studied candidate genes have been determined to confer even a minor effect on risk association. Many studies have provided conflicting conclusions due to limitations in study design that potentially affect the power of statistical analysis. Future directions such as genomewide association studies (GWAS) and whole exome or even whole genome sequencing are discussed as possible avenues to identify genes that affect risk for human NTDs. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:6–15.
Neuropathology and structural changes in hydrocephalus
Authors: Del Bigio Marc R.
Published: April 2010

In the context of spina bifida, hydrocephalus is usually caused by crowding of the posterior fossa with obstruction to cerebrospinal fluid flow from the forth ventricle, and less often by malformation of the cerebral aqueduct. Enlargement of the cerebral ventricles causes gradual destruction of periventricular white matter axons. Motor, sensory, visual, and memory systems may be disturbed through involvement of the long projection axons, periventricular structures including the corpus callosum, and the fimbria‐fornix pathway. Secondary changes occur in neuronal cell bodies and synapses, but there is minimal death of neurons. The clinical syndrome of hydrocephalic brain dysfunction is thus due to subcortical disconnection. Some of the brain dysfunction is reversible by shunting, probably through restoration of cerebral blood flow and normalization of the extracellular environment. However, destroyed axons cannot be restored. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:16–22.
Transition to adult health care for adolescents with spina bifida: Research issues
Authors: Sawyer Susan M. , Macnee Sarah
Published: April 2010

The increasing survival of children and young people with congenital disabilities such as spina bifida (SB) provides a challenge to health care systems globally about how best to respond to the multitude of health, developmental, and psychosocial needs of those affected by this complex disorder across the lifespan, not just in childhood and adolescence. The goal of transition to adult health care is to maximize lifelong functioning through the provision of quality, developmentally appropriate health care that continues uninterrupted as the individual moves from adolescence to adulthood. The objective of this article is to outline the type of evidence we have around transition to adult health care in young people with SB, and to identify what additional research evidence would help inform the development of models of clinical care for young adults. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:60–65.
Neonatal amygdala or hippocampus lesions influence responsiveness to objects
Authors: Bliss‐Moreau Eliza , Toscano Jessica E. , Bauman Melissa D. , Mason William A. , Amaral David G.
Published: April 2010

Medial temporal lobe brain structures, such as the amygdala, play an important role in the normal perception and generation of emotional behavior. Little research, however, has assessed the role of such structures across the neurodevelopmental trajectory. We assessed emotional behavioral responses of rhesus macaques that received bilateral ibotenic acid lesions of the amygdala or hippocampus at 2 weeks of age and sham‐operated controls. At 9 and 18 months of age, animals interacted with novel objects that varied in visual complexity as a means of varying emotional salience. All animals behaved differently in the presence of visually simple, as compared to complex, objects, suggesting that they were sensitive to variation in emotional salience. Across both experiments, amygdala‐lesioned animals appeared to be less behaviorally inhibited insofar as they explored all objects most readily. Interestingly, hippocampus‐lesioned animals' propensity for exploration mirrored that of control animals in some contexts but that of amygdala‐lesioned animals in other contexts. At 18 months of age, both amygdala‐lesioned and hippocampus‐lesioned animals were judged to be less fearful than controls during the testing procedure. Implications for understanding the neurobiology of emotional behavior are discussed. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 487–503, 2010.
Children's and adults' salivary alpha‐amylase responses to a laboratory stressor and to verbal recall of the stressor
Authors: Yim Ilona S. , Granger Douglas A. , Quas Jodi A.
Published: April 2010

Salivary alpha‐amylase (sAA), an enzyme produced by the salivary glands, increases in response to physical and psychosocial stressors in adults. Whether similar increases are evident among children, though, is less clear, and there is a lack of studies directly comparing children's and adults' sAA responses to an identical stressor. In this study, 24 children (9–12 years; 12 female) and 26 adults (18–23 years; 16 female) were exposed to an identical psychosocial laboratory stressor and a recall interview regarding that stressor after a 2‐week delay. Saliva was collected before and 1, 10, 20, and 30 min after the stressor/recall interview. Among adults, concentrations of sAA increased on both study days, but similar increases were not detected among children. Findings suggest developmental differences in sAA reactivity, and underscore the need to characterize the confluence of elements that will reliably elicit sAA responses to mild stress in youth. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 598–602, 2010.
Evidence for neural stem cells in the medaka optic tectum proliferation zones
Authors: Alunni Alessandro , Hermel Jean‐Michel , Heuzé Aurélie , Bourrat Franck , Jamen Françoise , Joly Jean‐Stéphane
Published: April 2010

Few adult neural stem cells have been characterized in vertebrates. Although teleosts continually generate new neurons in many regions of the brain after embryogenesis, only two types of neural stem cells (NSCs) have been reported in zebrafish: glial cells in the forebrain resembling mammalian NSCs, and neuroepithelial cells in the cerebellum. Here, following our previous studies on dividing progenitors (Nguyen et al. [1999]: J Comp Neurol 413:385–404.), we further evidenced NSCs in the optic tectum (OT) of juvenile and adult in the medaka, Oryzias latipes. To detect very slowly cycling progenitors, we did not use the commonly used BrdU/PCNA protocol, in which PCNA may not be present during a transiently quiescent state. Instead, we report the optimizations of several protocols involving long subsequent incubations with two thymidine analogs (IdU and CldU) interspaced with long chase times between incubations. These protocols allowed us to discriminate and localize fast and slow cycling cells in OT of juvenile and adult in the medaka. Furthermore, we showed that adult OT progenitors are not glia, as they express neither brain lipid‐binding protein (BLBP) nor glial fibrillary acidic protein (GFAP). We also showed that expression of pluripotency‐associated markers (Sox2, Musashi1 and Bmi1) colocalized with OT progenitors. Finally, we described the spatio‐temporally ordered population of NSCs and progenitors in the medaka OT. Hence, the medaka appears as an invaluable model for studying neural progenitors that will open the way to further exciting comparative studies of neural stem cells in vertebrates. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 693–713, 2010
Protein kinase C regulates mitochondrial targeting of Nur77 and its family member Nor‐1 in thymocytes undergoing apoptosis
Authors: Thompson Jennifer , Burger Megan L. , Whang Hannah , Winoto Astar
Published: April 2010

Nur77 orphan steroid receptor and its family member Nor‐1 are required for apoptosis of developing T cells. In thymocytes, signals from the TCR complex induce Nur77 and Nor‐1 expression followed by translocation from the nucleus to mitochondria. Nur77 and Nor‐1 associate with Bcl‐2 in the mitochondria, resulting in a conformation change that exposes the Bcl‐2 BH3 domain, a presumed pro‐apoptotic molecule of Bcl‐2. As Nur77 and Nor‐1 are heavily phosphorylated, we examined the requirement of Nur77 and Nor‐1 phosphorylation in mitochondria translocation and Bcl‐2 BH3 exposure. We found that HK434, a PKC agonist, in combination with calcium ionophore, can induce Nur77 and Nor‐1 phosphorylation, translocation, Bcl‐2 BH3 exposure and thymocyte apoptosis. Inhibitors of both classical and novel forms of PKC were able to block this process. In contrast, only the general but not classical PKC‐specific inhibitors were able to block the same process initiated by PMA, a commonly used PKC agonist. These data demonstrate a differential activation of PKC isoforms by PMA and HK434 in thymocytes, and show the importance of PKC in mitochondria translocation of Nur77/Nor‐1 and Bcl‐2 conformation change during TCR‐induced thymocyte apoptosis.